Epidemic Respiratory Disease - The pneumonias and other infections of the repiratory tract

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Title: Epidemic Respiratory Disease - The pneumonias and other infections of the repiratory tract - accompanying influenza and measles
Author: Small, James C., Opie, Eugene Lindsay, Rivers, Thomas M., Blake, Francis G.
Language: English
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EPIDEMIC RESPIRATORY DISEASE
The Pneumonias and Other Infections of the Respiratory Tract
Accompanying Influenza and Measles

EUGENE L. OPIE, M.D.

COLONEL, M. R. C., U. S. ARMY; PROFESSOR OF PATHOLOGY, WASHINGTON
UNIVERSITY SCHOOL OF MEDICINE

FRANCIS G. BLAKE, M.D.

MAJOR, M. R. C., U. S. ARMY; ASSOCIATE MEMBER OF THE ROCKEFELLER
INSTITUTE FOR MEDICAL RESEARCH

JAMES C. SMALL, M.D.

FORMERLY FIRST LIEUTENANT, M. C., U. S. ARMY; BACTERIOLOGIST,
PHILADELPHIA GENERAL HOSPITAL

THOMAS M. RIVERS, M.D.

FORMERLY FIRST LIEUTENANT, M. C., U. S. ARMY; ASSOCIATE IN BACTERIOLOGY,
JOHNS HOPKINS UNIVERSITY

_ILLUSTRATED_

ST. LOUIS
C. V. MOSBY COMPANY
1921

_Press of
C. V. Mosby Company
St. Louis, U. S. A._

INTRODUCTION

Death from lobar pneumonia, bronchopneumonia and measles, fatal with few
exceptions in consequence of complicating pneumonia, constituted in 1916
approximately one-sixth (16.8 per cent) of the mortality in the army,[1]
whereas in 1917 the same diseases were responsible for nearly two-thirds
(61.7 per cent) of all deaths. During the first half of 1918 the
incidence of pneumonia steadily increased and in some army camps there
were extensive outbreaks of unusually severe pneumonia.

In July, 1918, the Surgeon General assigned a group of medical officers
to the study of the pneumonias prevalent in the army and stationed them
at Camp Funston, Kansas. At the base hospital of this camp all cases of
pneumonia occurring among troops assembled in the camp were studied, but
during the month of August there were few cases of pneumonia and these
were of mild type.

Pneumonia which occurred at Camp Funston during August was almost wholly
limited to recently recruited colored troops from southern states
(Louisiana, Mississippi). There was a low rate of mortality, and few
complications. This pneumonia exhibited a noteworthy difference in
etiology from that usually seen in civil life, for it was associated
with a high incidence of those types of pneumococci which occur in the
mouths of healthy men, namely, Pneumococcus atypical II,[2] Type III,
and the group of microorganisms represented by Type IV. Pneumococcus
Type I was encountered in only a few instances and Type II was not
found, although these two microorganisms are responsible for two-thirds
of the lobar pneumonia which occurs in civil life.

During the investigation at Camp Funston the Commission had the
courteous cooperation of Major Willard Stone, Director of Medical
Service, and received much valuable assistance from Lieutenant A.
McGlory, Registrar of the Base Hospital.

A review of the accurately compiled records of the base hospital was
made in order to obtain a history of the pneumonias and other
respiratory diseases which had occurred throughout the existence of the
camp, established in September, 1917. It soon became evident that a
disease recognized as influenza had been prevalent throughout this
period and its incidence had shown a close parallel with that of acute
bronchitis. At the same time there had been much pneumonia and a high
death rate from this disease. The chart[3] which was constructed showed
that the disease which had been designated influenza assumed epidemic
proportions in March, 1918. Any doubt that may have been entertained
concerning the nature of the disease is dispelled by the characters of
this epidemic which, beginning at the end of February, reached its
height on March 12 and rapidly subsided; 1,127 men with influenza
entered the base hospital between March 4 and March 29 and many more
were treated in the infirmaries of the camp. In April there was a second
wave of influenza and in May a third, each in large part limited to
newly drafted men brought into the camp shortly before these outbreaks.
Corresponding to the epidemic of influenza there was a great increase of
pneumonia, reaching a maximum about one week after the height of the
incidence of influenza; subsequently the incidence of pneumonia
increased after each one of the secondary waves of influenza. Pneumonia
following measles occurred throughout the history of the camp; in
November and December, 1917, there was a severe outbreak of pneumonia
following measles and the mortality was high. Our conclusions in regard
to the pneumonias which occurred during the history of Camp Funston were
as follows:

1. Pneumonia of a relatively stationary camp population, such as that
which occurred among white troops during the period of our
investigation, was in considerable part caused by Pneumococcus Types I
and II and resembled the pneumonia of civil life.

2. Pneumonia of newly drafted colored troops from southern states during
the period of our investigation was caused in great part by pneumococci
of those types which occur in the mouths of healthy men, namely, Types
IV, III and atypical II.

3. Pneumonia caused by influenza occurred after the epidemic of
influenza which we have described. The report states: “With the
information available it is not possible to draw a sharp line between
(1) the pneumonia of the stable camp population, (2) the pneumonia of
the newly drafted southern troops, and (3) the pneumonia following
influenza. It is possible that influenza, in greater or less degree,
also acts as a predisposing factor in the production of the first and
second varieties.”

4. Pneumonia with measles was a frequent and unusually fatal type of the
disease. The most important causes of pneumonia during the history of
the camp were influenza and measles.

Evidence is not lacking that influenza occurred in epidemic form in
other widely separated camps in the United States during the spring of
1918. Vaughan and Palmer[4] state that a disease strongly resembling
influenza became prevalent in the Oglethorpe camps about March 18, 1918,
and continued three weeks; during this time the number sent to hospital
or to quarters with this disease was 1,468 in a total strength of
28,586. Pneumonia does not appear to have followed this epidemic.

Miller and Lusk[5] found the ordinary type of pneumonia prevalent at
Camp Dodge, Iowa, until March 18 to 20, 1918, when abruptly the
streptococcus type predominated and there was a great increase in the
rate of mortality. A mild tracheitis, they state, was widespread in the
camp during March.

In March, 1918, one member of our commission saw an outbreak of
influenza at Fort Sam Houston which was identical in its clinical
characters with the disease which appeared as a pandemic in the fall of
1918.

The report of the Surgeon General[6] for 1919 shows that there was a
sharp increase of the incidence of influenza in the army during March,
reaching a maximum in April. The rate of influenza for 1,000 troops fell
to its original level through May and June and finally rose to a great
height in September and October.

Influenza in epidemic form made its appearance in the army camps of the
United States during March, 1918. The symptomatology of the disease
associated with its peculiar epidemiology as seen at Camp Funston make
its recognition unquestionable. The disease had doubtless been present
in this camp since its establishment in September, 1917, but did not
assume epidemic proportions until the spring of 1919.

Pneumonia followed the epidemics of influenza which occurred in the
spring of 1918 and exhibited characters similar to those of the
pneumonias which followed the pandemic of September and October, 1918.
In both instances the height of the outbreak of pneumonia has been one
week after the maximum incidence of influenza.

Influenza became epidemic in Spain about the middle of May and in other
countries received the name “Spanish influenza” which is not more
applicable than the designation “Russian influenza” often applied to the
disease during the pandemic of 1889–90.

The studies of MacNeal[7] have shown that the first epidemic of
influenza in the American Expeditionary Force in France occurred about
April 15, 1918, at a rest camp near Bordeaux, reached its height on
April 22 and ceased May 5. The disease was of a mild character with few
complications. Localized epidemics were reported from various camps and
hospitals during May and June, when the disease, MacNeal states, had
become widespread in all sections of the American Expeditionary Force in
France and in the French and British armies as well. Influenza had
become epidemic in the Italian navy in the first two weeks of May. The
belief that the disease was introduced from America, the author thinks,
is “probably completely disproved by the fact that the epidemic was
subsequently introduced into America in August and September and found
there a most fertile soil for its spread.” This view is disproved by the
demonstration that influenza had appeared as scattered epidemics in the
army camps in March, 1918. There is little reason to doubt that
influenza in the American Expeditionary Force was brought from America.

At the end of August our commission was transferred from Camp Funston to
Camp Pike, where throughout the history of the encampment pneumonia had
been so prevalent that it had given the camp the rank of third in death
rate from lobar pneumonia and fourth in death rate from bronchopneumonia
among 32 camps established in this country. We arrived at Camp Pike
September 5 and were stationed at the base hospital. Our work was
facilitated by the hearty cooperation of the commanding officer, Major
Morton R. Gibbons, who neglected no opportunity to promote the
investigation. Our work was cordially aided by Major Carl R. Comstock,
Director of the Medical Service, and by Major Henry H. Lissner, who
later occupied this position. Work in the laboratory of the hospital
received the valuable cooperation of Major Allen J. Smith, Director of
the Laboratory, who placed at our disposal every facility available.
Lieutenant James R. Davis, who was for a time in charge of the
laboratory, effectively assisted the work.

The commission consisted of the following officers: E. L. Opie, Colonel,
M. R. C.; Allen W. Freeman, Major, M. C.; Francis G. Blake, Major, M. R.
C., James C. Small, Lieutenant, M. C. and Thomas M. Rivers, Lieutenant,
M. C. Major Freeman acted as epidemiologist and will publish a report
upon the epidemiology of influenza and pneumonia at Camp Pike. On
October 11 the laboratory car “Lister” in charge of Lieutenant Warren H.
Butz was assigned to the commission. Lieutenant Harry D. Bailey was
attached to the commission on October 14 and later assisted in its work.
Valuable technical assistance was given by Sergeant Charles Behre, by
Wm. E. Hoy, detailed from the Army Medical Museum, and by Thomas Payne.

Study of the pathology of the lesions concerned was completed in the
Pathological Laboratory of Washington University School of Medicine.

The existence of an epidemic of influenza at Camp Pike was recognized on
September 23, when 214 cases of influenza were admitted to the base
hospital. Preceding this date and beginning September 1 there had been a
gradual increase of the number of patients admitted with the diagnosis
of acute bronchitis. It is noteworthy that the demonstration of B.
influenzæ had been regarded as essential for a diagnosis of influenza
and since this microorganism had not been found, instances of acute
inflammation of the respiratory passages with the symptoms of influenza
were classified under a variety of names.

After September 23 influenza was recognized by its symptoms. The number
of cases increased with great rapidity and on September 27 reached over
1,000 per day; this number was approximately maintained during one week
and after October 3 the epidemic gradually subsided. Among 52,551 men in
the camp, including those who arrived during October, 12,393 were
attacked by influenza; of these 1,499 suffered with pneumonia and 466
died. The height of the outbreak of pneumonia followed approximately one
week after that of influenza. The statistics from September 20 to
October 14 collected by Major Freeman show that pneumonia following
influenza, like the pneumonia at Camp Funston during the interepidemic
period, has a conspicuous tendency to select men who have been in the
camp less than one month, designated in Table I as new recruits:

TABLE I

════════════════════════════════╤══════════╤═════════════╤═════════════
│POPULATION│ INFLUENZA │ PNEUMONIA
────────────────────────────────┼──────────┼──────┬──────┼──────┬──────
„ │ „ │ No. │ Per │ No. │ Per
│ │ │cent. │ │cent.
────────────────────────────────┼──────────┼──────┼──────┼──────┼──────
Men in camp more than one month │ 27,782│ 4,462│ 15.6│ 493│ 1.7
New recruits │ 23,769│ 7,263│ 30.6│ 1006│ 4.2
────────────────────────────────┼──────────┼──────┼──────┼──────┼──────
Total │ 51,551│11,725│ 22.7│ 1499│ 2.9
────────────────────────────────┴──────────┴──────┴──────┴──────┴──────

New recruits were nearly two and a half times as susceptible to
pneumonia as men who had been in camp more than one month. This
statement does not take into consideration differences in the
environment and mode of living of the new men.

In view of the existing uncertainty concerning the bacteriology of
influenza and its associated pneumonias, the commission has availed
itself of the opportunity afforded by the epidemic of influenza to
determine what bacteria were present in the nasopharynx and sputum in
these diseases. The examinations have been necessarily limited to a
small proportion of the immense number of patients admitted to the
hospital with influenza and pneumonia. Autopsies on those who have died
with pneumonia have offered a more direct means of determining the
relation of bacteria to inflammation of the bronchi and lungs. An
attempt has been made to classify the pneumonias following influenza and
to determine their relation to the complex bacterial flora of the
injured respiratory passages. These studies have shown very early the
threatening prevalence of streptococcus pneumonia, and appropriate
measures have been taken to combat the spread of this infection. No
better illustration could be furnished to demonstrate the value of
routine performance of autopsies as a means for the recognition of
obscure epidemic disease.

In view of the wide difference of opinion concerning the pathology of
influenzal pneumonia special study has been given to the lesions of the
disease, because the epidemic has furnished the unique opportunity of
examining all instances of pneumonia accurately referable to an epidemic
of influenza attacking a large but definitely defined group of
individuals (50,000 troops). In a civil hospital there is often great
difficulty in deciding, even in the presence of an epidemic, if death
from pneumonia is the result of influenza, but at Camp Pike the relation
of the heightened death rate to the epidemic has excluded all save a
trivial error in determining the relation of fatal pneumonia to
influenza.

At the direction of Col. F. F. Russell, who has promoted the work of the
commission by unfailing aid, a special study has been made of the
relation of hemolytic streptococcus to the complications of measles.

During the later period of the investigation at Camp Pike experiments
were performed on monkeys to determine the pathogenicity of B. influenzæ
and of microorganism isolated from the pneumonias following influenza.
Typical lobar pneumonia was produced in monkeys by intratracheal
injection of pneumococci. These experiments are described in an
appendix.

The Surgeon General has approved the publication of this report but the
authors alone are responsible for the views expressed.

EUGENE L. OPIE.

Washington University
School of Medicine

CONTENTS

CHAPTER I
PAGE
THE ETIOLOGY OF INFLUENZA. (BY FRANCIS G. BLAKE, M.D.; THOMAS M.
RIVERS, M.D.; JAMES C. SMALL, M.D.) 25

Discussion, 43; Conclusions, 49.

CHAPTER II

CLINICAL FEATURES AND BACTERIOLOGY OF INFLUENZA AND ITS ASSOCIATED
PURULENT BRONCHITIS AND PNEUMONIA. (BY FRANCIS G. BLAKE, M.D.,
AND THOMAS M. RIVERS, M.D.) 51

Influenza, 52; Purulent Bronchitis, 56; Pneumonia, 59;
Hemolytic Streptococcus Pneumonia Following Influenza, 70;
Bacillus Influenzæ Pneumonia Following Influenza, 72; Summary,
73; Discussion, 76.

CHAPTER III

SECONDARY INFECTION IN THE WARD TREATMENT OF INFLUENZA AND
PNEUMONIA. (BY EUGENE L. OPIE, M.D.; FRANCIS G. BLAKE, M.D.;
JAMES C. SMALL, M.D.; AND THOMAS M. RIVERS, M.D.) 83

Secondary Infection with S. Hemolyticus in Pneumonia, 84;
Secondary Infection with Pneumococcus in Pneumonia, 91;
Secondary Contact Infection in Influenza, 95; Methods for the
Prevention of Secondary Contact Infection in Influenza and
Pneumonia, 98; Summary, 106.

CHAPTER IV

THE PATHOLOGY AND BACTERIOLOGY OF PNEUMONIA FOLLOWING INFLUENZA.
(BY E. L. OPIE, M.D.; F. G. BLAKE, M.D.; AND T. M. RIVERS, M.D.) 107

Bronchitis, 142; Lobar Pneumonia, 154; Bronchopneumonia, 162;
Peribronchial Hemorrhage and Pneumonia, 189; Suppurative
Pneumonia with Necrosis and Abscess Formation, 199;
Interstitial Suppurative Pneumonia, 209; Suppurative Pneumonia
with Multiple Clustered Abscesses Caused by Staphylococci,
225; Empyema, Pericarditis and Peritonitis, 232;
Bronchiectasis, 239; Unresolved Bronchopneumonia, 261.

CHAPTER V

SECONDARY INFECTION IN THE WARD TREATMENT OF MEASLES. (BY JAMES C.
SMALL, M.D.) 282

Hemolytic Streptococci with Measles at Camp Pike, 297;
Complications of Measles, 303; The Dissemination of Hemolytic
Streptococci in Wards, 315; Carriers of Hemolytic
Streptococci, 321.

CHAPTER VI

THE PATHOLOGY AND BACTERIOLOGY OF PNEUMONIA FOLLOWING MEASLES. (BY
EUGENE L. OPIE, M.D.; FRANCIS G. BLAKE, M.D.; JAMES C. SMALL,
M.D.; AND THOMAS M. RIVERS, M.D.) 334

Changes in Bronchi, 336; Lobar Pneumonia, 337;
Bronchopneumonia, 340; Suppurative Pneumonia, 347; Pneumonia
Associated with Acute Infectious Diseases other than Influenza
and Measles, 353.

CHAPTER VII

SUMMARY OF THE INVESTIGATION AND CONCLUSIONS REACHED. (BY EUGENE
L. OPIE, M.D.) 359

Lobar Pneumonia, 362; Bronchopneumonia, 363; Streptococcus
Pneumonia, 365; Staphylococcus Pneumonia, 366; Empyema, 366;
Bronchiectasis, 367; Unresolved Bronchopneumonia, 368; B.
Influenzæ, 369; Pneumococcus, 372; S. Hemolyticus, 374;
Nonhemolytic Streptococci, 376; Staphylococci, 377; Pneumonia
of Measles, 378; The Transmission of Streptococcus Pneumonia,
381; Transmission of Pneumococcus Pneumonia, 383; Prevention
of the Transmission of Pneumonia, 383.

APPENDIX

EXPERIMENTAL INOCULATION OF MONKEYS WITH BACILLUS INFLUENZÆ AND
MICROORGANISMS ISOLATED FROM THE PNEUMONIAS OF INFLUENZA. (BY
EUGENE L. OPIE, M.D.; ALLEN W. FREEMAN, M.D.; FRANCIS G. BLAKE,
M.D.; JAMES C. SMALL, M.D.; AND THOMAS M. RIVERS, M.D.) 387

Inoculation of the Nose and Pharynx with B. Influenzæ, 389;
Introduction of Bacillus Influenzæ into the Trachea, 391;
Introduction of B. Influenzæ and S. Hemolyticus into the
Trachea, 392; Introduction of B. Influenzæ and of Pneumococcus
or of Pneumococcus Alone into the Trachea, 393.

ILLUSTRATIONS

CHARTS PAGE
1. The onset of cases of pneumonia shown by autopsy to be
uncomplicated by secondary infection with hemolytic
streptococcus and of cases of streptococcus pneumonia 141

2. The date of onset of cases in which autopsy demonstrated
lobar pneumonia 161

3. Shows the relation of the epidemic of measles to that of
influenza at Camp Pike, and the relations of the
pneumonia following measles to both measles and influenza 293

4. Shows the time interval between the onset of measles and
the onset of the subsequent pneumonia in the 56 cases of
pneumonia following measles at Camp Pike 306

5. Shows the time relation between the identification of
hemolytic streptococci in the throats and the development
of otitis media in 27 cases shown to be due to hemolytic
streptococci 314

FIG.
1. Acute bronchitis showing engorgement of blood vessels of
mucosa and elevation of epithelium by serum and blood 146

2. Acute bronchopneumonia with nodules of peribronchiolar
consolidation and purulent bronchitis 167

3. Acute bronchopneumonia with peribronchiolar consolidation 169

4. Acute bronchopneumonia with peribronchiolar consolidation 170

5. Bronchopneumonia with hemorrhagic peribronchiolar
consolidation 174

6. Acute bronchopneumonia with confluent gray lobular
consolidation in lower part of upper lobe and hemorrhagic
peribronchiolar pneumonia in lower lobe; purulent
bronchitis 180

7. Bronchopneumonia with purulent bronchitis and peribronchial
hemorrhage 190

8. Streptococcus pneumonia with massive necrosis 201

9. Abscess below pleura with perforation caused by hemolytic
streptococci 202

10. Interstitial suppurative pneumonia; interstitial septa are
the site of suppuration and lymphatics are distended with
purulent fluid; empyema 211

11. Suppurative interstitial pneumonia 212

12. Suppurative interstitial pneumonia 216

13. Suppurative interstitial pneumonia showing a dilated
lymphatic 217

14. Endophlebitis occurring in association with suppurative
pneumonia 219

15. Abscesses in two clusters caused by S. aureus in upper part
of right upper lobe 227

16. Abscesses in cluster caused by S. aureus at apex of right
lobe 228

17. Acute bronchiectasis showing fissures penetrating into
bronchial wall and at one place entering alveolar tissue 246

18. Acute bronchiectasis showing fissures in the bronchial wall
extending into neighboring alveoli which in zone about
are filled with fibrin 247

19. Acute bronchiectasis; the bronchial wall indicated by
engorged mucosa shows a varying degree of destruction,
fissures extending into and through the bronchial wall 248

20. Acute bronchiectasis with destruction of bronchial wall
exposing alveoli filled with fibrin 249

21. Bronchiectasis with fissures extending through the
bronchial wall into alveolar tissue which is site of
fibrinous pneumonia 251

22. Regeneration of epithelium over fissures which have been
formed in the wall of a bronchus 252

23. Squamous epithelium growing over the defect in the
bronchial wall 253

24. Acute bronchiectasis with fissures extending through
bronchial wall which is marked by great engorgement of
blood vessels 255

25. Advanced bronchiectasis throughout lower left lobe 258

26. Unresolved bronchopneumonia with tubercle-like nodules of
peribronchiolar consolidation best seen in lower lobe;
bronchiectasis 268

27. Unresolved pneumonia with peribronchial formation of
fibrous tissue; bronchiectasis 270

28. Unresolved pneumonia with bronchiectasis showing new
formation of fibrous tissue about a greatly dilated
bronchus of which the epithelial lining has been lost 271

29. Lobar pneumonia following measles 338

30. Unresolved bronchopneumonia with measles showing new
formation of fibrous tissue about a bronchus and in
immediately adjacent alveolar walls 342

31. Unresolved bronchopneumonia with measles showing a nodule
of chronic fibrous pneumonia surrounding a respiratory
bronchiole 343

32. Unresolved bronchopneumonia with measles showing chronic
pneumonia about a respiratory bronchiole and alveolar
duct 344

33. Experimental lobar pneumonia in the stage of gray
hepatization produced by injection of Pneumococcus III
into the trachea of a monkey 395

EPIDEMIC RESPIRATORY DISEASE

THE PNEUMONIAS AND OTHER INFECTIONS OF THE RESPIRATORY TRACT
ACCOMPANYING INFLUENZA AND MEASLES

CHAPTER I
THE ETIOLOGY OF INFLUENZA

FRANCIS G. BLAKE, M.D.; THOMAS M. RIVERS, M.D.; JAMES C. SMALL, M.D.

The bacteriologic investigation which will be described was made at Camp
Pike, Arkansas, during the period of the influenza epidemic from
September 6 to December 5, 1918. The data presented are limited to
observations made during life in uncomplicated cases of influenza and to
control studies in normal individuals, and in cases of measles.
Bacteriologic studies made at autopsy will be described in a subsequent
part of this report.

Because of the wide variations in opinion concerning the relationship of
various bacteria to influenza that have arisen during the progress of
the recent pandemic, a brief review of the salient features of the
earlier literature seems advisable. In 1892 Pfeiffer[8] found a small,
Gram-negative, hemophilic bacillus in all cases of influenza, often in
almost pure culture, both during life and at autopsy. He stated that the
organism was found only in cases of influenza or in those convalescent
from the disease. Similar bacilli occasionally found in other conditions
he classified as pseudoinfluenza bacilli. He furthermore showed that
freshly isolated cultures were pathogenic for monkeys, producing a
disease not unlike influenza, though lacking in what he considered the
characteristic lung lesions. He therefore felt justified in claiming
that this bacillus, which he designated B. influenzæ, was the cause of
epidemic influenza. Pfeiffer’s work, though hailed by many as
unassailable, has failed to stand the test of time in two respects. It
has been definitely shown, by Wollstein[9] in particular, that there is
no justification for recognizing a group of pseudoinfluenza bacilli,
organisms so classified by Pfeiffer being indistinguishable from B.
influenzæ. Furthermore, numerous investigations have demonstrated that
B. influenzæ may frequently be found in a variety of diseases affecting
the respiratory tract and in a small proportion of normal individuals.
Kretz[10] found it 47 times in 950 examinations, usually associated with
disease of the respiratory tract. Süsswein,[11] Liebscher,[12]
Jehle,[13] Wollstein,[9] Davis[14] and many others have demonstrated its
presence in cases of measles. Lord[15] isolated B. influenzæ in 30 per
cent of 186 sputums from patients with acute and chronic infection of
the respiratory tract. Boggs[16] found it in frequent association with
chronic bronchiectasis. Wollstein[9][17] showed that it was often
present in the respiratory diseases of infants, and was not an
infrequent cause of meningitis. Rosenthal[18] found that one in six of
normal individuals harbors influenza bacilli and therefore considered it
purely a saprophyte, a position, of course, thoroughly untenable in the
face of indisputable evidence that it may be highly pathogenic. The
widely accepted statement that B. influenzæ is nonpathogenic for animals
has apparently served in considerable degree to shake belief in its
etiologic relationship to epidemic influenza. It would appear, however,
that this opinion is not founded upon fact. Reference is again made to
the work of Wollstein[19], who has shown that virulent strains of B.
influenzæ, when freshly isolated from the human host, are highly
pathogenic for rabbits and monkeys and that nearly all strains are more
or less pathogenic for mice and guinea-pigs.

None of these modifications of Pfeiffer’s original work, however, would
seem to constitute any valid reason for abandoning the conception of the
etiologic importance of B. influenzæ. On the contrary, they are quite in
harmony with well-established facts concerning other bacteria which
cause infections of the respiratory tract. Such bacteria are frequently
found in normal individuals leading a saprophytic existence, are often
associated with other disease conditions, and tend to show marked
variations in virulence.

Since the outbreak of scattered epidemics of influenza beginning in
1915–16, which finally culminated in the pandemic of 1918–19, a vast
amount of literature on the subject has appeared. No attempt has been
made thoroughly to analyze this, because much of it is not available,
much of it abounds in contradictions which it is difficult to harmonize
at the present time, and much of it has been written on the basis of
insufficient data gathered under the handicap of war conditions by men
without sufficient time to undertake special investigation, or it is
feared, in many instances, not sufficiently qualified by previous
bacteriologic training.

The sum and substance of opinion in 1918 would seem to be best
summarized by quoting from the published report compiled by the British
Medical Research Commission:[20] “Although Pfeiffer may yet furnish
reasons why the verdict should not be pronounced, there is already
sufficient material to shake the orthodox conception out of its high
altar. Two facts stand out prominently: the generally acknowledged, or
by some reluctantly admitted, absence of B. influenzæ from organs on
postmortem examinations, and the universally recorded findings of
diplostreptococci, singly or in association with the Pfeiffer bacillus.”
Comment on this opinion will be made in the general discussion at the
end of this paper.

In undertaking a study of the bacteriology of influenza, it seemed
essential to bear in mind certain clinical features of the disease which
will be discussed in greater detail in a subsequent paper. It suffices
to say for our present purpose that it is felt that influenza in itself
should be regarded as a self-limited disease of short duration (two to
five days in most instances), the most prominent local manifestation of
which is a rapidly progressing attack upon the mucous membranes of the
respiratory tract. Among the cases observed during the epidemic at Camp
Pike uncomplicated influenza never proved fatal and death invariably was
associated with a complicating pneumonia. In a large majority of cases
pneumococci, S. hemolyticus, or less frequently other bacteria in
addition to B. influenzæ were associated with the pneumonia. It is felt,
therefore, that in any attempt to determine the primary cause of
influenza bacteriologic studies made during life in early uncomplicated
cases of the disease are of primary importance and that the bacteriology
of the sputum of patients with complicating pneumonia and the
bacteriology of autopsies can only properly be used as valuable
supplements to data so obtained.

Since cultures from the respiratory tract must often of necessity
contain many bacteria which play no part in the production of influenza,
it is essential to have a working knowledge of the bacteria that may be
encountered by the methods employed. It is also important that such
knowledge as may have been gained in interepidemic periods be amplified
by study of the bacterial flora present at various periods throughout
the course of an epidemic, both in normal individuals and in other
disease conditions. These points have been borne in mind throughout the
present study and such observations have formed an essential part of the
work.

=Methods.=—In an investigation of this nature the culture methods
employed should be suitably directed to determine primarily what
bacteria are present and in what relative proportion they exist. The use
of culture or animal inoculation methods that are highly selective in
character, enhancing the growth of certain bacteria and retarding or
inhibiting the growth of others, are of great additional value, but can
only properly be used secondarily in order to augment the results
obtained by nonselective culture methods. As the most suitable medium
for the purpose in hand plain meat infusion agar, titrating 0.1+ to 0.3+
to phenolphthalein, to which 5 per cent of sterile defibrinated horse
blood was added, was used. Since growth on freshly poured plates is
greatly superior to that on plates that have been stored, the agar was
melted as needed, the blood being added when the medium had cooled to
approximately 45° C. Cultures from the nose and throat were made by
swabbing the mucous membranes with a sterile applicator, touching the
applicator to a small area on the surface of a blood agar plate, and
spreading the inoculum over the surface of the medium with a platinum
needle, insuring as wide a separation as possible. Direct cultures of
selected and washed specimens of sputum were made when possible. In many
instances, of course, it was impossible to get sufficiently satisfactory
specimens to permit of washing, especially when cultures were made very
early in the disease. To supplement direct culture of the sputum the
mouse inoculation method as employed for the determination of
pneumococcus types was used. This is, of course, a highly selective
method, of particular value in the detection of pneumococcus and B.
influenzæ when they are present in relatively small numbers as compared
with other bacteria. Plates were examined after twenty to twenty-four
hours’ incubation and again at the end of thirty-six to forty-eight
hours when necessary.

In the present study, attention has been centered upon B. influenzæ, S.
hemolyticus, and the various immunologic types of pneumococci, other
organisms encountered having played no significant part in the cases
studied except in rare instances. B. influenzæ was identified by its
morphologic, staining and cultural characteristics and conformed to the
classical description given by Pfeiffer. S. hemolyticus was identified
by its morphologic, staining, and cultural characteristics on blood
agar, supplemented by a confirmatory hemolytic test with washed sheep
corpuscles, and bile solubility test. Pneumococci were identified by
morphologic, staining and cultural characteristics, bile solubility
test, and agglutination with specific antipneumococcus immune sera. Note
was made in most instances of the presence of other organisms, such as
members of the Gram-negative diplococcus, staphylococcus, diphtheroid
and streptococcus viridans groups, but no attempt was made further to
isolate or identify them.

=Bacillus Influenzæ in Cases of Influenza.=—On October 10, 1918, at the
height of the epidemic at Camp Pike, search for B. influenzæ was made in
a group of 23 consecutive cases of uncomplicated influenza from one to
six days after the onset of the disease. From each individual
simultaneous cultures on blood agar plates were made (a) from the nose,
(b) from the throat, and (c) from the sputum, and the sputum from each
case was injected into the peritoneal cavity of a white mouse. A similar
study of 5 consecutive cases was made on November 19. The results are
presented in Table II.

By means of multiple cultures taken simultaneously from different
portions of the respiratory tract no difficulty was encountered in
demonstrating B. influenzæ in all these cases of uncomplicated
influenza. Not only was B. influenzæ found in all cases, but often in
very large numbers predominating over all other bacteria on at least one
of the plates from each patient, and in occasional instances occurring
in nearly pure culture. One culture made about two hours after onset of
the initial coryza is of interest. There was at the time a profuse
serous nasal discharge. One drop of this allowed to fall on the surface
of a blood agar plate gave a practically pure culture of B. influenzæ.

TABLE II

PRESENCE OF B. INFLUENZÆ IN 28 CASES OF INFLUENZA

═══════════╤═══════════╤═══════════╤═══════════╤═══════════╤═══════════
NO. │ DAY OF │ NOSE │ THROAT │ SPUTUM │ SPUTUM
│ DISEASE │ │ │ CULTURE │ PASSED
│ │ │ │ │ THROUGH
│ │ │ │ │ MOUSE
───────────┼───────────┼───────────┼───────────┼───────────┼───────────
1│ 1 │ + │ + │ + │ +
2│ 4 │ − │ + │ + │ +
3│ 5 │ − │ − │ + │ −
4│ 4 │ − │ − │ + │ +
5│ 3 │ − │ − │ + │ +
6│ 4 │ − │ + │ + │ c
7│ 2 │ − │ + │ − │ c
8│ 4 │ + │ + │ + │ −
9│ 5 │ − │ + │ + │ +
10│ 2 │ + │ − │ − │ −
11│ 2 │ − │ + │ c │ +
12│ 3 │ c │ + │ + │ +
13│ 3 │ − │ − │ − │ +
14│ 2 │ − │ − │ + │ +
15│ 3 │ c │ − │ − │ +
16│ 1 │ − │ + │ + │ +
17│ 3 │ − │ + │ − │ +
18│ 4 │ + │ + │ c │ +
19│ 6 │ − │ − │ + │ +
20│ 1 │ − │ + │ + │ +
21│ 2 │ − │ + │ − │ +
22│ 4 │ + │ − │ + │ +
23│ 3 │ c │ − │ − │ +
24│ 2 │ + │ − │ − │ −
25│ 1 │ − │ − │ + │ +
26│ 5 │ − │ − │ + │ +
27│ ? │ − │ + │ − │ +
28│ 1 │ − │ − │ + │ +
───────────┼───────────┼───────────┼───────────┼───────────┼───────────
│ │ 6 │ 14 │ 17 │ 22
───────────┴───────────┴───────────┴───────────┴───────────┴───────────

c indicates that the plate was contaminated.

During the latter part of November and in early December a small
secondary wave of influenza occurred at Camp Pike. In a series of 48
consecutive cases, B. influenzæ was readily found in all by means of
combined throat cultures and mouse inoculation of the sputum, 33 times
(68.7 per cent) in the throat cultures, 39 times (81.3 per cent) in the
sputum. These cases were cultured on admission to the receiving ward of
the hospital within twenty-four to forty-eight hours after onset and
were all early cases of influenza without complications at the time the
cultures were made. In 90 more consecutive cases in this series 62 or
68.9 per cent showed B. influenzæ in a single throat culture taken on
admission.

A summary of all cultures made in cases of uncomplicated influenza is
presented in Table III.

TABLE III

PRESENCE OF B. INFLUENZÆ IN CASES OF INFLUENZA

════════════════════════════════════════════╤════════╤═════════════════
│ NUMBER │
METHOD │OF CASES│ B. INFLUENZÆ
│CULTURED│ FOUND
────────────────────────────────────────────┼────────┼────────┬────────
„ │ „ │ NUMBER │PER CENT
────────────────────────────────────────────┼────────┼────────┼────────
Nose culture │ 28│ 6│ 21.4
Throat culture │ 166│ 109│ 65.7
Sputum culture │ 28│ 17│ 60.7
Sputum (mouse passage) │ 76│ 61│ 80.3
Combined nose, throat and sputum cultures │ │ │
and sputum inoculation │ 28│ 28│ 100
Combined throat cultures and sputum │ │ │
inoculation │ 48│ 48│ 100
────────────────────────────────────────────┴────────┴────────┴────────

Of any single method used the intraperitoneal inoculation of a white
mouse with a specimen of the patient’s sputum proved the most efficient
in demonstrating the presence of B. influenzæ. No single method served
to demonstrate B. influenzæ in all cases, but by simultaneous cultures
from the nose, throat, and deeper air passages no difficulty was met in
showing that B. influenzæ was invariably present, usually in abundance
somewhere in the respiratory tract during the acute stage of the
disease. This result is not out of harmony with the rapidly progressive
character of the attack upon the mucous membranes of the respiratory
tract in influenza.

Of interest in this connection are certain observations which suggest
that the presence of B. influenzæ in predominant numbers at least is in
many cases coincident with the acute stage of influenza and that the
organisms show a tendency rapidly to diminish in abundance with the
progress of the disease to recovery. In 82 cases of influenza cultured
on the day of admission to the hospital, B. influenzæ was present in 52
(63.4 per cent) of the throat cultures. Repeated throat cultures in this
group of cases from the fourth to the eighth day after admission when
the temperature had fallen to normal, showed that B. influenzæ was still
present in demonstrable numbers in the throat of only 25 cases or 30.5
per cent. Not only was there a material reduction in the number of
patients in whom B. influenzæ could be demonstrated by the throat
culture method, but the contrast in the predominance of B. influenzæ on
the plates made early in the disease with those made during
convalescence was often very striking. It is only fair to say, however,
that some cases continued to carry B. influenzæ in their throats in
large numbers throughout the period of observation.

=Presence of Pneumococcus in Cases of Influenza.=—It seemed of some
importance to determine the prevalence of pneumococcus in cases of
influenza, not because of any possibility that pneumococci might bear an
etiologic relationship to the disease, but more by way of comparison
with the prevalence of B. influenzæ, since both organisms are found in
the mouths of normal individuals and are also frequently found together
in the pneumonias that complicate influenza. The results obtained in
cases of influenza early in the disease before the development of either
a purulent bronchitis or of pneumonia are presented. The presence of
pneumococcus was determined by the intraperitoneal inoculation of white
mice with the saliva or sputum.

Twenty-four cases examined on September 27 and 28 gave the results shown
in Table IV. These patients had been in the hospital from two to five
days at the time the determinations were made.

TABLE IV

PNEUMOCOCCUS IN CASES OF INFLUENZA

═══════════════════════════════════╤═════════════════╤═════════════════
│ NUMBER │ PER CENT
───────────────────────────────────┼─────────────────┼─────────────────
Pneumococcus, Type I │ 0│ 0
Pneumococcus, Type II │ 0│ 0
Pneumococcus, Atypical II │ 0│ 0
Pneumococcus, Type III │ 2│ 8.3
Pneumococcus, Group IV │ 15│ 62.5
No pneumococci found │ 7│ 29.2
───────────────────────────────────┴─────────────────┴─────────────────

From November 27 to December 1, the pneumococci present in 47
consecutive cases of influenza were determined. In this group specimens
of sputum were collected shortly after admission of the patients to the
receiving ward of the hospital. The results are shown in Table V.

TABLE V

PNEUMOCOCCI IN CASES OF INFLUENZA

═══════════════════════════════════╤═════════════════╤═════════════════
│ NUMBER │ PER CENT
───────────────────────────────────┼─────────────────┼─────────────────
Pneumococcus, Type I │ 0│ 0
Pneumococcus, Type II │ 0│ 0
Pneumococcus, Atypical II │ 2│ 4.3
Pneumococcus, Type III │ 0│ 0
Pneumococcus, Group IV │ 25│ 53.2
No pneumococci found │ 20│ 42.5
───────────────────────────────────┴─────────────────┴─────────────────

The results obtained show that pneumococci found in early uncomplicated
cases of influenza, both early and late in the course of the epidemic,
differ in no respect from those found in the mouths of normal
individuals at any time.

Similar studies of the prevalence of S. hemolyticus as determined by
throat cultures in early cases of influenza are shown in Table VI.

The only point of interest in these observations is the increased
prevalence of S. hemolyticus in cases examined late in the epidemic of
influenza as compared with that found early in the epidemic. The
significance of this will be discussed in other parts of this report.

TABLE VI

S. HEMOLYTICUS IN CASES OF INFLUENZA

══════════════╤══════════════╤═════════════╤═════════════╤═════════════
│ │ S. │ S. │ PER CENT
DATE │ NUMBER OF │ HEMOLYTICUS │ HEMOLYTICUS │POSITIVE FOR
│CASES CULTURED│ FOUND │ NOT FOUND │ S.
│ │ │ │ HEMOLYTICUS
──────────────┼──────────────┼─────────────┼─────────────┼─────────────
Sept. 25–26 │ 100│ 6│ 94│ 6
Nov. 27–Dec. 5│ 138│ 39│ 99│ 28.3
──────────────┴──────────────┴─────────────┴─────────────┴─────────────

=Presence of Bacillus Influenzæ in Normal Men.=—For comparison with the
results obtained in cases of influenza a fairly extensive study of the
prevalence of B. influenzæ in normal individuals has been made at
various times prior to and throughout the course of the epidemic. This
was deemed of special importance, since it was obvious that the results
obtained by previous workers during interepidemic periods would not in
all probability coincide with those obtained in the presence of a
widespread epidemic of influenza where the opportunity for the
dissemination of B. influenzæ was almost unlimited.

From the results obtained in the multiple cultures in cases of influenza
it is obvious that only like methods can be compared. The results
obtained in normal individuals have, therefore, been tabulated in groups
dependent upon the culture method employed. These groups have been
subdivided according to the time and the place of the study, such
explanatory notes as seem necessary being added. (See Tables VII-IX.)

The most striking feature of the figures presented in Table VII is the
wide variation in the incidence of B. influenzæ in different groups
varying all the way from 11.1 to 68 per cent. Analysis of these
differences brings out certain points of great interest. It is apparent
that the percentage of cases carrying B. influenzæ depended in large
part upon the prevalence of respiratory diseases in the group from which
the data were obtained. In the studies made at Camp Funston prior to the
fall outbreak of influenza in epidemic proportions, it is noteworthy
that “bronchitis” and pneumonia were prevalent throughout the summer in
those groups showing a relatively high incidence of B. influenzæ. At the
time these studies were made the presence of influenza in these
organizations was not recognized, but in view of knowledge gained
throughout the course of the epidemic at Camp Pike, it seems not
improbable that influenza in mild form was present throughout the summer
in certain organizations at Camp Funston. This would seem more likely in
view of the fact that this commission has clearly demonstrated that a
considerable epidemic of influenza swept through Camp Funston in March,
1918, and was followed by recurring smaller epidemics in April and
May.[21] In contrast with these groups showing a high incidence of B.
influenzæ is that of the 210th Engineers, an organization entirely free
from respiratory diseases during the period of our study.

TABLE VII

INCIDENCE OF B. INFLUENZÆ IN NORMAL MEN AS DETERMINED BY
INTRAPERITONEAL INOCULATION OF WHITE MICE WITH SALIVA OR SPUTUM

════╤═════════╤═════════════╤════════╤═════════╤═════════╤═════════════
DATE│ PLACE │ORGANIZATION │ NUMBER │ B. │PER CENT │ REMARKS
│ │ │EXAMINED│INFLUENZÆ│POSITIVE │
│ │ │ │ PRESENT │ FOR B. │
│ │ │ │ │INFLUENZÆ│
────┼─────────┼─────────────┼────────┼─────────┼─────────┼─────────────
1918│ │ │ │ │ │
Aug.│Camp │22 Prov. │ 25│ 6│ 24│Bronchitis
13│Funston, │Colored Co. │ │ │ │and pneumonia
│Kans. │164th Depot │ │ │ │were
│Detention│Brigade │ │ │ │prevalent in
│Camp, No.│ │ │ │ │this
│2 │ │ │ │ │organization
│ │ │ │ │ │of recently
│ │ │ │ │ │drafted
│ │ │ │ │ │negroes
│ │ │ │ │ │during July
│ │ │ │ │ │and August,
│ │ │ │ │ │1918
────┼─────────┼─────────────┼────────┼─────────┼─────────┼─────────────
Aug.│Camp │Co. D. 3rd │ 25│ 11│ 44│Recently
18│Funston, │Dev. Bn. │ │ │ │drafted
│Kans. │ │ │ │ │southern
│Detention│ │ │ │ │negroes not
│Camp, No.│ │ │ │ │fit for full
│2 │ │ │ │ │military
│ │ │ │ │ │duty.
│ │ │ │ │ │Bronchitis
│ │ │ │ │ │and pneumonia
│ │ │ │ │ │were
│ │ │ │ │ │prevalent in
│ │ │ │ │ │this
│ │ │ │ │ │organization
│ │ │ │ │ │during July
│ │ │ │ │ │and August,
│ │ │ │ │ │1918
────┼─────────┼─────────────┼────────┼─────────┼─────────┼─────────────
Aug.│Camp │70th Inf. │ 25│ 11│ 44│25 men
20│Funston, │ │ │ │ │presenting
│Kan. │ │ │ │ │themselves at
│ │ │ │ │ │sick call for
│ │ │ │ │ │various
│ │ │ │ │ │complaints;
│ │ │ │ │ │not strictly
│ │ │ │ │ │normal;
│ │ │ │ │ │respiratory
│ │ │ │ │ │diseases not
│ │ │ │ │ │prevalent
────┼─────────┼─────────────┼────────┼─────────┼─────────┼─────────────
Aug.│Ft. │Quarters 4 M │ 32│ 16│ 50│Recently
22│Riley, │M.O.T.C. │ │ │ │drafted white
│Kan. │ │ │ │ │men of 4 to 8
│ │ │ │ │ │weeks’
│ │ │ │ │ │service.
│ │ │ │ │ │Pneumonia
│ │ │ │ │ │fairly
│ │ │ │ │ │prevalent in
│ │ │ │ │ │this
│ │ │ │ │ │organization
────┼─────────┼─────────────┼────────┼─────────┼─────────┼─────────────
Aug.│Camp │210th Eng. │ 27│ 3│ 11.1│About one
26│Funston, │ │ │ │ │mile distant
│Kan. │ │ │ │ │from Camp
│ │ │ │ │ │Funston
│ │ │ │ │ │proper. No
│ │ │ │ │ │sickness in
│ │ │ │ │ │this
│ │ │ │ │ │organization
────┼─────────┼─────────────┼────────┼─────────┼─────────┼─────────────
Nov.│Hot │Drafted men │ 50│ 11│ 22│50 men
12│Springs, │assembled to │ │ │ │selected from
│Ark. │entrain for │ │ │ │isolated farm
│ │camp │ │ │ │communities;
│ │ │ │ │ │12 gave a
│ │ │ │ │ │history of
│ │ │ │ │ │“influenza”
│ │ │ │ │ │within the
│ │ │ │ │ │preceding 8
│ │ │ │ │ │weeks
────┼─────────┼─────────────┼────────┼─────────┼─────────┼─────────────
Nov.│Camp │Miscellaneous│ 26│ 13│ 50│12 of this
25│Pike, │ │ │ │ │group had
│Ark. │ │ │ │ │influenza
│ │ │ │ │ │during the
│ │ │ │ │ │epidemic
────┼─────────┼─────────────┼────────┼─────────┼─────────┼─────────────
Dec.│Camp │Miscellaneous│ 25│ 17│ 68│12 of this
10│Pike, │ │ │ │ │group had
│Ark. │ │ │ │ │influenza
│ │ │ │ │ │during the
│ │ │ │ │ │epidemic
────┼─────────┼─────────────┼────────┼─────────┼─────────┼─────────────
│Summary: │Normals │ 235│ 88│ 37.4│
│ │Cases of │ 76│ 61│ 80.3│
│ │influenza │ │ │ │
│ │(for │ │ │ │
│ │comparison) │ │ │ │
────┴─────────┴─────────────┴────────┴─────────┴─────────┴─────────────

On November 12 search was made for B. influenzæ in 50 normal drafted men
who had assembled at Hot Springs, Ark., on that date preparatory to
entraining for Camp Pike. These men were all from isolated farming
communities where influenza was only moderately prevalent and where
there was little opportunity for the wide dissemination of B. influenzæ
such as occurs when large bodies of men are assembled in camps. Twelve
of the 50 gave a history of influenza within the preceding eight weeks.
The cultures were made by the same methods as those used at Camp Pike,
the laboratory car “Lister” being taken to Hot Springs for that purpose.
The incidence of B. influenzæ was only 22 per cent. In striking contrast
with this figure are the figures of 50 and 68 per cent obtained in the
last two groups studied at Camp Pike after the epidemic had swept
through the camp: 24 of the 51 men in these groups had influenza during
the epidemic.

It is of interest to record that the incidence of pneumococcus in these
cases was approximately the same in all groups and bore no relation to
the prevalence of influenza, bronchitis, or pneumonia.

TABLE VIII

INCIDENCE OF B. INFLUENZÆ IN NORMAL MEN AS DETERMINED BY THROAT CULTURES
ON BLOOD AGAR PLATES

═══════╤════════╤═════════════╤════════╤═════════╤═════════╤════════════
DATE │ PLACE │ORGANIZATION │ NUMBER │ B. │PER CENT │ REMARKS
│ │ │EXAMINED│INFLUENZÆ│POSITIVE │
│ │ │ │ PRESENT │ FOR B. │
│ │ │ │ │INFLUENZÆ│
───────┼────────┼─────────────┼────────┼─────────┼─────────┼────────────
Sept. │Camp │Med. │ 82│ 14│ 17.1│82 throat
14–Oct.│Pike, │Detachment, │ │ │ │cultures in
5 │Ark. │Base Hos.; │ │ │ │42
│ │personnel on │ │ │ │individuals
│ │measles wards│ │ │ │
───────┼────────┼─────────────┼────────┼─────────┼─────────┼────────────
Nov. │Camp │Miscellaneous│ 296│ 71│ 23.9│Number among
5–9 │Pike, │ │ │ │ │this group
│Ark. │ │ │ │ │who had had
│ │ │ │ │ │influenza
│ │ │ │ │ │not recorded
───────┼────────┼─────────────┼────────┼─────────┼─────────┼────────────
Nov. 12│Hot │Drafted men │ 64│ 0│ 0│Men, in
│Springs,│assembled to │ │ │ │large part
│Ark. │entrain for │ │ │ │from
│ │camp │ │ │ │isolated
│ │ │ │ │ │farm
│ │ │ │ │ │communities;
│ │ │ │ │ │13 gave a
│ │ │ │ │ │history of
│ │ │ │ │ │“influenza”
│ │ │ │ │ │within the
│ │ │ │ │ │preceding 8
│ │ │ │ │ │weeks
───────┼────────┼─────────────┼────────┼─────────┼─────────┼────────────
Nov. 25│Camp │Miscellaneous│ 26│ 13│ 50│12 of this
│Pike │ │ │ │ │group had
│ │ │ │ │ │influenza
│ │ │ │ │ │during the
│ │ │ │ │ │epidemic
───────┼────────┼─────────────┼────────┼─────────┼─────────┼────────────
Dec. 10│Camp │Miscellaneous│ 25│ 13│ 52│12 of this
│Pike │ │ │ │ │group had
│ │ │ │ │ │influenza
│ │ │ │ │ │during the
│ │ │ │ │ │epidemic
───────┼────────┼─────────────┼────────┼─────────┼─────────┼────────────
│Summary │Normals │ 493│ 111│ 22.5│
│ │Cases of │ 166│ 109│ 65.7│
│ │influenza │ │ │ │
│ │(for │ │ │ │
│ │comparison) │ │ │ │
───────┴────────┴─────────────┴────────┴─────────┴─────────┴────────────

The results obtained by throat culture are quite similar to those
obtained by the mouse inoculation method. The entire absence of B.
influenzæ in the group of 64 throat cultures made in the draft men
assembled at Hot Springs as compared with the relatively high incidence
in the last two groups examined at Camp Pike is very striking.

In consideration of the figures presented in Table IX it is important to
remember that the group of 50 men from Hot Springs were all from
isolated farm communities, had not previously been assembled and had not
been in continuous contact with a widespread epidemic of influenza. On
the other hand, the two groups of normal men at Camp Pike were studied
immediately after the epidemic had swept through the camp and had been
constantly in contact with epidemic influenza for a period of three
months, 24 of the 51 actually having had the disease during this period.
The fact that in the group of men from Hot Springs, B. influenzæ was
found only by the mouse inoculation method is noteworthy, since it
indicates that the organism was present in relatively small numbers and
could be detected only by a highly selective method.

TABLE IX

INCIDENCE OF B. INFLUENZÆ IN NORMAL MEN CONTRASTED WITH THAT IN EARLY CASES OF
INFLUENZA AS DETERMINED BY MULTIPLE CULTURES FROM NOSE, THROAT, AND SPUTUM

════╤════════╤═════════╤════════╤══════════════════════════════════════════════
DATE│ PLACE │ GROUP │ NUMBER │ PER CENT SHOWING B. INFLUENZÆ
│ │ │EXAMINED│
────┼────────┼─────────┼────────┼────────┬────────┬───────┬───────────┬────────
„ │ „ │ „ │ „ │ NOSE │ THROAT │SPUTUM │ SPUTUM │ BY
│ │ │ │ │ │DIRECT │ MOUSE │MULTIPLE
│ │ │ │ │ │CULTURE│INOCULATION│CULTURES
────┼────────┼─────────┼────────┼────────┼────────┼───────┼───────────┼────────
Nov.│Hot │Normal │ 50│ 0│ 0│ 0│ 22│ 22
12 │Springs,│draft men│ │ │ │ │ │
│Ark. │assembled│ │ │ │ │ │
│ │to │ │ │ │ │ │
│ │entrain │ │ │ │ │ │
│ │for camp │ │ │ │ │ │
│ │ │ │ (4 │ (31 │ │ │
│ │ │ │cultures│cultures│ │ │
│ │ │ │ only) │ only) │ │ │
────┼────────┼─────────┼────────┼────────┼────────┼───────┼───────────┼────────
Nov.│Camp │Normal │ 26│ 38.6│ 50│ 34.6│ 50│ 80.8
25 │Pike │men; 12 │ │ │ │ │ │
│ │had │ │ │ │ │ │
│ │influenza│ │ │ │ │ │
│ │during │ │ │ │ │ │
│ │the │ │ │ │ │ │
│ │epidemic │ │ │ │ │ │
────┼────────┼─────────┼────────┼────────┼────────┼───────┼───────────┼────────
Dec.│Camp │Normal │ 25│ 48│ 52│ 24│ 68│ 88
10 │Pike │men; 12 │ │ │ │ │ │
│ │had │ │ │ │ │ │
│ │influenza│ │ │ │ │ │
│ │during │ │ │ │ │ │
│ │the │ │ │ │ │ │
│ │epidemic │ │ │ │ │ │
────┼────────┼─────────┼────────┼────────┼────────┼───────┼───────────┼────────
Oct.│Camp │Patients │ 28│ 21.4│ 50│ 60.7│ 78.6│ 100
10 │Pike │with │ │ │ │ │ │
and │ │influenza│ │ │ │ │ │
Nov.│ │in Base │ │ │ │ │ │
19 │ │Hos. │ │ │ │ │ │
────┴────────┴─────────┴────────┴────────┴────────┴───────┴───────────┴────────

Summary of the results obtained in normal men shows that the incidence
of B. influenzæ in normal individuals from isolated communities or in
groups free from respiratory diseases prior to the occurrence of the
fall epidemic was relatively low, namely, 10 to 20 per cent; that in
observations made before the fall epidemic in groups in which
“bronchitis” and pneumonia were fairly prevalent, B. influenzæ was found
much more frequently, namely, in 25 to 50 per cent of the cases; and
that in groups studied at intervals during the epidemic the incidence of
B. influenzæ rapidly rose, reaching 85 per cent at the end of the
epidemic. In contrast with this, B. influenzæ was found in 100 per cent
of cases of influenza without reference to the time at which they
occurred during the epidemic. It is obvious that the high percentage of
normal men carrying B. influenzæ found at the end of the epidemic can
depend only on the wide dissemination of B. influenzæ that must occur
during epidemic times.

=Bacillus Influenzæ in Measles.=—Since the presence of B. influenzæ in
other diseases than influenza has been advanced as an argument against
its causal relationship to influenza, an extensive study of the
incidence of B. influenzæ in the throats of measles patients was made
during the period of the epidemic of influenza at Camp Pike from
September 10 to October 20. In all a total of 830 throat cultures in 487
cases of measles were made, many cases being cultured repeatedly at
weekly intervals. The results have been condensed as far as possible and
are presented in Tables X, XI, XII.

TABLE X

INCIDENCE OF B. INFLUENZÆ IN 400 CONSECUTIVE CASES OF MEASLES AS
DETERMINED BY THROAT CULTURE AT TIME OF ADMISSION TO THE BASE HOSPITAL

═════════════════╤═════════════════╤═══════════════════════════════════
DATE │ NUMBER OF CASES │ B. INFLUENZA FOUND
─────────────────┼─────────────────┼─────────────────┬─────────────────
„ │ „ │ NUMBER │ PER CENT
─────────────────┼─────────────────┼─────────────────┼─────────────────
Sept. 16–Oct. 4 │ 100│ 27│ 27
Oct. 4–Oct. 10 │ 100│ 32│ 32
Oct. 10–Oct. 15 │ 100│ 32│ 32
Oct. 15–Oct. 19 │ 100│ 48│ 48
─────────────────┴─────────────────┴─────────────────┴─────────────────

The prevalence of B. influenzæ in cases of measles during the period of
the influenza epidemic corresponded very closely with that found in
normal individuals under similar circumstances. The increasing
proportion of cases carrying B. influenzæ as the epidemic of influenza
advanced is further evidence of the wide dissemination of the organism
during the epidemic.

TABLE XI

INCIDENCE OF B. INFLUENZÆ IN 830 THROAT CULTURES IN 487 CASES OF
MEASLES; CULTURES REPEATED AT WEEKLY INTERVALS

═════════════════╤═════════════════╤═══════════════════════════════════
DATE │ NUMBER OF CASES │ B. INFLUENZA FOUND
─────────────────┼─────────────────┼─────────────────┬─────────────────
„ │ „ │ NUMBER │ PER CENT
─────────────────┼─────────────────┼─────────────────┼─────────────────
Sept. 10–15 │ 47│ 15│ 31.9
Sept. 16–29 │ 106│ 33│ 31.1
Sept. 30–Oct. 6 │ 122│ 38│ 31.1
Oct. 7–13 │ 235│ 96│ 40.8
Oct. 14–20 │ 320│ 157│ 49.1
─────────────────┼─────────────────┼─────────────────┼─────────────────
Total │ 830│ 339│ 40.8
─────────────────┴─────────────────┴─────────────────┴─────────────────

TABLE XII

TOTAL NUMBER OF B. INFLUENZÆ CARRIERS AMONG 223 CASES OF MEASLES AS
DETERMINED BY REPEATED THROAT CULTURES AT WEEKLY INTERVALS AFTER
ADMISSION TO HOSPITAL

══════════╤══════════╦═════════╤═══════════════════╦═══════════════════
TIMES │NUMBER OF ║NUMBER OF│B. INFLUENZÆ FOUND ║ TOTAL CARRIERS IN
CULTURED │ CASES ║CULTURES │ ║ ONE OR MORE
│ ║ │ ║ CULTURES
──────────┼──────────╫─────────┼─────────┬─────────╫─────────┬─────────
„ │ „ ║ „ │ NUMBER │PER CENT ║ NUMBER │PER CENT
──────────┼──────────╫─────────┼─────────┼─────────╫─────────┼─────────
2│ 129║ 1st│ 37│ 28.7║ 82│ 63.6
│ ║ 2nd│ 63│ 48.8║ │
──────────┼──────────╫─────────┼─────────┼─────────╫─────────┼─────────
3│ 69║ 1st│ 20│ 28.9║ 52│ 75.4
│ ║ 2nd│ 31│ 44.9║ │
│ ║ 3rd│ 33│ 47.8║ │
──────────┼──────────╫─────────┼─────────┼─────────╫─────────┼─────────
4│ 25║ 1st│ 6│ 24║ 21│ 84.0
│ ║ 2nd│ 10│ 40║ │
│ ║ 3rd│ 13│ 52║ │
│ ║ 4th│ 14│ 56║ │
──────────┴──────────╨─────────┴─────────┴─────────╨─────────┴─────────

It is evident from the figures presented in Table XII that a large
percentage of the measles cases studied were at one time or another
carriers of B. influenzæ. In consideration of this fact, it must be
borne in mind that all these cases were cultured during the period when
the influenza epidemic was at its height and that many of these cases
had influenza while in the hospital for measles. No data are available
as to the exact number, since a definite diagnosis of influenza could
hardly be made during the acute stage of measles. It is probable that
approximately 25 per cent developed influenza, since that was the
incidence of influenza in the total population of Camp Pike. The
consistent increase in the percentage of influenza carriers clearly
demonstrates that this was due to wide dissemination of B. influenzæ
with the progress of the epidemic. Another point of exceeding interest
is that the percentage of measles cases carrying B. influenzæ in the
throat was lowest during the acute stage of the disease and increased
during convalescence. This is in direct contrast with the results found
in cases of influenza where the number of cases carrying B. influenzæ in
the throat was highest during the acute stage and rapidly diminished in
uncomplicated cases with the onset of convalescence.

=Summary.=—Multiple cultures made simultaneously from the nose, throat
and lower respiratory tract showed that B. influenzæ was invariably
present in all cases of influenza from the onset of the disease. Not
only was B. influenzæ present in all cases, but it was frequently
present in predominant numbers, sometimes in nearly pure culture. In the
majority of cases that went on to rapid recovery without the development
of an extensive bronchitis or complicating pneumonia, the predominance
of B. influenzæ over other organisms rapidly diminished coincident with
onset of convalescence. Many cases, however, continued to carry B.
influenzæ in large numbers in the throat throughout convalescence. No
data on the possible duration of the carrier state have been obtained.
By the culture methods employed no other organism has been found that
would suggest any etiologic relationship to the disease. The two
organisms most frequently associated with B. influenzæ in postinfluenzal
pneumonias, pneumococcus and S. hemolyticus, have not differed in their
incidence in early uncomplicated cases of influenza from that found in
normal individuals.

The incidence of B. influenzæ in normal men, in different groups
studied, has varied between 11.1 and 88 per cent. This wide variation
has depended upon the prevalence of respiratory diseases, more
particularly influenza, in the groups studied and the opportunity
thereby offered for the wide dissemination of B. influenza. With the
progress of the epidemic, the number of normal men carrying B. influenzæ
has steadily increased until it reached its maximum at the end of the
epidemic.

The incidence of B. influenzæ in cases of measles studied during the
epidemic of influenza has been relatively high though never equaling
that found in cases of influenza. As in normal men, the incidence in
cases of measles has steadily increased during the period of the
epidemic. Repeated throat cultures at weekly intervals in cases of
measles have shown that approximately 80 per cent became temporary
carriers of B. influenzæ at one time or another during the period of the
epidemic. Many of these cases had influenza during the time that they
were in the hospital. The carrier state in cases of measles was found to
bear no relation to the acute stage of the disease since the number of
carriers at the time of admission to the hospital was considerably lower
than that found during convalescence as determined by repeated cultures
in the same cases.

Discussion

The bacteriologic studies in cases of influenza described in this report
fully support Pfeiffer’s claim that B. influenzæ is invariably present
in the disease. It is particularly important to note that these results
were obtained in early uncomplicated cases of influenza and are not
dependent upon cultures made from cases complicated by pneumonia or
obtained at autopsy. In view of this fact the tendency so apparent in
much of the recent literature to relegate B. influenzæ to a place of
secondary or minor importance in the disease seems hardly justifiable.
It would seem that this tendency is largely dependent upon three
factors: first, the failure of many to find B. influenzæ either during
life or at autopsy in any considerable proportion of cases; second, the
frequent failure to draw a clear distinction between influenza itself
and the pneumonia to which it predisposes with a consequent overemphasis
upon autopsy bacteriology where a considerable variety of secondary
organisms have attracted particular attention; and third, an incorrect
interpretation of the undoubtedly large number of B. influenzæ carriers
found among normal individuals and those with other diseases during the
period of the epidemic and to less extent in interepidemic times.

Since the majority of workers who are thoroughly familiar with the
technic of cultivating B. influenzæ have encountered little difficulty
in finding it in a large majority of cases, it is felt that the
considerable number of negative reports that have appeared can depend
only upon the unfamiliarity of those who have failed to find it with the
proper bacteriologic methods. This is quite apparent in many of the
reports that have been published, and is not surprising in the face of
the excessive demand for well-trained bacteriologists occasioned by the
war.

One important feature in the successful isolation of B. influenzæ from
all cases that has been brought out in the course of the work here
reported, is the necessity of making simultaneous cultures from all
portions of the respiratory tract, since by no single culture method was
it found possible to find the organism in all cases. It has been pointed
out that one of the most characteristic local phenomena of the disease
is the rapidly progressing attack upon the mucous membranes of the
respiratory tract. It seems quite possible that B. influenzæ in
predominant numbers at least may be found in many cases only at the
crest of the wave, if we may speak of it as such. By way of analogy is
the well-recognized fact that the successful isolation of streptococcus
from cases of erysipelas often depends upon taking cultures from the
margin of the advancing lesion. While definite proof is lacking for this
opinion, it would seem to receive some support from the observation that
B. influenzæ rapidly disappears from the throat with the onset of
convalescence in a considerable proportion of cases. It is felt that
these observations, establishing the predominance of B. influenzæ in the
early acute stages of the disease, are of considerable significance,
especially when exactly the reverse condition was found in studying the
incidence of the organism in cases of measles.

In consideration of the primary cause of influenza, attention has often
been focused upon the many different bacteria found in autopsy cultures.
The most prominent of these are the ill-defined diplostreptococci of the
European writers, the various immunologic types of pneumococci, and S.
hemolyticus. Other microorganisms less frequently found are
staphylococci, M. catarrhalis, nonhemolytic streptococci, and B. mucosus
capsulatus. It is not within the scope of this paper to discuss their
relation to the various types of pneumonia found at autopsy, but their
very multiplicity would seem sufficient _prima facie_ evidence that they
bear no etiologic relationship to influenza and must be regarded only as
secondary invaders. If any further support for this opinion were
necessary, it may be found in the studies upon the incidence of
pneumococcus and S. hemolyticus in early cases of influenza described in
this report. Both were found to occur in the same proportions in which
they may be found in normal individuals at any time.

Although Pfeiffer maintained that B. influenzæ was found only in true
epidemic influenza, the incorrectness of this contention has been
thoroughly established by many reliable investigators and it has been
shown beyond question that influenza bacilli may always be found in a
small proportion of normal individuals and are not infrequently found in
other respiratory diseases.

The fairly extensive study that has been made of the incidence of B.
influenzæ in normal men and in cases of measles has clearly demonstrated
that the proportion of carriers found in any group depends upon the
prevalence of influenza in the group studied and that with the progress
of the epidemic the percentage of carriers has steadily increased. When
one considers that the opportunity for the dissemination of B. influenzæ
by contact infection is almost unlimited during an epidemic of the
proportions of that which has swept over the country, this is not at all
surprising. That such a large number of normal individuals became
carriers of B. influenzæ during the epidemic would seem to be sufficient
evidence that actual dissemination does occur and to controvert the
theory that in actual cases of influenza, conditions are established in
the respiratory tract whereby B. influenzæ, always present in small
numbers, is enabled to “grow out” and become the predominant organism.
From a consideration of all the observations made as to the incidence of
B. influenzæ in various conditions it would appear that the carrier
condition is quite analogous to that found with many other bacteria, and
may be divided into three groups: (_a_) acute carriers, those having
influenza, (_b_) contact carriers, those who during epidemic times
become temporary carriers of the organism without contracting the
disease, and (_c_) chronic carriers, the relatively small number of
normal individuals or those with chronic respiratory conditions who
carry B. influenzæ over long periods of time. From the facts at hand
this would seem to be the most probable explanation of the conditions
found. It is certainly true that the established presence of
pneumococcus, B. diphtheriæ, meningococcus and many other organisms in a
varying proportion of normal individuals is not regarded as sufficient
evidence to exclude them as the etiologic agents of the diseases which
they cause.

It is quite obvious that if B. influenzæ is to be regarded as the cause
of epidemic influenza, it must change quite rapidly under certain
circumstances from a relatively saprophytic organism to a relatively
virulent pathogenic organism, and conversely return to its avirulent
state following the passage of an epidemic. Animal experimentation has
taught us that virulence is acquired by the rapid passage of an organism
from host to host. That an opportunity for the rapid transference of B.
influenzæ from man to man was provided by the assembling of large groups
of individuals relatively susceptible to respiratory diseases in our
camps and cantonments is by no means impossible. It has been clearly
shown by Vaughn and Palmer[22] that men from rural districts are very
susceptible to respiratory diseases and that the camps in which such men
were assembled suffered most heavily in this respect during the winter
of 1917–18. This Commission has clearly demonstrated that an epidemic of
influenza swept through Camp Funston[21] in the spring of 1918 and that
a similar epidemic occurred at Camp Pike. Accumulating evidence will
undoubtedly show that like epidemics existed in many of our southern
camps (Vaughn and Palmer,[22] Soper[23]). It is of considerable interest
that B. influenzæ was found in almost one-half of the cases of
bronchopneumonia studied by Cole and MacCallum[24] at Fort Sam Houston
in February and March, 1918. This relation is especially noteworthy,
since an epidemic of influenza was seen by one of us (Blake) among the
troops at Kelly Field and Fort Sam Houston during these months. That
similar conditions existed in European armies as early as 1916–17 is
suggested by the reports of Hammond, Rolland, and Shore[25] and of
Abrahams, Hallows, Eyre, and French[26] on epidemics of “purulent
bronchitis” with bronchopneumonia in the British army. B. influenzæ was
found abundantly in these cases.

Theoretically, under the conditions outlined above, ideal opportunities
have been provided for B. influenzæ to build up sufficient virulence to
enable it to produce the pandemic of 1918–19. While it is thoroughly
recognized that these considerations are in the main hypothetical, it is
felt that they are by no means beyond the bounds of possibility, and for
that reason are offered as suggestions worthy of further investigation.

It is, of course, perfectly possible on the basis of the observations
presented still to regard B. influenzæ as a secondary invader which
makes its appearance in all cases of influenza simultaneously with the
onset of clinical symptoms. Final proof of its causal relationship to
the disease must depend upon the production of influenza by experimental
inoculation. Results hitherto obtained in attempts to produce the
disease experimentally have been contradictory. Pfeiffer[8] claimed to
have produced a disease in monkeys in some respects resembling influenza
by the intratracheal injection of freshly isolated cultures of B.
influenzæ. Wollstein,[19] in studies upon the pathogenicity of various
strains, has shown that B. influenzæ is generally pathogenic for mice
and guinea-pigs without respect to source or virulence for man.
Pathogenicity for rabbits and monkeys, on the other hand, was possessed
only by strains that were highly virulent for man. She furthermore
pointed out that for successful animal experimentation, it is imperative
that inoculations be carried out immediately after the isolation of the
bacilli because they rapidly lose virulence by subculture on artificial
media. It is felt that failure to appreciate these facts has been
responsible for the often repeated statement that B. influenzæ is not
pathogenic for animals.

In a series of animal experiments carried out by this commission
recorded in an appendix to this report, sixteen-hour cultures of B.
influenzæ freshly isolated from early cases of influenza were
demonstrated to be pathogenic for monkeys, both by inoculation of the
nasal and pharyngeal mucosa and by intratracheal injection. Monkeys so
inoculated developed coryza, epistaxis, tracheitis, bronchitis, and
extreme prostration. Experiments with forty-eight-hour cultures of
strains preserved by subculture during from ten to fifteen days failed
to demonstrate pathogenicity for monkeys. Proof that these monkeys had
influenza can depend only upon the demonstration that they suffered with
a disease having the clinical character and pathologic lesions of
influenza.

The reported failure to produce influenza in man by direct inoculation
with freshly isolated cultures of B. influenzæ in experiments conducted
on volunteers by the United States Public Health Service[27] at Gallops
Island, Boston, is interesting, but would seem to lack definite
significance since attempts to transmit the disease from man to man by
direct contact also failed. Since all the subjects of these experiments
had been previously exposed to influenza during the epidemic, 30 per
cent actually having contracted the disease, it would seem probable that
the remaining 70 per cent were only very slightly if at all susceptible.
It is noteworthy that the attack rate of influenza in most army groups
was approximately 20 to 30 per cent during the epidemic, the remaining
70 to 80 per cent failing to contract the disease though equally
exposed. No other explanation presents itself except that influenza is
no longer transmissible when clinical symptoms have appeared.

Conclusions

1. Consideration of all the evidence available makes it seem highly
probable that B. influenzæ is the specific etiologic agent of epidemic
influenza, because (_a_) it is always present in early uncomplicated
cases of influenza; (_b_) it is predominantly so during the acute stage
of the disease in cases going on to rapid recovery without development
of complications; (_c_) its presence in varying numbers in normal
individuals and in other diseases of the respiratory tract is not valid
evidence against its etiologic relationship to influenza, but on the
contrary is quite in harmony with what should be expected from our
knowledge of other bacteria known to be the etiologic agents of various
respiratory diseases; (_d_) its rapidly increasing prevalence in normal
individuals simultaneously with the progress of the epidemic indicates
that actual dissemination of B. influenzæ readily occurs and is very
widespread during pandemic times; (_e_) cultures of B. influenzæ freshly
isolated from early acute cases of influenza are pathogenic for animals,
and may produce in monkeys a disease closely resembling influenza.

2. Final proof of the exact relationship of B. influenzæ to influenza
must depend upon (_a_) more definite knowledge of the immunology both of
the organism and of the disease, and (_b_) knowledge of the pathologic
lesions of influenza and the production of these lesions in animals by
inoculation with B. influenzæ.

CHAPTER II
CLINICAL FEATURES AND BACTERIOLOGY OF INFLUENZA AND ITS ASSOCIATED
PURULENT BRONCHITIS AND PNEUMONIA

FRANCIS G. BLAKE, M.D., AND THOMAS M. RIVERS, M.D.

The material presented in this section of the report consists of
clinical and bacteriologic observations made during the course of an
investigation of influenza and its associated bronchitis and pneumonia
at Camp Pike, Ark., between September 6 and December 15, 1918,
comprising part of a correlated study of the epidemiology, bacteriology,
pathology, and clinical features of these diseases. The bacteriologic
studies are in the main limited to those made during life, those made at
necropsy being reported in another section of this report.

=Methods.=—All cases upon which the clinical and bacteriologic data
presented are based, were examined by the authors and our own clinical
histories and physical examinations were recorded. This was considered
of special importance, since in studying a group of diseases in which
secondary infection of the respiratory tract might supervene at any
time, it was essential to determine as far as possible the exact
clinical condition of the patient at the time when bacteriologic
examinations were made. The bacteriologic methods employed were the
direct culture of nose and throat swabbings and of selected and washed
specimens of sputum on the surface of 5 per cent defibrinated horse
blood agar plates, the intraperitoneal inoculation of white mice with
specimens of sputum according to the method described by Blake[28] for
the determination of pneumococcus types, and in some cases the method of
Avery.[29] B. influenzæ pneumococci and hemolytic streptococci were
identified by the methods described elsewhere. Note was made in most
instances of the presence of other organisms such as members of the
Gram-negative diplococcus group, staphylococci, diphtheroids, and
members of the streptococcus viridans group, but no attempt was made to
further isolate or identify them since they played no significant part
in the cases studied except in rare instances.

Influenza

The fall epidemic of influenza at Camp Pike began about September 1,
1918, and reached epidemic proportions on September 23 when 214 cases
were admitted to the base hospital. The epidemic was at its height from
September 27 to October 3, during which period there were in the
neighborhood of 1,000 new cases daily. From this date until October 31
the number of new cases occurring daily steadily decreased and by the
latter date the epidemic was over. Scattered cases continued to occur,
however, throughout November, and during the last week of this month and
the first week of December a second epidemic wave of relatively mild
character occurred. From September 1 to October 31 the total number of
cases of influenza reporting sick was 12,393. During the same period
there were 1,499 cases of pneumonia with 466 deaths.

Influenza as observed at Camp Pike differed in no essential respects
from that occurring elsewhere. In brief, it presented itself as a highly
contagious, self-limited infectious disease of relatively short duration
in most instances, the principal manifestations of which were sudden
onset with high fever, profound prostration, severe aching pains in back
and extremities, conjunctival injection, flushing of the face, neck, and
upper thorax often amounting to a true erythema, and a rapidly
progressing attack upon the mucous membranes of the respiratory tract as
manifested by coryza, pharyngitis, tracheitis and bronchitis with a
marked tendency to hemorrhage; in itself it is rarely serious, but in
reality serious because of the large number of individuals attacked and
temporarily incapacitated and because it predisposed to widespread and
highly fatal secondary infection of the lungs.

=Clinical Features.=—A clinical study of 100 consecutive cases of
influenza admitted during the height of the epidemic was made.

The onset was sudden, in most instances being initiated with marked
sensations of chilliness in 82 cases. Although a severe chill was
probably relatively uncommon, 44 of these patients considered the
symptom of sufficient severity to describe it as such. This was
accompanied by extreme general malaise with severe aching pains
throughout the whole body. Intense backache was complained of in 40
cases, headache in 54 cases. A varying degree of prostration, sometimes
leading to complete collapse, was almost universal; 5 patients
complained of extreme asthenia and 2 of marked dizziness. At time of
admission to the hospital the face, neck and upper chest exhibited a
uniform erythematous flush, never macular in appearance. The conjunctivæ
were deeply injected, but lacrimation was not noticeable and a true
exudative conjunctivitis was not encountered. Onset was accompanied by a
sharp elevation of temperature ranging from 100° F. to 106° F., in most
cases being between 102° F. and 105° F., at the time of admission. No
constant type of temperature curve was maintained. Excluding the 15
cases in this group that developed pneumonia, the temperature was well
sustained throughout the course of the disease in 46, irregular in 33,
and definitely remittent in 6. The duration of the fever varied between
one and seven days, the temperature having returned to normal in all but
19 of the 85 cases by the end of four days. The duration of fever was
one day in 18 cases, two days in 12, three days in 19, four days in 17,
five days in 10, six days in 4, and seven days in 5. Of the 4 cases with
fever for six days, 2 had a fairly extensive bronchitis, 1 a laryngitis.
Of the 5 cases with fever of seven days’ duration, 3 had signs of an
extensive bronchitis, 2 of only a mild bronchitis.

The pulse was relatively slow in rate as compared with the degree of
temperature elevation, running between 90 and 100 beats per minute in
the large majority of cases. At the height of the disease it was full
and easily compressed. No irregularities were noticed. With recovery it
fell promptly to normal. The respiratory rate showed only moderate
elevation, being between 20 and 26 in most cases. In a few instances a
rate as high as 32 was recorded at time of admission to the hospital,
but this promptly fell with rest in bed. A respiratory rate rising above
26 after the third or fourth day of the disease nearly always indicated
a beginning pneumonia. With recovery the rate promptly fell to normal.
Cyanosis did not occur in the absence of pneumonia.

Aside from the manifestations of a profound toxemia, influenza was
preeminently characterized by symptoms of respiratory tract infection.
The appearance of respiratory symptoms occurred at varying intervals
after the onset of the disease, being well developed by the end of
twenty-four hours in most cases. A progressive attack upon the mucous
membranes of the respiratory tract was universal, beginning with coryza
and pharyngitis and progressing to tracheitis or _vice versa_. Further
extension of the infection to the bronchi, however, was by no means
universal, 49 cases in the group studied recovering without developing
evidence of bronchitis. Sore throat was rarely complained of, and
laryngitis, possibly due to secondary infection, occurred only once. The
progress of the infection was marked subjectively by sensations of
irritation, stinging, and a feeling of tightness. A profuse, thin,
mucoid exudate appeared; the pharyngeal walls and the soft palate showed
a characteristic deep red granular appearance. The onset of tracheitis
began with a sense of burning and tightness beneath the sternum
accompanied by a harassing cough, at first nonproductive, later with the
outpouring of an exudate becoming productive. The sputum varied in
character between a scanty, thin, mucoid sputum and a profuse, frankly
purulent sputum in cases subsequently developing an extensive
bronchitis. Hemorrhage from the mucous membranes was common. Epistaxis
occurred in 12 per cent of the cases and was often profuse. The sputum
contained fresh blood in varying amounts in 24 per cent of the cases; 51
per cent of the cases developed signs of bronchitis. In 15 of these the
bronchitis was mild, probably limited to the larger bronchi, physical
examination showing only inconstant sibilant and musical râles. The
sputum in these cases was neither profuse nor frankly purulent; 36 cases
developed a fairly extensive purulent bronchitis as manifested by more
or less diffusely scattered moist râles and by moderately copious
mucopurulent or frankly purulent sputum. This bronchitis was not
accompanied by an increase in the respiratory rate or by cyanosis unless
pneumonia subsequently developed.

Gastrointestinal symptoms were insignificant: 8 patients complained of
nausea early in the disease and 6 of them vomited. Diarrhea occurred in
only 1 case, constipation being the rule. The spleen was palpable in 21
cases, but this is of doubtful significance, since nearly all the
patients came from malarial regions. Jaundice was not noted. Aside from
the profound depression, sometimes amounting to stupor, mental symptoms
were not noted except in 1 case which showed a mild delirium.

Influenza, although _per se_ a self-limited disease of short duration,
frequently leads to the development of serious complications, the most
important of which are pneumonia and purulent bronchitis with a varying
degree of bronchiectasis. In the group of 100 cases of influenza
studied, purulent bronchitis developed in 36 instances, pneumonia in 15;
in 3 cases there was lobar pneumonia, in 12 bronchopneumonia. Further
discussion of these complications is reserved for the sections dealing
with them in detail. Other complications were relatively rare. Otitis
media occurred in one case and frontal sinusitis in one. No fatalities
were observed among cases of uncomplicated influenza, the deaths that
occurred being invariably associated with a secondary pneumonia due in
nearly all instances to secondary infection with pneumococci or
hemolytic streptococci.

Purulent Bronchitis

It has been stated that a considerable number of cases of influenza
developed a more or less extensive purulent bronchitis. This term is
used as descriptive of a group of cases showing clinically evidence of a
diffuse bronchitis as manifested by numerous medium and fine moist râles
scattered throughout the chest and evidence of a definitely purulent
inflammatory reaction as indicated by the expectoration of fairly
copious amounts of mucopurulent or frankly purulent sputum. This
condition is regarded as quite distinct, on the one hand, from the
common type of mucoid bronchitis frequently associated with “common
colds” and a fairly common feature of uncomplicated cases of influenza,
in which physical examination of the chest reveals only transient
sibilant and musical râles without evidence of extension to finer
bronchi, and, on the other hand, from bronchopneumonia.

=Bacteriology.=—Thirteen cases of purulent bronchitis following
influenza in none of which was there any evidence of pneumonia at the
time cultures of the sputum were made nor later were subjected to
careful bacteriologic study. Specimens of bronchial sputum were
collected in sterile Petri dishes and selected portions thoroughly
washed to remove surface contaminations before bacteriologic
examinations were made. The results are shown in Table XIII.

TABLE XIII

BACTERIOLOGY OF THE SPUTUM IN CASES OF PURULENT BRONCHITIS FOLLOWING
INFLUENZA

════╤══════════════════════════╤═════════════════════╤═════════════════
CASE│ STAINED FILM OF SPUTUM │ DIRECT CULTURE ON │MOUSE INOCULATION
│ │ BLOOD AGAR PLATE │
│ │ │
────┼──────────────────────────┼─────────────────────┼─────────────────
GJ │B. influenzæ + + + │B. influenzæ + + + + │B. influenzæ
│ │ │Pneumococcus
│Gram + diplococci + │Pneumococcus + │(type
│ │ │undetermined)
WAL │B. influenzæ + + │B. influenzæ + + + │
│Gram + diplococci + + │Pneumococcus IV + + │
TH │B. influenzæ + + + │B. influenzæ + + + + │
│Gram + diplococci + + + │Pneumococcus IV + + │
LH │B. influenzæ + │B. influenzæ + + │
│Gram + diplococci + │Pneumococcus IV + + │
FBD │Gram + diplococci + + + + │Pneumococcus IV + + +│Pneumococcus IV
│ │B. influenzæ + │B. influenzæ
Wa │B. influenzæ + + │B. influenzæ + + │
│Gram + diplococci + + │Pneumococcus IV + + │
Sh │B. influenzæ + + + │B. influenzæ + + │
│Gram + diplococci + + │Pneumococcus IV + + +│
Wal │Gram + diplostrep + + + │S. viridans + + │
│B. influenzæ + │B. influenzæ + + │
CLF │B. influenzæ + + + + + │ │B. influenzæ
│Gram + diplococci + │ │Pneumococcus IV
NCC │B. influenzæ + + │B. influenzæ + + + │B. influenzæ
│Gram − micrococcus + │M. catarrhalis + + │M. catarrhalis
│Gram + diplostrep. + │S. viridans + + │
JCM │B. influenzæ + + + │B. influenzæ + + + + │B. influenzæ
│Gram + streptococcus + │S. hemolyticus + │S. hemolyticus
│Gram − micrococcus + │M. catarrhalis + │Pneumococcus IV
│Gram + diplococcus + │ │
Bl │B. influenzæ + │ │B. influenzæ
│Gram + diplococcus + │ │Pneumococcus IIa
Bu │B. influenzæ + + + + │B. influenzæ + + + │B. influenzæ
│Gram + diplococcus + + + +│Pneumococcus IV + + +│Pneumococcus IV
────┴──────────────────────────┴─────────────────────┴─────────────────

From the data presented in Table XIII it is evident that a mixed
infection existed in all cases. The results obtained by stained sputum
films and by direct culture on blood agar plates are of special
significance. B. influenzæ was present in all cases, being the
predominant organism in 6 cases, abundantly present in others, and few
in number in 2. Of other organisms the pneumococcus was most frequently
found, occurring in 11 of the 13 cases, in all but 2 instances being
present in considerable numbers. S. viridans was encountered twice, once
in association with a Gram-negative micrococcus resembling M.
catarrhalis culturally. S. hemolyticus was found once, together with M.
catarrhalis and a few pneumococci, Type IV, coming through in the mouse
only and of doubtful significance. The stained sputum films and direct
cultures always showed these organisms present in sufficient abundance
to indicate that they were present in the bronchial sputum and were not
merely contaminants from the buccal mucosa.

It seems quite probable from these results that purulent bronchitis
following influenza is, in most cases at least, due to mixed infection
of the bronchi and should be looked upon as a complication of influenza.
Whether the condition may be caused by infection with B. influenzæ alone
is difficult to say. No evidence that it may be caused by B. influenzæ
alone was obtained in the cases studied. It is not intended to enter
here into a discussion as to whether B. influenzæ should be regarded as
a secondary invader or not; the other organisms encountered certainly
are. It would seem most probable that purulent bronchitis is caused by
the mixed infection of B. influenzæ and various other organisms,
commonly the pneumococcus, but that the condition is initiated by the
invasion of the bronchi by these other organisms in the presence of a
preceding infection with B. influenzæ.

=Clinical Features.=—Purulent bronchitis following influenza began
insidiously without any prominent symptoms to mark its onset. About the
third or fourth day of influenza, when recovery from the primary disease
might be looked for, the patient would begin to cough more frequently,
raising increasing amounts of mucopurulent sputum. This sputum was
yellowish green in color, copious in amount, and often somewhat nummular
in character, sometimes streaked with blood. These symptoms were
accompanied by the appearance of coarse, medium and fine moist râles
more or less diffusely scattered throughout the chest and usually most
numerous over the lower lobes. The percussion note, breath and voice
sounds, and vocal and tactile fremitus remained normal. There was no
increase in the respiratory rate or pulse rate, and cyanosis did not
develop in the absence of a beginning pneumonia. Many such cases, of
course, developed bronchopneumonia; in this event areas showing
diminished resonance, suppressed breath sounds, and fine crepitant râles
with the “close to the ear” quality would appear, the respiratory rate
would become increased and cyanosis would become evident. In those cases
of purulent bronchitis not developing pneumonia, a moderate elevation of
temperature, rarely above 101° F., and irregular in character usually
occurred and persisted for a few days or a week.

Many cases maintained a persistent cough, raising considerable amounts
of sputum throughout the period of their convalescence in the hospital,
which was often considerably prolonged when this complication of
influenza occurred. Although no clinical data are available on such
cases over a prolonged period of observation, it seems probable that
some of them, at least, had developed some degree of bronchiectasis.
This would seem all the more probable, since many cases of pneumonia
following influenza showed at autopsy extensive purulent bronchitis with
well-developed bronchiectasis. Bronchiectasis will be discussed in
greater detail in another section of this report. It is this group of
cases with more or less permanent damage to the bronchial tree that
makes this type of bronchitis following influenza a serious complication
of the disease.

Pneumonia

The opportunity presented for a correlated study of the clinical
features, bacteriology, and pathology of pneumonia following influenza
throughout the period of the epidemic at Camp Pike from September 6,
1918, to December 15, 1918, made it evident that this pneumonia could be
regarded as an entity in only one respect, namely, that influenza was
the predisposing cause. Clinically, bacteriologically, and
pathologically it presented a very diversified picture ranging all the
way from pneumococcus lobar pneumonia to hemolytic streptococcus
interstitial and suppurative pneumonia with the picture modified to a
varying extent by the preceding or concomitant influenzal infection.

One hundred and eleven consecutive cases in which careful clinical and
bacteriologic studies were made form the basis of the material
presented. Of these cases, 38 came to necropsy so that ample opportunity
was presented to correlate the clinical and bacteriologic studies made
during life with the pathology and bacteriology at necropsy. It has
seemed advisable to group the cases primarily on an etiologic basis with
secondary division according to clinical features in so far as this can
be done. Bacteriologic studies showed that at the time of onset these
pneumonias were either pneumococcus pneumonias or mixed pneumococcus and
influenza bacillus pneumonias in nearly all instances. Certain of these
cases later became complicated by a superimposed hemolytic streptococcus
or a staphylococcus infection. In a few instances hemolytic
streptococcus pneumonia directly followed influenza without an
intervening pneumococcus infection. B. influenzæ was present in varying
numbers in nearly all cases. In only 2 instances however, was it found
unassociated with pneumococci or hemolytic streptococci, once alone and
once with S. viridans.

Clinically the cases fell into four main groups: (1) Lobar pneumonia;
(2) lobar pneumonia with purulent bronchitis; (3) bronchopneumonia
(pneumococcus); (4) bronchopneumonia (streptococcus). It should be borne
in mind, however, that the picture was a complex one and that correct
clinical interpretation was not always possible, since many cases did
not conform sharply to any one type and superimposed infections during
the course of the disease often modified the picture.

=Pneumococcus Pneumonia Following Influenza.=—Bacteriologic examination
of selected and washed specimens of sputum coughed from the lungs at
time of onset of pneumonia showed the various immunologic types of
pneumococcus to be present in 105 cases. The incidence of the different
types is shown in Table XIV.

TABLE XIV

TYPES OF PNEUMOCOCCUS IN 105 CASES OF PNEUMOCOCCUS PNEUMONIA FOLLOWING
INFLUENZA

═══════════════════════╤═════════╤═════════════════╤═════════╤═════════
│ LOBAR │BRONCHOPNEUMONIA │ TOTAL │PER CENT
│PNEUMONIA│ │ │
───────────────────────┼─────────┼─────────────────┼─────────┼─────────
Pneumococcus, Type I │ 8│ 0│ 8│ 7.6
Pneumococcus, Type II │ 3│ 1│ 4│ 3.8
Pneumococcus, II atyp. │ 12│ 7│ 9│ 18.1
Pneumococcus, Type III │ 3│ 3│ 6│ 5.7
Pneumococcus, Group IV │ 32│ 36│ 68│ 64.8
───────────────────────┴─────────┴─────────────────┴─────────┴─────────

The most noteworthy feature of the figures in Table XIV is the high
proportion of pneumonias due to types of pneumococci found in the mouths
of normal individuals, 93 cases or 88.6 per cent, being caused by
Pneumococcus Types II atypical, III, and IV. This is in harmony with the
results generally reported and is in all probability due to the fact
that in patients with influenza pneumococci, which under normal
conditions would fail to cause pneumonia, readily gain access to the
respiratory tract and produce the disease. It is also of interest that
with one exception the highly parasitic pneumococci of Types I and II
were associated with pneumonias clinically lobar in type.

Superimposed infection of the lungs with other types of pneumococci than
those primarily responsible for the development of pneumonia occurred
not infrequently in this group of cases either during the course of the
disease or shortly after recovery from the first attack of pneumonia.
Pneumococcus Type II infection was superimposed upon or shortly followed
pneumonia caused by Group IV pneumococci in 4 instances, by Pneumococcus
II atypical in 1 instance. In 1 case pneumonia due to Pneumococcus II
atypical occurred three days after recovery from a Pneumococcus Type I
pneumonia, in another case Pneumococcus Type III infection was
superimposed upon a pneumonia originally due to a pneumococcus of Group
IV. These cases are presented in detail in another section of this
report, and in several instances were shown to be directly due to
contact infection from patients in neighboring beds.

In a similar manner, superimposed infection with S. hemolyticus at some
time during the course of the pneumonia occurred in 13 cases in this
group, with fatal result in all but one. Streptococcus infection
occurred in pneumonia due to Pneumococcus II atypical once, to
Pneumococcus Type III once, and to pneumococci of Group IV eleven times.
Nine of these cases were free from hemolytic streptococci at the time of
onset of the pneumonia, 4 showed a very few colonies of hemolytic
streptococci in the first sputum culture made.

B. influenzæ was found in the sputum coughed from the deeper air
passages in the majority of cases, being present in 80, or 76.2 per
cent, of the 105 cases. In the 58 cases of lobar pneumonia it was found
41 times, or 70.7 per cent, in the 47 cases of bronchopneumonia 39
times, or 82.9 per cent. The abundance of B. influenzæ in the sputum
varied greatly in different cases. Microscopic examination of stained
sputum films and direct culture of the sputum on blood agar plates
showed that in general it was more abundant in the mucopurulent sputum
from cases of bronchopneumonia than in the mucoid rusty sputum from
cases of lobar pneumonia. This was by no means an invariable rule,
however, since in the former the bacilli were sometimes very few in
number, in the latter quite abundant. Whether B. influenzæ shared in the
production of the actual pneumonia in these cases is difficult to decide
and cannot be stated on the basis of the bacteriologic and clinical
observations which have been made.

=Clinical Features.=—One of the most striking aspects of pneumococcus
pneumonia following influenza was the diversity of clinical pictures
presented. These varied all the way from the classical picture of lobar
pneumonia to that of bronchopneumonia of all grades of severity from the
rapidly fatal coalescing type to that of very mild character with very
slight signs of consolidation. For this reason it is questioned whether
there is any real justification for speaking of a typical influenzal
pneumonia, an opinion that seems well supported by the diversified
picture found at the necropsy table.

For purposes of presentation, pneumococcus pneumonia following influenza
may be divided into three clinical groups: (1) Lobar pneumonia; (2)
lobar pneumonia with purulent bronchitis; (3) bronchopneumonia. No
accurate data are available as to the relative frequency with which
these three types occurred at Camp Pike. In the group of 105 cases
studied there were 58 cases of lobar pneumonia, 11 of which had purulent
bronchitis, and 47 cases of bronchopneumonia. The majority of these
cases, however, occurred during the early days of the epidemic of
influenza and probably show a considerably higher proportion of lobar
pneumonias than actually occurred in the total number of pneumonias
throughout the epidemic. This is indicated by the fact that of 100
consecutive cases of influenza selected for observation at the height of
the epidemic, 3 developed clinical evidence of lobar pneumonia and 12 of
bronchopneumonia.

(1) Lobar pneumonia presenting the typical clinical picture with sudden
onset, tenacious rusty sputum, sustained temperature, and physical signs
of complete consolidation of one or more lobes occurred in 47 cases; 36
cases in this group definitely followed influenza. In 11 cases no
certain clinical evidence of a preceding influenza was obtained, and it
is probable that some of these represent cases of pneumonia occurring
independently of the epidemic of influenza.

The onset of pneumonia in this group of cases occurred from four to nine
days after the onset of influenza and with few exceptions was ushered in
by a chill and pain in the chest. In several instances the patient had
apparently recovered from influenza as evidenced by fall of temperature
to normal. After twenty-four to seventy-two hours of normal temperature
the patient would have a chill and develop lobar pneumonia. In the
majority of cases, however, lobar pneumonia developed while the patient
was still sick with influenza. The course of the disease, symptomatology
and physical signs were quite characteristic of lobar pneumonia and
require no special comment. Recovery by crisis occurred in 21 cases, by
lysis in 8. Pneumococcus empyema developed in 3 cases, fibrinopurulent
pericarditis in 3 and all but 1 of these 6 cases terminating fatally.

In Table XV 5 fatal cases of lobar pneumonia, which illustrate some of
the unusual features of the disease when it follows influenza, have been
summarized. The first 2 cases represent examples of recurring attacks of
pneumonia which developed shortly after recovery from the first attack,
in both instances being due to types of pneumococci different from those
causing the first attack. The third case represents an example of
superimposed infection of the lungs with hemolytic streptococci and
staphylococci during the course of a pneumonia due to Pneumococcus IV
and disappearance of the latter organism from the tissues so that it was
not found at time of necropsy. The last 2 cases are examples of
fulminating rapidly fatal cases of lobar pneumonia associated with mixed
infections of pneumococci and hemolytic streptococci, the streptococci
probably being secondary in both cases. Cases like the few examples
cited above, which occurred not infrequently throughout the epidemic of
influenza, serve to illustrate the difficulties which may be met in
attempting to correlate the clinical, bacteriologic and pathologic
features of pneumonia following influenza unless careful bacteriologic
examinations are made both during life and at the necropsy table in the
same group of cases.

TABLE XV

CASES OF LOBAR PNEUMONIA FOLLOWING INFLUENZA

════╤═════════╤══════════╤══════════════════╤════════════════════════════════
CASE│ONSET OF │ ONSET OF │SPUTUM EXAMINATION│ COURSE OF PNEUMONIA
│INFLUENZA│PNEUMONIA │ │
────┼─────────┼──────────┼─────┬────────────┼────────────────────────────────
│ │ │DATE │BACTERIOLOGY│
────┼─────────┼──────────┼─────┼────────────┼────────────────────────────────
Pul │Sept. 7 │Sept. 9 │Sept.│Pn. IV ++++ │Recovery by crisis on Sept. 14.
│ │1st attack│10 │B. inf. +++ │On Sept. 21 developed lobar
│ │bronchopn.│ │ │pneumonia. Died Sept. 30
│ │ │ │ │
────┼─────────┼──────────┼─────┼────────────┼────────────────────────────────
Lew │Sept. 16 │Sept. 20 │Sept.│Pn. I +++ │Lobar pn., recovery by crisis
│ │chill │22 │B. inf. + │Sept. 29. Developed 2nd attack
│ │ │ │ │lobar pn. on Oct. 2. Died Oct. 8
│ │ │ │ │
│ │ │ │ │
│ │ │ │ │
────┼─────────┼──────────┼─────┼────────────┼────────────────────────────────
Col │Sept. 20 │Sept. 24 │Sept.│Pn. IV ++ │Severe lobar pneumonia. Died on
│ │ │27 │ │Sept. 30
│ │ │ │ │
│ │ │ │ │
│ │ │ │ │
────┼─────────┼──────────┼─────┼────────────┼────────────────────────────────
Gar │Sept. 23 │Sept. 28 │Sept.│Pn. IV ++ │Fulminating rapidly fatal lobar
│ │ │30 │S. hem. + │pneumonia. Died Sept. 30
│ │ │ │B. inf. + │
│ │ │ │ │
────┼─────────┼──────────┼─────┼────────────┼────────────────────────────────
Hol │Sept. 25 │Sept. 30 │Sept.│Pn. III ++ │Fulminating rapidly fatal lobar
│ │ │30 │B. inf. ++ │pneumonia. Died Oct. 1.
│ │ │ │ │
│ │ │ │ │
│ │ │ │ │
│ │ │ │ │
│ │ │ │ │
────┴─────────┴──────────┴─────┴────────────┴────────────────────────────────

════╤══════════════════════════════════════════════════
CASE│ NECROPSY
│
────┼────────────────────────────────┬─────────────────
│ DIAGNOSIS │ BACTERIOLOGY
────┼────────────────────────────────┼─────────────────
Pul │Lobar pneumonia. Gray │H.B. Pn. II
│hepatization L.L, L.U, R.L. │Br. Pn. II ++++
│ │B. inf. +++
│ │R.L. Pn. II + +
────┼────────────────────────────────┼─────────────────
Lew │Lobar pneumonia. Gray │H.B. Pn. II atyp.
│hepatization R.U. │Br. B. inf. ++++
│Fibrinopurulent pleurisy │Pn. IIa +++
│ │S. hem. +
│ │Staph. +
│ │R.U. Pn. IIa ++++
────┼────────────────────────────────┼─────────────────
Col │Lobar pneumonia. Red │H.B. S. hem.
│hepatization all lobes. │Br. S. hem. ++++
│Serofibrinous pl., rt. 125 c.c. │Staph. +
│ │L.L. S. hem. ++++
│ │Staph. +
────┼────────────────────────────────┼─────────────────
Gar │Lobar pneumonia. Engorgement and│H.B. S. hem.
│red hepatization L.U., R.U. │Br. S. hem. ++++
│ │B. inf. +++
│ │L.U. S. hem. ++++
────┼────────────────────────────────┼─────────────────
Hol │Lobar pneumonia. Engorgement all│H.B. sterile
│lobes │Br. B. inf. ++++
│ │Pn. III ++
│ │S. hem. +
│ │R.L. Pn. III ++++
│ │B. inf. ++
│ │S. hem. +
────┴────────────────────────────────┴─────────────────

L.L. R.L., etc., indicates lobes involved. H. B. = Heart’s blood. Br. =
bronchus.

(2) There were 11 cases of lobar pneumonia with purulent bronchitis in
the group studied. Clinically, they closely resembled the cases in the
preceding group except in so far as the picture was modified by the
presence of the purulent bronchitis. All directly followed influenza.
The sputum, instead of being rusty and tenacious, was profuse and
mucopurulent, usually streaked with blood. Stained films and direct
culture on blood agar plates showed pneumococci in abundance and B.
influenzæ in varying numbers, in only two instances the predominant
organism. The physical signs were those of lobar pneumonia with, in
addition, those of a diffuse bronchitis as manifested by medium and
coarse moist râles throughout both chests. Five cases recovered by
crisis; 6 terminated fatally and in all of them the clinical diagnosis
of lobar pneumonia with purulent bronchitis was confirmed at necropsy.

(3) Forty-seven cases in the group studied presented the clinical
picture of bronchopneumonia. The onset of pneumonia in these cases was
in most instances insidious and appeared to occur as a continuation of
the preceding influenza. The temperature, instead of falling to normal
after from three to four days, remained elevated or rose higher, the
respiratory rate began to rise, a moderate cyanosis appeared, the cough
increased, and the sputum became more profuse, usually being
mucopurulent and blood streaked, sometimes mucoid with fresh blood. The
pulse showed little change at first, being only moderately accelerated.
Pleural pain, so characteristic of the onset of lobar pneumonia, was
rarely complained of, but a certain amount of substernal pain was
common, probably due to the severe tracheobronchitis. Physical
examination at this time revealed small areas showing relative dullness,
diminished or nearly absent breath sounds, and fine crepitant râles.
These areas usually appeared first posteriorly over the lower lobes.

The subsequent course of the disease showed the widest variation from
mild cases with limited pulmonary involvement going on to prompt
recovery in four or five days with defervescence by lysis or crisis to
those presenting the picture of a rapidly progressive and coalescing
pneumonia with fatal outcome. In the milder cases the diagnosis of
pneumonia depended in considerable part upon the general symptoms of
continued fever, increased respiratory rate, and slight cyanosis.
Definite pulmonary signs were always present if carefully looked for,
though sometimes not outspoken. Areas of bronchial breathing and
bronchophony often appeared late, sometimes not until the patient was
apparently recovering. In the severe cases cyanosis became intense and
an extreme toxemia dominated the picture. In certain of these cases
there was an intense pulmonary edema. The respiratory rate showed wide
variation, the breathing in some cases being rapid and gasping, in
others comparatively quiet. Progressive involvement of the lungs
occurred with the development of marked dullness, loud bronchial
breathing and bronchophony. Abundant medium and coarse moist râles were
heard throughout the chest, probably due in considerable part to the
extensive bronchitis almost universally present. An active delirium was
not uncommon. Signs of pleural involvement, even in the most severe and
extensive cases, rarely occurred, except in those cases in which a
hemolytic streptococcus infection supervened.

Of the 47 cases in this group, 29 recovered; 14 by crisis, 15 by lysis.
The average duration of illness from the onset of influenza until
recovery from the pneumonia was ten days, the majority of these cases
being relatively mild in character with pneumonia of three to six days’
duration. Empyema with ultimate recovery occurred in 1 of these cases,
Pneumococcus Type II being the causative organism.

There were 18 fatal cases in the group. Nine of these are summarized in
Table XVI as illustrative of the frequently complex character of
bronchopneumonia following influenza and because of the interest
attaching to the bacteriologic examinations made during life and at
necropsy. Case 70 is a typical instance of the rapidly progressive type
of confluent lobular pneumonia with extensive purulent bronchitis,
intense cyanosis, and appearance of suffocation, with which pneumococci,
in this case Pneumococcus IV, and B. influenzæ are commonly associated.
Case 59 is illustrative of the small group of bronchopneumonias
following influenza which die, often unexpectedly, after a long drawn
out course, in this instance three weeks after onset. Examination of the
sputum at the time the pneumonia began, showed Pneumococcus Type IV and
B. influenzæ. At necropsy there was a lobular pneumonia with clustered
small abscesses, probably due to a superimposed infection with S.
aureus. There was a well-developed bronchiectasis in the left lower
lobe. Cultures taken at autopsy showed a sterile heart’s blood, which is
not infrequently the case in cases of pneumococcus lobular pneumonia
after influenza. Cultures from the consolidated portions of the lung
showed no growth, the pneumococcus having disappeared as might be
expected from the duration of the case. B. influenzæ together with
staphylococci were found in the bronchi. In Cases 50 and 56 a second
attack of pneumonia caused by a different type of pneumococcus from that
responsible for the first attack occurred, the second attack in both
instances being due to contact infection with Pneumococcus Type II from
a patient in a neighboring bed suffering with Pneumococcus Type II
pneumonia. Both cases showed at necropsy the type of confluent lobular
pneumonia so commonly found in pneumococcus pneumonias following
influenza. Case 107 illustrates well the extent to which mixed
infections may occur, especially when cases are treated in crowded
hospital wards. The sputum at time of onset showed Pneumococcus IV in
abundance and a few staphylococci. At necropsy there was a confluent
lobular pneumonia with clustered abscesses, purulent bronchitis, and
bronchiectasis in the left lower lobe. The heart’s blood was sterile,
the lungs showed Pneumococcus Type III and staphylococci. B. influenzæ
was not found, but through oversight, no cultures were taken from the
bronchi. Cases 92, 99, 102, and 104 are all examples of superimposed
hemolytic streptococcus infection occurring in the presence of a
Pneumococcus Type IV pneumonia, with the picture of interstitial
suppuration, abscess formation, and empyema due to S. hemolyticus on the
background of a pneumococcus lobular pneumonia found at necropsy. All
showed abundant pneumococci and B. influenzæ in the sputum and were free
from hemolytic streptococci at time of onset of pneumonia, except Case
92 which showed 2 colonies of S. hemolyticus in the first sputum culture
made. At time of death the pneumococci had disappeared in all cases and
were replaced by hemolytic streptococci.

TABLE XVI

CASES OF BRONCHOPNEUMONIA FOLLOWING INFLUENZA

════╤═════════╤═════════╤══════════════════╤═══════════════════════════
CASE│ONSET OF │ONSET OF │SPUTUM EXAMINATION│ COURSE OF PNEUMONIA
│INFLUENZA│PNEUMONIA│ │
────┼─────────┼─────────┼─────┬────────────┼───────────────────────────
│ │ │DATE │BACTERIOLOGY│
────┼─────────┼─────────┼─────┼────────────┼───────────────────────────
70│Sept. 18 │Sept. 21 │Sept.│B. inf. ++++│Diffuse bronchitis with
│ │ │22 │Pn. IV ++ │rapidly progressive
│ │ │ │ │confluent bronchopneumonia.
│ │ │ │ │Died Sept. 24
│ │ │ │ │
────┼─────────┼─────────┼─────┼────────────┼───────────────────────────
59│Sept. 13 │Sept. 18 │Sept.│Pn. IV +++ │Bronchopneumonia with long
│ │ │19 │B. inf. + │drawn out course. Died Oct.
│ │ │ │ │4
│ │ │ │ │
────┼─────────┼─────────┼─────┼────────────┼───────────────────────────
50│Sept. 14 │Sept. 17 │Sept.│Pn. IV +++ │Mild bronchopneumonia
│ │ │18 │ │improving on Sept. 24. On
│ │ │ │ │Sept. 26 became suddenly
│ │ │ │ │worse and died on Sept. 30
│ │ │ │ │
│ │ │ │ │
────┼─────────┼─────────┼─────┼────────────┼───────────────────────────
56│Sept. 10 │Sept. 17 │Sept.│Pn. IIa +++ │Bronchopneumonia with
│ │ │18 │ │recovery by crisis on Sept.
│ │ │ │ │19. Developed a second
│ │ │ │ │attack of pneumonia and
│ │ │ │ │died Sept. 29
────┼─────────┼─────────┼─────┼────────────┼───────────────────────────
107│Sept. 27 │Sept. 29 │Oct. │Pn. IV +++ │Diffuse bronchitis and
│ │ │1 │B. inf. + │severe bronchopneumonia.
│ │ │ │Staph. + │Died Oct. 5
│ │ │ │ │
────┼─────────┼─────────┼─────┼────────────┼───────────────────────────
92│Sept. 23 │Sept. 28 │Oct. │B. inf. │Severe bronchopneumonia
│ │ │1 │+++++ │with empyema. Died Oct. 5
│ │ │ │Pn. IV +++ │
│ │ │ │S. hem. 2 │
│ │ │ │col. │
────┼─────────┼─────────┼─────┼────────────┼───────────────────────────
99│Sept. 24 │Sept. 29 │Oct. │B. inf. ++++│Diffuse purulent bronchitis
│ │ │1 │Pn. IV ++ │with bronchopneumonia. Died
│ │ │ │S. vir. + │Oct. 7
────┼─────────┼─────────┼─────┼────────────┼───────────────────────────
102│Sept. 24 │Sept. 28 │Oct. │Pn. IIa +++ │Severe bronchopneumonia
│ │ │1 │B. inf. ++ │with empyema. Died Oct. 4
│ │ │ │ │
│ │ │ │ │
────┼─────────┼─────────┼─────┼────────────┼───────────────────────────
104│Sept. 26 │Oct. 1 │Oct. │B. inf. ++++│Diffuse purulent bronchitis
│ │ │1 │Pn. IV +++ │with severe
│ │ │ │ │bronchopneumonia. Developed
│ │ │ │ │streptococcus empyema. Died
│ │ │ │ │Oct. 11
────┴─────────┴─────────┴─────┴────────────┴───────────────────────────

════╤══════════════════════════════════════════════════════════════════
CASE│ NECROPSY
│
────┼─────────────────────────────────┬────────────────────────────────
│ DIAGNOSIS │ BACTERIOLOGY
────┼─────────────────────────────────┼────────────────────────────────
70│Nodular and diffuse confluent │H.B. sterile
│lobular pneumonia. Purulent │Br. B. inf. ++++
│bronchitis. Bronchiectasis │Pn. IV ++
│ │Lun. B.inf. +++
│ │Pn. IV +++
────┼─────────────────────────────────┼────────────────────────────────
59│Lobular pneumonia, with clustered│H.B. sterile
│abscesses. Bronchiectasis │Br. B.inf. +++
│ │Staph. ++
│ │R.L. no growth.
────┼─────────────────────────────────┼────────────────────────────────
50│Nodular and confluent lobular │H.B. sterile
│pneumonia. Purulent bronchitis │Br. B.inf. +++
│ │Staph +
│ │R.L. Pn. II +++
│ │B.inf. +
│ │L.U. Pn. II +++
────┼─────────────────────────────────┼────────────────────────────────
56│Confluent lobular pneumonia │H.B. Pn. II
│ │Br. Pn. II +++
│ │B.inf. ++
│ │L.L. Pn. II +++
│ │B.inf. +
────┼─────────────────────────────────┼────────────────────────────────
107│Confluent lobular pneumonia with │H.B. sterile
│clustered abscesses. Pur. │R.L. Pn. III ++
│bronchitis and bronchiectasis │Staph. ++
│ │L.L. Staph. ++
────┼─────────────────────────────────┼────────────────────────────────
92│Lobular pneumonia. Empyema. │H.B. S.hem.
│Purulent bronchitis │Br. B.inf. +++
│ │S.hem. +++
│ │R.L. S.hem. +++
│ │B.inf. ++ Emp. S.hem.
────┼─────────────────────────────────┼────────────────────────────────
99│Bronchopneumonia. Purulent │H.B. S.hem.
│bronchitis │Br. B.inf. +++ Lun. S.hem. +++
│ │S.hem. ++ B. inf. +
────┼─────────────────────────────────┼────────────────────────────────
102│Lobular pneumonia with │H.B. S.hem.
│interstitial suppuration. Pur. │Br. B.inf. +++
│bronchitis. Empyema │S.hem. +++
│ │R.L. S.hem. +++
────┼─────────────────────────────────┼────────────────────────────────
104│Nodular bronchopneumonia with │H.B. S.hem.
│interstitial suppuration. Pur. │R.L. S.hem. ++++
│bronchitis and bronchiectasis. │Emp S.hem.
│Empyema. │
│ │
────┴─────────────────────────────────┴────────────────────────────────

The cases cited in the preceding paragraph are illustrative examples
from a series of over 250 necropsies which are described in another
section of this report. They serve to indicate clearly the extent to
which mixed and superimposed infections of the lungs may occur in
pneumonia following influenza and leave little doubt that a considerable
proportion of the deaths from influenzal pneumonia are due to this
circumstance.

Hemolytic Streptococcus Pneumonia Following Influenza

But 4 cases of hemolytic streptococcus pneumonia directly following
influenza without an intervening pneumococcus infection of the lungs
occurred in the group of cases studied clinically. Superimposed
infection with S. hemolyticus, however, occurred not infrequently during
the course of pneumococcus pneumonia following influenza, as has been
stated above. This occurred 3 times in lobar pneumonia and 10 times in
bronchopneumonia, with fatal outcome in all but 1 case.

=Bacteriology.=—Bacteriologic examination of the sputum in the 4 cases
of streptococcus pneumonia directly following influenza showed S.
hemolyticus present in abundance. B. influenzæ was also present in large
numbers in 3 cases, but was not found in the fourth. In 1 case a
Gram-negative micrococcus resembling M. catarrhalis was also present in
large numbers in the sputum. Pneumococci were not found either by direct
culture on blood agar plates or by inoculation of the sputum
intraperitoneally in white mice.

In the 13 cases of superimposed hemolytic streptococcus infection
occurring during the course of pneumococcus pneumonia, bacteriologic
examination of the sputum by direct culture and by mouse inoculation
shortly after onset of the pneumonia showed Pneumococci (atypical II
once, Type III once, Group IV eleven times) B. influenzæ present in
large numbers, and no hemolytic streptococci except in 4 instances in
which a very few organisms were present. Subsequent invasion of the
lower respiratory tract by S. hemolyticus was shown to occur by means of
cultures of empyema fluids or by cultures made at necropsy.

=Clinical Features.=—The 4 cases of hemolytic streptococcus pneumonia
following influenza that occurred in this series resembled in all
respects the secondary streptococcus pneumonias of the winter and spring
of 1918 and presented no features requiring special comment. The onset
resembled that of pneumococcus bronchopneumonia, the disease appearing
to develop as a continuation of the preceding influenza. The sputum was
profuse and mucopurulent in 3 cases, mucoid and bloody in the other. Two
cases ran a severe and rapid course with the development of empyema
early in the disease and fatal outcome. The other 2 cases ran only
moderately severe courses without developing empyema and recovered by
lysis in twenty and fifteen days, respectively, after the onset of
influenza. Clinical differentiation between streptococcus and
pneumococcus bronchopneumonia following influenza did not seem possible
without bacteriologic examination of the sputum except in those cases of
the streptococcus group which developed an extensive pleural effusion
early in the disease.

The advent of superimposed hemolytic streptococcus infection of the
lower respiratory tract during the course of pneumococcus pneumonia
following influenza presented no clinical features that made diagnosis
certain without bacteriologic examination. The sudden occurrence of a
pleural exudate during the course of the disease seemed of particular
significance, especially since empyema in the bronchopneumonias
following influenza was exceedingly rare in the absence of hemolytic
streptococcus infection. Other suggestive symptoms were a chill during
the course of the disease, a sudden turn for the worse in cases
apparently doing well, or the development of a cherry red cyanosis. None
of these features, however, was sufficiently constant or distinctive of
streptococcus invasion to be depended upon and when they occurred, were
merely indications for further bacteriologic examination.

Bacillus Influenzæ Pneumonia Following Influenza

Bacteriologic evidence that cases of pneumonia following influenza might
be due to B. influenzæ alone was very meager in the group of cases
studied clinically at Camp Pike; in fact, no convincing evidence was
obtained that such cases occurred. In one case B. influenzæ alone was
found in the sputum coughed from the deeper air passages, and in another
case B. influenzæ with a few colonies of S. viridans was found. Both
were cases of bronchopneumonia, mild in character, and recovered
promptly. They presented no clinical features by which they could be
distinguished from cases of pneumococcus bronchopneumonia.

It has been previously stated that B. influenzæ was found in all early
uncomplicated cases of influenza somewhere in the respiratory tract;
that it was present together with other organisms, notably pneumococcus
in the sputum from cases of purulent bronchitis following influenza; and
that it was found in the sputum coughed from the lung in approximately
80 per cent of cases of pneumonia complicating influenza. In 35 cases it
was very abundant, often being the predominating organism. In all these
cases, however, pneumococci or hemolytic streptococci were also present
in considerable numbers at the time of onset of the pneumonia. It is
impossible to say merely from the clinical and bacteriologic data under
consideration what part B. influenzæ played in the development of the
actual pneumonia in these cases. Discussion of this subject is therefore
reserved for the section of this report dealing with the pathology and
bacteriology of pneumonia following influenza.

Summary

Influenza as observed at Camp Pike presented itself as a highly
contagious infectious disease, the principal clinical manifestations of
which were, sudden onset with high fever, profound prostration with
severe aching pains in the head, back and extremities, erythema of the
face, neck and upper chest with injection of the conjunctivæ, and a
rapidly progressive attack upon the mucous membranes of the respiratory
tract as evidenced by coryza, pharyngitis, tracheitis and bronchitis
with their accompanying symptoms. In the majority of cases it ran a
short self-limited course, rarely of more than four days’ duration, and
was never fatal in the absence of a complicating pneumonia.

Bacteriologic examination in early uncomplicated cases of the disease
showed the B. influenzæ of Pfeiffer to be present in all cases, often in
predominating numbers. It was found more abundantly present during the
acute stage of the disease than during convalescence in uncomplicated
cases. No other organisms of significance were encountered by the
methods employed.

Purulent bronchitis of varying extent developed in approximately 35 per
cent of the cases and often prolonged the course of the illness to a
considerable extent. Bacteriologic studies showed that it was invariably
associated with a mixed infection of the bronchi with B. influenzæ and
other bacteria, in most instances the pneumococcus, and indicated that
it should be regarded as a complication rather than as an essential part
of influenza. Its clinical features consisted of a mild febrile
reaction, frequent cough with the raising of considerable amounts of
purulent sputum, and the physical signs of a more or less diffuse
bronchitis. It led to a varying degree of bronchiectasis in at least
some instances.

Pneumonia complicating influenza presented a very diversified picture
and appeared to have only one constant character, namely, that influenza
was the predisposing cause. It may be best classified on an etiologic
basis since the clinical features to some extent and the pathology to a
much greater extent depended upon the infecting bacteria in a given
case.

Bacteriologic examination showed that a very large proportion of the
cases was due to infection with the different immunologic types of
pneumococci or to a mixed infection with B. influenzæ and pneumococci.
The types of pneumococci commonly found in normal mouths, namely, II
atypical, III, and IV, comprised approximately 88 per cent of these, the
highly parasitic Pneumococci Types I and II, but 12 per cent. A small
number of cases were due to hemolytic streptococci or to mixed infection
with B. influenzæ and S. hemolyticus. No certain evidence was obtained
that pneumonia was due to B. influenzæ alone. This organism was present
in varying numbers, however, in approximately 80 per cent of the sputums
examined, and it seems fairly certain that it must have played at least
a part in the development of the pneumonia in many of the cases in which
it was found. Superimposed infections with other types of pneumococci
than those primarily responsible for the development of pneumonia, with
hemolytic streptococci and with Staphylococcus aureus occurred
frequently in cases of pneumococcus or mixed pneumococcus and B.
influenzæ pneumonia and undoubtedly contributed to a considerable extent
in increasing the number of deaths.

Three clinical types of pneumococcus pneumonia following influenza
occurred: lobar pneumonia, lobar pneumonia with purulent bronchitis, and
bronchopneumonia. Lobar pneumonia was usually sudden in onset and ran
the characteristic course of the primary disease. Lobar pneumonia with
purulent bronchitis similarly ran the characteristic course of the
primary disease but presented the unusual picture of lobar pneumonia
with mucopurulent rather than rusty, tenacious sputum and numerous moist
râles throughout the unconsolidated portions of the lungs. The cases of
bronchopneumonia ran a very variable course from mild cases of a few
days’ duration and meager signs of consolidation to rapidly progressive
cases with signs of extensive pulmonary involvement. Purulent bronchitis
was very frequently associated with bronchopneumonia.

Hemolytic streptococcus pneumonia following influenza presented the
clinical picture of bronchopneumonia and was not readily distinguished
on clinical grounds from pneumococcus bronchopneumonia except in those
cases which developed a pleural exudate early in the disease. The advent
of tertiary infection of the lower respiratory tract with hemolytic
streptococci in cases of secondary pneumococcus pneumonia presented no
symptoms sufficiently constant or certain to make clinical diagnosis
easy. The development of empyema in pneumococcus bronchopneumonia
usually meant streptococcus infection.

Pure B. influenzæ pneumonia, if such cases existed, presented no
diagnostic features by which it could be distinguished from pneumococcus
bronchopneumonia following influenza. It was impossible to determine on
clinical and bacteriologic grounds alone what part the prevalent
influenza bacilli played in the causation of the actual pneumonia.

Discussion

That wide variations in the conception of influenza have arisen during
the recent pandemic, even a hasty review of the literature makes clear.
In its essence this divergence of opinion seems to depend upon whether
pneumonia is considered an essential part of influenza or a complication
due either to the primary cause of influenza or to secondary infection.
One extreme is expressed by Dunn[30] who says “the so-called
complication is the disease,” the other by Fantus[31] who finds
influenza a relatively mild disease with pneumonia a relatively
infrequent and largely preventable complication.

A similar divergence of opinion prevails with respect to the
bacteriology of influenza. There is fairly general agreement that the
members of the pneumococcus and streptococcus groups and to a less
extent other organisms are responsible for a large proportion of the
secondary pneumonias, and but few observers hold that they possess any
etiologic relationship to influenza. No such uniformity of opinion
exists, however, with respect to the relation of B. influenzæ to
influenza and to the complicating pneumonia. By some it is considered
the primary cause of influenza, by others it is regarded as a secondary
invader responsible for a certain proportion of the secondary
pneumonias, and by still others it is not considered to bear any
relation either to influenza or its complications.

A limited number of references to the extensive literature of the recent
pandemic will amply serve to illustrate the various points of view that
have developed.

Keegan[32] regards pneumonia as a complication and considers that B.
influenzæ, the probable cause of influenza, is the primary cause of the
pneumonia which may or may not be still further complicated by
pneumococcus or streptococcus infection as a terminal event.
Christian[33] states that epidemic influenza causes a clinically
demonstrable bronchitis and bronchopneumonia in the larger proportion of
cases, and lays particular emphasis upon the fact that it is quite
incorrect to consider fatalities in the epidemic as due to influenza
uncomplicated by bronchopneumonia. Blanton and Irons[34] speak of
influenza as an “antecedent respiratory infection” of undetermined
etiology, and believe that pneumonia when it occurs is due to autogenous
infection by a variety of secondary invaders, principally of the
pneumococcus and streptococcus groups. Hall, Stone, and Simpson[35]
regard pneumonia strictly as a complication and quite distinct from
influenza itself. Synnott and Clark[36] believe that the infection is
characterized by a progressive intense exudative inflammation of the
respiratory tract often terminating in an aspiration pneumonia with a
variety of conditions found at autopsy and a multiplicity of secondary
organisms responsible for the fatal termination. B. influenzæ was
usually found but always with other organisms. Friedlander and his
collaborators[37] speak of a fulminating fatal type of influenza with
acute inflammatory pulmonary edema, but regard true bronchopneumonia as
secondary, due to infection with pneumococcus or S. hemolyticus. B.
influenzæ was not found more frequently than under normal conditions.
Brem[38] and his collaborators present a clear cut clinical picture both
of influenza and the secondary pneumonia to which it predisposes,
regarding the latter as definitely due to secondary infection with
pneumococcus, streptococcus or B. influenzæ, the virus of influenza
being unknown. Ely[39] and his collaborators make no distinction between
influenza and pneumonia, and apparently consider the epidemic due to a
hemolytic streptococcus of indefinite and inconstant characters. The
Camp Lewis Pneumonia Unit[40] states “the process [influenza], whether
mild or severe, is etiologically and pathologically the same; * * *.” B.
influenzæ was not found. In a report of The American Public Health
Association[41] it is stated that deaths resulting from influenza are
commonly due to pneumonias resulting from an invasion of the lungs by
one or more forms of streptococci, by one or more forms of pneumococci,
or by the so-called influenza bacillus. This invasion is apparently
secondary to the initial attack. Wolbach[42] found B. influenzæ in a
high proportion of cases, not infrequently in pure culture in the lung,
and believes that there is a true influenzal pneumonia whether B.
influenzæ is the cause of the primary disease or not. Spooner, Scott and
Heath[43] isolated B. influenzæ in a high percentage of cases and
consider it reasonable to suppose that it was the prime factor in the
epidemic. Kinsella[44] found B. influenzæ infrequently and regards it as
a secondary invader. MacCallum[45] regards B. influenzæ as a secondary
invader and believes that it is responsible for a form of purulent
bronchitis and bronchopneumonia following certain cases of influenza.
Pritchett and Stillman[46] found B. influenzæ in 93 per cent of cases of
influenza and bronchopneumonia. Hirsch and McKinney[47] state that B.
influenzæ played no rôle in the epidemic at Camp Grant and apparently
consider it due to a specially virulent pneumococcus.

No further references to the extensive literature of the recent pandemic
seem necessary, since those cited above serve to illustrate the various
points of view that exist. A similar diversity of opinion may be found
in the reports from foreign sources.

It would appear that much of the divergence of opinion that has been
formed has depended to a considerable extent upon the conditions under
which cases have been observed. This is clearly brought out by
contrasting the experience of Fantus[39] dealing with private cases in
civilian practice, where pneumonia was relatively uncommon, with that of
others dealing only with cases in large hospitals, where those admitted
have been in large part selected seriously ill patients with a high
incidence of pneumonia, the milder cases comprising from 60 to 90 per
cent of those attacked by influenza never reaching the hospital.
Variations in opinion with respect to the bacteriology of the epidemic,
especially in regard to B. influenzæ, would appear to be due for the
most part to differences in bacteriologic technic, in some degree to
differences in interpretation. Accumulating evidence can leave little
doubt that B. influenzæ was at least extraordinarily and universally
prevalent throughout the period of the epidemic and thereafter, and that
earlier reports of failure to find it were due to the use of methods
unsuitable for its detection and isolation.

The opportunity afforded the commission at Camp Pike to devote their
full time to a systematic and correlated group study of the epidemic
simultaneously from many aspects throughout its whole course made it
apparent that influenza _per se_ is in the large majority of instances,
in spite of the initial picture of profound prostration, a relatively
mild disease which tends to rapid spontaneous recovery. This opinion is
supported by the fact that the disease during the first waves of the
epidemic in this country, which it is now recognized occurred pretty
generally in the army camps during the spring of 1918, was so mild that
it attracted only passing attention, since the disease at that time was
not sufficiently virulent to predispose to any alarming amount of
pneumonia. With the return of the epidemic in the late summer and early
fall, however, the disease had attained such a high degree of virulence
that it predisposed to an appalling amount of severe and often rapidly
fatal pneumonia, which often detracted attention from the real nature of
the preceding disease. Yet even during the fall epidemic from 60 to 90
per cent of the cases of influenza proceeded to rapid recovery without
developing complications. On this ground alone it would seem only
logical to regard pneumonia strictly as a complication of influenza
rather than as an essential part of the disease, irrespective of whether
the pneumonia may be caused by the primary cause of influenza or not.
The complexity of the clinical features, the bacteriology and pathology
of the pneumonias following influenza lend further support to this
opinion.

It seems better, therefore, to consider influenza first as a disease by
itself and subsequently to take up the question of pneumonia and the
relation of influenza to it.

The most striking clinical features of influenza are its epidemic
character, its involvement of the respiratory tract, its extremely
prostrating effect, and the often surprising rapidity with which the
individual cures himself. These features strongly suggest that the
etiologic agent of the disease is an organism subject to rapid changes
in virulence; that it is confined to the respiratory tract where it
produces a superficial inflammatory reaction giving rise to the
characteristic symptoms of coryza, pharyngitis and tracheitis; that it
elaborates a poison, possibly a true toxin, readily absorbed by the
lymphatics, the effect of which is manifested in the profound
prostration, severe aching pains, erythema, and leucopenia; and that it
may either disappear promptly from the respiratory mucous membrane at
time of recovery or may persist, leading a relatively saprophytic
existence for an indefinite period of time, being no longer harmful to
the individual, at least more than locally, because of an acquired
immunity. Furthermore, in our opinion, the very brief incubation period
suggests that the disease is bacterial in origin, rather than that it is
analogous to the exanthemata, the majority of which present a
comparatively long, fairly constant, incubation period.

B. influenzæ has characteristics in accord with the clinical features of
influenza. It is an organism of very labile virulence; it is always
present in our experience on the mucous membranes of the respiratory
tract in early uncomplicated cases of influenza, often in overwhelming
numbers; in only very exceptional instances, in adults at least, does it
invade the body producing a general infection, as the numerous reports
of negative blood cultures testify; recent investigations by Parker[48]
and others indicate that it is capable of producing a toxin quickly
fatal for rabbits; it is predominantly present in the respiratory tract
during the active stage of the disease and disappears in a considerable
proportion of cases at time of recovery, while in others, more
particularly those that develop an extensive secondary bronchitis and
bronchiectasis it may persist for an indefinite period of time.

It is, of course, fully appreciated that the foregoing is in the main
merely argumentative reasoning and it is put forth only to suggest that
B. influenzæ merits a much closer scrutiny with respect to its etiologic
relationship to influenza than the trend of present opinion has awarded
it.

Although there remains some difference of opinion as to the relation of
influenza to pneumonia, the majority of observers concur in regarding
pneumonia as a complication and this would seem to be the only logical
interpretation of the facts available. The same may be said with respect
to purulent bronchitis and bronchiectasis. It is of considerable
significance in this connection that pneumonia following influenza
presents no uniform clinical picture, no uniform bacteriology and no
uniform pathology. Whether the predisposition of patients with influenza
to contract pneumonia is preponderantly due to lowering of general
resistance to infection by the extremely prostrating effect of the
disease and the inhibition of leucocytic defense, or to a destruction of
local resistance against bacterial invasion by reason of profound injury
to the bronchial mucosa, or to a combination of both factors, is
difficult to say. It seems most probable that both are concerned. At any
rate it seems clear that in the presence of influenza a considerable
variety of organisms which under ordinary conditions do not find
lodgement in the lungs are able to gain access to the lower respiratory
tract and produce pneumonia.

CHAPTER III
SECONDARY INFECTION IN THE WARD TREATMENT OF INFLUENZA AND PNEUMONIA

EUGENE L. OPIE, M.D.; FRANCIS G. BLAKE, M.D.; JAMES C. SMALL, M.D.; AND
THOMAS M. RIVERS, M.D.

One of the most pressing problems that presented itself in the care of
influenza and pneumonia patients in the army cantonments during the
recent epidemic was the danger of secondary contact infection because of
the overcrowding of the base hospitals, nearly all of which were taxed
far beyond the limits of their capacity. That this danger was very real
was fully demonstrated by certain studies in ward infection that this
commission was able to make at Camp Pike[49]. It is the purpose of the
present section of the report to present these studies and to discuss
the means whereby this danger may be most successfully met.

It is perhaps well, first to define exactly what is meant by secondary
contact infection in influenza and pneumonia. In our experience at Camp
Pike it was found that a very large percentage of the pneumonias
following influenza were accompanied by secondary infection with
pneumococcus, some few being caused by hemolytic streptococcus. The
types of pneumococcus encountered were almost entirely those that are
found normally in the mouths of healthy men, approximately 85 per cent
being Types II atypical, III, and IV. It has been generally accepted
that infection with these types of pneumococci is usually
autogenous—that is, that under the proper conditions of lowered
resistance an individual becomes infected with the pneumococcus that he
carries in his own mouth. Many observations made during the course of
the present work have suggested that this is probably not so in many
instances and that the influenza patient may not be so much in danger
from the pneumococcus that he normally carries in his own mouth as he is
from that carried by his neighbor, in other words, he is in danger from
contact infection. The same considerations hold true with respect to
hemolytic streptococcus infection. Secondary contact infection in cases
of already existing pneumonia following influenza were found to occur
frequently. These were for the most part caused by hemolytic
streptococcus infection superimposed upon a pneumococcus pneumonia. Many
instances of double pneumococcus infection, however, either coincident
with or following one another were encountered.

Secondary Infection with S. Hemolyticus in Pneumonia

Pneumonia caused by streptococci was repeatedly observed[50] during the
pandemic of influenza which occurred in 1889–90. With clearer
recognition of the characters which distinguish varieties of
streptococci several observers have shown that secondary infection with
hemolytic streptococci may occur during the course of pneumonia and
though definite evidence has been lacking have suggested that it may be
acquired within hospital wards. That a similar secondary infection with
S. hemolyticus in pneumococcus pneumonias following influenza occurred
not infrequently at Camp Pike during the epidemic was shown by
bacteriologic studies made during life and at autopsy in a considerable
series of cases. During the early days of the epidemic of influenza,
secondary streptococcus infection was almost entirely limited to certain
wards which were opened for the care of the rapidly increasing number of
patients with pneumonia. During this period these wards were
overcrowded, organization was incomplete, and the opportunities for
transfer of infection from patient to patient were almost unlimited. The
spread of streptococcus contagion and its fatal effect may be clearly
brought out by comparison of these wards with wards that had long been
organized for the care of patients with pneumonia.

Ward 3 had been in use for the care of patients with pneumonia for some
time prior to the outbreak of influenza. It was provided with sheet
cubicles and conducted by medical officers, nurses and enlisted men
accustomed to the care of patients with pneumonia, ordinary precautions
being taken against transfer of infection from one patient to another.
The data in Table XVII show the average number of patients in the ward,
the number of new cases of pneumonia admitted, and the number of deaths
among patients admitted during the corresponding period, for three
periods of ten days each from September 6 to October 5. The types of
infection in fatal cases as determined by cultures taken at autopsy are
also shown.

TABLE XVII

PNEUMONIA IN WARD 3

═════╤════════╤════════╤═════════════╤═════════════════════════════════════
│AVERAGE │ NUMBER │TOTAL DEATHS │ CULTURES AT AUTOPSY
│ NUMBER │ OF │ AMONG │
│ OF │PATIENTS│ PATIENTS │
│PATIENTS│ADMITTED│ ADMITTED │
│IN WARD │ │ DURING THE │
│ │ │CORRESPONDING│
│ │ │ PERIOD │
─────┼────────┼────────┼──────┬──────┼────────────┬───────────┬────────────
„ │ „ │ „ │NUMBER│ PER│PNEUMOCOCCUS│ S.│UNDETERMINED
│ │ │ │ CENT│ │HEMOLYTICUS│(NO AUTOPSY)
─────┼────────┼────────┼──────┼──────┼────────────┼───────────┼────────────
Sept.│ 18.6│ 11│ 3│ 27.2│ 3│ 0│ 0
6–15 │ │ │ │ │ │ │
Sept.│ 46.1│ 52│ 16│ 30.7│ 13│ 1│ 2
16–25│ │ │ │ │ │ │
Sept.│ 58.6│ 23│ 8│ 34.7│ 5│ 1│ 2
26–Oct.│ │ │ │ │ │ │
5 │ │ │ │ │ │ │
─────┴────────┴────────┴──────┴──────┴────────────┴───────────┴────────────

During the period from September 6 to 15, just prior to the outbreak of
influenza in epidemic proportions, the ward had an average population of
18.6 patients. The total number of new patients admitted was 11, of whom
3 died, a mortality of 27.2 per cent. All these cases were pneumococcus
pneumonias as determined by bacteriologic examination of the sputum at
time of admission. The 3 fatal cases showed pneumococcus infection at
autopsy. During the second period, from September 16 to 25, with the
outbreak of the epidemic of influenza, the ward rapidly filled with new
cases of pneumonia, attaining an average population of 46.1 patients. Of
the 52 new cases admitted 16 died, a mortality of 30.7 per cent. Again
all the cases admitted during this period in which bacteriologic
examination of the sputum was made, were found to be pneumococcus
pneumonias with one exception. This case, admitted on September 21 and
dying two days later, had a hemolytic streptococcus pneumonia.
Fortunately, though quite by accident, he was placed in a bed at one end
of the porch and no transmission of streptococcus infection to other
cases in the ward took place. At autopsy 13 cases showed pneumococcus
infection; the foregoing case, hemolytic streptococcus. During the third
period from September 26 to October 5 the ward became even more crowded,
having an average of 58.6 patients; 23 new cases were admitted, 8 of
whom died, a mortality of 34.7 per cent. Autopsy showed that 5 of these
were pneumococcus pneumonias and 1 was caused by hemolytic streptococcus
infection. It is noteworthy that the death rate from pneumonia gradually
increased as the ward became more and more crowded. This may possibly be
attributed in part to the increasing severity of the pneumonia during
the early days of the influenza epidemic. That it was in part directly
due to secondary contact infection with pneumococcus will be shown when
the transmission of pneumococcus infection is discussed. In spite of the
overcrowding of the ward the introduction of 2 cases of streptococcus
pneumonia did not cause an outbreak of streptococcus infection. Whether
this was due to precautions taken against the transfer of infection or
was merely a matter of good luck is difficult to say, in view of the
fact that a considerable amount of transfer of pneumococcus infection
from one patient to another did occur.

Ward 8 had long been used for the care of colored patients with
pneumonia. As in Ward 3 cubicles were in use and ordinary precautions
against the transfer of infection were used. The data are presented in
Table XVIII.

TABLE XVIII

PNEUMONIA IN WARD 8

═══════╤════════╤════════╤═════════════╤═════════════════════════════════════
│AVERAGE │ NUMBER │TOTAL DEATHS │ CULTURES AT AUTOPSY
│ NUMBER │ OF │ AMONG │
│ OF │PATIENTS│ PATIENTS │
│PATIENTS│ADMITTED│ ADMITTED │
│IN WARD │ │ DURING THE │
│ │ │CORRESPONDING│
│ │ │ PERIOD │
───────┼────────┼────────┼──────┬──────┼────────────┬───────────┬────────────
„ │ „ │ „ │NUMBER│ PER │PNEUMOCOCCUS│ S. │UNDETERMINED
│ │ │ │ CENT │ │HEMOLYTICUS│(NO AUTOPSY)
───────┼────────┼────────┼──────┼──────┼────────────┼───────────┼────────────
Sept. │ │ │ │ │ │ │
6–20 │ 25.5│ 18│ 2│ 11.1│ 2│ 0│ 0
Sept. │ 46.1│ 59│ 20│ 33.9│ 10│ 1│ 9
21–Oct.│ │ │ │ │ │ │
5 │ │ │ │ │ │ │
───────┴────────┴────────┴──────┴──────┴────────────┴───────────┴────────────

During the period from September 6 to 20, prior to the outbreak of
influenza in epidemic proportions among the colored troops, the ward had
an average population of 25.5 patients; 18 new cases of pneumonia were
admitted during this period, all of whom were pneumococcus pneumonias as
determined by bacteriologic examination of the sputum at time of
admission to the ward. Only 2 died, a mortality of 11.1 per cent,
autopsy cultures showing pneumococcus in both cases. All these patients
were treated on the porch of the ward while they were acutely sick.
During the second period from September 21 to October 5, when the
influenza epidemic was at its height, the ward rapidly filled with
active cases of pneumonia and became distinctly crowded. It contained an
average of 46.1 patients, but had actually reached a population of 64
patients at the end of the period. Of the 59 new cases admitted, 20
died, a mortality of 33.9 per cent, 10 with pneumococcus pneumonia, one
with hemolytic streptococcus pneumonia. In 9 there was no autopsy. The
conditions in Ward 8 were quite analogous to those in Ward 3. In spite
of the overcrowding during the second period no outbreak of secondary
infection with S. hemolyticus occurred, but secondary pneumococcus
infection did occur as will be shown below.

In contrast with these two wards are Wards 1 and 2 in which widespread
secondary contact infection with S. hemolyticus took place. Ward 2 was
opened September 26, at the beginning of the period when 20 new wards
for pneumonia were organized. From September 26 to October 1 the cubicle
system was not in use, the ward was crowded, organization was imperfect,
and few precautions were taken to prevent transfer of infection from one
patient to another. On October 2 the cubicle system was installed and
precautions against transfer of infection were instituted. The data are
shown in Table XIX.

TABLE XIX

PNEUMONIA IN WARD 2

═════╤════════╤═════════╤═════════════╤═════════════════════════════════════
│ │ │TOTAL DEATHS │
│AVERAGE │ │ AMONG │
│ NUMBER │NUMBER OF│ PATIENTS │
│ OF │PATIENTS │ ADMITTED │ CULTURES AT AUTOPSY
│PATIENTS│ADMITTED │ DURING THE │
│IN WARD │ │CORRESPONDING│
│ │ │ PERIOD │
─────┼────────┼─────────┼──────┬──────┼────────────┬───────────┬────────────
„ │ „ │ „ „ │NUMBER│ PER │PNEUMOCOCCUS│ S. │UNDETERMINED
│ │ │ │ CENT │ │HEMOLYTICUS│(NO AUTOPSY)
─────┼────────┼─────────┼──────┼──────┼────────────┼───────────┼────────────
Sept.│ 10│ 10 40│ 27│ 67.5│ 0│ 23│ 4
26 │ │ │ │ │ │ │
Sept.│ 27│ 17 „ │ „ │ „ │ „ │ „ │ „
27 │ │ │ │ │ │ │
Sept.│ 40│ 13 „ │ „ │ „ │ „ │ „ │ „
28 │ │ │ │ │ │ │
─────┼────────┼─────────┼──────┼──────┼────────────┼───────────┼────────────
Sept.│ 51│ 12 17│ 6│ 35.3│ 2│ 2│ 2
29 │ │ │ │ │ │ │
Sept.│ 49│ 1 „ │ „ │ „ │ „ │ „ │ „
30 │ │ │ │ │ │ │
Oct. │ 43│ 4 „ │ „ │ „ │ „ │ „ │ „
1 │ │ │ │ │ │ │
─────┼────────┼─────────┼──────┼──────┼────────────┼───────────┼────────────
Oct. │ 47│ 6 10│ 4│ 40.0│ 2│ 1│ 1
2 │ │ │ │ │ │ │
Oct. │ 42│ 0 „ │ „ │ „ │ „ │ „ │ „
3 │ │ │ │ │ │ │
Oct. │ 41│ 4 „ │ „ │ „ │ „ │ „ │ „
4 │ │ │ │ │ │ │
─────┴────────┴─────────┴──────┴──────┴────────────┴───────────┴────────────

During the first three days 40 patients with pneumonia were admitted to
the ward. Of these 40 patients, 27 died, a mortality of 67.5 per cent.
Cultures at autopsy showed that 23 of these died with hemolytic
streptococcus infection, none of pneumococcus infection. In four there
was no autopsy. To appreciate the full significance of these figures it
must be emphasized that these patients at time of admission to the ward
in no way differed from those admitted to Ward 3 during the
corresponding period and were not in any sense selected cases. The type
of infection in 9 of these patients had been determined by bacteriologic
examination of the sputum just prior to or immediately after admission
to the ward before opportunity for secondary contact infection in this
ward had occurred. All 9 were shown to have pneumococcus pneumonia free
from hemolytic streptococci at that time. All 9 died, 7 with secondary
streptococcus infection as shown by cultures taken at autopsy, 1 with a
secondarily acquired Pneumococcus Type III infection—sputum showed a
Pneumococcus Type IV on admission—and in 1 there was no autopsy. In view
of the fact that bacteriologic examination of the sputum in cases of
pneumonia following influenza had shown that the large majority of them
were due to pneumococcus infection, it is probable that most of the
other cases of pneumonia admitted to this ward were pneumococcus
pneumonias at time of admission, and that they acquired the
streptococcus infection after admission.

During the next three days 17 new patients were admitted, of whom 6
died, a mortality of 35.3 per cent. Cultures at autopsy showed
pneumococcus infection in 2, streptococcus in 2. It is noteworthy that
the porch was first put into use on September 29. Of the 12 patients
admitted on this date, 8 were treated throughout the acute stage of
their illness on the porch. Of these 8 patients but one died, of a
Pneumococcus Type IV infection and none became infected with S.
hemolyticus. From October 4 to October 6, 10 patients were admitted, of
whom 4 died. Cultures at autopsy showed pneumococcus infection in 2,
hemolytic streptococcus in 1.

The widespread prevalence of hemolytic streptococcus infection in this
ward as compared with its almost entire absence in Wards 3 and 8 is very
striking. Cultures made during life and at autopsy have shewn clearly
that it was due to rapid spread of contagion throughout the ward. The
almost unlimited opportunities for transfer of infection from patient to
patient, during the first six days the ward was in use, undoubtedly
greatly facilitated this spread. From the data available it is
impossible to state exactly when and by which patients hemolytic
streptococcus infection was introduced into the ward, but it must have
been very early since the death rate was very high from the beginning,
and the first 23 cases coming to autopsy died with streptococcus
infection.

Ward 1 was opened on September 24. From that date until October 2 no
cubicles were in use and few precautions were taken against transfer of
infection. On October 2 cubicles were installed and ordinary precautions
to prevent transfer of infection were instituted. On October 6 the ward
was closed to further admissions. The data presented in Table XX are
divided into two periods, because on September 29 and 30, 4 patients
with streptococcus pneumonia were admitted to the ward.

TABLE XX

PNEUMONIA IN WARD 1

═══════╤════════╤════════╤═════════════╤═════════════════════════════════════
│AVERAGE │ NUMBER │TOTAL DEATHS │ CULTURES AT AUTOPSY
│ NUMBER │ OF │ AMONG │
│ OF │PATIENTS│ PATIENTS │
│PATIENTS│ADMITTED│ ADMITTED │
│IN WARD │ │ DURING THE │
│ │ │CORRESPONDING│
│ │ │ PERIOD │
───────┼────────┼────────┼──────┬──────┼────────────┬───────────┬────────────
„ │ „ │ „ │NUMBER│ PER │PNEUMOCOCCUS│ S. │UNDETERMINED
│ │ │ │ CENT │ │HEMOLYTICUS│(NO AUTOPSY)
───────┼────────┼────────┼──────┼──────┼────────────┼───────────┼────────────
Sept. │ 35.8│ 34│ 11│ 32.3│ 5│ 3│ 3
24–29 │ │ │ │ │ │ │
Sept. │ 55.3│ 40│ 24│ 60.0│ 6│ 14│ 4
30–Oct.│ │ │ │ │ │ │
5 │ │ │ │ │ │ │
───────┴────────┴────────┴──────┴──────┴────────────┴───────────┴────────────

During the first period from September 24 to 29 the ward contained an
average of 35.8 patients, being only moderately crowded; 34 cases of
pneumonia were admitted, of whom 11 died, a mortality of 32.3 per cent.
It is noteworthy that deaths among this group which occurred prior to
September 30 were due to pneumococcus infection with one exception, a
patient entering the ward on September 26 and dying the following day.
Of the other 2 patients in this group who died with hemolytic
streptococcus pneumonia, 1 was admitted to the ward on September 25, was
shown to be free from S. hemolyticus on September 30, and died on
October 12 with a secondarily acquired streptococcus pneumonia and
empyema; the other was admitted on September 29 with streptococcus
pneumonia and died the following day.

During the second period from September 30 to October 5 the ward
contained an average of 55.3 patients, being very overcrowded; 40 new
cases of pneumonia were admitted of whom 24 died, a mortality of 60 per
cent. Cultures taken at autopsy showed that 6 died of pneumococcus
pneumonia, 14 with hemolytic streptococcus infection. As in Ward 2,
patients admitted to this ward were in no way selected and were
probably, as experience has shown, in large part pneumococcus pneumonias
at time of admission. The widespread dissemination of hemolytic
streptococcus and its fatal effect following the introduction of the
organism on September 29 and 30 is only too evident.

TABLE XXI

SECONDARY INFECTION WITH PNEUMOCOCCUS TYPE II

═════════════╤═════════╤═════════╤══════════════╤══════════════════════
NAME │ BED │ADMITTED │PNEUMOCOCCUSIN│ SECONDARY INFECTION
│OCCUPIED │ │ SPUTUM ON │
│ │ │ ADMISSION │
─────────────┼─────────┼─────────┼──────────────┼─────────┬────────────
„ │ „ │ „ │ „ │ DATE │PNEUMOCOCCUS
│ │ │ │ │ AT AUTOPSY
─────────────┼─────────┼─────────┼──────────────┼─────────┼────────────
Pvt. Wolfe │No. 6 │Sept. 17 │IV │Sept. 23 │II[51]
Pvt. Pullam │No. 5 │Sept. 9 │IV │Sept. 24 │II
Pvt. Swain │No. 3 │Sept. 16 │II │ │
─────────────┴─────────┴─────────┴──────────────┴─────────┴────────────

Secondary Infection with Pneumococcus in Pneumonia

The foregoing studies have shown that hemolytic streptococcus infection
may spread by contagion throughout an entire ward with great rapidity.
Other observations have demonstrated that pneumococcus infection may be
transmitted in the same way. Only three instances of this nature will be
cited. The first occurred in Ward 3 (Table XXI). Between September 6 and
16 no cases of pneumonia caused by Pneumococcus Type II had been
admitted to the ward. On September 16 Pvt. Swain was admitted to the
ward and placed in Bed 3. Bacteriologic examination of his sputum showed
that his pneumonia was caused by Pneumococcus Type II. At this time Pvt.
Pullam, who had been admitted to the ward on September 9 with a
pneumococcus Type IV pneumonia, occupied Bed 5 separated from Bed 3 by
one intervening bed. He had had his crisis on September 14 and was doing
well, his temperature being normal. On September 24 he developed a
second attack of pneumonia and died on September 30. Cultures at autopsy
showed Pneumococcus Type II in heart’s blood and lung, Pneumococcus Type
II and B. influenzæ in the right bronchus. Pvt. Wolfe was admitted to
the ward with bronchopneumonia on September 17 and placed in Bed 6 next
to Pvt. Pullam. Pneumococcus Type IV and B. influenzæ were found in his
sputum. His temperature had fallen to normal by lysis on September 21
and he was doing well. On September 23 his temperature suddenly rose and
he developed a second attack of pneumonia. Pneumococcus Type II was
isolated by blood culture on this date. He recovered. In both instances
Pneumococcus Type II was acquired after the admission of a patient with
a Pneumococcus Type II pneumonia, the opportunity for contact infection
having been favored by the association of these patients in adjoining
beds.

TABLE XXII

SECONDARY INFECTION WITH PNEUMOCOCCUS TYPE II

═════════════╤═════════╤══════════╤════════════╤═══════════════════════
│ BED │ │PNEUMOCOCCUS│
NAME │OCCUPIED │ ADMITTED │IN SPUTUM ON│ SECONDARY INFECTION
│ │ │ ADMISSION │
─────────────┼─────────┼──────────┼────────────┼──────────┬────────────
„ │ „ │ „ │ „ │ DATE │PNEUMOCOCCUS
│ │ │ │ │ AT AUTOPSY
─────────────┼─────────┼──────────┼────────────┼──────────┼────────────
Pvt. Smith │No. 26 │Sept. 18 │II │ │II
Pvt. Thompson│No. 28 │Sept. 17 │Atyp. II │Sept. 21 │II
Pvt. Linehan │No. 30 │Sept. 16 │IV │Sept. 26 │II
─────────────┴─────────┴──────────┴────────────┴──────────┴────────────

The second instance is almost identical and occurred on the opposite
side of Ward 3 at about the same time (Table XXII). Pvt. Linehan was
admitted on September 16 and placed in Bed 30. Pneumococcus Type IV was
found in his sputum. Pvt. Thompson was admitted the following day with a
Pneumococcus II atypical pneumonia and placed in Bed 28. The next day
Pvt. Smith was admitted and placed in Bed 26. Pneumococcus Type II was
found in his sputum. On September 19 Pvt. Thompson recovered by crisis
and was doing well. On September 21 he had a chill, his temperature rose
to 104.4° F. and he developed a second attack of pneumonia. He died on
September 29; cultures at autopsy showing Pneumococcus Type II in
heart’s blood and left pleural cavity, Pneumococcus Type II and B.
influenzæ in bronchus and lung. Pvt. Linehan had begun to improve on
September 24 and his temperature was falling by lysis. On September 26
he became worse, developed signs of pericarditis and died on September
30. Cultures from lungs and bronchus at autopsy showed Pneumococcus Type
II and B. influenzæ. In both instances the fatal secondary infection
with Pneumococcus Type II was undoubtedly acquired from Pvt. Smith in
the nearby bed.

The third instance occurred in Ward 8 (Table XXIII). Pvts. Lewis and
Scott were admitted on September 21 and were placed in adjoining beds,
50 and 51. Lewis showed Pneumococcus Type I in his sputum, Scott
Pneumococcus II atypical. The following day Pvts. Pighee, Jones, and
Columbus were admitted and given Beds 48, 49 and 53 respectively. All
showed Pneumococcus II atypical in the sputum. Pvt. Lewis with
Pneumococcus Type I pneumonia recovered by crisis on September 29. His
temperature remained normal until October 2 when it suddenly rose to
104.2° F. He developed a second attack of pneumonia and died on October
8. Cultures at autopsy from heart’s blood and lung showed Pneumococcus
II atypical, from the bronchus Pneumococcus II atypical and B.
influenzæ. It is, of course, impossible to say from which one of his
neighbors Pvt. Lewis acquired his second pneumococcus infection.

TABLE XXIII

SECONDARY INFECTION WITH PNEUMOCOCCUS II ATYPICAL

═════════════╤═════════╤══════════╤════════════╤═══════════════════════
│ BED │ │PNEUMOCOCCUS│
NAME │OCCUPIED │ ADMITTED │IN SPUTUM ON│ SECONDARY INFECTION
│ │ │ ADMISSION │
─────────────┼─────────┼──────────┼────────────┼──────────┬────────────
„ │ „ │ „ │ „ │ DATE │PNEUMOCOCCUS
│ │ │ │ │ AT AUTOPSY
─────────────┼─────────┼──────────┼────────────┼──────────┼────────────
Pvt. Pighee │No. 48 │Sept. 22 │Atyp. II │ │
Pvt. Jones │No. 49 │Sept. 22 │Atyp. II │ │
Pvt. Lewis │No. 50 │Sept. 21 │I │Oct. 2 │Atyp. II
Pvt. Scott │No. 51 │Sept. 21 │Atyp. II │ │
Pvt. Columbus│No. 53 │Sept. 22 │Atyp. II │ │
─────────────┴─────────┴──────────┴────────────┴──────────┴────────────

It is noteworthy that these instances of secondary contact infection
with pneumococci occurred in wards where every precaution was supposedly
taken to prevent transfer of infection from one patient to another. It
is true however that the wards were greatly overcrowded at the time.
Many other instances of secondary pneumococcus infection in cases of
pneumonia following influenza were encountered in which it was
impossible to trace the source of infection, many combinations of
different types of pneumococcus being found. There were two instances in
which Pneumococcus Type IV was found in the sputum by inoculation of
white mice shortly after onset of pneumonia, whereas secondary infection
with other types was found at autopsy, one with Pneumococcus Type II,
one with Pneumococcus Type III. In 2 cases by inoculation of white mice,
two types of pneumococcus were found simultaneously in the sputum
coughed from the lung, in one Pneumococcus Types III and IV, in the
other Pneumococcus Types I and IV. There were 5 cases in which two types
of pneumococcus were found in cultures at autopsy as shown in Table
XXIV. Combined pneumococcus infections of this nature are almost never
encountered in pneumonia occurring under normal conditions in the
absence of epidemic influenza.

TABLE XXIV

MIXED PNEUMOCOCCUS INFECTIONS IN PNEUMONIA

═════════════════╤═════════════════════════════════════════════════════
NAME │ CULTURES AT AUTOPSY
─────────────────┼─────────────────┬─────────────────┬─────────────────
„ │ HEART’S BLOOD │ BRONCHUS │ LUNGS
─────────────────┼─────────────────┼─────────────────┼─────────────────
Pvt. Gal. │ │Pn. Type III │Pn. Type III
│ │B. influenzæ │Pn. Type IV
│ │Staphylococcus │B. influenzæ
─────────────────┼─────────────────┼─────────────────┼─────────────────
Pvt. Sug. │Pn. Type III │Pn. Type III │Pn. Type III
│ │Pn. Type IV │Pn. Type IV
│ │B. influenzæ │B. influenzæ
│ │Staphylococcus │
─────────────────┼─────────────────┼─────────────────┼─────────────────
Pvt. Hig. │S. hemolyticus │ │Pn. Type II
│ │ │Pn. Type IV
│ │ │S. hemolyticus
│ │ │Staph. aureus
─────────────────┼─────────────────┼─────────────────┼─────────────────
Pvt. Can. │Pn. Type I │ │Pn. Type III
│ │ │S. hemolyticus
─────────────────┼─────────────────┼─────────────────┼─────────────────
Pvt. Fer. │Sterile │Pn. Type IV │Pn. Type I
│ │B. influenzæ │Pn. Type IV
│ │Staphylococcus │B. influenzæ
─────────────────┴─────────────────┴─────────────────┴─────────────────

The foregoing data show that infection with one type of pneumococcus may
readily be superimposed upon or closely follow infection with another
type. Cases have been cited in which it was clearly demonstrated that
this was due to contact infection. It is furthermore evident that
pneumonia caused by one type of pneumococcus affords no reliable
immunity against pneumonia caused by another type. The same conditions
that favored the spread of hemolytic streptococcus infection also
favored the transfer of pneumococcus infection from patient to patient.

Secondary Contact Infection in Influenza

The material so far presented has dealt with contact infection in cases
of pneumonia following influenza. That a similar contact infection in
cases of influenza treated in crowded hospital wards is responsible in
considerable degree for the development of pneumonia in cases of
influenza seems quite probable. It has already been stated that this
pneumonia was found in large part to be caused by infection with types
of pneumococcus that are found in the mouths of normal individuals. It
has been fairly definitely established by Stillman[52] that lobar
pneumonia caused by pneumococcus Types I and II is in all probability
due to contact infection, and definite instances of such infection by
Pneumococcus Type II have been reported above. In a recent communication
Stillman[53] has furthermore shown that of the various groups of
Pneumococcus II atypical those most frequently associated with pneumonia
are rarely found in normal mouths, while those infrequently associated
with pneumonia are more commonly found. Whether similar considerations
will hold true for pneumococci of Group IV can only be determined by
further investigation. It has been stated that certain observations made
during the course of this work have suggested that cases of pneumonia
which complicate influenza may be due to contact rather than to
autogenous infection. The data available are far too limited to
establish this fact and it would require a very extensive study to
furnish conclusive evidence.

Certain general observations have suggested this point of view. It is
well recognized that the incidence of pneumonia in patients with
influenza has been much higher where overcrowding has existed. It would
seem probable that this has been in large part due to the greater
opportunity for the dissemination of organisms capable of producing
pneumonia and the consequently increased opportunity for secondary
contact infection among patients treated under such conditions. The not
infrequent occurrence of influenzal pneumonia due to combined infections
of the different types of pneumococci, hemolytic streptococci,
staphylococci, and other bacteria, instances of which have been cited,
is in harmony with this view, especially since pneumonia under ordinary
conditions is rarely found to be associated with mixed infections of
this nature. It is true that healthy individuals occasionally carry more
than one type of pneumococcus simultaneously in the mouth, though this
is very infrequent, and autogenous infection occurring in such
individuals might account in some instances for the mixed pneumococcus
infections encountered. By way of analogy it has been clearly shown in
other studies by the Commission on the relation of hemolytic
streptococcus carriers to the complications of measles, that secondary
infection of the respiratory tract with S. hemolyticus is in very large
part due to contact infection, the chronic carrier rarely developing
complications due to this organism.

To obtain further light on this question the type of pneumococcus
present in the mouths of 46 consecutive cases of early uncomplicated
influenza was determined by the mouse inoculation method at time of
admission to the receiving ward of the hospital before the patients had
been associated, with the purpose of determining if cases among this
group which subsequently developed pneumonia might be shown to have
acquired a pneumococcus which they did not carry at time of admission.
This group of patients was treated in a special ward set apart for the
purpose. The patients were assigned to beds in rotation and confined in
bed until thoroughly convalescent. Beds were well separated and
cubicles, masks and gowns were in use. Cultures were made from the ward
personnel. By these procedures an accurate record was kept of all
sources of pneumococcus infection. The types of pneumococcus found in
the mouths of these patients at time of admission are shown in Table
XXV.

TABLE XXV

TYPES OF PNEUMOCOCCI IN THE MOUTHS OF INFLUENZA PATIENTS

═══════════════════════════════════════════════════════════════════════
PNEUMOCOCCUS NUMBER PER CENT
───────────────────────────────────────────────────────────────────────
Pneumococcus, Type I 0 0
Pneumococcus, Type II 0 0
Pneumococcus, II atypical 1 2.2
Pneumococcus, Type III 0 0
Pneumococcus, Group IV 25 54.3
No pneumococci found 20 43.5
───────────────────────────────────────────────────────────────────────

Only 1 patient in this group developed pneumonia. At time of admission
he had no pneumococcus in his mouth as determined by inoculation of a
white mouse with his sputum. Examination of the sputum by the same
method at time of onset of pneumonia three days after admission showed
Pneumococcus Type III. The only ascertainable source of infection in
this case was one of the ward attendants who carried Pneumococcus Type
III in his throat in sufficiently large numbers to be demonstrable by
direct culture and who frequently came in contact with the patient. In
this instance the development of pneumonia was probably due to contact
infection. An extensive study of this nature would be necessary to
determine in what proportion of cases pneumonia following influenza is
caused by secondary contact infection and in what proportion to
autogenous infection. It is at least evident that contact infection with
a type of pneumococcus found in the mouth of normal individuals may
occur in influenza and be responsible for the development of pneumonia.
Therefore every precaution should be taken to prevent it.

Methods for the Prevention of Secondary Contact Infection in Influenza
and Pneumonia

The methods at present in vogue for preventing the spread of contagion
in wards devoted to the care of patients with influenza and pneumonia
may be briefly enumerated: The separation of patients by means of sheet
or screen cubicles, the wearing of masks and gowns by the ward personnel
and to some extent by convalescent patients who are up and about the
ward, and in some hospitals the separation of streptococcus carriers
from noncarriers as determined by throat culture at time of admission.
That these methods are of some value in preventing spread of infection
cannot be denied, and it is probable that they are fairly effective
under ordinary conditions when conscientiously carried out. That they
inevitably break down in the presence of an overwhelming epidemic when
hospital wards become overcrowded is only too evident. Under such
conditions the sheets hung between the beds are constantly being
displaced and are slight proof against a patient’s curiosity as to the
identity and condition of the man in the adjoining bed; masks cannot be
worn by patients seriously ill with pneumonia, during the very time when
they are most dangerous and in greatest danger and those worn by the
ward personnel are very rarely sufficiently well made to prevent spread
of contagion by droplet infection as the studies of Haller and
Colwell[54] and Doust and Lyon[55] have shown; the separation of
streptococcus carriers from noncarriers as at present carried out cannot
keep pace with the ever increasing influx of patients nor with the
rapidity of the spread of the hemolytic streptococcus, in part because
of the time required to make the bacteriologic diagnosis, in part
because the amount of work involved cannot be accomplished by the
laboratory personnel available. That this is so will be shown in data
presented below. Not only do these methods break down in the face of an
epidemic, but they often provide a false sense of security.

In searching for a solution of the problem it is essential to have the
following considerations clearly in mind. Every patient with influenza
must be considered a potential source of pneumococcus or hemolytic
streptococcus infection for his neighbor until he is proved otherwise by
bacteriologic examination. Every person engaged in the care of patients
with respiratory diseases must also be regarded as a potential source of
danger. Pneumonia cannot be regarded as one disease but must be looked
upon as a group of different diseases, with more or less similar
physical signs and symptoms, it is true, but caused by a considerable
variety of bacteria, infection with any one of which not only provides
no protection against infection with another, but may even render the
individual more susceptible to secondary infection. Therefore, every
patient with pneumonia must be regarded as an actual source of danger to
his neighbor, at least until it is established that he has the same type
of infection. All these considerations are especially true in the
presence of influenza, for it has become evident that many organisms
readily gain access to the lung and produce pneumonia in patients with
influenza which under ordinary circumstances fail to cause disease of
the respiratory organs.

Since secondary infection in respiratory disease is undoubtedly spread
in large part by droplet and contact infection, the prevention of
secondary infection must depend upon the elimination of these methods of
transmission. Three solutions present themselves: (1) Ward treatment
with absolute elimination of overcrowding and much wider separation of
patients than has hitherto been deemed necessary; (2) segregation of
patients according to type of bacterial infection; (3) effective
individual isolation of every patient.

It has been clearly shown that treatment of influenza and pneumonia in
overcrowded wards even with the use of such precautions to prevent
transfer of infection as cubicles, masking of attendants and patients,
etc., is attended by serious danger of contact infection and that such
infection will almost inevitably occur. This is not at all surprising
when it is remembered that we are treating in the same ward, in the case
of pneumonia, a group of what are in reality entirely different
diseases, all of which may be transmitted from one patient to another,
and in the case of influenza a group of individuals who carry a variety
of potentially pathogenic bacteria. No one would expect to treat cases
of scarlet fever, measles, and diphtheria together in a hospital ward
without having contact infection result. Among patients ill with
influenza and postinfluenzal pneumonia, certainly streptococcus
pneumonia and to some extent pneumococcus pneumonia may be transmitted
quite as readily as any of these diseases. In view of these
considerations it must be apparent if ward treatment of these diseases
is to be continued without respect to type of bacterial infection, not
only that overcrowding is absolutely contraindicated but also that much
wider separation of patients than has hitherto been regarded as
necessary is imperative. Furthermore, beds should be separated by
permanent cubicles that cannot readily be displaced. Patients should be
confined to their cubicles until thoroughly convalescent and when up and
about should not be allowed to enter cubicles occupied by patients still
sick. Medical officers, nurses and attendants who come into contact with
the patients should use the same rigid precautions that are used in the
care of patients with typhoid or erysipelas or meningitis with the
additional use of means to prevent droplet infection of the patients,
always bearing in mind that the respiratory tract in patients with
influenza or postinfluenzal pneumonia is as susceptible to secondary
infection as the postpartum uterus or an open surgical wound. In other
words, the most rigid aseptic technic should be maintained. The
recognition of a case of streptococcus pneumonia in a ward should be an
indication for immediate quarantine of the ward until it has been shown
by bacteriologic examination that there is no longer danger of spread of
streptococcus contagion. This is done in the case of meningitis or
diphtheria, neither of which diseases is comparable with streptococcus
pneumonia in rapidity of spread or in resulting fatality.

Segregation of patients in wards according to type of bacterial
infection while theoretically an improvement over the indiscriminate
mixing of patients with many different types of infection presents many
practical difficulties which make it impossible to carry out in the
presence of an overwhelming epidemic. It is quite obvious that grouping
of influenzal patients on the basis of the types of pneumococci that
they carry in their mouths is impossible since the great majority of
mouth pneumococci belong to Group IV and comprise a heterologous
immunologic group. The separation of influenza patients who carry S.
hemolyticus from those who do not would appear to offer a more hopeful
field. Since we cannot make an immediate distinction between
streptococcus carriers and noncarriers by inspection of the patient,
this procedure requires the taking of throat cultures at time of
admission to the hospital, the holding of patients for eighteen to
twenty-four hours in receiving wards until the bacteriologic diagnosis
has been made, and their subsequent distribution to streptococcus and
nonstreptococcus wards. This is feasible when the admission rate is low
and the number of streptococcus carriers found at time of admission is
small. In the presence of an influenza epidemic it immediately becomes
impossible to carry out in base hospitals as now constituted, since the
demand for beds under such conditions at once converts a large part of
the hospital into a group of receiving wards with little room remaining
for subsequent separation of patients. The amount of bacteriologic work
involved at once becomes prohibitive and the time required to make the
bacteriologic diagnosis defeats its purpose since it allows the spread
of hemolytic streptococcus to occur in the receiving wards during the
interval.

The foregoing statements are based on results obtained in an attempt to
separate streptococcus carriers from noncarriers in a limited group of
cases of influenza at Camp Pike, the investigation being conducted
during a secondary wave of influenza between November 27 and December 5.
A special group of five wards consisting of one receiving ward and four
distributing wards were set aside for the study. Cubicles, masks and
gowns were in use and the wards were not crowded. The personnel on these
wards did not carry S. hemolyticus in their throats. Patients entering
the receiving ward were assigned to beds in rotation. Throat cultures
were made on blood agar plates at time of admission. The plates were
examined promptly the next morning, the diagnosis of S. hemolyticus
being made by the characteristic hemolytic colonies and microscopic
examination of stained smears. By this method a report reached the
receiving ward at 9:30 a.m. and patients were promptly evacuated to the
streptococcus and nonstreptococcus wards, where they were again assigned
to beds in rotation, remaining confined in bed until convalescent.
Confirmation of all strains of hemolytic streptococcus was subsequently
carried out by isolation in pure culture, bile solubility test, and
hemolytic test with washed sheep corpuscles. All cases free from
hemolytic streptococci at time of admission who were sent to the “clean”
wards were recultured daily throughout the period of study, those
acquiring a hemolytic streptococcus being transferred to a streptococcus
ward as soon as the bacteriologic diagnosis was made. The results are
shown in Table XXVI.

TABLE XXVI

S. HEMOLYTICUS IN CASES OF INFLUENZA

══════════╤══════════╤═══════════════════╦═════════════════════════════
DATE │ PATIENTS │THROAT CULTURES ON ║ “CLEAN” CASES ACQUIRING S.
│ ADMITTED │ ADMISSION. S. ║ HEMOLYTICUS IN THE HOSPITAL
│ TO │ HEMOLYTICUS: ║
│RECEIVING │ ║
│ WARD │ ║
──────────┼──────────┼─────────┬─────────╫─────────┬─────────┬─────────
„ │ „ │ + │ − ║WHILE IN │WHILE IN │ TOTAL
│ │ │ ║REC. WARD│ “CLEAN” │
│ │ │ ║ │ WARD │
──────────┼──────────┼─────────┼─────────╫─────────┼─────────┼─────────
Nov. 27 │ 12│ 4│ 8║ 0│ 2│ 2
Nov. 28 │ 8│ 2│ 6║ 0│ 1│ 1
Nov. 29 │ 17[56]│ 8│ 9║ 1│ 2│ 3
Nov. 30 │ 11│ 2│ 9║ 3│ 0│ 3
Dec. 1 │ 10│ 5│ 5║ 0│ 0│ 0
Dec. 2 │ 37│ 16│ 21║ 1│ 1│ 2
Dec. 3 │ 21│ 8│ 13║ 0│ 2│ 2
Dec. 4 │ 32[56]│ 11│ 21║ 4│ 2│ 6
Dec. 5 │ 17│ 10│ 7║ 5│ 0│ 5
──────────┼──────────┼─────────┼─────────╫─────────┼─────────┼─────────
Totals │ 165│ 66│ 99║ 14│ 10│ 24
──────────┴──────────┴─────────┴─────────╨─────────┴─────────┴─────────

One hundred and sixty-five cases were admitted to the receiving ward
during the period of study as cases of influenza. Of these, 137 had
influenza; 4 of those with influenza had pneumonia at time of admission,
23 had acute follicular tonsillitis, 3 epidemic cerebrospinal
meningitis, 1 scarlet fever, and 1 Vincent’s angina. Sixty-six cases (40
per cent) showed hemolytic streptococcus in the throat at time of
admission and were sent to the streptococcus wards; 99 cases (60 per
cent) were negative for hemolytic streptococcus on admission, and of
these 91 were sent to the “clean” influenza wards. Twenty-four of these
clean cases subsequently became positive for S. hemolyticus. It is
especially noteworthy that 14 of them acquired a hemolytic streptococcus
during the short period that they were held in the receiving ward
awaiting the report of the culture taken at time of admission, the first
culture taken shortly after admission to the “clean” wards being
positive. This result was undoubtedly due to the fact that these cases
were unavoidably associated in the receiving ward with many carriers of
hemolytic streptococcus. It is evident that cases which were supposedly
free from streptococci but which in reality had picked up the organism
in the receiving ward were constantly being sent to the “clean” wards.
It is furthermore evident that if the precaution had not been taken of
reculturing all clean cases on day of admission to the “clean” wards and
daily thereafter these wards would soon have become saturated with
hemolytic streptococci. Even under these conditions, 10 cases, after
varying periods in the “clean” wards, acquired the organism in their
throats. When it is stated that it required the full time of two men
under very special conditions to carry out this work in a very limited
number of cases and that it failed to keep “clean” wards free from
hemolytic streptococci, it is only too apparent that the efficient
separation of carriers from noncarriers in the presence of an epidemic
of influenza is an impossible task.

The segregation of pneumococcus pneumonias following influenza according
to type of infection is obviously impossible, since they are caused by
an almost unlimited variety of immunologic types as far as present
knowledge goes.

Even the efficient separation of streptococcus pneumonias from
pneumococcus pneumonias would require a considerable team of workers and
the closest cooperation between laboratory and ward staffs, so that no
case of pneumonia would be sent to a pneumonia ward until the
bacteriologic diagnosis had been made. In our experience this is rarely
considered feasible even under ordinary conditions, and in the presence
of an epidemic is nearly impossible because of the volume of work
involved and the delay necessitated by bacteriologic methods. It is,
nevertheless, absolutely essential if highly fatal ward epidemics of
streptococcus pneumonia are to be prevented.

In view of the considerations discussed above, it is believed that the
clear and most fundamental indication for the management of epidemic
respiratory diseases in the army is to scatter patients as widely as
possible instead of following the time-honored custom of concentrating
them. In brief, abandon open ward treatment and adopt effective
individual isolation of every case, maintaining as strict a quarantine
as is demanded in other highly contagious and infectious diseases. The
adoption of a strict aseptic technic in the handling of these patients
is an evident corollary. Only by this means can the serious and highly
fatal secondary hospital infections, which occur in influenza and
pneumonia when these diseases are present in epidemic form, be
prevented.

The prevention of secondary infection, prior to admission to the
hospital, is another and more difficult problem. That opportunity for
secondary contact infection in cases of influenza before patients reach
the hospital is great seems unquestionable, since many cases have
already developed these infections at time of admission. During the
epidemic patients were crowded in regimental infirmaries, in ambulances,
and in the receiving office of the hospital with every opportunity for
droplet infection present. No study has been made of this question, but
it seems reasonable that the same methods of prevention should apply,
namely, effective separation of patients.

It is not within the scope of this paper to discuss details of method,
but anything that is possible becomes feasible as soon as sufficient
evidence can be brought to bear that it is a necessity. In the present
instance it would seem that any means that can be used to reduce
materially the terrific toll taken by respiratory diseases is an
absolute necessity.

Summary

1. Secondary contact infection with pneumococci not infrequently occurs
in patients with pneumonia following influenza when they are treated in
hospital wards.

2. Secondary contact infection with S. hemolyticus readily occurs in
patients with pneumonia and may spread rapidly throughout an entire ward
with highly fatal results.

3. Secondary contact infection may be responsible for the development of
pneumonia in patients with influenza.

4. Ward treatment of these diseases is fraught with serious danger which
is greatly increased by overcrowding, by imperfect separation of
patients by cubicles, and by imperfect aseptic technic of medical
officers, nurses, and attendants.

5. It is probable that secondary contact infection can be effectively
prevented only by individual isolation and strict quarantine of every
patient.

CHAPTER IV
THE PATHOLOGY AND BACTERIOLOGY OF PNEUMONIA FOLLOWING INFLUENZA

E. L. OPIE, M.D.; F. G. BLAKE, M.D.; AND T.M. RIVERS, M.D.

Many observers have described isolated phases of the recent epidemic and
of past epidemics of influenza. Few have had an opportunity to follow
the pathology of influenza from the onset of an epidemic through a
period of several months and to observe the succession of acute and
chronic changes which occur in the lungs. Our commission arrived on
September 5, 1918, at Camp Pike two weeks before the outbreak of
influenza. The commission had previously made a careful study of the
clinical course, the bacteriology and to a limited extent the pathology
of pneumonia occurring at Camp Funston where there was little if any
influenza. Study of the records preserved at the base hospital at Camp
Funston had convinced us that this camp had passed through an epidemic
of influenza during the spring of 1918, this epidemic being followed by
a very severe outbreak of pneumonia. Our investigation at Camp Funston
had brought to our attention those phases of pneumonia which with the
facilities of a base hospital laboratory could be most profitably
studied with a view to determining the causation, the epidemiology and
the prevention of the pneumonias prevalent in the American army.

Study of pneumonia after death offers the only opportunity of
determining the relation of pulmonary lesions to the considerable
variety of microorganism associated with them. Clinical diagnosis
furnishes no certain criterion for distinguishing lobar and
bronchopneumonia; suppurative pneumonia is rarely recognizable during
life. The relation of pneumococci, streptococci, staphylococci or B.
influenzæ to one or other type of pneumonia can be determined with
accuracy only after death; for the demonstration of one or more of these
microorganisms in material obtained from the upper respiratory passages
in life, though of value, furnishes us no definite evidence that the
organism which has been identified has entered the lung and passed from
the bronchi to produce pneumonia.

Study of autopsies following examination of the sputum during life has
shown that an individual primarily attacked by influenza may suffer with
a succession of pneumonias, one microorganism having prepared the way
for another. The complexity of the subject is much increased by the
truth that pyogenic microorganisms, like the tubercle bacilli, are
capable of producing a considerable variety of pulmonary lesions.

Examination of the lungs of a large number of individuals who have died
as the result of pneumonia following influenza has disclosed a
succession of acute and chronic diseases. Immediately succeeding the
height of the epidemic of influenza, death occurred with acute lobar
pneumonia or with diffusely distributed hemorrhagic bronchopneumonia
caused in the majority of instances by Pneumococcus IV in association
with B. influenzæ. Superimposed infection with hemolytic streptococci
increased in frequency and in individuals who had occupied certain wards
was almost invariable. At a later period, from one to two months
following the maximum incidence of influenza chronic lesions, namely,
bronchiectasis, unresolved pneumonia, and chronic empyema were common
and often occurred as the result of influenza which had had its onset at
the height of the epidemic.

When influenza attacked the encampment, about 50,000 troops were
quartered in it, and for a considerable period no more troops were
brought into the camp and none left it. All cases of pneumonia occurring
among these troops were brought to the base hospital so that the
autopsies which were studied were representative of all the pneumonias
following influenza in this limited group of men. It is noteworthy that
autopsy disclosed no instance of fatal influenza unaccompanied by
pneumonia.

=Pneumonia of Influenza.=—Knowledge concerning the bacteriology of the
pneumonia of influenza dates from the study of the epidemic of 1889–90.
The frequency with which Diplococcus lanceolatus occurred in association
with influenzal pneumonia was well recognized, although several
observers, notably Finkler[57] and Ribbert,[58] found Streptococcus
pyogenes so often that they attributed the pneumonia of influenza to
this microorganism.

During a subsidiary outbreak of influenza occurring in 1891–92
Pfeiffer[59] discovered the microorganism which he believed was the
cause of the disease. Pneumonia, he believed, was caused by the invasion
of this microorganism into the lung, and the pneumonia of influenza, if
death occurred at the height of the disease, was characterized not only
by the presence of the bacillus of influenza, but was recognizable by
its anatomic peculiarities. He described lobular patches of
consolidation which were separated from one another by air containing
tissue or were confluent, so that, although the lobular character was
still recognizable, whole lobes might be affected. The consolidated
tissue was dark red and within each lobular area were small, yellowish
gray spots varying in size from that of a pinhead to a pea. In the mucus
of the larynx and trachea were numerous microorganisms, including
diplococci and streptococci, among which influenza bacilli were
predominant; in the larger bronchi, bacteria other than influenza
bacilli were less abundant, whereas in the finer bronchi filled with
purulent fluid and in the lung tissue influenza bacilli had undivided
sway. Pfeiffer stated that the changes described were found when death
occurred at the height of the disease, whereas other pulmonary lesions
might be sequelæ of this typical influenzal pneumonia.

Observations upon the pathology of influenzal pneumonia made during the
epidemic of 1889–92 have been collected in the monograph of
Leichtenstern[60] published in 1896. He combats the opinion held by some
observers that pneumonia with influenza is always catarrhal and cites
many writers to prove that lobar pneumonia not infrequently accompanies
the disease. Indeed, some have found “croupous” pneumonia more often
than “catarrhal.” Krannhals[61] at Riga found typical fibrinous
pneumonia in 53 instances, doubtful forms in 22 and bronchopneumonia in
37. Cruickshank[62] in England found croupous forms predominant. Among
43 autopsies performed upon individuals dead with influenza
Birch-Hirschfeld[63] found 11 instances of croupous lobar pneumonia, 8
instances of croupous lobular pneumonia and 24 instances of catarrhal
pneumonia. Leichtenstern thinks that the atypical symptomatology of
lobar pneumonia with influenza—for example, the purulent character of
the sputum—has led many physicians to believe that lobar pneumonia
rarely occurs. It is equally true that many instances of confluent
lobular pneumonia are mistaken for lobar.

There appears to be no comprehensive description of the pneumonias of
influenza based upon the epidemics of 1889–92. Descriptions dating from
this period are much obscured by attempts to separate croupous or
fibrinous from catarrhal pneumonias. Croupous lobular pneumonia has been
recognized, for example, by Birch-Hirschfeld. Leichtenstern describes a
form of pneumonia which he regards as neither lobar nor lobular although
it implicates whole lobes; the consolidated tissue is homogeneous and
varies in color from fleshy red to bluish red; it is tough and elastic
in consistency. The author thinks that it is an error to regard this
lesion as a confluent lobular pneumonia.

Kuskow[64], who has discussed the pathology of influenza in considerable
detail, has seldom seen lobar pneumonia but has almost invariably found,
even when there is lobar distribution of the lesion, lobular patches of
consolidation involving groups of lobules, single lobules or only parts
of lobules; the lung tissue has been hyperemic and in places edematous.

Opinions concerning the pathology and bacteriology of the pneumonias of
influenza, published since the recent epidemic, have varied almost as
much as those just cited. Few observers have had the opportunity of
making a considerable number of observations under conditions which
determine the relation of the pulmonary lesions to the primary disease.

Keegan[65] has found with influenza a massive and confluent
bronchopneumonia, frequently resembling lobar pneumonia but
distinguishable particularly in its early stages when the cut section of
the consolidated lung has a finely granular character and each
bronchiole stands out as a grayish area with intervening dark red
alveolar tissue.

Symmers[66] states that the pneumonia of influenza is a confluent
lobular exudative and hemorrhagic pneumonia which bears a close
resemblance to the pneumonic variety of bubonic plague.

Our commission[67] published a preliminary report on pneumonia following
influenza observed at Camp Pike. The occurrence of purulent bronchitis,
distention of lungs, peribronchial hemorrhage and bronchiectasis were
described. B. influenzæ was isolated from the bronchi in approximately
85 per cent of instances of influenzal pneumonia but from the
consolidated lung in less than half this number of autopsies. Lobar
pneumonia was present in a large proportion of autopsies but was less
frequent than bronchopneumonia. Bronchopneumonic consolidation is in
part red, lobular and confluent, in part nodular; pneumococci have a
predominant part in the production of these lesions. Three types of
suppurative pneumonia are described: (_a_) Abscess caused by hemolytic
streptococci usually in contact with the pleura and accompanied by
empyema; (_b_) Suppuration of interstitial tissue of the lung caused by
hemolytic streptococci and accompanied by empyema; (_c_) multiple foci
of suppuration clustered about a bronchus of medium size and caused by
staphylococci. We have expressed the opinion that B. influenzæ descends
into the bronchi; pneumococci, usually Type IV, may enter the lung and
produce either lobar or bronchopneumonia. Hemolytic streptococci may
descend and infect the pneumonic lung causing death often before
suppuration has occurred. Epidemics of such superimposed streptococcus
pneumonia in wards of the hospital were described.

LeCount[68] says: “The pneumonia of influenza is commonly referred to as
bronchopneumonia. It may be so designated, but it differs from other
bronchopneumonias in its predilection for the periphery of the lungs and
in the extent to which the inflammation is hemorrhagic.”

MacCallum[69] states that the following types of pneumonia following
influenza may be recognized. 1. Pneumococcus pneumonia. The lobular
character of the consolidation is in these cases well marked, although
it tends to lose its definiteness through the confluence of adjacent
areas. The cut surface of the lung shows in the more acute cases a
peculiar lobular or confluent consolidation which corresponds well with
what is commonly written of the stage of engorgement in the description
of lobar pneumonia. Later stages in the pneumonia show within these
areas patches of rough gray consolidated tissue from which definite
plugs of exudate project. 2. Staphylococcal pneumonia. 3. Streptococcal
pneumonia. There is lobular pneumonia, the interlobular septa are
edematous and, microscopically, bronchi and alveoli are loaded with
streptococci. Whole areas of lung, though retaining their form, are
entirely necrotic. Lymphatics are distended with exudate containing
streptococci in great numbers, but in none of these cases is
interstitial bronchopneumonia found. 4. Pneumonia produced by B.
influenzæ of Pfeiffer. The lung is studded with palpable shot-like
grayish yellow nodules; the bronchi exude thick yellow pus, which
contains influenza bacilli. Microscopically, the walls of the bronchi
are found to be thickened by mononuclear infiltration and new formation
of connective tissue. The walls of the alveoli are thickened and
indurated and the alveoli often contain fibrin in process of
organization. Absence of conspicuous changes in lymphatics, absence of
intense pleural infection and relatively scant numbers of polynuclear
leucocytes in the exudate within the alveoli and bronchial walls are,
MacCallum states, all that distinguish this pulmonary change from the
interstitial bronchopneumonia caused by the hemolytic streptococcus and
described by him in previous papers.

Lyon[70] designates the pulmonary lesion following influenza,
hemorrhagic pneumonitis, the lung tissue containing serous fluid loaded
with red blood corpuscles; in many instances there was such scant
consolidation that the process could not be regarded as a true
pneumonia. In 35 instances the lesion was lobular in distribution and in
16 instances was sufficiently extensive to be designated lobar, but it
was not typical lobar pneumonia, and, often associated with lobular
patches of consolidation, appeared to be a confluent lobular pneumonia.

Goodpasture and Burnett[71] say: “The difficulties of analyzing the
pulmonary lesions in any group of influenza pneumonias as they have
appeared in this epidemic, are very apparent to anyone who has had an
opportunity to observe the bacteriology and pathology of this
accompaniment of the disease.” There is an acute outflow of the fluid
elements of the blood and of hemorrhage into the lung tissue filling the
alveoli in lobular areas and not infrequently in an entire lobe. By a
special method of staining these authors have studied the distribution
of Gram-negative bacilli with the morphology of B. influenzæ. The fact
that in certain very early cases demonstrable bacteria of any kind are
scarce or not found at all, has lead them to believe “notwithstanding
the demonstration of influenza bacilli in pure culture in the lung in
all but one instance, that at this stage organisms are comparatively few
within the alveoli, and the primary injury is due to a very potent toxic
agent elaborated in and disseminated through the larger air passages. In
the later stages or from the beginning, if the injury be slight, the
infection focalizes about the bronchi or their terminations, so that the
bronchial and lobular distribution becomes very conspicuous.” Typical
lobar pneumonia with “croupous” exudate within the alveoli occurs in
cases complicated by secondary pneumococcus infection.

Wolbach[72] has found that two types of pneumonia are characteristic of
influenza. In cases in which death has occurred within a few days after
onset of pulmonary signs, the lung tissue is dark red and “meaty in
consistency” and contains abundant blood-tinged serous fluid which drips
from the cut surface. The other type of lesion is found in patients who
have lived for ten days or more after onset of the disease; there is
extensive bronchitis, bronchopneumonia, discrete or confluent, and
peribronchitis. The lungs are voluminous and the smaller bronchi are
distended. Microscopically, there is peribronchitis with extensive
infiltration of the interlobular septa and organization in alveoli and
bronchioles. This lesion is that designated by MacCallum as
“interstitial bronchopneumonia.” Wolbach thinks that the two types of
lesion represent different stages of the same process. He regards as
distinctive of the pneumonias of influenza the presence of hyalin fibrin
lining distended air spaces. With the two types of lesion which have
been described, B. influenzæ was the only organism which could be
cultivated, and the author associates these distinctive conditions with
that microorganism.

=Streptococcus Pneumonia.=—Finkler emphasized the importance of
streptococcus pneumonia as a complication of influenza. In 1888 he
described instances of acute primary streptococcus pneumonia observed in
1887 and 1889. This form of pneumonia, Finkler thought, occurred in Bonn
in epidemic form before the influenza epidemic of 1889–90 and, he
states, exhibited an astonishing similarity to the pneumonia of
influenza. He thought that later there was in Bonn a mixed infection of
influenza and primary streptococcus pneumonia. In one type of
streptococcus pneumonia, described by Finkler, there was lobular
consolidation which in multiple patches produced “pseudolobar”
consolidation; the consolidated lung was smooth and red, and similar to
spleen, rather than hepatized. In another group of instances the lesion
merited the name “erysipelas of the lung.” The lesion was an acute
interstitial pneumonia in some places, a cellular or occasionally
fibrinous pneumonia with involvement of the interstitial tissue in other
places. There was edematous swelling and accumulation of leucocytes in
the interstices between the alveoli and about the blood vessels and
bronchi. Finkler stated that the similarity to erysipelas might suggest
that the lymphatics contain streptococci, but this relation did not
exist although large lymphatic channels were occasionally filled with
coagulum. He asserted that the disease was contagious and cited cases
which he believed had their origin in hospital wards.

The widespread occurrence of streptococcus pneumonia in the army camps
in this country attracted attention during the first months of 1918.
Cummings, Spruit and Lynch[73] at Fort Sam Houston, Texas, recognized
the prevalence of streptococcus pneumonia, both as a complication of
measles and in association with lobar pneumonia, and showed that the
microorganism concerned was a hemolytic streptococcus. In 7 autopsies
upon individuals with lobar pneumonia, they found pneumococcus alone in
2 instances and pneumococcus and hemolytic streptococcus or hemolytic
streptococcus alone in 5 instances. Hemolytic streptococcus was found in
all of 24 instances of bronchopneumonia, three-fourths of which followed
measles. They recommend the bacteriologic examination of the throat of
patients with measles and the segregation of those who harbor hemolytic
streptococci.

Cole and MacCallum[74] have published almost simultaneously, with that
just cited, a report upon the pneumonia which has occurred at Fort Sam
Houston and have shown the importance of hemolytic streptococci in its
causation. They have found two varieties of pneumonia, namely, acute
lobar pneumonia which does not differ essentially from that which occurs
elsewhere and bronchopneumonia which in most cases has followed measles
and is caused by S. hemolyticus. They think this infection is usually
acquired in the hospital. They believe that the pulmonary lesions are
characteristic. In this publication and elsewhere MacCallum has
designated the lesion “interstitial bronchopneumonia.”

The epidemic of streptococcus pneumonia and empyema occurring at Camp
Dodge, Iowa, from March 20 to May 10 is described by Miller and
Lusk[75]. During this period there were 400 cases of pneumonia, whereas
from September 20, 1917, to March 20 there had been only 276 instances
of lobar pneumonia. The type of pneumonia changed, there was more severe
intoxication and empyema became very frequent; in 85 of 95 exudates
streptococci were found. The outbreak of pneumonia bore no relation to
measles. The authors state that a mild tracheitis was prevalent in the
cantonment during March, and whenever a large group of soldiers
congregated coughing was noticeable.

MacCallum[76] studied the pneumonia at Camp Dodge during May and found
17 instances of the lesion which he had designated interstitial
bronchopneumonia; of these, 9 followed measles, although in the earlier
part of the epidemic there appear to have been, he states, few such
cases. Cultures made at autopsy, except in a few fatal cases of
uncomplicated lobar pneumonia caused by the pneumococcus, showed the
hemolytic streptococcus in every situation throughout the respiratory
tract and pleura.

The pneumonia which occurred at Camp Funston is of special interest to
our commission because we were for a time stationed at this camp and had
the opportunity of following in the excellent records of the hospital
the history of the occurrence of pneumonia during the year following the
establishment of the camp in September, 1917. Stone, Phillips and
Bliss[77] have described the outbreak of pneumonia which occurred in
March, 1918. At this time there was, the authors state, severe pneumonia
with frequent empyemas due to hemolytic streptococci. This condition
which did not follow measles was responsible for the greatly increased
death rate in March; 9 deaths occurred in February, 45 in March, 25 in
April and 14 in May. They found during March 26 instances of multiple
pulmonary abscess. In 29 autopsies they found a pleural lesion which
they designate “subcostosternal pus pockets”; it occurs only in
association with empyema caused by hemolytic streptococci.

Our commission[78] has shown that an epidemic of influenza, well
characterized by its epidemiology and symptoms, preceded and accompanied
the outbreak of pneumonia just described. Between March 4 and 29 1,127
men from Camp Funston, which then contained 29,000 men, were sent to the
base hospital with influenza and many more were treated in the
infirmaries of the camp; on March 11 107 patients with influenza were
admitted to the hospital. The greatest incidence of pneumonia in the
history of the encampment up to this time occurred between March 9 and
29, immediately following the outbreak of influenza, the maximum
incidence of pneumonia occurring five days after the maximum for
influenza.

The foregoing observations are cited to prove that streptococcus
pneumonia, which occurred during the spring of 1918 at Camp Funston and
doubtless at other camps, had its origin in influenza and did not differ
in character from that which occurred on a much larger scale in the fall
of 1918.

=Table of Autopsies.=—In order to present as briefly as possible the
data upon which the present study has been based, autopsies have been
assembled in tabular form in the order of their performance (Table
XXVII). During the early period of the epidemic autopsies were performed
on all who died with pneumonia, but later, with increase in the number
of deaths, this became impossible and autopsies were performed on all
those who died in certain wards.

Comparison of charts representing incidence of influenza and of deaths
from pneumonia furnishes evidence that fatal pneumonia during the period
of investigation was with few exceptions referable to influenza. During
two weeks, namely, from September 1 to 14, before the presence of the
epidemic was evident, there were only 2 fatal cases of pneumonia. In
most instances the relation of pneumonia to influenza is established by
a definite history of influenza having its onset during the epidemic.
Bronchopneumonia usually develops gradually as a sequence of influenza
in which purulent bronchitis has occurred. Lobar pneumonia may develop
in cases of influenza complicated by purulent bronchitis. In some
instances there is apparent recovery from influenza indicated by return
of temperature to normal; after from one to three days of normal
temperature there is typical lobar pneumonia with rusty sputum. In many
instances of pneumonia having their onset at the height of the epidemic
of influenza, the history indicates that pneumonia was present
immediately after the onset of symptoms, so that the onset resembled
that of pneumonia rather than of influenza.

Cases of pneumonia following measles have been excluded from the table
in order that they may be studied separately and compared with the
pneumonias of influenza. It is noteworthy that the lesions of pneumonia
following measles have shown a very close resemblance to the pneumonias
of influenza, with regard both to pathologic characters and to
bacteriology.

Five instances of pneumonia following typhoid fever (Autopsies 245 and
329), scarlet fever (Autopsy 311) or mumps (Autopsies 403 and 417) have
been excluded from the table. These secondary pneumonias are grouped as
an appendix to the section on pneumonia following measles. It is not
improbable that individuals with the diseases named are just as
susceptible as others to influenza. Included in the table is an instance
(Autopsy 487) in which a definite attack of influenza preceded scarlet
fever.

TABLE XXVII

═══════╤════╤════════╤════════╤═════════╤═════════╤══════════╤═════════
NO. OF │RACE│ LENGTH │DURATION│DURATION │CLINICAL │ PURULENT │ LOBAR
AUTOPSY│ │ OF │ OF │ OF │DIAGNOSIS│BRONCHITIS│PNEUMONIA
│ │MILITARY│ILLNESS │PNEUMONIA│ │ │
│ │SERVICE │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
229 │ W │ 1m │ 12+ │ 12+ │ L │ P │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
231 │ W │ 2m │ 13 │ 4 │ B │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
232 │ W │ 14d │ 9 │ 6? │ B │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
233 │ C │ 11m │ 5 │ 2 │ L │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
236 │ W │ 3w │ 8 │ 7+ │ L │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
237 │ W │ 10d │ 8 │ 2 │ L │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
238 │ W │ 2d │ 8 │ 5 │ L │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
239 │ W │ 11d │ 9 │ 5 │ L │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
240 │ W │ 13d │ 8 │ 4 │ L │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
241 │ W │ 14d │ 5 │ 5 │ L │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
242 │ C │ 14d │ 7 │ 4 │ L │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
243 │ W │ 15d │ 5 │ 5 │ L │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
244 │ C │ 1m │ 6 │ 3 │ B │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
246 │ C │ 2m │ 6 │ 3 │ L │ P │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
247 │ W │ 10d │ 10 │ 5 │ L │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
248 │ W │ 1m │ 4 │ 2+ │ I │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
249 │ W │ 15d │ 12 │ 6+ │ L │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
250 │ W │ 14d │ 11 │ 7 │ L │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
251 │ W │ 25d │ 7 │ 1 │ B │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
252 │ W │ 21d │ 14 │ 12 │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
253 │ W │ 12d │ 19 │ 12+ │ B │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
254 │ W │ 21d │ 7 │ 6+ │ B │ P │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
255 │ W │ 12d │ 5 │ 4? │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
256 │ W │ 17d │ 8 │ 4 │ B │ P │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
257 │ C │ 21d │ 10 │ 7+ │ L │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
258 │ W │ 1m │ 6 │ 2+ │ B │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
259 │ W │ 3m │ 4 │ 1 │ B │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
260 │ W │ 1m │ 2 │ 1 │ L │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
261 │ W │ 2m │ 7 │ 5+ │ B │ P │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
262 │ W │ 12d │ 5 │ 4? │ B │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
263 │ W │ 21d │ 7 │ 5 │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
264 │ W │ 21d │ 10 │ 7 │ L │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
265 │ W │ 14d │ 7 │ 6+ │ L │ │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
266 │ W │ 1m │ 7 │ 2 │ L │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
267 │ W │ 2m │ 22 │ 10 │ B │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
268 │ W │ 2m │ 6 │ 4? │ L │ │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
269 │ W │ 25d │ 8 │ 2 │ L │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
270 │ W │ 17d │ 18 │ 3 │ L │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
271 │ W │ 2d │ 12 │ 5 │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
272 │ W │ 3m │ 7 │ 2 │ L │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
273 │ W │ 1m │ 8 │ 4+ │ L │ │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
274 │ W │ 2w │ 9 │ 5 │ B │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
275 │ W │ 4m │ 9 │ 4 │ L │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
276 │ W │ 1m │ 6 │ 4+ │ L │ │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
277 │ W │ 21d │ 10 │ 3 │ L │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
278 │ W │ 2m │ 16 │ 6+ │ L │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
279 │ W │ │ │ │ L │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
280 │ W │ 21d │ 8 │ 8 │ L │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
281 │ W │ 21d │ 9 │ 5 │ L │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
282 │ W │ 1m │ 10 │ ? │ B │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
283 │ W │ 7d │ 19 │ 8 │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
284 │ W │ 21d │ 11 │ ? │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
285 │ W │ │ 11 │ 9? │ B │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
286 │ W │ 20d │ 9 │ 4+ │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
287 │ W │ 3m │ 12 │ 4 │ L │ P │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
288 │ W │ 1m │ 10 │ 5 │ B │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
289 │ W │ 19d │ 12 │ 7 │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
290 │ W │ 1m │ 3+ │ 3+ │ B │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
291 │ W │ 2w │ 18 │ 11 │ B │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
292 │ W │ 3m │ 5 │ 5 │ L │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
293 │ W │ 2m │ 3+ │ 3+ │ L │ P │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
295 │ W │ 1m │ 12 │ 5 │ L │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
296 │ W │ 16d │ 18 │ 3 │ L │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
297 │ W │ 1m │ 5 │ ? │ I │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
298 │ C │ 21d │ 13 │ 10 │ B │ P │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
299 │ W │ 28d │ 9 │ 3 │ L │ P │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
300 │ C │ 22d │ 16 │ 12+ │ L │ P │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
301 │ W │ 1m │ 7 │ 5 │ B │ │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
302 │ C │ 5d │ 6 │ 3+ │ B │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
303 │ W │ 1m │ 7 │ 3+ │ L │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
304 │ W │ 4m │ 10 │ 2? │ L │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
305 │ W │ 5m │ 3+ │ 3+ │ L │ │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
306 │ W │ 1y │ 6+ │ 3 │ B │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
308 │ W │ 1m │ 6 │ 6 │ L │ │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
309 │ W │ 1m │ 4 │ 2? │ L │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
310 │ W │ 21d │ ? │ 3? │ L │ │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
312 │ W │ 1m │ 17 │ 7 │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
313 │ W │ 1y │ 5 │ 2 │ B │ │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
314 │ W │ 1m │ 3+ │ 3+ │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
315 │ W │ 1m │ 9 │ 2 │ B │ │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
316 │ W │ 1m │ 11 │ 4 │ L │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
317 │ W │ 13d │ 9 │ 2 │ L │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
318 │ W │ 2m │ 8 │ 3 │ L │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
319 │ W │ 1m │ 4+ │ 4+ │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
320 │ C │ 5m │ 1+ │ 1+ │ L │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
321 │ W │ 28d │ 4+ │ 4+ │ L │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
322 │ W │ 10d │ 8 │ 6 │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
323 │ W │ 2m │ 12 │ 4 │ B │ │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
324 │ W │ 22d │ 9 │ 6 │ B │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
325 │ W │ 1m │ 8 │ 8 │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
326 │ W │ 1m │ 5+ │ 2 │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
327 │ W │ 1m │ 4 │ ? │ B │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
328 │ W │ 5m │ 13 │ 3+ │ L │ P │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
330 │ W │ 1m │ 10 │ 3 │ L │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
331 │ W │ 1m │ 12 │ 11+ │ B │ P │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
332 │ W │ 1m │ 17 │ 3 │ L │ P │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
333 │ W │ 19d │ 15 │ 7 │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
334 │ W │ 14d │ 16 │ 5 │ B │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
335 │ W │ 1m │ 7 │ ? │ ? │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
336 │ W │ 2m │ 12 │ 6 │ B │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
337 │ W │ 1m │ 9 │ 2? │ L │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
338 │ W │ 1m │ 7 │ 5+ │ B │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
339 │ W │ 2m │ 9 │ 6? │ L │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
340 │ W │ 35d │ 8 │ 3 │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
341 │ W │ 3m │ 6 │ 4+ │ │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
342 │ W │ 2m │ 9 │ 3? │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
343 │ W │ 1m │ 11 │ 1? │ L │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
344 │ W │ 4m │ 13 │ 6 │ L │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
345 │ W │ 1d │ ? │ 7 │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
346 │ W │ 26d │ 16 │ 10 │ B │ P │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
347 │ C │ 3d │ 10 │ 3 │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
348 │ C │ 4d │ 8 │ 8 │ B │ P │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
349 │ W │ 2d │ 12 │ 6 │ L │ P │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
350 │ W │ 2m │ 6 │ 2? │ B │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
351 │ C │ 4m │ 4 │ 3+ │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
352 │ C │ 2m │ 8 │ 4 │ L │ P │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
353 │ C │ 6m │ 18 │ 18 │ L │ P │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
354 │ W │ 15d │ 2+ │ 2 │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
355 │ W │ 21d │ 7 │ 7 │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
356 │ C │ 5d │ 8 │ 4 │ L │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
357 │ W │ 1m │ 10 │ 6+ │ L │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
358 │ W │ 1m │ 15 │ 6? │ L │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
359 │ W │ 1m │ 7+ │ ? │ L │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
360 │ W │ 36d │ 10 │ 3 │ L │ P │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
361 │ W │ 3m │ 8 │ 2 │ L │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
362 │ W │ 4m │ 15 │ 13+ │ L │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
363 │ W │ 3m │ 8 │ 1+ │ L │ P │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
364 │ W │ 6d │ 9 │ 5+ │ B │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
365 │ W │ 2m │ 11 │ 2 │ B │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
366 │ W │ 6d │ 8 │ 1+ │ B │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
367 │ W │ 22d │ 15 │ 8+ │ L │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
368 │ C │ 4d │ 15 │ 11+ │ L │ P │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
369 │ W │ 68d │ 7+ │ 4 │ B │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
370 │ W │ 17d │ 17 │ 14 │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
372 │ W │ 1m │ 17 │ 5 │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
373 │ W │ 4d │ 11 │ 1? │ B │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
374 │ C │ 4d │ 10 │ 5 │ L │ P │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
375 │ C │ 4d │ 12 │ 6 │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
376 │ W │ 1m │ 10 │ 7+ │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
377 │ W │ 1m │ 7 │ 4? │ B │ P │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
378 │ W │ 1m │ 28 │ 7 │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
379 │ W │ 11m │ 7 │ 1 │ B │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
380 │ W │ 3m │ 11 │ ? │ B │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
381 │ W │ 21d │ 13 │ 9? │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
382 │ W │ 1m │ 9 │ 6+ │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
383 │ W │ 2m │ 9 │ 2 │ L │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
384 │ W │ 1m │ 13 │ 5 │ L │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
385a │ W │ 3w │ 12 │ 6? │ B │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
385b │ W │ 2m │ 11 │ 4 │ L │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
385c │ W │ 24d │ 17 │ 10 │ B │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
386 │ W │ 1m │ ? │ 5 │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
387 │ W │ 3w │ 19 │ 9 │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
388 │ W │ 3m │ 11 │ 7 │ L │ P │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
389 │ W │ 1m │ 15 │ 15 │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
391 │ W │ 25d │ 13 │ 13 │ L │ P │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
392 │ W │ 1m │ 12 │ 8+ │ L │ P │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
393 │ W │ 1m │ 20 │ 4 │ L │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
394 │ W │ 21d │ ? │ ? │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
395a │ W │ 1m │ 19 │ 11? │ L │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
395b │ W │ 3m │ 12 │ 3? │ B │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
396 │ W │ 2m │ 7 │ 1+ │ B │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
397 │ W │ 21d │ 22 │ 14 │ B │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
398 │ W │ 1m │ 16 │ 6? │ B │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
399 │ W │ 1m │ 18 │ 4 │ L │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
400 │ W │ 1m │ 15 │ 11+ │ L │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
401 │ W │ 1m │ 13+ │ 9 │ B │ P │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
402 │ W │ 1m │ 14 │ 8 │ B │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
404 │ │ │ │ │ B │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
405 │ W │ 21d │ 13 │ 11+ │ B │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
406 │ C │ 2d │ 18 │ 15? │ L │ P │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
408 │ C │ 1m │ 13 │ ? │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
409 │ C │ 6d │ 12 │ 9+ │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
410 │ W │ 35d │ 13+ │ 13+ │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
411 │ W │ 3m │ 16 │ 2 │ B │ P │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
412 │ W │ 1m │ 15 │ 13? │ L │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
413 │ C │ 2m │ 13 │ 8+ │ L │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
414 │ C │ 7d │ 18 │ 4 │ L │ P │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
415 │ C │ 16d │ 8 │ 6+ │ L │ P │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
416 │ C │ 7d │ 14 │ 6? │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
418 │ W │ 2m │ 19 │ 4 │ B │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
419 │ W │ 4m │ 20 │ ? │ L │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
420 │ W │ 1m │ 11 │ 3 │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
421 │ W │ 21d │ 19 │ 15? │ B │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
422 │ W │ 3m │ 11+ │ 11+ │ B │ P │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
423 │ W │ 1m │ 16 │ 12? │ B │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
424 │ W │ 5y │ 14 │ 6 │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
425 │ W │ 1m │ 29 │ 14 │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
426 │ W │ 4m │ 20 │ 13 │ ? │ │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
427 │ W │ 1m │ 16 │ ? │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
428 │ W │ 3w │ 25 │ 21 │ L │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
429 │ C │ 2m │ 7+ │ 5 │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
430 │ W │ 2m │ 16+ │ 7 │ L │ P │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
431 │ W │ 21d │ 23 │ 18 │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
432 │ W │ 42d │ 19 │ 12+? │ L │ P │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
433 │ W │ 1m │ 19 │ 17 │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
434 │ W │ 4m │ 14+ │ 10 │ L │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
435 │ W │ 1m │ 16+ │ 2? │ B │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
436 │ C │ 11m │ 5 │ 3+? │ B │ │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
437 │ C │ 5m │ 11 │ 7? │ L │ P │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
440 │ W │ 1m │ 19 │ 12? │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
445 │ W │ 1m │ 27 │ 16? │ │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
446 │ W │ 8d │ 13 │ ? │ │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
447 │ W │ 8d │ 10 │ 2 │ B │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
448 │ W │ 70d │ 17 │ 14+ │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
449 │ W │ 2m │ 27 │ 13+ │ B │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
452 │ W │ 4m │ 14 │ 9 │ B │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
451 │ C │ 2m │ 7 │ 3+ │ B │ │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
455 │ C │ │ 26 │ 22+ │ B │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
456 │ W │ 1m │ 23+ │ 20+ │ L │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
457 │ W │ 17m │ 17+ │ 17+ │ B │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
458 │ W │ 11m │ 10 │ 8+? │ L │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
459 │ C │ 10d │ 6 │ 3 │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
460 │ W │ 1m │ 17 │ 17 │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
461 │ C │ 5d │ 14 │ 8+ │ L │ P │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
462 │ C │ 5d │ 15+ │ 12 │ B │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
463 │ W │ 3m │ 20 │ 12 │ B │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
464 │ C │ 21d │ 24 │ 17? │ L │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
465 │ W │ 1m │ 24+ │ 11 │ LB │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
466 │ W │ 2d │ 13 │ 3 │ B │ │ +
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
467 │ W │ 3m │ 30 │ 25? │ B │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
468 │ W │ 1m │ 22+ │ 6 │ L │ P │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
469 │ W │ 1m │ 25 │ 12 │ B │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
471 │ C │ │ 6+? │ 4 │ L │ P │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
472 │ W │ 1m │ 37 │ 21 │ B │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
473 │ W │ 2w │ 28+ │ 24 │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
474 │ W │ 1m │ 36 │ 31+ │ L │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
476 │ W │ 7d │ 6 │ 2 │ B │ P │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
477 │ W │ 5d │ 9 │ 5 │ B │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
478 │ W │ 2m │ 9 │ 3 │ L │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
479 │ C │ 8d │ 29 │ 15 │ L │ P │ +
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
480 │ W │ 4m │ 31+ │ 29 │ B │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
482 │ W │ 2m │ 11 │ 5+ │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
485 │ W │ 3d │ 9+ │ 3+ │ B │ P │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
487 │ W │ 21d │ 55 │ 40 │ B │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
488 │ W │ 4d │ 16 │ 8 │ L │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
489 │ C │ 8d │ 11 │ 4 │ B │ P │ +
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
494 │ W │ 2m │ 11 │ 3 │ L │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
498 │ W │ 1y │ 6 │ 1? │ L │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
499 │ W │ 5m │ 36 │ 5 │ B │ P │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
504 │ W │ 3m │ 6 │ 3 │ L │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┼────┼────────┼────────┼─────────┼─────────┼──────────┼─────────
506 │ W │ 8m │ 7+ │ 2? │ B │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
│ │ │ │ │ │ │
───────┴────┴────────┴────────┴─────────┴─────────┴──────────┴─────────

═══════╤═══════════════╤═══════════════╤═════════════╤═════════════
NO. OF │PERIBRONCHIOLAR│ HEMORRHAGIC │ LOBULAR │PERIBRONCHIAL
AUTOPSY│ CONSOLIDATION │PERIBRONCHIOLAR│CONSOLIDATION│CONSOLIDATION
│ │ CONSOLIDATION │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
229 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
231 │ │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
232 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
233 │ │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
236 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
237 │ │ + │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
238 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
239 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
240 │ M │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
241 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
242 │ │ + │ + │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
243 │ M │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
244 │ M │ + │ + │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
246 │ M │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
247 │ M │ + │ + │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
248 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
249 │ M │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
250 │ M │ │ + │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
251 │ │ + │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
252 │ M │ │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
253 │ M │ │ + │ +
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
254 │ M │ │ + │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
255 │ M │ + │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
256 │ M │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
257 │ │ │ + │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
258 │ M │ │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
259 │ │ │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
260 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
261 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
262 │ │ │ + │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
263 │ │ │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
264 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
265 │ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
266 │ │ + │ + │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
267 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
268 │ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
269 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
270 │ │ │ + │ h
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
271 │ │ │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
272 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
273 │ + │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
274 │ │ │ + │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
275 │ M │ + │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
276 │ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
277 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
278 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
279 │ │ + │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
280 │ │ + │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
281 │ │ + │ + │ h
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
282 │ │ │ + │
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
283 │ + │ + │ + │ M
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
284 │ │ + │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
285 │ M │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
286 │ M │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
287 │ + │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
288 │ M │ │ + │ h
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
289 │ M │ │ + │ M
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
290 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
291 │ + │ │ + │ M
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
292 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
293 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
295 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
296 │ + │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
297 │ │ │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
298 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
299 │ │ │ │
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
300 │ M │ │ │ h
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
301 │ │ │ │
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
302 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
303 │ │ │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
304 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
305 │ │ │ │
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
306 │ │ │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
308 │ │ │ + │
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
309 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
310 │ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
312 │ M │ │ + │ h
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
313 │ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
314 │ │ │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
315 │ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
316 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
317 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
318 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
319 │ │ │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
320 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
321 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
322 │ │ │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
323 │ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
324 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
325 │ M │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
326 │ │ │ + │ h
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
327 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
328 │ │ │ │
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
330 │ M │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
331 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
332 │ M │ │ │ h
───────┼───────────────┼───────────────┼─────────────┼─────────────
333 │ M │ │ + │
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
334 │ M │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
335 │ │ │ + │
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
336 │ M │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
337 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
338 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
339 │ │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
340 │ │ + │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
341 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
342 │ │ + │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
343 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
344 │ │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
345 │ + │ + │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
346 │ M │ + │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
347 │ │ │ + │ h
───────┼───────────────┼───────────────┼─────────────┼─────────────
348 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
349 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
350 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
351 │ │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
352 │ │ + │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
353 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
354 │ M │ │ │ h
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
355 │ │ + │ │
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
356 │ │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
357 │ │ + │ + │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
358 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
359 │ M │ │ │ h
───────┼───────────────┼───────────────┼─────────────┼─────────────
360 │ + │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
361 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
362 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
363 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
364 │ │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
365 │ │ + │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
366 │ M │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
367 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
368 │ M │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
369 │ │ + │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
370 │ + │ │ + │
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
372 │ │ + │ + │ Mh
───────┼───────────────┼───────────────┼─────────────┼─────────────
373 │ │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
374 │ │ │ │ +
───────┼───────────────┼───────────────┼─────────────┼─────────────
375 │ + │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
376 │ │ + │ + │ M
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
377 │ │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
378 │ + │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
379 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
380 │ + │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
381 │ │ │ + │
│ │ │ │
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
382 │ + │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
383 │ │ │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
384 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
385a │ │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
385b │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
385c │ M │ + │ + │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
386 │ │ + │ + │
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
387 │ │ + │ + │ +
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
388 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
389 │ │ + │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
391 │ + │ │ + │ h
───────┼───────────────┼───────────────┼─────────────┼─────────────
392 │ M │ │ │ +
───────┼───────────────┼───────────────┼─────────────┼─────────────
393 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
394 │ │ + │ + │ h
───────┼───────────────┼───────────────┼─────────────┼─────────────
395a │ M │ │ + │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
395b │ │ │ + │ h
───────┼───────────────┼───────────────┼─────────────┼─────────────
396 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
397 │ M │ │ + │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
398 │ + │ │ │ M
───────┼───────────────┼───────────────┼─────────────┼─────────────
399 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
400 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
401 │ M │ │ │ h
───────┼───────────────┼───────────────┼─────────────┼─────────────
402 │ M │ │ + │ +
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
404 │ + │ + │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
405 │ M │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
406 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
408 │ │ + │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
409 │ │ + │ + │ M
───────┼───────────────┼───────────────┼─────────────┼─────────────
410 │ + │ │ + │ M
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
411 │ │ + │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
412 │ │ │ │ M
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
413 │ │ + │ + │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
414 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
415 │ │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
416 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
418 │ │ │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
419 │ + │ │ + │ M
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
420 │ │ + │ │ M
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
421 │ │ │ + │ M
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
422 │ │ + │ │ M
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
423 │ + │ │ │ M
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
424 │ │ │ + │ +
───────┼───────────────┼───────────────┼─────────────┼─────────────
425 │ + │ │ + │ M
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
426 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
427 │ │ + │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
428 │ M │ │ + │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
429 │ + │ │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
430 │ │ + │ │
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
431 │ + │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
432 │ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
433 │ M │ + │ │ M
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
434 │ │ │ + │
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
435 │ │ + │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
436 │ │ │ │
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
437 │ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
440 │ + │ + │ + │ M
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
445 │ M │ │ │ h
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
446 │ │ + │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
447 │ │ │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
448 │ + │ │ + │ Mh
───────┼───────────────┼───────────────┼─────────────┼─────────────
449 │ + │ + │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
452 │ M │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
451 │ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
455 │ │ + │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
456 │ │ + │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
457 │ + │ + │ + │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
458 │ │ + │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
459 │ │ + │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
460 │ + │ │ + │ M
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
461 │ M │ + │ │
│ │ │ │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
462 │ │ │ + │
───────┼───────────────┼───────────────┼─────────────┼─────────────
463 │ + │ │ + │ Mh
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
464 │ │ │ + │
│ │ │ │
│ │ │ │
───────┼───────────────┼───────────────┼─────────────┼─────────────
465 │ M │ │ │
│ │ │ │
│ │ │ │
│ │ │ │
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466 │ │ │ + │
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467 │ │ + │ + │
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468 │ │ │ + │
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469 │ + │ │ + │
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471 │ │ │ │
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472 │ + │ + │ + │
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473 │ + │ │ + │
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474 │ │ │ │
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476 │ M │ │ + │
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477 │ │ + │ + │
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478 │ │ │ + │
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479 │ M │ │ │
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480 │ │ │ + │
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482 │ + │ + │ + │ M
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485 │ M │ │ │
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487 │ + │ │ │
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488 │ M │ │ │
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489 │ │ + │ │ M
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494 │ │ │ + │ h
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498 │ │ │ + │
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499 │ M │ │ │
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504 │ M │ │ │
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506 │ │ │ + │
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───────┴───────────────┴───────────────┴─────────────┴─────────────

═══════╤═══════╤════════════╤═════════╤═══════╤══════════════
NO. OF │ABSCESS│INTERSTITIAL│MULTIPLE │EMPYEMA│BRONCHIECTASIS
AUTOPSY│ │SUPPURATIVE │ABSCESSES│ │
│ │ PNEUMONIA │ IN │ │
│ │ │CLUSTERS │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
229 │ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
231 │ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
232 │ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
233 │ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
236 │ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
237 │ N │ │ │ E │
───────┼───────┼────────────┼─────────┼───────┼──────────────
238 │ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
239 │ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
240 │ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
241 │ │ │ │ │
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───────┼───────┼────────────┼─────────┼───────┼──────────────
242 │ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
243 │ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
244 │ │ │ │ │ +
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
246 │ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
247 │ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
248 │ + │ │ │ E │
───────┼───────┼────────────┼─────────┼───────┼──────────────
249 │ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
250 │ │ │ │ E │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
251 │ + │ + │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
252 │ │ │ │ │
│ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
253 │ │ │ │ E │
│ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
254 │ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
255 │ + │ │ │ E │
│ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
256 │ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
257 │ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
258 │ + │ │ │ E │
│ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
259 │ + │ + │ │ │
│ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
260 │ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
261 │ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
262 │ + │ │ │ E │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
263 │ + │ │ │ E │
│ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
264 │ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
265 │ │ │ │ │
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│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
266 │ │ │ │ │
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───────┼───────┼────────────┼─────────┼───────┼──────────────
267 │ │ │ │ │
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───────┼───────┼────────────┼─────────┼───────┼──────────────
268 │ │ │ │ │
│ │ │ │ │
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───────┼───────┼────────────┼─────────┼───────┼──────────────
269 │ │ │ │ │
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───────┼───────┼────────────┼─────────┼───────┼──────────────
270 │ │ │ │ │
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│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
271 │ │ │ │ │
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───────┼───────┼────────────┼─────────┼───────┼──────────────
272 │ │ │ │ │
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273 │ N │ │ │ E │
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───────┼───────┼────────────┼─────────┼───────┼──────────────
274 │ N │ │ │ │
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275 │ N │ │ │ │
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276 │ │ │ │ │
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───────┼───────┼────────────┼─────────┼───────┼──────────────
277 │ + │ │ │ │
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───────┼───────┼────────────┼─────────┼───────┼──────────────
278 │ + │ │ │ E │
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───────┼───────┼────────────┼─────────┼───────┼──────────────
279 │ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
280 │ │ │ + │ │
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───────┼───────┼────────────┼─────────┼───────┼──────────────
281 │ │ │ │ │
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282 │ + │ │ │ E │
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283 │ │ │ │ │ +
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───────┼───────┼────────────┼─────────┼───────┼──────────────
284 │ + │ │ │ E │
│ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
285 │ │ + │ │ E │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
286 │ │ │ + │ │
│ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
287 │ │ │ │ │ +
│ │ │ │ │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
288 │ + │ │ │ E │ +
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
289 │ │ │ │ │ +
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│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
290 │ + │ │ │ │
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───────┼───────┼────────────┼─────────┼───────┼──────────────
291 │ │ │ │ │ +
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292 │ + │ │ │ E │
│ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
293 │ │ │ │ │
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295 │ + │ + │ │ E │ +
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───────┼───────┼────────────┼─────────┼───────┼──────────────
296 │ + │ │ │ E │ +
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───────┼───────┼────────────┼─────────┼───────┼──────────────
297 │ │ │ │ │
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───────┼───────┼────────────┼─────────┼───────┼──────────────
298 │ │ │ │ │
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───────┼───────┼────────────┼─────────┼───────┼──────────────
299 │ │ │ │ │
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───────┼───────┼────────────┼─────────┼───────┼──────────────
300 │ │ │ │ │
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301 │ │ │ │ │
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302 │ │ │ │ │
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303 │ │ │ │ │
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304 │ │ │ │ │
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305 │ │ │ │ │
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306 │ │ │ │ │
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308 │ │ │ │ │
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309 │ + │ │ │ E │
───────┼───────┼────────────┼─────────┼───────┼──────────────
310 │ │ │ │ │
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───────┼───────┼────────────┼─────────┼───────┼──────────────
312 │ N │ │ │ │ +
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313 │ │ │ │ │
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314 │ │ │ │ │ +
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315 │ │ │ │ │
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316 │ │ │ │ │
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317 │ │ │ │ │
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318 │ │ │ │ │
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319 │ │ │ │ │
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320 │ │ │ │ │
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321 │ │ │ │ E │
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322 │ │ │ + │ │ +
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323 │ │ │ │ │
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324 │ │ │ │ │
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325 │ N │ + │ │ │ +
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326 │ │ │ │ │
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327 │ │ │ │ │
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328 │ │ │ │ │
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330 │ N │ + │ │ E │
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331 │ │ │ │ │
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332 │ │ │ │ │
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333 │ │ │ + │ │ +
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334 │ N │ + │ │ E │
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335 │ │ │ │ │
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336 │ │ │ │ │ +
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337 │ │ │ │ │
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338 │ │ │ │ │
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339 │ │ │ │ │
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340 │ │ │ │ │
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341 │ │ │ │ │
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342 │ │ │ │ │
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343 │ │ │ │ E │
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344 │ + │ │ │ E │
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345 │ + │ │ │ E │
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346 │ N │ │ │ │
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347 │ │ │ │ │
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348 │ │ │ │ │
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349 │ │ │ │ │
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350 │ │ │ │ │
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351 │ │ │ │ │
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352 │ │ │ │ │ +
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353 │ │ │ │ E │
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354 │ + │ │ │ E │
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355 │ + │ │ │ E │
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356 │ │ │ │ │
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357 │ │ │ │ │
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358 │ │ │ │ E │
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359 │ │ │ │ │ +
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360 │ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
361 │ │ │ │ │
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362 │ │ │ │ │
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363 │ │ │ │ │
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364 │ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
365 │ │ │ │ │
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366 │ │ │ │ │
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367 │ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
368 │ │ │ │ │
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369 │ N │ + │ │ E │
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370 │ │ │ + │ │
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372 │ │ │ │ │ +
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373 │ │ │ │ │
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374 │ │ │ │ │ +
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375 │ │ │ │ │ +
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376 │ + │ │ │ E │ +
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377 │ │ │ │ │
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378 │ + │ │ │ E │ +
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379 │ │ + │ │ E │
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380 │ + │ │ │ │
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381 │ + │ │ │ E │ +
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382 │ │ │ │ │
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383 │ + │ │ │ │
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384 │ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
385a │ + │ │ │ E │
───────┼───────┼────────────┼─────────┼───────┼──────────────
385b │ │ │ │ │
───────┼───────┼────────────┼─────────┼───────┼──────────────
385c │ │ + │ │ │ +
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───────┼───────┼────────────┼─────────┼───────┼──────────────
386 │ │ │ │ │
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387 │ + │ │ │ E │ +
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388 │ │ │ │ │
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389 │ │ + │ │ E │ +
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392 │ │ │ │ │
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393 │ │ │ │ │
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488 │ + │ │ │ E │ +
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───────┴───────┴────────────┴─────────┴───────┴──────────────

═══════╤════════════════╤══════════╤════════╤════════╤════════╤════════
NO. OF │ UNRESOLVED │ORGANIZING│BACTERIA│BACTERIA│BACTERIA│BACTERIA
AUTOPSY│BRONCHOPNEUMONIA│BRONCHITIS│ IN │ IN │IN LUNG │IN BLOOD
│ │ │ SPUTUM │BRONCHUS│ │OF HEART
│ │ │ │ │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
229 │ │ │ Pn. I. │ │ │ 0
│ │ │B. inf. │ │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
231 │ │ │ │ │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
232 │ │ │Pn. IIa.│ │Pn. IIa.│Pn. IIa.
│ │ │B. inf. │ │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
233 │ │ │Pn. IIa.│ │ │ Pn.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
236 │ │ │Pn. IV. │ │B. inf. │ 0
│ │ │B. inf. │ │ Staph. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
237 │ │ │ St. h. │ │ │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
238 │ │ │Pn. IV. │ │ │ Pn. IV
│ │ │B. inf. │ │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
239 │ │ │Pn. II. │ │Pn. II. │Pn. II.
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
240 │ │ │Pn. IV. │B. inf. │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
241 │ │ │Pn. IV. │ │ │Pn. IV.
│ │ │B. inf. │ │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
242 │ │ │Pn. IIa.│ │ │Pn. IIa.
│ │ │B. inf. │ │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
243 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
244 │ │ │ │Pn. IV. │Pn. IV. │ 0
│ │ │ │B. inf. │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
246 │ │ │Pn. IIa.│ │ │ 0
│ │ │B. inf. │ │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
247 │ │ │Pn. IV. │ │ │Pn. IV.
│ │ │B. inf. │ │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
248 │ │ │ │ St. h. │ St. h. │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
249 │ │ │ │ │ │Pn. III.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
250 │ │ │Pn. IIa.│ │ │Pn. IIa.
│ │ │B. inf. │ │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
251 │ │ │ │ │ St. h. │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
252 │ │ │ │Pn. II. │Pn. II. │ 0
│ │ │ │B. inf. │B. inf. │
│ │ │ │ St. v. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
253 │ │ │Pn. Ia. │Pn. II. │Pn. II. │Pn. II.
│ │ │ │B. inf. │B. inf. │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
254 │ │ │ │ Pn. I. │ Pn. I. │ 0
│ │ │ │B. inf. │ Staph │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
255 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │Pn. IIa.│ │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
256 │ │ │ │ Pn. │Pn. IIa.│Pn. IIa.
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
257 │ │ │ │B. inf. │ │ Pn. I.
│ │ │ │ Staph │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
258 │ │ │ │ │ St. h. │ St. h.
│ │ │ │ │Pn. IV. │
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
259 │ │ │ │ │ St. h. │ St. h.
│ │ │ │ │Pn. III.│
│ │ │ │ │ Staph. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
260 │ │ │ │ │ │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
261 │ │ │ │B. inf. │ │ 0
│ │ │ │Pn. IV. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
262 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
263 │ │ │ │ │ St. h. │ St. h.
│ │ │ │ │B. inf. │ Staph.
│ │ │ │ │ Staph. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
264 │ │ │Pn. IV. │ St. h. │ St. h. │ St. h.
│ │ │ Staph. │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
265 │ │ │ │ St. h. │Pn. IV. │ St. h.
│ │ │ │ Staph. │B. inf. │
│ │ │ │ inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
266 │ │ │ St. h. │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
267 │ │ │Pn. IV. │Pn. II. │Pn. II. │Pn. II.
│ │ │ │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
268 │ │ │Pn. III.│Pn. III.│Pn. III.│ 0
│ │ │ B. │B. inf. │B. inf. │
│ │ │ │ St. h. │ St. h. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
269 │ │ │Pn. IV. │Pn. IV. │Pn. IV. │ 0
│ │ │ B. │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
270 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │ Staph. │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
271 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │Pn. IV. │ │
│ │ │ │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
272 │ │ │ │ │ │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
273 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │Pn. IV. │
│ │ │ │ Staph. │ Staph. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
274 │ │ │Pn. IV. │ St. h. │ St. h. │ St. h.
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
275 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │B. inf. │Pn. IV.
│ │ │ │ Staph. │ Staph. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
276 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │Staph B.│Pn. IV. │
│ │ │ │ inf. │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
277 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │ Staph │ Staph │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
278 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
279 │ │ │ │ │ Pn. IV │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
280 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │ │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
281 │ │ │ │ │ St. h. │ St. h.
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
282 │ │ │Pn. IV. │ St. h. │ St. h. │ St. h.
│ │ │B. inf. │B. inf. │Pn. II. │Pn. II.
│ │ │ │ Pn. II │ │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
283 │ │ │ │B. inf. │ Staph. │Pn. IV.
│ │ │ │Pn. IV. │B. inf. │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
284 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │ │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
285 │ │ │Pn. IIa.│ St. h. │ St. h. │ St. h.
│ │ │B. inf. │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
286 │ │ │ │Pn. IV. │ 0 │Pn. IV.
│ │ │ │B. inf. │ │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
287 │ │ │ │Pn. IV. │Pn. IV. │Pn. IV.
│ │ │ │B. inf. │ B inf. │
│ │ │ │ Staph. │ Staph. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
288 │ │ │ St. h. │ St. h. │ St. h. │ St. h.
│ │ │B. inf. │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
289 │ │ │ │Pn. IV. │Pn. IV. │Pn. IV.
│ │ │ │B. inf. │ │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
290 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
291 │ │ │Pn. IV. │B. inf. │ 0 │ 0
│ │ │B. inf. │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
292 │ │ │ │ │ St. h. │ St. h.
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
293 │ │ │ │Pn. III.│Pn. III.│Pn. III.
│ │ │ │B. inf. │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
295 │ │ │Pn. IV. │ St. h. │ │ St. h.
│ │ │ St. h. │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
296 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
297 │ │ │ │B. inf. │Pn. IV. │ 0
│ │ │ │Pn. IV. │B. inf. │
│ │ │ │ St. h. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
298 │ │ │ │Pn. IIa.│Pn. IIa.│
│ │ │ │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
299 │ │ │ │B. inf. │ │
│ │ │ │Pn. IV. │ │
│ │ │ │ Staph. │ │
│ │ │ │ St. h. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
300 │ │ │Pn. IIa.│Pn. IIa.│Pn. IIa.│
│ │ │B. inf. │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
301 │ │ │ │Pn. IV. │Pn. IV. │
│ │ │ │B. inf. │ │
│ │ │ │ Staph. │ │
│ │ │ │ St. h. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
302 │ │ │ │Pn. IV. │Pn. IV. │
│ │ │ │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
303 │ │ │ │ Staph. │Pn. IV. │
│ │ │ │Pn. IV. │B. inf. │
│ │ │ │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
304 │ │ │ │ St. h. │ St. h. │
│ │ │ │B. inf. │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
305 │ │ │ │B. inf. │B. inf. │
│ │ │ │ St. h. │ St. h │
│ │ │ │Pn. IV. │Pn. IV. │
│ │ │ │ Staph. │ Staph. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
306 │ │ │ │B. inf. │ 0 │ 0
│ │ │ │Pn. IV. │ │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
308 │ │ │ │Pn. IV. │ St. h. │Pn. IV.
│ │ │ │B. inf. │ │
│ │ │ │ St. h. │ │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
309 │ │ │ │ │ St. h. │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
310 │ │ │ │Pn. III.│Pn. III.│
│ │ │ │B. inf. │Pn. IV. │
│ │ │ │ Staph. │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
312 │ │ │Pn. IV. │ St. h. │ St. h. │ St.
│ │ │B. inf. │B. inf. │B. inf. │
│ │ │ St. h. │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
313 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │ │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
314 │ │ │ │Pn. IV. │Pn. IV. │Pn. IV.
│ │ │ │B. inf. │ │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
315 │ │ │ │ │Pn. IV. │Pn. IV.
│ │ │ │ │B. inf. │
│ │ │ │ │ Staph. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
316 │ │ │ │B. inf. │Pn. III.│Pn. III.
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
317 │ │ │ │Pn. IV. │Pn. IV. │
│ │ │ │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
318 │ │ │ │Pn. IV. │Pn. IV. │
│ │ │ │B. inf. │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
319 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │ Staph. │B. inf. │
│ │ │ │ │ Staph. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
320 │ │ │ │Pn. IIa.│Pn. IIa.│Pn. IIa.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
321 │ │ │ │B. inf. │Pn. IV. │Pn. IV.
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
322 │ │ │Pn. IV. │ │Pn. III.│ 0
│ │ │ │ │ Staph. │
│ │ │ │ │ aur. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
323 │ │ │ │Pn. IV. │ │ 0
│ │ │ │B. inf. │ │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
324 │ │ │ │ Pn. I. │ 0 │ Pn. I.
│ │ │ │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
325 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │ │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
326 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │B. inf. │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
327 │ │ │ │ │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
328 │ │ │ │Pn. III.│Pn. III.│ Pn.
│ │ │ │Pn. IV. │Pn. IV. │ III.
│ │ │ │B. inf. │B. inf. │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
330 │ │ │ │ │Pn. IV. │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
331 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
332 │ │ │ │ │ │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
333 │ │ │ │ Staph. │ Staph. │Pn. IIa.
│ │ │ │aur. B. │aur. Pn.│
│ │ │ │inf. St.│IIa. St.│
│ │ │ │ h. │ h. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
334 │ │ │ │ │ St. h. │ St. h.
│ │ │ │ │ Staph │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
335 │ │ │ │ │ St. v. │Pn. IV.
│ │ │ │ │B. inf. │
│ │ │ │ │ Staph. │
│ │ │ │ │Pn. IV. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
336 │ │ │ │ │ │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
337 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
338 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
339 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
340 │ │ │ │ │ │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
341 │ │ │ │ │ │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
342 │ │ │ │ │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
343 │ │ │ │ │Pn. IV. │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
344 │ │ │ │ │ │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
345 │ │ │ │ │Pn. III.│
│ │ │ │ │ St. h │
│ │ │ │ │ Staph. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
346 │ │ │B. inf. │ St. h. │ St. h. │ St. h.
│ │ │Pn. IV. │B. inf. │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
347 │ │ │ │ │ │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
348 │ │ │ │ │ │Pn. IIa.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
349 │ │ │ │ │Pn. III │ Pn. I.
│ │ │ │ │ St. h │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
350 │ │ │ │ │ │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
351 │ │ │ │ │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
352 │ │ │ │ │ │Pn. IIa.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
353 │ │ │ Pn. I. │B. inf. │Pn. IIa.│Pn. IIa.
│ │ │B. inf. │ Pn. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
354 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │ │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
355 │ │ │ │ St. h. │ St. h. │ 0
│ │ │ │B. inf. │B. inf. │
│ │ │ │Pn. IV. │ Staph. │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
356 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
357 │ │ │ │ │Pn. IV. │Pn. IV.
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
358 │ │ │ │ │ │Pn. IIa.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
359 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
360 │ │ │ │ │ │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
361 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
362 │ │ │ │ │ │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
363 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
364 │ │ │ │ │ │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
365 │ │ │ │ │Pn. IV. │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
366 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
367 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
368 │ │ │ │ │ │ Pn. I.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
369 │ │ │ St. h. │ │ St. h. │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
370 │ + │ + │[No. St.│ Staph. │ Staph. │ 0
│ │ │ h.] │aur. Pn.│ aur │
│ │ │ │ IV. B. │ │
│ │ │ │ inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
372 │ │ │ │ │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
373 │ │ │ │ │ │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
374 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
375 │ │ │ │ │ │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
376 │ │ │[No. St │ St. h. │ St. h. │ St. h.
│ │ │ h.] │B. inf. │ │
│ │ │ │ Staph. │ │
│ │ │ │ aur. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
377 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
378 │ │ │ │ St. h. │ St. h. │Pn. IIa.
│ │ │ │B. inf. │B. inf. │
│ │ │ │Pn. IIa.│Pn. IIa.│
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
379 │ │ │ │B. inf. │ ? │Pn. IIa.
│ │ │ │ + │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
380 │ │ │ │ │Pn. III.│Pn. III.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
381 │ │ │ │ │ St. h. │ St. h.
│ │ │ │ │Pn. II. │
│ │ │ │ │Pn. IV. │
│ │ │ │ │ Staph. │
│ │ │ │ │ aur. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
382 │ │ │ │ │ │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
383 │ │ │ │ │B. inf. │Pn. III.
│ │ │ │ │Pn. III.│
│ │ │ │ │ St. h. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
384 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
385a │ │ │ │ │ St. h. │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
385b │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
385c │ │ │ │ │ St. h. │ St. h.
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
386 │ │ │ │ │Pn. III.│Pn. III.
│ │ │ │ │B. inf. │
│ │ │ │ │ Staph. │
│ │ │ │ │ aur. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
387 │ │ │ │ St. h. │ Staph. │ St. h.
│ │ │ │B. inf. │alb Pn. │
│ │ │ │ Staph. │ II. B. │
│ │ │ │aur. Pn.│ inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
388 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
389 │ │ │ │ │ St. h. │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
391 │ │ │ │ │Pn. IV. │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
392 │ │ │ │ │ │Pn. II.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
393 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
394 │ │ │ │ │ │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
395a │ + │ │ │ │ St. h. │ St. h.
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
395b │ │ │ │ │Pn. IIa.│Pn. IIa.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
396 │ │ │ │ │ │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
397 │ │ │ │ │ St. h. │ St. h.
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
398 │ + │ │ │ │ │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
399 │ │ │ │ │ │Pn. IIa.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
400 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
401 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
402 │ + │ + │ │ │ │Pn. IV.
│ │ │ │ │ │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
404 │ │ │ │ │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
405 │ │ │ │ │ │ Pn.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
406 │ │ │ │ │ │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
408 │ │ │ │ │ │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
409 │ │ │ │ │ │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
410 │ │ │ │ │ St. h. │
│ │ │ │ │B. inf. │
│ │ │ │ │ Staph. │
│ │ │ │ │ aur. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
411 │ │ │ │ │Pn. IIa.│Pn. IIa.
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
412 │ │ │ │Pn. II. │ │Pn. II.
│ │ │ │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
413 │ │ │ │ │Pn. III.│Pn. III.
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
414 │ │ │ │ │Pn. IIa.│Pn. IIa.
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
415 │ │ │ │ │ St. h. │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
416 │ │ │ │Pn. IV. │Pn. IV. │Pn. IV.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
418 │ │ │ │ │Pn. IIa.│Pn. IIa.
│ │ │ │ │ St. v. │
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
419 │ │ │ │Pn. II. │Pn. II. │ 0
│ │ │ │B. inf. │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
420 │ + │ + │ │ │ St. h. │ St. h.
│ │ │ │ │B. inf. │
│ │ │ │ │ Staph. │
│ │ │ │ │ aur. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
421 │ + │ + │ │ │Pn. IV. │ St. h.
│ │ │ │ │ St. h. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
422 │ + │ │ │ │Pn. IIa.│ 0
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
423 │ + │ │ │ │ St. h. │ St. h.
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
424 │ │ │ │ │Pn. IV. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
425 │ + │ │ │ │ St. h. │ St. h.
│ │ │ │ │B. inf. │
│ │ │ │ │ Staph. │
│ │ │ │ │ alb. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
426 │ │ │ │ │Pn. IIa.│Pn. IIa.
│ │ │ │ │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
427 │ │ │ │ │ St. h. │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
428 │ + │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
429 │ │ │ │ │B. inf. │ 0
│ │ │ │ │ Staph. │
│ │ │ │ │ alb │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
430 │ │ │ │ │ St. h. │ St. h.
│ │ │ │ │B. inf. │
│ │ │ │ │ Staph. │
│ │ │ │ │ aur. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
431 │ + │ │ │ │ 0 │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
432 │ │ │ │ │B. inf. │Pn. IIa.
│ │ │ │ │Pn. IIa.│
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
433 │ + │ │ │ │ St. h. │ 0
│ │ │ │ │B. inf. │
│ │ │ │ │ Staph. │
│ │ │ │ │ aur. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
434 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │ Staph. │
│ │ │ │ Staph. │ aur. │
│ │ │ │ aur. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
435 │ │ │ │ St. h. │B. inf. │ St. h.
│ │ │ │B. inf. │ + │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
436 │ │ │ │Pn. IIa.│Pn. IIa.│Pn. IIa.
│ │ │ │B. inf. │ │
│ │ │ │ Staph. │ │
│ │ │ │ aur. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
437 │ │ │ │ │ │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
440 │ + │ │ │B. inf. │B. inf. │ 0
│ │ │ │ Staph. │ Staph. │
│ │ │ │ aur. │ aur. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
445 │ │ + │ │ Staph. │ Staph. │ St. h.
│ │ │ │ aur. │aur. Pn.│
│ │ │ │ │ IV. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
446 │ │ │ │ │ 0 │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
447 │ │ │ │ Staph. │B. coli.│ 0
│ │ │ │ aur. │ Staph. │
│ │ │ │ │ aur. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
448 │ │ │ │ 0 │ 0 │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
449 │ + │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. coli.│B. coli.│
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
452 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
451 │ │ │ │B. coli.│Pn. IIa.│Pn. IIa.
│ │ │ │ Staph. │B. inf. │
│ │ │ │ St. v. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
455 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
456 │ │ │ │B. coli.│ │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
457 │ + │ + │ │Pn. IV. │ │
│ │ │ │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
458 │ │ │ │Pn. IV. │ │ 0
│ │ │ │B. inf. │ │
│ │ │ │ St. v. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
459 │ │ │ │ Staph. │ │ 0
│ │ │ │aur. Pn.│ │
│ │ │ │ IV. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
460 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │B. inf. │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
461 │ │ │ │ Staph. │ │ Pn. I.
│ │ │ │aur. Pn.│ │
│ │ │ │ I. St. │ │
│ │ │ │ h. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
462 │ │ │ │ │ │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
463 │ + │ │ │B. inf. │B. inf. │ 0
│ │ │ │ Staph. │ Staph. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
464 │ │ │ │B. inf. │B. inf. │ 0
│ │ │ │ Pn. I. │ Pn. I. │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
465 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │ │
│ │ │ │ Staph. │ │
│ │ │ │ St. v. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
466 │ │ │ │Pn. IIa.│Pn. IIa.│Pn. IIa.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
467 │ │ │ │ St. h. │ 0 │ St. h.
│ │ │ │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
468 │ │ │ │ Staph. │B. inf. │ 0
│ │ │ │aur. B. │ St. v. │
│ │ │ │inf. St.│ │
│ │ │ │ v. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
469 │ + │ │ │ │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
471 │ │ │ │Pn. IV. │ Pn. I. │ 0
│ │ │ │B. inf. │Pn. IV. │
│ │ │ │ Staph. │B. inf. │
│ │ │ │ aur. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
472 │ + │ │ │B. coli.│ St. h. │ St. h.
│ │ │ │ │B. coli.│
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
473 │ + │ + │ │B. inf. │ St. v. │Pn. III.
│ │ │ │ St. v. │ │
│ │ │ │ Staph. │ │
│ │ │ │M. cat. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
474 │ │ │ │ St. v. │ St. h. │ St. h.
│ │ │ │B. inf. │ │B. inf.
│ │ │ │M. cat. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
476 │ │ │ │ │ │ 0
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
477 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. coli.│B. coli.│
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
478 │ │ │ │ │ St. h. │ St. h.
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
479 │ │ │ │B. inf. │ St. h. │ St. h.
│ │ │ │ St. h. │ Staph. │
│ │ │ │ Staph. │ aur. │
│ │ │ │M. cat. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
480 │ │ │ │ Staph. │ Staph. │B. coli.
│ │ │ │aur. St.│aur. B. │ St.
│ │ │ │ v. │inf. St.│
│ │ │ │ │ v. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
482 │ │ │ │B. inf. │B. inf. │ 0
│ │ │ │Pn. IV. │Pn. IV. │
│ │ │ │ St. h. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
485 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │ │
│ │ │ │ Staph. │ │
│ │ │ │aur. B. │ │
│ │ │ │ coli. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
487 │ + │ │ │B. inf. │B. inf. │ St. h.
│ │ │ │ St. h. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
488 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │Pn. IIa.│ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
489 │ │ │ │B. inf. │Pn. IV. │ 0
│ │ │ │Pn. IV. │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
494 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │B. inf. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
498 │ │ │ │ St. v. │ St. v. │ St. v.
│ │ │ │ │ Staph. │
│ │ │ │ │ aur. │
│ │ │ │ │ Staph. │
│ │ │ │ │ alb. │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
499 │ │ + │ │ St. h. │ 0 │ St. h.
│ │ │ │B. inf. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
504 │ │ │ │ St. h. │ St. h. │ St. h.
│ │ │ │B. inf. │ │
│ │ │ │ Staph. │ │
───────┼────────────────┼──────────┼────────┼────────┼────────┼────────
506 │ │ │ │Pn. IV. │Pn. IV. │Pn. IV.
│ │ │ │B. inf. │ Staph. │
│ │ │ │ Staph. │ aur. │
│ │ │ │aur. M. │ │
│ │ │ │ cat. │ │
───────┴────────────────┴──────────┴────────┴────────┴────────┴────────

In successive columns the table gives the autopsy number, race, and
length of military service. These factors have had an important
influence upon the incidence of influenza and pneumonia and have been
discussed in a preliminary report.[79] The duration of illness (4th
column of table), counted from the date of onset of symptoms of
influenza or in some instances, when the earliest symptoms were those of
pneumonia, from onset of pneumonia, can usually be determined
accurately. The duration of pneumonia (5th column of table) is much more
uncertain, because its determination dates from the first recognition of
the physical signs of pneumonia.

=Clinical Diagnosis.=—The clinical diagnosis recorded upon the clinical
history of the patient is given in column 6. Many clinicians have been
impressed with the difficulty of determining during life the type of
pneumonia associated with influenza. The occurrence of purulent
bronchitis, the frequent coexistence of lobar and bronchopneumonia and
an atypical onset often make the recognition of lobar pneumonia more
difficult than usual. The diffuse consolidation of confluent lobular
pneumonia increases the difficulty of recognizing bronchopneumonia. In
the table (column 6) lobar pneumonia is indicated by L.,
bronchopneumonia by B. Among 227 autopsies the clinical diagnosis agreed
with the condition found at autopsy in 109 instances (48 per cent); in
35 instances (15.4 per cent) both lobar and bronchopneumonia were found
at autopsy and a diagnosis of one or other was made during life. In 83
instances (36.6 per cent) the diagnosis made during life was incorrect.
Cases admitted to the base hospital at Camp Pike were as carefully
studied as the conditions in a base hospital during an epidemic
permitted and diagnosis of pneumonia was doubtless as accurate as in
other base hospitals. Statistics from military and other hospitals based
upon clinical diagnosis of the pneumonias of influenza are probably
subject to an error of at least 1 in 3 cases, and conclusions based upon
them are almost valueless.

The inaccuracy of clinical diagnosis of the pneumonia of influenza is
further illustrated by a consideration of lobar pneumonia. This
diagnosis on the one hand was made 136 times and was correct 67 times
and incorrect 69 times; on the other hand, lobar pneumonia was found at
autopsy 98 times and had been diagnosed in only 67 of these cases (68.4
per cent).

=Classification of the Pulmonary Lesions of Influenza.=— Influenzal
pneumonia exhibits the following noteworthy characters:

1. Acute bronchitis with injury or destruction of lining epithelium and
accumulation of inflammatory exudate within the lumen.

2. Hemorrhagic pneumonia with accumulation of blood within the alveoli
and within and about the bronchi.

3. Susceptibility of bronchi and pulmonary tissue to secondary pyogenic
infection with necrosis and suppuration.

4. Bronchiectasis.

5. Tendency to the occurrence of chronic pneumonia following failure of
pneumonia to undergo resolution.

All these changes are doubtless referable to the severity of the primary
injury to the lower air passages.

In the presence of destructive changes in the bronchi many bacterial
species, including B. influenzæ, pneumococci of various types,
streptococci (notably hemolytic streptococci) and staphylococci may
invade the lungs and produce acute inflammation. The anatomic characters
of the pneumonic lesions following influenza are equally varied.

In order to obtain insight into the pathogenesis of these lesions, it is
desirable to imitate the historical development of knowledge concerning
the characters and causes of disease, namely, first to define accurately
the lesions concerned and later to determine with what microorganisms
these lesions are associated. The difficulties of this undertaking are
increased by the multiplicity of the microorganisms concerned and by the
well-known truth that the same microorganism, _e. g._, the tubercle
bacillus, may produce widely different anatomic lesions.

In the table of autopsies the following lesions are listed:

=Column 7. Purulent bronchitis.=—“P” indicates that the small
bronchi contain mucopurulent fluid.

=Column 8. Lobar pneumonia.=—The occurrence of the lesion is
indicated by the plus sign (+).

=Column 9. Peribronchiolar consolidation.=—The presence of nodular
patches of consolidation about respiratory bronchioles is indicated
by the plus sign (+) when the lesion has been recognized at the time
of autopsy. When the lesion has been first recognized by microscopic
examination the letter “M” is used.

=Column 10. Hemorrhagic peribronchiolar consolidation.=—The
occurrence of this lesion which represents the preceding on a
background of hemorrhage is indicated by the plus sign (+).

=Column 11. Lobular consolidation.=—The presence of the lesion is
indicated by the plus sign (+).

=Column 12. Peribronchial consolidation.=—Peribronchial pneumonia
recognized at the time of autopsy is indicated by the plus sign (+).
Peribronchial pneumonia recognized microscopically is indicated by
“M.” The presence of peribronchial hemorrhage without consolidation
is indicated by “h.”

=Column 13. Abscess formation with pneumonia.=—Suppuration with
abscess formation almost invariably just below the pleura is
indicated by the plus sign (+). Necrosis of lung tissue recognized
microscopically and unaccompanied by suppuration is indicated by
“N.”

=Column 14. Suppurative interstitial pneumonia.=—This lesion
invariably associated with suppurative lymphangitis is indicated by
the plus sign (+).

=Column 15. Multiple abscess in clusters.=—Abscesses in clusters
about a bronchus of medium size are indicated by the plus sign (+).

=Column 16. Empyema.=—The presence of the lesion is indicated by
“E.”

=Column 17. Bronchiectasis.=—“B” indicates the lesion.

=Column 18. Unresolved bronchopneumonia.=—Presence of the lesion is
indicated by the plus sign (+).

=Column 19. Organizing bronchitis and bronchiolitis.=—“O” indicates
the lesion.

The lesions of columns 7 to 12 are acute inflammatory processes, columns
9 to 12 represent different types of bronchopneumonia. Columns 13 to 15
represent suppurative lesions. Columns 17 to 19 represent chronic
lesions. A survey of the table shows the predominance of acute lesions
in the early period of the study and the gradual increase of chronic
lesions.

The last four columns of the table of autopsies give the bacteriology of
the sputum during life and the bacteria found in the bronchi, in the
lungs, and in the blood of the heart after death.

=Mortality of Pneumonia Following Influenza.=—From September 6 to
December 15, 250 autopsies were performed on patients who had died with
pneumonia at the base hospital at Camp Pike, and with few exceptions
bacteriologic cultures were made from them. Although it was not possible
to perform autopsies on all who died, those which were performed afford
a fair index of all deaths, for throughout the epidemic of influenza and
its outbreak of pneumonia approximately one half of all who died were
examined after death. The relation of autopsies to deaths is shown by a
comparison by weeks of the number of deaths and number of autopsies
during the months of September and October.

═══════════════════════╤═══════════════════════╤═══════════════════════
WEEK │ DEATHS │ AUTOPSIES
───────────────────────┼───────────────────────┼───────────────────────
Sept. 1–7 │ 1│ 1
Sept. 8–14 │ 1│ 1
Sept. 15–21 │ 4│ 3
Sept. 22–28 │ 15│ 14
Sept. 29–Oct. 5 │ 121│ 67
Oct. 6–12 │ 191│ 78
Oct. 13–19 │ 78│ 43
Oct. 20–27 │ 22│ 15
Oct. 28–31 │ 8│ 6
│ ———│ ———
│ 441│ 228
───────────────────────┴───────────────────────┴───────────────────────

For most of these autopsies there is a record of the date of onset of
the illness, namely, influenza, which finally resulted in pneumonia and
death. Comparison of the number of cases of influenza which developed on
any day with the number of fatal cases which had their onset on the same
day will determine the mortality of influenza at different periods of
the epidemic. Chart 1 shows the number of cases of influenza which had
their onset on each day from September 1 to October 31 and the number of
fatal cases with autopsy which had their origin on corresponding days.
The comparison by weeks between autopsies and total number of deaths
shows that the autopsies represent with considerable accuracy the
deaths. If there is any error it occurs at the height of the outbreak of
pneumonia from September 29th to October 5th and not at its beginning,
or end. The chart shows that the highest mortality occurred among cases
of influenza which had their origin at the beginning of the epidemic
from September 21 to October 1, whereas after October 1, though the
maximum number of cases of influenza occurred on October 3, very few
developed fatal pneumonia.

=Mortality from Pneumococcus and Streptococcus Pneumonias.=—By referring
fatal cases of streptococcus pneumonia back to their date of origin it
is possible to determine what proportion of the cases of influenza,
which developed on any day, died with infection by hemolytic
streptococcus. The accompanying chart (Chart 1) shows that infection
with hemolytic streptococci has been very frequent at the beginning of
the epidemic of influenza (shown by area with double hatch in chart)
that is, from September 20 to 30 and subsequently has gradually
diminished so that few cases have had their onset in the second half of
the epidemic from September 30 to October 15.

Pneumococcus pneumonia uncomplicated by streptococcus infection (shown
by area with single hatch in chart) pursued a course which more closely
conformed to the curve representing influenza. The cases of influenza
which resulted fatally bore a fairly constant ratio to the total number
of cases of influenza from the onset of the epidemic until October 1,
but subsequently few cases of influenza developed fatal pneumococcus
pneumonia.

These charts arranged with reference to the onset of fatal pneumonias
dissociate very clearly the outbreak of streptococcus pneumonia, which
reached its height at the beginning of the influenza epidemic, from the
uncomplicated pneumococcus pneumonia which reached its maximum at the
midpart of the influenza epidemic and then abruptly abated.

[Illustration:

Chart 1—Showing the relation of (_a_) onset of cases of pneumonia
shown by autopsy to be uncomplicated by secondary infection with
hemolytic streptococcus, indicated by upper continuous line with
single hatch, and of (_b_) onset of fatal cases of streptococcus
pneumonia, indicated by the lower continuous line with double hatch,
to (_c_) the occurrence of influenza, indicated by the broken line.
The onset of each case of fatal pneumonia is represented by a single
square.
]

Our study of ward infection in pneumonia furnishes an explanation of the
outbreak of fatal streptococcus pneumonia coincident with the initial
stage of the influenza epidemic. This outbreak is a true epidemic of
streptococcus infection superimposed, in many instances at least, upon
preexisting pneumococcus pneumonia, but in some instances, doubtless, a
primary streptococcus pneumonia, following the bronchitis of influenza.
In the absence of secondary streptococcus infection a very large
proportion of these individuals would have recovered. This epidemic of
streptococcus pneumonia, it has been shown, was the result of
unfavorable conditions produced by great overcrowding of the hospital
and in the early part of the epidemic by inadequate separation of those
with streptococcus infection from those with none. With control of these
conditions, streptococcus pneumonia rapidly diminished.

Greater susceptibility to pneumococcus pneumonia in the early than in
the late period of the epidemic is perhaps explained by differences in
the severity of influenza; the more susceptible individuals were
attacked by influenza in the early period, whereas the less susceptible
did not acquire the disease until they had been exposed to an immensely
increased number of infected individuals. A better explanation is
furnished by the greater opportunity at the beginning of the epidemic
for the transmission of microorganisms causing pneumonia, for at this
time patients with influenza were crowded together and methods to
prevent the transmission of infection were little used.

Bronchitis

Clinical study has shown that purulent bronchitis (see Fig. 2) occurs in
about one-third of the cases of influenza. In a large proportion of
cases of bronchitis there is no clinical evidence of pneumonia. The
bronchial lesions found in association with the pneumonia of influenza
are an index of the ability of the agent, which causes influenza, to
injure the bronchi.

In those who have died with pneumonia following influenza the large
bronchi (with cartilage) are intensely injected, so that the mucosa has
a deep red color which on cross section contrasts very sharply with the
pearly white of the cartilage. Superficial injury to the bronchi is not
infrequently evident in the larger bronchial branches; superficial loss
of epithelium is indicated by erosion of the surface, whereas somewhat
deeper destructive changes are occasionally evident. Microscopic
examination accurately determines the degree of destructive change.

Purulent bronchitis was noted in 134 autopsies (55.6 per cent of
autopsies). From the small bronchi, in many instances, purulent fluid
welled up upon the cut surface of the lung, whereas in other instances
tenacious mucopurulent fluid could be squeezed from small, cut bronchi
by pressure upon lung tissue. The consistency of the material within the
bronchi varied greatly, ranging from a viscid and tenacious mucus of
creamy, yellow color to a thin, turbid, gray fluid. The coexistence of
local inflammatory or of general edema of the lungs modifies the
character of the material found in the bronchi at autopsy; with edema
the purulent exudate is in some instances diluted so that a thin cloudy
fluid flows from the small bronchi. In the presence of advanced edema of
the lungs the bronchi rarely if ever contain purulent exudate. The
underlying changes in the bronchi are more significant than the
character of the exudate found at autopsy. Nevertheless, the group of
cases in which the diagnosis of purulent bronchitis has been made,
because small and medium sized bronchi have contained purulent or
mucopurulent exudate, represents instances of readily recognizable
bronchitis of considerable severity.

With few exceptions, purulent bronchitis was diffusely distributed in
the lungs; occasionally it was observed in one lung alone, and in
several instances was limited to the bronchi at the base of a lung,
usually of the left lung.

In a considerable proportion of instances of purulent bronchitis
abnormal distention of the lungs was noted. On removal from the chest
the lungs fail to collapse and retain the size and shape of the thorax.
Even after section is made through the organ, parts of the lung fail to
collapse and have a resistant cushion-like consistency. This condition
is present where the lung tissue is air containing and dry, and occurs
when very small bronchi contain tenacious mucous exudate which becomes
apparent upon the cut surface after the sectioned lung is squeezed.
Microscopic examination shows that the alveolar ducts and infundibula
are distended with air, though the respiratory bronchioles contain
inflammatory exudate. Complete obstruction of the bronchi is followed by
absorption of air from the tributary pulmonary tissue with atelectasis.
It is not improbable that partial obstruction, permitting the
penetration of air with inspiration, produces distention of air
containing tissue.

It is furthermore probable that cyanosis, which is a conspicuous feature
of many instances of pneumonia following influenza, is referable, in
part at least, to obstruction of the bronchi by mucopurulent exudate.

The term pneumonia will refer to those inflammatory changes in the lung
which are found within the alveoli; it will include inflammatory changes
in the alveoli surrounding the respiratory bronchioles, in the alveolar
ducts and infundibula and in their tributary alveoli. Bronchitis will be
described by defining the changes which occur (a) in the small bronchi
with no cartilage or mucous glands, and (b) in the large bronchi
including the primary branches of the trachea.

For convenience of description those bronchi may be designated small,
which have no cartilaginous plates in their wall. Larger bronchi have
cartilage and mucous glands, the latter situated in considerable part
outside the cartilaginous plates. These bronchi, of which the largest
are the right and left bronchi formed by bifurcation of the trachea,
diminish with repeated branching to a caliber of about 1 mm. Small
bronchi are lined by columnar ciliated epithelium; their wall consists
of very vascular connective tissue containing a layer of smooth muscle
and their caliber varies approximately from 1 to 0.5 mm. It is
convenient to designate as respiratory bronchioles[80] the terminal
ramifications of the bronchi; they are lined by a single layer of
columnar ciliated cells passing over into cuboidal nonciliated
epithelium and are beset with small air sacs lined by flat cells or
epithelial plates similar to those of the alveoli elsewhere. Not
infrequently these alveoli occur along only one side of the bronchiole,
the remainder of the circumference being covered by a continuous layer
of cubical epithelium. The respiratory bronchiole by branching along its
course or at its end is continued into several alveolar ducts which
unlike the respiratory bronchioles have no cubical or columnar
epithelium but are closely beset by alveoli lined by flat epithelial
plates. The alveolar duct is recognized by the absence of cubical
epithelium and the presence of bundles of smooth muscle which occur in
the wall. The infundibula or alveolar sacs arise as branches from the
alveolar ducts and like them are beset with alveoli, but smooth muscle
does not occur in their walls. The base of the infundibulum is wider
than its orifice, which Miller states is surrounded by a sphincter-like
bundle of smooth muscle.

Changes in the main bronchi and their primary branches are usually less
severe than those in bronchi of smaller size. The epithelium is often
intact, the superficial cells being columnar and ciliated, but not
infrequently desquamation of superficial cells has occurred and the
lower layers alone remain. Occasionally (Autopsy 471) there is necrosis
of epithelium with which, although the architecture of cells is
preserved, nuclei have disappeared. Accumulation of blood or serum may
separate epithelium from the underlying basement membrane (Fig. 1).
Complete loss of epithelium occurs, usually in small patches.

Polynuclear leucocytes are numerous upon the surface of the epithelium
and are sometimes fixed in process of migration through epithelium and
basement membrane.

[Illustration:

Fig. 1.—Acute bronchitis showing engorgement of blood vessels of
mucosa and elevation of epithelium by serum and blood. Autopsy 352.
]

The blood vessels of the mucosa are engorged. There is sometimes edema
or hemorrhage, and in the superficial part of the mucosa polynuclear
leucocytes are often fairly abundant. When superficial epithelium has
been lost, polynuclears are numerous immediately below the surface of
the exposed tissue. Fibrin is often present upon the denuded surface and
extends for a short distance into the tissue below. In the deeper part
of the mucosa, about the muscularis and especially about and between the
acini of the mucous glands, the tissue is infiltrated with lymphoid and
plasma cells.

Changes in the mucous glands are invariably present. These changes are
distention of ducts and acini with mucous, degenerative changes
occasionally ending in necrosis of cells, disappearance of acini, dense
infiltration of interstitial tissue with lymphoid and plasma cells and
finally proliferation of this interstitial tissue. The duct of a mucous
gland, dilated and filled with mucus, may be surrounded by lymphoid and
plasma cells in great number. Acini, similarly dilated, contain mucus
and are composed of cubical cells which have discharged their mucous
content. In some instances (_e. g._, Autopsy 257) the cells of the acini
have undergone necrosis; the cytoplasm stains homogeneously and the
nuclei have disappeared. Where necrosis has occurred, polynuclear
leucocytes may penetrate into the dead cells. In association with
degenerative changes in the acini there is abundant infiltration of the
interstitial tissue within and about the glands with lymphoid and plasma
cells. When the acini have disappeared there is proliferation of
fibroblasts and new formation of fibrous tissue, and mucous glands are
found in which a few atrophied acini are separated by newly formed
fibrous tissue.

With the bronchitis of influenza the small bronchi (with no cartilage or
mucous glands) show every stage of transition from early acute
inflammation characterized by accumulation of polynuclear leucocytes
within the lumen, engorgement of blood vessels, and infiltration of the
wall with polynuclear leucocytes, through various stages of destructive
changes to complete disappearance of the bronchial wall and formation of
an abscess cavity at the site of the bronchus. In the early stages of
acute bronchitis, hemorrhage is frequently associated with the lesion.
Blood may be abundant within the lumen of the bronchus, and in the
mucosa red blood corpuscles often infiltrate the tissue around greatly
distended blood vessels, or accumulating below the epithelium, separate
it from its basement membrane. Hemorrhage is not limited to the wall of
the bronchus, but frequently occurs into the alveoli in a zone
encircling the bronchus.

With acute bronchitis there may be desquamation of epithelial cells with
partial or complete loss of epithelial lining. In the smallest bronchi
the single layer of columnar cells may be separated in places from the
underlying tissue, so that intact rows of cells are found within the
lumen. In somewhat larger bronchi, lined by epithelium in multiple
layers, superficial columnar ciliated cells may be lost. In some
instances superficial epithelial cells appear to have lost their
cohesion and are separated by narrow spaces; in these instances,
polynuclear leucocytes are often numerous between epithelial cells.
Epithelium is occasionally separated from its basement membrane by small
accumulations of serum or blood. Occasionally necrosis of epithelial
cells with disappearance of nuclei is seen and is doubtless caused by
the action of bacteria; the affected cells may be raised from the
underlying tissue by accumulated serum (Autopsy 253). The changes which
have been described bring about partial or complete loss of the ciliated
lining of the bronchial tube.

The severity of changes in the bronchial wall is in direct relation to
the extent of destruction of the lining epithelium: when the epithelium
remains intact polynuclear leucocytes may be found in considerable
number immediately below it, but as the lesion progresses, cells in
great part mononuclear, namely, lymphoid and plasma cells, accumulate in
large number throughout the wall of the bronchus. There is often
abundant cellular infiltration within and about the bundles of the
muscular coat. The changes assume the character of chronic inflammation.

When the lining epithelium of the bronchus is lost, fibrin tends to
accumulate over the surface of the defect, to which it is firmly
attached. It remains separated by a conspicuous space from adjacent
intact epithelium over which it may project. This superficial network of
fibrin merges with a similar network, extending to a variable depth
within the tissue. What may well be described as coagulative necrosis
has often occurred, and structures, such as white fibrous bundles or
wall of blood vessels, are marked out by hyaline material which merges
with fibrin. When the walls of the blood vessels which are invariably
engorged are involved, the lumen is plugged by a fibrinous thrombus.

Little patches of fibrin adherent to the inner surface of the bronchus
may occur in spots where epithelium has been lost; with uniform loss of
epithelium the entire circumference may be lined with fibrin forming a
circular zone occasionally quite uniform in thickness.

Accumulations of polynuclear leucocytes doubtless bring about conditions
which cause solution of fibrin or prevent its formation (when
disintegration of leucocytes sets free leucoprotease in abundance). The
activity of the infecting microorganisms, usually hemolytic streptococci
or staphylococci, may cause complete necrosis of a part or all of the
bronchial wall. The cavity which is formed may penetrate into lung
tissue that has previously undergone pneumonic consolidation.

Further changes caused by the bronchitis of influenza will be considered
under peribronchial hemorrhage and edema, peribronchial pneumonia and
bronchiogenic abscess. Purulent bronchitis is almost invariably
associated with dilatation of the bronchi, the affected bronchi being
distended with pus. With increasing dilatation bronchiectasis becomes
evident upon gross examination of the tissue, and is much more advanced
in the small bronchi than in the larger cartilaginous passages. This
subject will be further considered under bronchiectasis.

In association with the acute bronchitis of influenza the epithelium of
bronchi not infrequently looses its superficial columnar ciliated cells
and assumes some of the characters of a squamous epithelium being
covered by polygonal or flat cells (Figs. 17 and 18). The condition is
often described a “squamous metaplasia,” although it doubtless
represents a stage of regeneration following injury rather than a true
metaplasia. The basal cells of the epithelium have a cubical or columnar
form; above them the cells become polygonal and as the surface is
approached, cells are flat and even scale-like. The nuclei of these
superficial cells are often lost. There is no close resemblance to the
squamous epithelium of the skin, for intercellular bridges are not seen.

This change may occur within six days after onset of influenza, though
in most instances the duration of illness has been two weeks or more. It
may affect either large or small bronchi, but it is more frequently
found in the latter. Whenever ciliated columnar cells are lost,
superficial cells tend to become flat. Epithelium on one side of a
bronchus may have a squamous character, whereas that elsewhere is
columnar and ciliated. The flat epithelium may undergo thickening so
that it is 0.1 mm. or more in thickness. It is noteworthy that
regenerating epithelium growing over a denuded surface has the squamous
character which has been described (Plate XIV, Fig. 22).

=Bacteriology of the Bronchitis of Influenza.=—With the pneumonia of
influenza, bronchitis is invariably present. Cultures have been made
from the right or left main bronchus or from the very small bronchi
which contained purulent exudate. A routine method of making the culture
has been adopted. The right main bronchus, exposed by drawing the right
lung out of the chest and toward the midline, was widely seared with a
hot knife; the bronchus was partially cut across through the seared
surface with a heated knife and a platinum needle inserted into the
lumen. The bacteria obtained named in the approximate order of their
relative frequency have been: B. influenzæ, pneumococci, hemolytic
streptococci, staphylococci (aureus and albus), B. coli, S. viridans, M.
catarrhalis, and diphthoid bacilli which have not been identified. Mixed
infections occurred in most instances. The following list arranged by
grouping bacteria in the order cited above, shows how varied have been
the combinations which occur:

B. influenzæ 3
Pneumococci 5
S. hemolyticus 3
Staphylococci 3
B. coli 3
S. viridans 1
B. influenzæ, pneumococci 17
B. influenzæ, S. hemolyticus 18
B. influenzæ, staphylococci 4
Pneumococci, S. hemolyticus 1
Pneumococci, staphylococci 3
S. hemolyticus, staphylococci 4
S. hemolyticus, B. coli 2
Staphylococci, S. viridans 1
B. influenzæ, pneumococci, S. hemolyticus 6
B. influenzæ, pneumococci, staphylococci 15
B. influenzæ, pneumococci, S. viridans 2
B. influenzæ, S. hemolyticus, staphylococci 16
B. influenzæ, S. hemolyticus, M. catarrhalis 1
B. influenzæ, staphylococci, S. viridans 1
Pneumococci, S. hemolyticus, staphylococci 3
Staphylococci, B. coli, S. viridans 1
B. influenzæ, pneumococci, S. hemolyticus, staphylococci 7
B. influenzæ, pneumococci, staphylococci, M. catarrhalis 1
B. influenzæ, S. hemolyticus, staphylococci, B. coli 1
B. influenzæ, S. hemolyticus, staphylococci, S. viridans 1
B. influenzæ, S. hemolyticus, staphylococci, M. catarrhalis 1
B. influenzæ, staphylococci, S. viridans, M. catarrhalis 1

B. influenzæ has been present in the bronchi in 79.3 per cent of
instances of pneumonia referable to influenza. Combinations which have
been found most frequently are B. influenzæ and pneumococci (17
instances), B. influenzæ and hemolytic streptococci (18 instances), or
the same combinations with staphylococci, namely, B. influenzæ,
pneumococci and staphylococci (15 instances), and B. influenzæ,
hemolytic streptococci and staphylococci (16 instances). There is little
doubt that B. influenzæ was not identified in some instances in which it
was present; when other microorganisms are very numerous its
inconspicuous colonies may be overgrown even though the presence of
pneumococci, streptococci or staphylococci tends to increase the size of
its colonies. Moreover, it is not improbable that the microorganism may
disappear from the bronchi. Comparison with observations made upon
influenza suggests that multiple methods of examination might have
demonstrated a much higher incidence of B. influenzæ. Throat cultures
alone made during life demonstrated the presence of B. influenzæ in only
65.7 per cent of patients with acute influenza, whereas when cultures
were made from the nose, throat and sputum, and a mouse was inoculated
with sputum from each patient, B. influenzæ was found in every instance.
After the acute stage of the disease had passed, the number of
microorganisms diminished, and in many instances B. influenzæ
disappeared from the upper air passages. In some of our autopsies B.
influenzæ doubtless present during life has similarly disappeared before
death due to pneumonia caused by pneumococci or streptococci. In view of
these considerations it is not improbable that B. influenzæ demonstrated
by a single culture in 80 per cent of instances has been constantly
present.

Table XXVIII represents the incidence of pneumococci, hemolytic
streptococci, staphylococci, and B. influenzæ in the bronchi, lungs and
blood of those individuals with pneumonia in whom bacteriologic
examination has been made at autopsy. The number of cultures made from
the bronchi, lungs or blood of the heart is given in the second column
of the table and in other columns are given the incidence in number and
percentage of the microorganisms which have been mentioned.

TABLE XXVIII

════════╤════════╤═════════════════╤═════════════════
│ NO. OF │ │ HEMOLYTIC
│CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI
────────┼────────┼────────┬────────┼────────┬────────
│ │ NO. │PER CENT│ NO. │PER CENT
│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────┼────────
Bronchus│ 121│ 56│ 46.3│ 58│ 47.9
Lung │ 153│ 68│ 44.4│ 77│ 50.3
Blood │ 218│ 87│ 39.9│ 85│ 39.0
────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════
│ │
│ STAPHYLOCOCCI │ B. INFLUENZÆ
────────┼────────┬────────┼────────┬────────
│ NO. │PER CENT│ NO. │PER CENT
│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────
Bronchus│ 61│ 50.4│ 96│ 79.3
Lung │ 37│ 24.2│ 70│ 45.7
Blood │ 1│ 0.5│ 1│ 0.5
────────┴────────┴────────┴────────┴────────

Cultures from the bronchus represent the bacteriology of the bronchitis
of influenza. Infection of the lung following influenza doubtless occurs
by way of the bronchi, so that the bacteria which cause pneumonia are
present in the bronchi before they enter the lung tissue. The figures in
Table XXVIII, similar to those previously cited, show the high incidence
of B. influenzæ, and the occurrence of pneumococci, hemolytic
streptococci and staphylococci each present in approximately half of all
autopsies.

The figures in Table XXVIII are an index of the capacity of the
microorganisms which enter the bronchi to invade the lungs and finally
the blood. Pneumococci were present in the bronchi in 46.3 per cent of
instances, in the lungs in only slightly less, and in approximately 40
per cent of autopsies they had penetrated into the blood. Hemolytic
streptococci enter the bronchi with the same frequency and exhibit an
equal ability to penetrate into the lungs and blood. Staphylococci enter
the bronchi in half of these individuals, but penetrate into the lungs
in only a fourth of the instances. They have entered the blood only once
(Autopsy 263) in this instance in association with hemolytic
streptococci. B. influenzæ has been present in the bronchi in
approximately 80 per cent of autopsies. It is noteworthy that it has
been found in the lung in little more than half this percentage of
instances and has entered the blood only once (Autopsy 474), in this
instance in association with hemolytic streptococci.

In a limited number of autopsies there was purulent bronchitis
recognized by the presence of mucopurulent exudate in small bronchi. It
has been stated that this group of cases is not sharply separable from
other instances of bronchitis, because in some cases death has occurred
before a purulent exudate has accumulated or in other instances a
purulent exudate has been displaced by edema. Table XXIX shows the
bacteriology of instances of purulent bronchitis:

TABLE XXIX

════════╤════════╤═════════════════╤═════════════════
│ NO. OF │ │ HEMOLYTIC
│CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI
────────┼────────┼────────┬────────┼────────┬────────
│ │ NO. │PER CENT│ NO. │PER CENT
│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────┼────────
Bronchus│ 66│ 33│ 50.0│ 32│ 48.5
────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════
│ │
│ STAPHYLOCOCCI │ B. INFLUENZÆ
────────┼────────┬────────┼────────┬────────
│ NO. │PER CENT│ NO. │PER CENT
│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────
Bronchus│ 36│ 54.5│ 53│ 80.3
────────┴────────┴────────┴────────┴────────

The percentages of various bacteria with purulent bronchitis do not
differ essentially from those obtained from all autopsies with
pneumonia. B. influenzæ is found in approximately 80 per cent of
autopsies. In 16 instances cultures were made from the purulent fluid
contained in a small bronchus and the incidence of B. influenzæ (namely,
81.4 per cent) has not differed from that in the main bronchus. In 7 of
8 instances in which cultures were made, both from the right main
bronchus and from the purulent fluid in a small bronchus, B. influenzæ
was found in one or other in all but one autopsy (87.5 per cent); in
this instance (Autopsy 472) respiratory disease began thirty-seven days
before death and cultures from large and small bronchi at autopsy were
overgrown by B. coli. Since observations upon influenza made during life
have shown that B. influenzæ is constantly demonstrable when multiple
methods are employed for its detection, the figures just cited give
support to the suggestion that B. influenzæ is constantly present in the
bronchi with the bronchitis of influenza.

Lobar Pneumonia

The frequency with which the confluent lobular consolidation of
bronchopneumonia involving whole lobes or parts of lobes follows
influenza has emphasized the desirability of distinguishing carefully
between lobar and confluent lobular pneumonia. The pulmonary lesion has
been designated lobar pneumonia when it exhibited the well-known
characters of this lesion, namely, firm consolidation of large parts of
lobes, coarse granulation of the cut surface, fibrinous plugs in the
bronchi and, on microscopic examination, homogeneous consolidation and
fibrinous plugs within the alveoli. With confluent lobular consolidation
of bronchopneumonia the consolidated area is in most cases obviously
limited by lobule boundaries, and well-defined lobules of consolidation
occur elsewhere in the lungs.

Lobar pneumonia occurred in 98 among 241 instances of pneumonia
following influenza, namely, in 40.7 per cent of autopsies.

The difficulty of separating lobar and bronchopneumonia following
influenza has been increased by the frequent combination of the two
lesions in the same individual. There were 34 instances in which lobar
and bronchopneumonia occurred together. The anatomic diagnosis of lobar
pneumonia was made only when lobes or parts of lobes were firmly
consolidated and exhibited the characters of the lesion enumerated
above; in several instances, in which there was some doubt concerning
the nature of the lesion, microscopic examination was decisive. The
associated bronchopneumonic lesions represented all the types which have
been associated with influenza. In the group of 34 cases of coexisting
lobar and bronchopneumonia, lobular consolidation occurred 10 times,
peribronchiolar consolidation 14 times (recognized in all but 4
instances by microscopic examination), hemorrhagic peribronchiolar
consolidation 9 times, peribronchial pneumonia 4 times. The intimate
relation of these lesions to changes in the bronchi is well shown by the
frequent presence of purulent bronchitis. The associated lesions of the
bronchi in these cases were as follows: purulent bronchitis in 23
instances; peribronchial hemorrhage in 6; bronchiectasis in 11. The
frequency of purulent bronchitis and other bronchial lesions in
association with coexisting lobar and bronchopneumonia is in sharp
contrast with the occurrence of these lesions in association with lobar
pneumonia alone; with 69 instances of lobar pneumonia alone purulent
bronchitis occurred 17 times and bronchiectasis once.

Lobar pneumonia following influenza passes through the usual stages of
red and gray hepatization. Red hepatization was found 16 times, combined
red and gray hepatization 28 times, and gray hepatization 20 times. The
average duration of pneumonia with red hepatization was 3.7 days, with
combined red and gray hepatization 5.1 days and with gray hepatization
7.5 days. These figures, it will be shown later, have some importance in
relation to the stage at which hemolytic streptococcus infects lungs the
site of lobar pneumonia.

=Bacteriology of Lobar Pneumonia.=—Table XXX is compiled with the
purpose of determining the bacteriology of the bronchi, lungs and
heart’s blood in autopsies performed on individuals with lobar
pneumonia. In some instances bacteriologic examination of one or other
of these organs was omitted; the percentage incidence is an index of the
presence of pneumococci, hemolytic streptococci, staphylococci or B.
influenzæ in the bronchi, lungs or heart’s blood and measures the
invasive power of these microorganisms during the course of lobar
pneumonia following influenza.

TABLE XXX

════════╤════════╤═════════════════╤═════════════════
│ NO. OF │ │ HEMOLYTIC
│CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI
────────┼────────┼────────┬────────┼────────┬────────
│ │ NO. │PER CENT│ NO. │PER CENT
│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────┼────────
Bronchus│ 44│ 56.9│ 14│ 31.8│ 22
Lung │ 53│ 77.3│ 13│ 24.5│ 8
Blood │ 87│ 65.5│ 11│ 12.6│
────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════
│ │
│ STAPHYLOCOCCI │ B. INFLUENZÆ
────────┼────────┬────────┼────────┬────────
│ NO. │PER CENT│ NO. │PER CENT
│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────
Bronchus│ 37│ 84.1│ 96│ 79.3
Lung │ 26│ 49.1│ 70│ 45.7
Blood │ │ │ 1│ 0.5
────────┴────────┴────────┴────────┴────────

Pneumococci, the recognized cause of lobar pneumonia, were found in the
lungs in 73.3 per cent of autopsies; failure to find the microorganism
in all instances is doubtless the result of its disappearance from the
lung, which, it is well known, occurs not infrequently particularly
during the later stages of the disease. In 65.5 per cent of instances of
fatal lobar pneumonia pneumococci have entered the heart’s blood.

Hemolytic streptococci unlike pneumococci were found more frequently in
the bronchi than in the lungs; this microorganism which exhibits little
tendency to disappear, once it has established itself within the body,
found entrance into the bronchi in 31.8 per cent of instances of lobar
pneumonia and in 24.5 per cent entered the lungs. Its invasive power is
further illustrated by its penetration into the heart’s blood
approximately in half this proportion of autopsies.

Staphylococci enter the bronchi in many instances (50 per cent), but
relatively seldom (15.1 per cent) invade the lung and rarely if ever
penetrate into the blood.

The high incidence, namely, 84.1 per cent, of B. influenzæ in the
bronchi is particularly noteworthy; it exceeds that of pneumococci, the
well-recognized cause of lobar pneumonia, within the lung. It is found
much less frequently within consolidated lung tissue and shows no
tendency to invade the heart’s blood. B. influenzæ finds the most
favorable conditions for its multiplication within the bronchi.

In view of the frequent occurrence of coexisting lobar and
bronchopneumonia it has appeared desirable to determine how far the
existence of obvious bronchopneumonia modifies the bacteriology of lobar
pneumonia. In Table XXXI the incidence of pneumococci, hemolytic
streptococci, staphylococci and B. influenzæ after death with lobar
pneumonia on the one hand is compared with their incidence after
combined lobar and bronchopneumonia on the other.

Pneumococci are found in the lung more frequently with lobar than with
combined lobar and bronchopneumonia. The incidence of hemolytic
streptococci and of staphylococci in the lung is on the contrary higher
when bronchopneumonia is associated with lobar pneumonia. It is not
improbable that these microorganisms have a part in the production of
associated bronchopneumonia. The frequency with which microorganisms
invade the blood is almost identical in the two groups.

TABLE XXXI

WITH LOBAR PNEUMONIA ALONE

════════╤════════╤═════════════════╤═════════════════
│ NO. OF │ │ HEMOLYTIC
│CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI
────────┼────────┼────────┬────────┼────────┬────────
│ │ NO. │PER CENT│ NO. │PER CENT
│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────┼────────
Bronchus│ 30│ 20│ 66.6│ 9│ 30
Lung │ 34│ 29│ 85.2│ 7│ 20.6
Blood │ 54│ 36│ 66.7│ 7│ 13
────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════
│ │
│ STAPHYLOCOCCI │ B. INFLUENZÆ
────────┼────────┬────────┼────────┬────────
│ NO. │PER CENT│ NO. │PER CENT
│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────
Bronchus│ 15│ 50│ 26│ 86.7
Lung │ 3│ 8.8│ 18│ 52.9
Blood │ │ │ │
────────┴────────┴────────┴────────┴────────

WITH COMBINED LOBAR AND BRONCHOPNEUMONIA

════════╤════════╤═════════════════╤═════════════════
│ NO. OF │ │ HEMOLYTIC
│CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI
────────┼────────┼────────┬────────┼────────┬────────
│ │ NO. │PER CENT│ NO. │PER CENT
│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────┼────────
Bronchus│ 14│ 9│ 64.3│ 5│ 34.3
Lung │ 19│ 12│ 63.2│ 6│ 31.6
Blood │ 33│ 21│ 63.1│ 4│ 12.1
────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════
│ │
│ STAPHYLOCOCCI │ B. INFLUENZÆ
────────┼────────┬────────┼────────┬────────
│ NO. │PER CENT│ NO. │PER CENT
│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────
Bronchus│ 7│ 50│ 11│ 78.6
Lung │ 5│ 26.3│ 8│ 42.1
Blood │ │ │ │
────────┴────────┴────────┴────────┴────────

The relative frequency with which different types of pneumococci produce
lobar pneumonia under the conditions existing when Camp Pike was
attacked by an epidemic of influenza is indicated by Table XXXII in
which instances of lobar pneumonia alone and of combined lobar and
bronchopneumonia are listed separately.

Pneumococcus I and II, which are found approximately in two-thirds of
instances of lobar pneumonia occurring in cities, have an insignificant
part in the production of these lesions. Pneumococcus IV and atypical
Pneumococcus II, which are commonly found in the mouth, are the
predominant cause of these lesions, and with Pneumococcus III, also an
inhabitant of the mouths of normal individuals, have been the cause of
two-thirds of all instances of lobar pneumonia observed in this camp.

TABLE XXXII

WITH LOBAR PNEUMONIA

════════╤════════╤═════════════════╤═════════════════╤═════════════════
│ NO. OF │ │ │ PNEUMOCOCCUS II
│CULTURES│ PNEUMOCOCCUS I │ PNEUMOCOCCUS II │ (Atyp.)
────────┼────────┼────────┬────────┼────────┬────────┼────────┬────────
│ │ NO. │PER CENT│ NO. │PER CENT│ NO. │PER CENT
│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────┼────────┼────────┼────────
Bronchus│ 30│ 1│ 3.3│ 1│ 3.3│ 4│ 13.3
Lung │ 34│ 1│ 2.9│ 2│ 5.9│ 9│ 26.5
Blood │ 54│ 2│ 3.7│ 2│ 3.7│ 12│ 22.2
────────┴────────┴────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════
│ │
│PNEUMOCOCCUS III │ PNEUMOCOCCUS IV
────────┼────────┬────────┼────────┬────────
│ NO. │PER CENT│ NO. │PER CENT
│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────
Bronchus│ 4│ 13.3│ 10│ 33.3
Lung │ 6│ 17.6│ 11│ 32.4
Blood │ 3│ 5.6│ 17│ 31.5
────────┴────────┴────────┴────────┴────────

WITH COMBINED LOBAR AND BRONCHOPNEUMONIA

════════╤════════╤═════════════════╤═════════════════╤═════════════════
│ NO. OF │ │ │ PNEUMOCOCCUS II
│CULTURES│ PNEUMOCOCCUS I │ PNEUMOCOCCUS II │ (Atyp.)
────────┼────────┼────────┬────────┼────────┬────────┼────────┬────────
│ │ NO. │PER CENT│ NO. │PER CENT│ NO. │PER CENT
│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────┼────────┼────────┼────────
Bronchus│ 14│ 2│ 14.3│ 1│ 7.1│ 3│ 21.4
Lung │ 19│ 1│ 5.3│ │ │ 5│ 26.3
Blood │ 33│ 2│ 6.1│ 3│ 9.1│ 4│ 12.1
────────┴────────┴────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════
│ │
│PNEUMOCOCCUS III │ PNEUMOCOCCUS IV
────────┼────────┬────────┼────────┬────────
│ NO. │PER CENT│ NO. │PER CENT
│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────
Bronchus│ │ │ 3│ 21.4
Lung │ │ │ 6│ 31.6
Blood │ │ │ 12│ 36.4
────────┴────────┴────────┴────────┴────────

There is no noteworthy difference in the occurrence of these types of
pneumococci among instances of lobar pneumonia, on the one hand, and of
combined lobar and bronchopneumonia, on the other. Different types
exhibit no noteworthy differences in their ability to penetrate into
lungs and blood.

=Hemolytic Streptococcus with Lobar Pneumonia.=—There can be no doubt
that the concurrent infection with microorganisms other than
pneumococcus modifies the progress of lobar pneumonia. With lobar
pneumonia alone hemolytic streptococci have entered the bronchi in 30
per cent of instances and have penetrated into the lungs in 20.6 per
cent; with associated lobar and bronchopneumonia the same microorganism
has entered the bronchi in 34.3 per cent of instances and invaded the
lung in 31.6 per cent. Hemolytic streptococci are the only
microorganisms other than pneumococci which, in association with lobar
pneumonia, have found their way from the lungs to the blood stream; more
than one-third of all instances of lobar pneumonia in which hemolytic
streptococci find entrance into the bronchi die with streptococcus
septicemia.

Separation of instances of lobar pneumonia into groups on the basis of
the occurrence of red or gray hepatization shows that infection with
hemolytic streptococcus is more likely to occur during the early stages
of the disease. The average duration of lobar pneumonia with red
hepatization has been 3.7 days, with red and gray hepatization, 5.1
days, and with gray hepatization, 7.5 days. Infection with hemolytic
streptococcus has occurred in association with red or gray hepatization
as shown in Table XXXIII.

TABLE XXXIII

═════════════════════════════╤═════════════╤═════════════╤═════════════
│ │ NO. WITH │PER CENT WITH
│ NO. OF │ HEMOLYTIC │ HEMOLYTIC
│ AUTOPSIES │STREPTOCOCCUS│STREPTOCOCCUS
─────────────────────────────┼─────────────┼─────────────┼─────────────
Lobar pneumonia with red │ │ │
hepatization │ 16│ 6│ 37.5
Lobar pneumonia with red and │ │ │
gray hepatization │ 28│ 6│ 21.4
Lobar pneumonia with gray │ │ │
hepatization │ 20│ 1│ 5.0
─────────────────────────────┴─────────────┴─────────────┴─────────────

Notwithstanding the longer duration of the disease and consequent
prolongation of exposure to infection, lobar pneumonia, which has
reached the stage of gray hepatization, has shown the smallest incidence
of infection with hemolytic streptococci. In the stage of gray
hepatization there is diminished susceptibility to secondary infection
with this microorganism.

Characteristic histologic changes have been found in the lungs of those
who have died with lobar pneumonia followed by invasion of lungs and
blood by hemolytic streptococci (_e. g._, Autopsies 273, 430), but with
no evidence of suppuration found at autopsy. Within the pneumonic lung
occur patches of necrosis implicating both exuded cells and alveolar
walls; in some places nuclei have disappeared; elsewhere nuclear
fragments are abundant. In these patches of necrosis Gram-positive
streptococci in short chains occur in immense number. In some instances
(_e. g._, Autopsies 273, 346, 479) interlobular septa are very edematous
and often contain a network of fibrin; lymphatics are dilated and
contain polynuclear leucocytes in abundance. Streptococci are found
within these lymphatics. The histologic changes which have been
described represent the earliest stages of abscess formation and
interstitial suppuration, lesions almost invariably caused by hemolytic
streptococci.

[Illustration:

Chart 2.—Showing the relation of (_a_) date of onset of cases in which
autopsy demonstrated lobar pneumonia, indicated by upper continuous
line with single hatch, and of (_b_) date of death of these cases,
indicated by lower continuous line with double hatch to (_c_) the
occurrence of influenza, indicated by the broken line, and to (_d_)
the total number of fatal cases of pneumonia, indicated by the
broken dotted line. Each case of fatal pneumonia is indicated by one
division of the scale as numbered on the left of the chart; cases of
influenza are indicated by the numbers on the right of the chart.
]

=Relation of Lobar Pneumonia to Influenza.=—Some writers have suggested
that lobar pneumonia, heretofore observed during the course of epidemics
of influenza, is an independent disease with no relation to influenza,
both diseases being referable perhaps to similar meteorologic or other
conditions. Chart 2, which shows by weeks from September 1 to October 31
the relation of deaths from lobar pneumonia (indicated by double hatch)
to deaths from all forms of pneumonia, disproves this suggestion. The
two curves follow parallel courses; that representing lobar pneumonia
reaches a maximum approximately one week after the outbreak of influenza
had reached its height. Lobar pneumonia, like other forms of pneumonia,
was secondary to influenza. When a chart is plotted to represent the
dates of onset of fatal cases of lobar pneumonia (indicated by single
hatch in Chart 2), it becomes evident that the greatest number of these
cases of pneumonia had their onset at the beginning of the influenza
epidemic, approximately one week before it reached its height. Fatal
lobar pneumonia developed less frequently in the latter part of the
epidemic; to obtain an explanation of this relation it is necessary to
chart separately cases of lobar pneumonia with secondary streptococcus
infection, for we have already learned that streptococcus infection was
the predominant cause of death in the early period of the influenza
epidemic. Exclusion of these instances of secondary streptococcus
infection makes no noteworthy change in the character of the chart.
Fatal lobar pneumonia, like all forms of fatal pneumonia (p. 140), was
more frequent in the first half than in the second half of the epidemic.
This difference is referable either to greater virulence of the virus of
influenza or to the greater susceptibility of those first selected by
the disease or, as more probable, to conditions such as crowding
together of patients with influenza, favoring the transmission of
microorganisms which cause pneumonia.

Bronchopneumonia

For the purpose of the present study it is convenient to group together
instances of bronchopneumonia which have been unaccompanied, on the one
hand, by lobar pneumonia (p. 155) or, on the other hand, by suppuration,
which with few exceptions is caused by hemolytic streptococci or by
staphylococci. A group of cases in which lobar and bronchopneumonia have
occurred in the same individual have already been considered. In many
instances, bronchopneumonia is accompanied by abscess formation or by
some other form of suppuration; these lesions will be discussed
elsewhere.

Bronchopneumonia unaccompanied by lobar pneumonia or by suppuration
occurred in 80 autopsies.

Pneumonic consolidation distributed with relation to the bronchi
exhibits considerable variety, and an attempt to define a type of
bronchopneumonia characteristic of influenza would be futile.
Nevertheless, the bronchopneumonia of influenza has in many instances
distinctive characters.

Lesions of bronchopneumonia which are frequently found in the autopsies
under consideration may be conveniently designated by descriptive terms,
indicative of their location in the lung tissue. These lesions, of which
two or more often occur in the same lung, are:

1. Peribronchiolar consolidation with which the inflammatory exudate is
limited to the alveoli in the immediate neighborhood of the bronchioles.

2. Hemorrhagic peribronchiolar consolidation in which gray patches of
peribronchiolar pneumonia occur upon a deep red background produced by
hemorrhage into alveoli. Pfeiffer believed that this lesion was
characteristic of influenza.

3. Lobular consolidation with which consolidation is limited to lobules
or groups of lobules.

4. Peribronchial pneumonia with which small bronchi are encircled by
pneumonic consolidation.

Each one of these lesions will be discussed separately.

Following is a list of the bacteria which have been isolated from the
consolidated lung of individuals with bronchopneumonia unaccompanied by
lobar pneumonia or by suppuration:

B. influenzæ 1
Pneumococci 5
S. hemolyticus 5
S. viridans 1
B. influenzæ, pneumococci 9
B. influenzæ, S. hemolyticus 4
B. influenzæ, staphylococci 4
Pneumococci, S. hemolyticus 1
Pneumococci, staphylococci 2
S. hemolyticus, staphylococci 1
S. hemolyticus, B. coli 1
Staphylococci, S. viridans 1
Staphylococci, B. coli 1
B. influenzæ, pneumococci, staphylococci 1
B. influenzæ, pneumococci, S. viridans 1
B. influenzæ, S. hemolyticus, staphylococci 2
B. influenzæ, pneumococci, staphylococci, S. viridans 1
No microorganisms found 6
——
47

The similarity of this list to that representing the bacteriology of
bronchitis is evident; there is the same multiplicity of microorganisms
and the frequent occurrence of mixed infections. B. influenzæ is much
less frequently found in the lung. The relative pathogenicity of the
large group of microorganisms enumerated above is better indicated by
the following list which shows what microorganisms have penetrated into
the blood in autopsies performed on individuals with bronchopneumonia:

Pneumococci 20
S. hemolyticus 23
S. viridans 1
Pneumococci, S. hemolyticus 2
No bacteria found 25
——
Total 71

Table XXXIV shows the percentage incidence of pneumococcus, hemolytic
streptococcus, staphylococcus and B. influenzæ in the bronchi, lungs and
blood and is inserted for comparison with the similar table (Table XXX)
showing the incidence of these bacteria in lobar pneumonia.

TABLE XXXIV

════════╤════════╤═════════════════╤═════════════════
│ NO. OF │ │ HEMOLYTIC
│CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI
────────┼────────┼────────┬────────┼────────┬────────
│ │ NO. │PER CENT│ NO. │PER CENT
│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────┼────────
Bronchus│ 37│ 19│ 48.6│ 13│ 35.1
Lung │ 47│ 20│ 42.6│ 14│ 29.8
Blood │ 70│ 22│ 31.4│ 24│ 34.3
────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════
│ │
│ STAPHYLOCOCCI │ B. INFLUENZÆ
────────┼────────┬────────┼────────┬────────
│ NO. │PER CENT│ NO. │PER CENT
│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────
Bronchus│ 22│ 59.5│ 28│ 75.7
Lung │ 13│ 27.7│ 23│ 48.9
Blood │ │ │ │
────────┴────────┴────────┴────────┴────────

Table XXXIV shows that pneumococci have a less important part in the
production of broncho than of lobar pneumonia; with lobar pneumonia this
microorganism was found in the lungs in 77.3 per cent of instances and
in the blood, in 65.5 per cent, whereas with bronchopneumonia it was
found in the lungs in 42.6 per cent and in the blood in 31.4 per cent.
Hemolytic streptococci (in lungs and blood) and staphylococci (in
lungs), on the contrary, were more common with bronchopneumonia, and
doubtless have a part in the production of the lesion. Streptococcus
viridans, B. coli and M. catarrhalis, which are not infrequently found
in the bronchi (p. 151), occasionally enter the lungs with
bronchopneumonia but are rarely found with lobar pneumonia. B. influenzæ
has been found in less than 80 per cent of instances in the bronchi and
in about half of the lungs, maintaining an incidence approximately the
same as that with lobar pneumonia.

Table XXXV shows the types of pneumococci found in association with
bronchopneumonia and is inserted for comparison with the similar table
(Table XXXII) showing types of pneumococci with lobar pneumonia.

With broncho as with lobar pneumonia pneumococci commonly found in the
mouth, namely, atypical II, and Types III and IV, have a more important
part in production of the lesion than the so-called fixed types, I and
II. Atypical Pneumococcus II has been less frequently encountered with
broncho than with lobar pneumonia.

TABLE XXXV

════════╤════════╤═════════════════╤═════════════════╤═════════════════
│ NO. OF │ │ │ PNEUMOCOCCUS II
│CULTURES│ PNEUMOCOCCUS I │ PNEUMOCOCCUS II │ (Atyp.)
────────┼────────┼────────┬────────┼────────┬────────┼────────┬────────
│ │ NO. │PER CENT│ NO. │PER CENT│ NO. │PER CENT
│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────┼────────┼────────┼────────
Bronchus│ 37│ 1│ 2.7│ 3│ 8.1│ │
Lung │ 47│ 2│ 4.3│ 2│ 4.3│ 2│ 4.3
Blood │ 70│ 1│ 1.4│ 1│ 1.4│ 5│ 7.1
────────┴────────┴────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════
│ │
│PNEUMOCOCCUS III │ PNEUMOCOCCUS IV
────────┼────────┬────────┼────────┬────────
│ NO. │PER CENT│ NO. │PER CENT
│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────
Bronchus│ │ │ 14│ 37.8
Lung │ 2│ 4.3│ 12│ 25.2
Blood │ 4│ 5.7│ 11│ 15.9
────────┴────────┴────────┴────────┴────────

=Peribronchiolar Consolidation.=—In many instances of bronchopneumonia,
usually in association with lobular or confluent consolidation, small
firm nodules of consolidation are clustered about the bronchioles (Fig.
2). These nodular foci of consolidation are usually 1.5 to 2 mm. in
diameter, being sometimes slightly smaller or slightly larger. They are
usually gray and occasionally surrounded by a red halo; sometimes they
are yellowish gray. They are clustered about the smallest bronchial
tubes to form groups which are from 0.5 to 1 cm. across. A group of
nodular foci of consolidation occupies the central part of a lobule of
lung tissue. When pneumonia has been of short duration these foci are
fairly soft and not sharply defined, and in many instances this form of
bronchopneumonia is first recognized by microscopic examination. When
the disease has lasted from ten days to two weeks, the consolidated
nodules are very firm and sharply circumscribed, closely resembling
tubercles. When they have assumed this character, microscopic
examination shows that chronic changes indicated by new formation of
interstitial tissue have occurred.

The lesion may be designated peribronchiolar consolidation. It has
occurred usually in association with other types of pneumonic lesion in
61 instances, being recognized at autopsy in 18 and by microscopic
examination in 43.

[Illustration:

Fig. 2.—Acute bronchopneumonia with nodules of peribronchiolar
consolidation and purulent bronchitis. Autopsy 429.
]

In association with this lesion there are almost invariably severe
lesions of the bronchi. Purulent bronchitis was noted in 47 of the 61
instances, in which this nodular bronchopneumonia was found at autopsy.
An index of the severity of the bronchial injury is the frequency with
which bronchiectasis has occurred; dilatation of small bronchi was
observed in 24 instances. In 10 instances the bronchi were encircled by
conspicuous zones of hemorrhage.

In association with this peribronchiolar lesion the lung is often
voluminous and fails to collapse on removal from the chest. Pressure
upon the lung squeezes from the smallest bronchi, both in the
neighborhood of the nodular consolidation and elsewhere, a droplet of
viscid, semifluid mucopurulent material. The presence of this tenacious
material throughout the small bronchi doubtless explains the failure of
the lung tissue to collapse. Interstitial emphysema has been present in
some of these lungs.

A red zone of hemorrhage has occasionally been observed about the foci
of peribronchiolar pneumonia. A further stage in the same process is
represented by hemorrhage into all of the alveoli separating these
patches of consolidation. This hemorrhagic lesion, which will be
described in more detail later, has been found repeatedly in the same
lung with peribronchiolar pneumonia, being present in 8 among the 61
autopsies cited. Lobular bronchopneumonia accompanied the
peribronchiolar lesion 27 times and lobar pneumonia accompanied it 20
times.

When an abscess caused by hemolytic streptococcus is associated with
peribronchiolar pneumonia, empyema is present, but otherwise pleurisy is
absent or limited to a scant fibrinous exudate.

[Illustration:

Fig. 3.—Acute bronchopneumonia with peribronchiolar consolidation; a
respiratory bronchiole partially lined by columnar epithelium passes
into alveolar duct and the adjacent alveoli are filled by
polynuclear leucocytes. Autopsy 333.
]

Histologic examination demonstrates very clearly the relation of this
lesion to the bronchioles (Fig. 3). These passages are filled and
distended with an inflammatory exudate consisting almost entirely of
polynuclear leucocytes. The respiratory bronchioles are beset with
alveoli often limited to one side of the tubule and these alveoli are
filled with leucocytes. The alveolar ducts, distinguishable from the
bronchioles by the absence of columnar or cubical epithelium and by
possession of smooth muscle, are similarly filled with leucocytes; the
numerous alveoli which form the walls of the alveolar ducts are
distended by an inflammatory exudate. In sections which pass through an
alveolar duct and one or more of its infundibula, the further extension
of the lesion may be determined (Fig. 4). The infundibulum in proximity
with the alveolar duct contains polynuclear leucocytes and the same
cells are seen in the alveoli which here form its wall, but the
intensity of the inflammatory reaction diminishes toward the periphery,
so that the distal part of the infundibulum, which is much distended and
in consequence more readily definable than usual, is free from
inflammatory exudate.

[Illustration:

Fig. 4.—Acute bronchopneumonia with peribronchiolar consolidation; a
respiratory bronchiole is in continuity with an alveolar duct and
two distended infundibula; alveoli about bronchiole, alveolar duct
and proximal part of infundibula contain polynuclear leucocytes, the
distal part of the infundibula showing no evidence of inflammation.
Autopsy 333.
]

Occasionally there is irregularly distributed hemorrhage and perhaps
some edema in the alveoli immediately adjacent to those which form the
peribronchiolar focus of inflammation. In such instances small bronchi,
that is, air passages, lined by columnar epithelium and devoid of
tributary alveoli, may be surrounded by a zone of hemorrhage;
immediately surrounding the bronchus, the wall of which shows intense
inflammation, alveoli, in a zone of which the radius represents several
alveoli, are filled with blood. This hemorrhagic zone is continued from
the bronchus over the focus of inflammation which surrounds the
bronchiole.

Another variation in the character of the lesion is doubtless referable
to variation in the severity of primary bronchial injury. Alveoli
immediately surrounding small bronchi are filled with dense plugs of
fibrin. The alveoli which besot the walls of the bronchioles contain
fibrin, but the alveolar duct and its tributary alveoli are filled with
polynuclear leucocytes.

The bacteria which have been cultivated from the lung in autopsies with
peribronchiolar pneumonia are as follows:

Pneumococcus 5
S. hemolyticus 8
B. influenzæ, pneumococcus 5
B influenzæ, S. hemolyticus 7
B. influenzæ, staphylococcus 1
Pneumococcus, staphylococcus 2
S. hemolyticus, staphylococcus 2
B. influenzæ, pneumococcus, S. hemolyticus 2
B. influenzæ, pneumococcus, staphylococcus 1
B. influenzæ, S. hemolyticus, staphylococcus 2
Pneumococcus, S. hemolyticus, staphylococcus 3
No organism 3
——
Total 41

The following list which shows the bacteria found in the blood is an
index to the pathogenicity of pneumococci and hemolytic streptococci:

Pneumococcus 22
S. hemolyticus 20
Pneumococcus, S. hemolyticus 1
No organism 14
——
Total 57

The percentage incidence of pneumococcus, hemolytic streptococcus,
staphylococcus and B. influenzæ in bronchus, lung and blood, given in
Table XXXVI, is inserted to indicate with what readiness each one of
these microorganisms passes from the bronchus through the lung into the
circulating blood.

TABLE XXXVI

══════════════╤═════════════╤═════════════╤══════════════╤═════════════
│PNEUMOCOCCUS │ HEMOLYTIC │STAPHYLOCOCCUS│B. INFLUENZA
│ │STREPTOCOCCUS│ │
──────────────┼─────────────┼─────────────┼──────────────┼─────────────
Bronchus │ 39.4%│ 57.7%│ 60.6%│ 84.8%
Lung │ 43.9%│ 61.0%│ 21.9%│ 43.9%
Blood │ 40.3%│ 36.8%│ 0. %│ 0. %
──────────────┴─────────────┴─────────────┴──────────────┴─────────────

B. influenzæ is present in the bronchi in a very large proportion (84.8
per cent) of those in whom this type of bronchopneumonia has been found
at autopsy; it is much less frequently recovered from the lungs.
Staphylococci, in part S. albus and in part S. aureus, are less
frequently found in the bronchi and are recovered from the lungs in a
relatively small proportion of autopsies. The percentage incidence of
pneumococci and streptococci in lungs and blood demonstrates the
pathogenicity of these microorganisms, for whereas pneumococci and
hemolytic streptococci are found in the consolidated lungs in 43.9 and
61.0 per cent of instances of the lesion respectively, they make their
way into the blood in 40.3 and 36.8 per cent of instances.

Coexisting infection with pneumococci and hemolytic streptococci has
been not uncommon e. g., Autopsy 275 in which both were in the blood; in
2 instances (Autopsies 333 and 378) in which pneumococci were obtained
from the blood, hemolytic streptococci were found in the lungs and
bronchi; in 3 instances (Autopsies 258, 273 and 445) in which hemolytic
streptococci were present in the blood, pneumococci were obtained from
the lungs.

In the group of autopsies under consideration, examination of the sputum
was made during life and after onset of pneumonia in 11 instances. The
microorganisms found in the sputum and at autopsy were as follows:

SPUTUM IN BLOOD, LUNGS OR BRONCHUS
AT AUTOPSY
Autopsy 240 Pneum. IV Pneum. IV
246 Pneum. atyp. II, B. inf.
247 Pneum. IV, B. inf. Pneum. IV
250 Pneum. atyp. II, B. inf. Pneum. atyp. II
253 Pneum. atyp. II Pneum. II
285 Pneum. atyp. II, B. Inf. S. hem., B. inf.
288 S. hem., B. inf. S. hem., B. inf.
291 Pneum. IV, B. inf. Staph., B. inf.
300 Pneum. atyp. II, B. inf. Pneum. atyp. II, B. inf.
312 Pneum. IV, S. hem., B. inf. S. hem., B. inf.
346 Pneum. IV, B. inf. S. hem., B. inf.

In 2 instances (Autopsies 285 and 346) among this small group of cases,
pneumococci but no hemolytic streptococci were found in the sputum
several days before death, whereas death occurred as the result of
secondary invasion with hemolytic streptococci and no pneumococci were
found at autopsy. It is probable that this sequence of events is not
uncommon. B. influenzæ finds its way into the bronchi and pneumococci
follow it; pneumonia limited to peribronchiolar alveoli may occur in
consequence of this invasion. Later hemolytic streptococci may follow
the same path and cause death with bacteremia.

=Hemorrhagic Peribronchiolar Consolidation.=—Peribronchiolar pneumonia
accompanied by diffuse accumulation of blood within the alveoli is one
of the most frequent complications of influenza. The lung tissue is
laxly consolidated, and on section there is a homogeneous dull deep red
background upon which are seen small gray spots (1.5 to 2 mm. in
diameter) grouped in clusters about the smallest bronchi (Fig. 5). Wide
areas of lung tissue are implicated and the lesion is more common in the
dependent parts of the lung than elsewhere. In common with other forms
of bronchopneumonia the lesion is in most instances associated with
changes in the bronchi; in 55 instances of hemorrhagic bronchiolar
pneumonia purulent bronchitis was found in 43 instances; it is
noteworthy that purulent bronchitis often is not evident in the presence
of pulmonary edema and edema is not infrequent with this pneumonic
lesion.

Microscopic examination demonstrates the presence of acute bronchitis;
the lumina of the small bronchi contain polynuclear leucocytes and red
blood corpuscles. Accumulation of blood may separate the epithelium from
the basement membrane. The mucosa immediately below the epithelium
contains polynuclear leucocytes in fair abundance and the blood vessels
of the bronchial wall are much engorged. Respiratory bronchioles are
distended with polynuclear leucocytes and red blood corpuscles. In a
zone about each bronchiole, in areas corresponding to the small gray
spots seen upon the cut surface of the lung, the alveoli are filled with
polynuclear leucocytes. In the lung tissue intervening between these
spots of leucocytic pneumonia the alveoli are distended with red blood
corpuscles.

[Illustration:

Fig. 5.—Bronchopneumonia with hemorrhagic peribronchiolar
consolidation.
]

In favorable sections it is occasionally possible to follow the
bronchiole and alveolar duct, both filled with leucocytes, into an
infundibulum. The proximal part of the infundibulum contains polynuclear
leucocytes, whereas the distal part and its tributary alveoli are filled
with serum and red blood corpuscles.

When the lesion has persisted for a short time there is evidence of
beginning migration of polynuclear leucocytes from the blood vessels
into the alveoli which are filled with blood. The alveolar walls contain
numerous polynuclear leucocytes and leucocytes which have entered the
intraalveolar blood are numerous in contact with the wall but occur in
scant number in the center of the alveolar lumen.

Alveolar epithelium in contact with the blood in the lumen is usually
swollen and often uniformly nucleated.

The inflammatory process is evidently transmitted from the bronchioles
and to a less degree from the small bronchi to the adjacent alveoli.
Polynuclear leucocytes fill the lumen of the bronchiole and the alveoli
immediately adjacent; at the periphery of the focus of pneumonia, the
alveoli may contain fibrin. In such instances small bronchi (lined by a
continuous layer of columnar epithelial cells) may be surrounded by
alveoli containing fibrin.

In sections from one part of the lung, the alveoli between the
peribronchiolar foci of pneumonia may be uniformly filled with red blood
corpuscles, whereas in sections from another part pneumonic foci may be
surrounded by a zone of intraalveolar hemorrhage or of hemorrhage and
edema outside of which some air-containing tissue occurs. There are
transitions between this halo of intraalveolar hemorrhage and edema
surrounding each bronchiolar focus and complete hemorrhagic infiltration
of all intervening alveoli.

Large mononuclear cells are occasionally fairly numerous within the
alveoli containing blood. These cells act as phagocytes ingesting red
corpuscles, so that at times they are filled with corpuscles.
Disintegration of red corpuscles occurs and brown pigment remains within
the cell. It is not uncommon to find numerous mononuclear pigment
containing cells which resemble those found with chronic passive
congestion of the lungs.

Lungs, the site of hemorrhagic peribronchiolar pneumonia, may undergo
chronic changes which will be described elsewhere.

The lesion which has been designated hemorrhagic peribronchiolar
pneumonia is that which Pfeiffer regarded as the characteristic type of
influenzal pneumonia. In the small bronchi containing pus and in lung
tissue, Pfeiffer states, influenza bacilli are predominant and present
in astonishing number in smear preparations. The demonstration of B.
influenzæ by cultures from pneumonic lung is mentioned by him but its
association with other microorganisms in such cultures is not discussed.

Microorganisms which we have isolated from the lungs of individuals with
hemorrhagic peribronchiolar pneumonia are as follows:

B. influenzæ 1
Pneumococcus 2
S. hemolyticus 10
B. influenzæ, pneumococcus 7
B. influenzæ, S. hemolyticus 3
B. influenzæ, staphylococcus 2
S. hemolyticus, B. coli 3
B. influenzæ, pneumococcus, staphylococcus 2
B. influenzæ, S. hemolyticus, staphylococcus 5
Pneumococcus, S. hemolyticus, staphylococcus 1
No organisms 2
——
Total 38

With this type of pneumonia B. influenzæ has not been isolated in pure
culture; B. influenzæ alone is recorded only once (Autopsy 435), but in
this instance the culture has been so obscured by contamination that the
occurrence of pneumococci or streptococci cannot be excluded; S.
hemolyticus has doubtless been present in this lung, for it has been
found in the heart’s blood, in the bronchus, and in the peritoneal
exudate of the same individual.

The incidence of pneumococci and hemolytic streptococci in this list
does not differ materially from that with peribronchiolar pneumonia
unaccompanied by extensive intraalveolar hemorrhage, though hemolytic
streptococci are somewhat more frequent with the hemorrhagic lesion. The
following table shows the frequency with which pneumococci and hemolytic
streptococci have penetrated into the blood:

Pneumococcus 11
S. hemolyticus 24
Pneumococcus, S. hemolyticus 1
No organism 12
——
Total 48

Table XXXVII showing the percentage incidence of pneumococci, hemolytic
streptococci, staphylococci and B. influenzæ further emphasizes the
similarity between the bacteriology of peribronchiolar pneumonia (Table
XXXVI) and the closely related hemorrhagic lesion:

TABLE XXXVII

══════════════╤═════════════╤═════════════╤══════════════╤═════════════
│ │ HEMOLYTIC │ │
│PNEUMOCOCCUS │STREPTOCOCCUS│STAPHYLOCOCCUS│B. INFLUENZÆ
──────────────┼─────────────┼─────────────┼──────────────┼─────────────
Bronchus │ 44.0%│ 64.0%│ 44.0%│ 72.0%
Lung │ 31.6%│ 57.9%│ 26.8%│ 52.6%
Blood of heart│ 25.0%│ 52.1%│ 0%│ 0%
──────────────┴─────────────┴─────────────┴──────────────┴─────────────

Pneumococci have been found in the lungs (31.6 per cent) and blood (25
per cent), somewhat less frequently than with peribronchiolar pneumonia
(43.9 and 40.3 per cent respectively), and hemolytic streptococci have
been found in the blood more frequently (52.1 per cent) than with the
latter (36.8 per cent) but otherwise the bacteriology of the two lesions
corresponds closely. The low incidence of B. influenzæ in the bronchi
(72 per cent) with hemorrhagic peribronchiolar pneumonia is perhaps
incorrect as the result of the relatively small number of bacteriologic
examinations (namely, 25), but the incidence of the same microorganism
in the lung has been higher (52.6 per cent) than with nonhemorrhagic
peribronchiolar lesion (43.9 per cent).

In some instances infection with hemolytic streptococci has occurred
after the onset of pneumonia. The following list compares the results of
bacteriologic examination of the sputum made after the onset of
pneumonia with that of blood, lungs or bronchus after death:

SPUTUM IN BLOOD, LUNGS OR BRONCHUS
AT AUTOPSY
Autopsy 237 S. hem. S. hem.
242 Pneum. atyp. II, B. inf. Pneum. atyp. II
247 Pneum. IV, B. inf. Pneum. IV
266 S. hem. S. hem., B. inf.
346 Pneum. IV, B. inf. S. hem., B. inf.
376 (No. S. hem.) S. hem., staph., B. inf.

Instances of secondary infection with hemolytic streptococcus occur in
the list, namely, Autopsies 346 and 376.

From the foregoing studies of the bacteriology of peribronchiolar and
hemorrhagic peribronchiolar pneumonia the following conclusions may be
drawn: (_a_) B. influenzæ is found in most instances of these lesions in
the bronchi and in about half of all instances in the lungs, but does
not occur unaccompanied by other microorganisms. (_b_) In a considerable
number of autopsies pneumococcus is the only microorganism that
accompanies B. influenzæ; from the lungs it penetrates into the blood
from which it is obtained in pure culture. (_c_) In a considerable
number of instances S. hemolyticus accompanies B. influenzæ, and in some
of these instances (representing a large proportion of the relatively
small number of cases examined during life), examination of the sputum
has demonstrated that infection has been secondary to a pneumonia with
which no hemolytic streptococci have been found in the sputum.

=Lobular Consolidation.=—Consolidation of scattered lobules or groups of
lobules has occurred in nearly all instances, namely, 71 of 80 autopsies
with bronchopneumonia unaccompanied by lobar pneumonia or by
suppuration. When death follows shortly after the onset of pneumonia,
patches of consolidation have a dull deep red color; blood-tinged fluid
escapes from the cut surface which is almost homogeneous or finely
granular. The consolidated tissue seen through the pleura, which is
raised above the general level, has a bluish red color. Isolated lobules
or groups of lobules which have undergone consolidation may be scattered
throughout the lungs, but not infrequently there is confluent
consolidation of the greater part of lobes, of whole lobes or of almost
an entire lung. Such lungs are very heavy and may weigh 1,400 or 1,500
grams; bloody serous fluid exudes from the cut surface. The lesion
resembles the red hepatization of lobar pneumonia, but confluent patches
of pneumonia are usually well defined by lobule boundaries. The tissue
is soft and the granulation of lobar pneumonia is absent. In many
instances the lobular or confluent areas of consolidation are reddish
gray; in some instances consolidated tissue is in places red and
elsewhere gray, and in a smaller group of autopsies there is gray
consolidation only (Fig. 6). Red lobular consolidation is often seen in
those who have died within the first four days following the onset of
pneumonia, but is almost equally frequent after from five to ten days;
the average duration of pneumonia in these cases was 5.5 days. Combined
red and gray consolidation was more frequently found when pneumonia had
lasted more than five days, the average duration of pneumonia being 7.3
days. The greater number of instances of gray consolidation were found
after seven days of pneumonia, the average duration of the disease being
10.0 days. These figures are cited to show that lobular, like lobar,
consolidation passes gradually from a stage of red to gray hepatization,
but the change occurs more slowly and is often long delayed.

Lobular pneumonia, which occurred 71 times among 80 cases classified as
bronchopneumonia, may be regarded as an almost constant lesion of the
disease. It is found not only in association with other lesions of
bronchopneumonia, but with lobar pneumonia of influenza as well.

The bacteriology of this lesion shows no deviation from that of the
slightly larger group of bronchopneumonia (p. 163). All types of
pneumococcus have been found in association with the lesion,
Pneumococcus I in 2 instances, Pneumococcus II in 1 instance; atypical
Pneumococcus II and Pneumococcus IV have been found much more
frequently. Pneumococci have been found in more than a third of these
autopsies (42.9 per cent in the lungs, 33.3 per cent in the blood);
hemolytic streptococci in less than one-third (28.5 per cent in the
lungs, 30.2 per cent in the blood).

[Illustration:

Fig. 6.—Acute bronchopneumonia with confluent gray lobular
consolidation in lower part of upper lobe and hemorrhagic
peribronchiolar pneumonia in lower lobe; purulent bronchitis.
]

The following list shows the bacteriology of a small group of autopsies
in which the sputum was examined after onset of pneumonia:

SPUTUM BLOOD, LUNGS OR BRONCHUS AT
AUTOPSY
Autopsy 233 Pneum. atyp. II Pneum.
237 S. hem. S. hem.
242 Pneum. atyp. II, B. inf. Pneum. atyp. II
250 Pneum. atyp. II, B. inf. Pneum. atyp. II
253 Pneum. atyp. II Pneum. atyp. II, staph., B.
inf.
266 S. hem. S. hem., B. inf.
274 Pneum. IV S. hem.
291 Pneum. IV, B. inf. Staph., B. inf.
312 Pneum. IV, S. hem., B. inf. S. hem., staph., B. inf.

In one instance of streptococcus pneumonia (Autopsy 274) infection with
streptococci occurred subsequent to the examination of the sputum made
five days before death; pneumococcus was found in the washed sputum.

With lobar pneumonia there was evidence that superimposed infection
occurred more frequently during the stage of red than of gray
hepatization. With the lobular consolidation of bronchopneumonia this
relation has not been found. Among 27 instances of red lobular
consolidation, hemolytic streptococcus has occurred 6 times, namely in
22.2 per cent; among 26 instances of red and gray consolidation, 8
times, namely, in 30.7 per cent; among 13 instances of gray
consolidation, 5 times, namely, in 38.5 per cent. Infection with
hemolytic streptococci is more frequent when the lesion has persisted to
the stage of gray hepatization. This difference between lobar and
bronchopneumonia is probably dependent in part at least upon the more
severe and persistent lesions of the bronchi with bronchopneumonia.

The histology of consolidation which is definitely limited to secondary
lobules or groups of lobules varies considerably. When death occurs in
the early stage of the lesion, consolidated patches are deep red and
somewhat edematous, so that bloody serous fluid escapes from the cut
surface of the lung and red blood corpuscles are present in the alveoli
in great abundance together with polynuclear leucocytes, fibrin and
serum in varying quantity. It is not uncommon to find evidence that the
lesion has had its origin in the bronchioles and extended from them to
other parts of the lobule. Polynuclear leucocytes may be relatively
abundant within and immediately about the bronchioles and alveolar
ducts, whereas the intervening alveoli and infundibula are filled with
red blood corpuscles among which are polynuclear leucocytes and perhaps
some fibrin. It may be evident that bronchiolar pneumonia with
hemorrhage into intervening alveoli is in process of transformation into
a more diffuse leucocytic pneumonia, for polynuclear leucocytes are
making their way from the alveolar wall into the blood-filled lumen and,
as the result of the presence of blood, remain for a time close to the
lining of the alveolus.

When the consolidated lobules have assumed a gray or reddish gray color,
polynuclear leucocytes are more abundant and often almost homogeneously
pack every alveolus within the boundaries of the lobule. In some
instances there is fibrin partially obscured by the presence of
leucocytes in great number.

Although fibrin is less abundant with bronchopneumonia than with lobar
pneumonia, nevertheless in a considerable proportion of instances it is
a very conspicuous element of the inflammatory exudate within the
bronchioles, alveolar ducts and alveoli. It is unusual to find the
alveolar ducts and alveoli uniformly plugged with fibrin containing
leucocytes; there is a variegated distribution of exudate which has
little resemblance to that of lobar pneumonia. Occasionally (Autopsies
242 and 247) polynuclear leucocytes fill the bronchioles, alveolar ducts
and infundibula, whereas the surrounding tributary alveoli contain
fibrin and polynuclear leucocytes in moderate number; red blood
corpuscles may be present in sufficient number to give a homogeneously
red color to the lobular consolidation.

In association with lobular pneumonia, fibrin within the lung tissue
undergoes certain changes which outline very sharply the alveolar ducts
and the other structures usually ill defined in preparations of the
lung. A remarkable appearance is produced by the deposit of hyalin
fibrin upon the surface of the alveolar ducts and infundibula. This
lesion has been described by LeCount.

Within the alveolar tissue of the lung, spaces are seen lined by a layer
of fibrin which stains homogeneously and very brightly with eosin. They
are recognized as alveolar ducts by the presence of scattered bundles of
smooth muscle in their wall. The layer of hyaline fibrin overlying the
surface of the alveolar duct usually forms a continuous lining and
covers over the orifices of the alveoli which surround the alveolar
duct. These ducts are rendered still more conspicuous by the character
of their contents which exhibits a sharp contrast with that of the
surrounding alveoli. The alveoli duct occasionally contains a bubble of
air, but more frequently it is filled with serum in which red blood
corpuscles are sometimes numerous. There is within the lumen scant
fibrin and very few cells, among which polynuclear leucocytes are
predominant. In the surrounding alveoli on the contrary leucocytes and
fibrin are abundant. A similar change is found in the infundibula very
clearly defined by their conical form, which is especially well outlined
below the pleura or in contact with interlobular septa. The infundibulum
is outlined by hyaline fibrin which passes over the orifices of the
tributary alveoli and separates the serous contents of the infundibulum
from the cellular fibrinous contents of the alveoli about.

The lesion which has been described is often associated with acute
bronchitis and bronchiolitis, and the alveoli immediately about the
respiratory bronchioles may be filled with polynuclear leucocytes. It is
very common to find large bubbles of air sharply defined within the
purulent contents of the bronchiole. In some lobules the alveolar ducts,
infundibula and alveoli intervening between these foci of leucocytic
pneumonia are almost uniformly filled with fibrin and polynuclear
leucocytes, but in other places the formation of complete layers of
hyaline fibrin is in process. Bubbles of air are often seen within the
alveolar ducts, and about them is an irregular layer of fibrin formed by
the penetration of air into a channel previously filled with a loose
network of fibrin containing serum in its meshes. The fibrin compressed
against the walls of alveolar duct and infundibulum remains as a compact
layer separating these structures from the alveoli which project from
their walls. The bubble of air is doubtless later absorbed and replaced
by serum, so that many alveolar ducts are filled with serum almost
wholly free from cells, whereas alveoli outside the fibrinous membrane
contain a network of fibrin with leucocytes in greater or less
abundance.

In association with this fibrinous pneumonia, which has been described,
hyaline thrombosis of the capillaries is not uncommon. This hyalin
material within the capillaries gives reactions of fibrin, and in
sections stained by the Gram-Weigert method for demonstration of fibrin,
these thrombosed vessels have the appearance of capillaries irregularly
injected with a blue material.

The interstitial tissue surrounding consolidated lobules is often
edematous; the lymphatics are distended with serum and contain a
moderate number of lymphocytes and polynuclear leucocytes.

Among the lungs which have been studied histologically, pneumococcus has
been almost invariably associated with the lobular lesions which have
just been described, whether hemorrhagic, leucocytic or fibrinous; the
histologic changes accompanying infection of the lung with streptococcus
will be described later. Pneumococcus has been cultivated from the
consolidated lung and is found in section of the lung. B. influenzæ is
found in cultures made from the bronchi. Table XXXVIII includes those
instances in which the histology of the consolidated lung accords with
the description given above.

TABLE XXXVIII

══════════╤═════════════╤════════════╤═══════════╤══════════╤══════════
NO. OF │CHARACTER OF │PREDOMINANT │ CULTURE │ CULTURE │ CULTURE
AUTOPSY │ LOBULAR │ TYPE OF │ FROM │FROM LUNG │ FROM
│CONSOLIDATION│INFLAMMATORY│ HEART’S │ │ BRONCHUS
│ │ EXUDATE │ BLOOD │ │
──────────┼─────────────┼────────────┼───────────┼──────────┼──────────
242 │ Red │ Fibrinous │ Pneum. │ │
│ │ │ atyp. II │ │
244 │ Red │ Leucocytic │ │Pneum. IV │Pneum. IV,
│ │ and │ │ B. inf. │ B. inf.
│ │hemorrhagic │ │ │
247 │Red and gray │ Fibrinous │ Pneum. IV │ │
249 │Red and gray │ Fibrinous │Pneum. III │ │
252 │Red and gray │ Fibrinous │ │Pneum. II │Pneum. II,
│ │ │ │ B. inf. │ B. inf.,
│ │ │ │ │ S. vir.
257 │Red and gray │ Leucocytic │ Pneum. I │ │ B. inf.,
│ │ │ │ │ staph.
303 │ Red │ Fibrinous │ │Pneum. IV │Pneum. IV,
│ │ │ │ B. inf. │ B. inf.,
│ │ │ │ │ staph.
314 │ ? │ Fibrinous │ Pneum. IV │Pneum. IV │Pneum. IV,
│ │ │ │ │ B. inf.,
│ │ │ │ │ staph.
336 │ Red │ Fibrinous │ │ │
395 │Red and gray │ Leucocytic │ Pneum. │ Pneum. │
│ │ │ atyp. II │ atyp. II │
464 │ Red │ Leucocytic │ │ Pneum. I │Pneum. I,
│ │ and │ │ B. inf. │ B. inf.,
│ │hemorrhagic │ │ │ staph.
476 │ Red │ Leucocytic │ │ │
│ │ and │ │ │
│ │hemorrhagic │ │ │
498 │Red and gray │ Fibrinous │ │ S. aur. │
506 │ Red │ Fibrinous │ Pneum. IV │Pneum. IV │Pneum. IV,
│ │ │ │ S. aur. │ B. inf.,
│ │ │ │ │ S. aur.,
│ │ │ │ │M. catarrh
──────────┴─────────────┴────────────┴───────────┴──────────┴──────────

Pneumococcus was found in all but 2 instances, and in one of these
(Autopsy 336) the only culture was from the heart’s blood and in the
other (Autopsy 498) cultures were unsatisfactory because proper media
were not obtainable. Pneumococci of Types I, II, II atypical, III and IV
are represented in the list. B. influenzæ has been found in a
considerable number of instances in which cultures have been made from
the lung and in every instance in which cultures have been made from the
bronchi. Staphylococci are often found in the bronchi, but in most
instances they do not penetrate into the lung.

Another group of cases of lobular pneumonia are important because in
association with necrosis of lung tissue recognized by the microscope
hemolytic streptococci have been found in the lungs. In such instances
serum is abundant and polynuclear leucocytes are relatively scant though
their distribution varies considerably; in some places leucocytes are
fairly abundant though elsewhere almost absent, but this distribution
bears no obvious relation to the bronchioles. In some instances
(Autopsies 274 and 487) red blood corpuscles are numerous but in others
(Autopsies 275 and 312) they are inconspicuous. The characteristic
feature of the lesion is the occurrence of patches of necrosis within
which the nuclei both of exudate and of alveolar walls have partially or
completely disappeared. In these areas of necrosis short chains of
streptococci are found in immense number whereas in living tissue they
are present in moderate number. There has been a relatively inactive
inflammatory reaction, great proliferation of streptococci and necrosis
of invaded tissue. The bacteriology of instances of lobular pneumonia
with necrosis is shown in Table XXXIX.

TABLE XXXIX

Lobular pneumonia, in some of these instances at least, has been caused
primarily by pneumococci; necrosis has been the result of secondary
invasion by streptococci. In Autopsy 275 Pneumococcus IV has been
obtained from the blood, but in the presence of streptococci has
presumably disappeared from the lung and bronchus. In the case
represented by Autopsy 274, Pneumococcus IV has been found in the sputum
five days before death at the onset of pneumonia, but at this time no
hemolytic streptococci have been found. In the case represented by
Autopsy 312, Pneumococcus IV, B. influenzæ and a few colonies of
hemolytic streptococci have been obtained from the sputum two days after
recognition of pneumonia and five days before death.

The hemorrhagic and edematous consolidation of the early pulmonary
lesions of influenzal pneumonia is their most distinctive feature. Red
confluent lobular pneumonia is frequently found in those who have died
within the first week following the onset of influenza. The lungs are
voluminous and heavy and may weigh as much as 1,500 grams; the pleura
which overlies the consolidated area is blue or plum colored and usually
shows scant if any evidence of pleurisy. Scattered patches of
consolidation are accurately limited to lobules, but in addition there
are large areas often involving the greater part of the lobes and not
infrequently situated in the lowermost part of the lower lobes. This
confluent consolidation may be obviously limited by lobule boundaries.
The consolidated tissue is deep red and laxly consolidated; red serous
fluid escapes from the cut surface. The lesion not infrequently occurs
in association with hemorrhagic peribronchiolar pneumonia.

The histology of this confluent lesion has been studied in Autopsies
242, 244, 303, 336, 464, 474 and 506. The histology varies, because, in
some instances, leucocytes, in other instances, fibrin, is abundant, but
the presence of red blood corpuscles in large number within the alveoli
gives a red color to the consolidated tissue. In these cases
pneumococci, associated in the lungs or in the bronchi with B.
influenzæ, have been the cause of pneumonia. In two autopsies studied
histologically (Autopsies 274 and 478) there was red lobular and
confluent pneumonia and the blood and lungs contain hemolytic
streptococci demonstrated by cultures; microscopic examination showed
the presence of a widespread necrosis of the lung tissue.

In the group of autopsies in Table XL there was red confluent lobular
pneumonia. These autopsies are separated from those just cited because
there was no histologic examination of the tissue.

TABLE XL

═════════════════╤═════════════════╤═════════════════╤═════════════════
NO. OF AUTOPSY │ BACTERIOLOGY OF │ BACTERIOLOGY OF │ BACTERIOLOGY OF
│ HEART’S BLOOD │ LUNGS │ BRONCHUS
─────────────────┼─────────────────┼─────────────────┼─────────────────
289 │ Pneum. IV │ Pneum. IV │ Pneum. IV, B.
│ │ │ inf., staph.
297 │ │ Pneum. IV, B. │ Pneum. IV, B.
│ │ inf. │inf., S. hem. (a
│ │ │ few)
306 │ │ │
339 │ Pneum. IV │ │
364 │ S. hem. │ │
418 │ Pneum. atyp. II │Pneum. atyp. II, │
│ │B. inf., S. vir. │
424 │ │ Pneum. IV. │
─────────────────┴─────────────────┴─────────────────┴─────────────────

This group of autopsies confirms the view that the red confluent lobular
pneumonia is caused by pneumococci in association with B. influenzæ.
Hemolytic streptococci may invade secondarily. In Autopsy 297 a few
hemolytic streptococci were found in the bronchus but apparently had not
entered the lungs. In the absence of histologic examination it is not
possible to determine if the invasion of hemolytic streptococcus (in
Autopsy 364) has caused necrosis of the pneumonic tissue.

[Illustration:

Fig. 7.—Bronchopneumonia with purulent bronchitis and peribronchial
hemorrhage.
]

Peribronchial Hemorrhage and Pneumonia

In a considerable number of instances, namely, in 19 autopsies,
hemorrhage about the small bronchi has been recognizable upon gross
examination of the lung. A conspicuous zone of hemorrhage 2 or 3 mm. in
thickness surrounds small (with no cartilage) often dilated bronchi and
on longitudinal section may be tracted for a considerable distance along
the bronchus (Fig. 7). In many additional instances peribronchial
hemorrhage has been found by microscopic examination. In some instances
the peribronchial zone of hemorrhage is firmer than the tissue elsewhere
and it is occasionally difficult to determine whether the lesion is
hemorrhage or pneumonia. In 7 instances frank red consolidation of
peribronchial tissue was recognized at autopsy; this lesion will be
considered later under peribronchial pneumonia. Hemorrhage about
bronchi, like other evidences of severe injury to bronchi following
influenza, is more frequently found in the lowermost parts of the lungs
than elsewhere. It is invariably associated with severe bronchitis; the
bronchi have contained purulent fluid in 15 of 19 instances of
peribronchial hemorrhage and in 10 instances the lesion has been
associated with dilatation of the bronchi.

Microscopic examination furnishes further evidence of the severity of
the bronchial changes which have brought about hemorrhage into the
surrounding alveoli. The lumen of the bronchus contains blood and
leucocytes; the epithelium is sometimes raised in places from the
underlying basement membrane by blood; blood vessels of the bronchial
wall are engorged, and there is hemorrhage into the tissue of the
bronchus. More frequently the bronchial epithelium is completely lost
and the denuded surface is often covered by a layer of fibrin intimately
adherent to the inflamed mucosa. Transitions between simple hemorrhage
and pneumonia are found, polynuclear leucocytes being mingled with red
blood corpuscles. In several instances the alveoli in immediate contact
with the bronchial wall have contained fibrin, whereas those in the
surrounding zone have contained blood.

Bacteria found in the bronchi in 10 instances of peribronchial
hemorrhage have been as follows:

Staphylococci 1
B. influenzæ, pneumococci 1
B. influenzæ, S. hemolyticus 2
B. influenzæ, pneumococci, staphylococci 1
B. influenzæ, S. hemolyticus, staphylococci 4
No organism found 1

The high incidence of B. influenzæ and the frequent association of B.
influenzæ and hemolytic streptococci are noteworthy. The instance in
which no organisms were found is probably due to a defect in media and
should perhaps be excluded from the list.

The percentage incidence of pneumococci, hemolytic streptococci,
staphylococci and B. influenzæ in the bronchus, lungs and blood of the
heart is an index of the facility with which these microorganisms
penetrate internal organs when the bronchi are the site of this
hemorrhagic lesion.

TABLE XLI

════════╤════════╤═════════════════╤═════════════════
│ NO. OF │ │ HEMOLYTIC
│CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI
────────┼────────┼────────┬────────┼────────┬────────
│ │ NO. │PER CENT│ NO. │PER CENT
│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────┼────────
Bronchus│ 10│ 2│ 20.0│ 6│ 60.0
Lung │ 13│ 4│ 30.8│ 7│ 53.8
Blood │ 17│ 4│ 23.5│ 9│ 52.9
────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════
│ │
│ STAPHYLOCOCCI │ B. INFLUENZÆ
────────┼────────┬────────┼────────┬────────
│ NO. │PER CENT│ NO. │PER CENT
│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────
Bronchus│ 6│ 60.0│ 8│ 80.0
Lung │ 3│ 23.1│ 5│ 38.5
Blood │ │ │ │
────────┴────────┴────────┴────────┴────────

When these figures are compared with those for all forms of bronchitis
no very noteworthy differences are found; the incidence of pneumococci
here is less and that of hemolytic streptococci greater. In association
with the severe changes present in the bronchi, hemolytic streptococci
which enter the lungs almost invariably find their way into the blood.

In 6 instances there has been frank pneumonic consolidation limited to a
zone encircling small and medium-sized bronchi which have often been
obviously dilated. On cross section these patches of pneumonia are
circular, from 1 to 2 cm. in diameter and each contains a bronchus at
its center. When the bronchus is cut longitudinally it is evident that
pneumonic consolidation forms a cylindrical sheath about the tube. The
consolidation varies in color from red to grayish red. In one instance
(Autopsy 253) the consolidated tissue has formed a gray zone in contact
with the bronchus and is red in a peripheral zone; microscopic
examination shows that the alveoli about the bronchus contain fibrin,
whereas those at a greater distance contain red blood corpuscles. In
this instance, the associated pneumonia in another part of the lung has
been somewhat anomalous and has had characters both of lobar and
bronchopneumonia, for scattered in the left lung there have been patches
of firm consolidation not more than 2 cm. across. The smaller of these
patches are deep red, but the larger are coarsely granular and gray in
the center. The patchy character of the lesion has suggested
bronchopneumonia, but the coarse granulation on section and the presence
of fibrinous plugs within the small bronchi have presented a close
resemblance to lobar pneumonia. This autopsy is one of the few instances
in which Pneumococcus II has been found, Pneumococcus II being present
in blood and lungs, B. influenzæ, in lungs and bronchi. In 2 additional
instances (Autopsies 374 and 392) peribronchial pneumonia, recognizable
at autopsy, has been associated with consolidation having the characters
of lobar pneumonia. In one instance, Autopsy 374, the right lung has
contained two patches of firm, mottled red and pinkish red coarsely
granular consolidation each about 6 cm. across, one situated in the
upper lobe and the other in the lower lobe. Elsewhere in the lung, in
definite relation to dilated bronchi, occur patches of firm, red,
coarsely granular consolidation from 1 to 1.5 cm. in diameter when cut
transversely. The bronchus in the center has contained purulent fluid.
In the opposite lung similar consolidation has been limited to zones
about dilated bronchi which contain purulent fluid. Pneumococcus IV has
been obtained from the blood of the heart.

The peribronchial pneumonia which has been described occurs in
association with evidence of profound injury to the bronchial wall. In 5
of 6 instances purulent bronchitis has been found at autopsy; in half of
these instances bronchiectasis has been noted. The epithelium of the
bronchus has been found separated from the underlying tissue by serous
exudate, blood and leucocytes; epithelial cells undergo necrosis and
disappear, the denuded surface being covered by fibrin. Necrosis extends
a varying depth into the wall of the bronchus; blood vessels are
engorged, and there is in some instances hemorrhage throughout the wall
of the bronchus.

The character of the exudate in the alveoli surrounding the bronchus
differs considerably in different instances. In some instances
(Autopsies 374 and 392) red blood corpuscles are predominant in the
alveoli in contact with the bronchial wall, whereas in a peripheral zone
polynuclear leucocytes are more abundant. In other instances (Autopsies
253 and 402) alveoli next the bronchial wall contain abundant fibrin and
these are surrounded by a zone in which the alveoli are filled with
blood.

Peribronchial pneumonia is the result of the direct extension of the
inflammatory process through the wall of the bronchus; it occurs when
the epithelium of the bronchus is destroyed and the underlying tissues
are injured, but may be present in a wide encircling zone even when the
lesion has not penetrated the bronchial wall. The distribution of the
pneumonia demonstrates very clearly that the inflammatory process does
not reach the affected peribronchial alveoli by way of the bronchioles
tributary to the bronchus.

The bacteriology of these instances of peribronchial pneumonia is
noteworthy. (Table XLII.)

TABLE XLII

═════════════════╤═════════════════╤═════════════════╤═════════════════
AUTOPSY │ BLOOD │ LUNG │ BRONCHUS
─────────────────┼─────────────────┼─────────────────┼─────────────────
253 │Pneum. II │Pneum. II, B. │Staph., B. inf.
│ │ inf. │
374 │Pneum. IV │ │
387 │Pneum. II, S. │Pneum. II, │Pneum. II, S.
│ hem. │ staph., B. inf.│ hem., staph.,
│ │ │ B. inf.
392 │Pneum. II │ │
402 │Pneum. IV, S. │ │
│ hem. │ │
424 │? │Pneum. IV │
─────────────────┴─────────────────┴─────────────────┴─────────────────

Pneumococcus has been found in every instance either in the lungs or
blood. Pneumococcus II, which has been uncommon with the pneumonia
following influenza at Camp Pike and has occurred only ten times in more
than 200 autopsies, has been present in one-half of these cases. The
constant association of the lesion with pneumococcus is particularly
significant when a comparison is made between the incidence of
pneumococcus with peribronchial hemorrhage, on the one hand, and
peribronchial pneumonia on the other; pneumococcus has been present in
less than a third of the instances of hemorrhage but in all instances of
pneumonia.

In addition to the instances in which gross peribronchial consolidation
has been noted at autopsy, microscopic examination has demonstrated the
presence of fibrinous pneumonia surrounding bronchi in a considerable
number of autopsies. In a zone encircling small bronchi (with no
cartilage) alveoli are filled by plugs of dense fibrin (Fig. 20)
containing in variable number polynuclear leucocytes and mononuclear
cells. The width of the zone is often equal or greater than the diameter
of the bronchus. Alveoli outside the zone of fibrinous inflammation may
contain red blood corpuscles or serum, and desquamated epithelial cells
are often abundant.

Of 21 instances of peribronchial fibrinous pneumonia 20 were associated
with purulent bronchitis. Further evidence of the relation of the lesion
to profound injury to the bronchi is its association with bronchiectasis
in 17 instances.

Peribronchial fibrinous pneumonia, like other lesions encircling the
small bronchi, bears a direct relation to the severity of microscopic
changes in the bronchus. The epithelium of the bronchus is either
partially or completely lost. Occasionally epithelium is raised by
hemorrhage or leucocytes from the underlying tissue but more frequently
it is wholly lost and the surface is covered by a layer of fibrin. In
the early stages of the lesion, polynuclear leucocytes may be numerous
throughout the bronchial wall, indicating that the inflammatory irritant
within the lumen is affecting the entire wall and extending its
influence to the surrounding pulmonary tissue. Later lymphoid and plasma
cells are more abundant than polynuclear leucocytes. Coagulative
necrosis and disintegration of the bronchial wall, proceeding from the
inner surface outward, may extend more or less deeply, and fibrinous
inflammation of adjacent alveoli is often more extensive about that
segment of the bronchus which shows the greatest change. In some
instances segments of the bronchial wall or even the entire wall has
disappeared, so that alveoli containing fibrin form part of the wall of
the cavity thus formed. When bronchiectasis has occurred, there are
often fissures from the lumen through the entire wall extending into the
surrounding lung tissue: here fibrinous pneumonia is particularly
conspicuous, occurring in a zone about the edges of the defect. This
deposition of fibrin within the alveoli adjacent to the injury doubtless
has a part in limiting the distribution of bacterial infection.
Nevertheless breaks in the continuity of the bronchial wall are not
essential to the production of the lesion and the irritant, which is
responsible for the lesion, may penetrate through the bronchial wall to
surrounding alveoli and from alveoli to other alveoli immediately
adjacent.

With this peribronchial pneumonia the smallest bronchi are distended
with pus and their walls are infiltrated with polynuclear leucocytes,
lymphoid and plasma cells. In a broad zone encircling the bronchus the
alveoli are filled with plugs of fibrin. Bronchioles are similarly
distended with polynuclear leucocytes; the alveoli which occur upon the
wall of the bronchiole are often limited to one side of the wall and are
filled with fibrin. This fibrin occasionally projects into the lumen of
the bronchiole and forms a continuous layer in contact with the wall on
the same side. The alveolar duct and infundibulum are distended with
polynuclear leucocytes. The alveoli upon the wall of the alveolar duct
and upon the proximal part of the infundibulum are filled with fibrin.
The bronchus, bronchiole, alveolar duct and part of the infundibulum are
thus surrounded by a continuous zone of alveoli containing fibrin. The
alveoli about the distal part of the infundibulum may be filled with
polynuclear leucocytes. Lung tissue between adjacent zones of fibrinous
pneumonia may contain serum and desquamated epithelial cells.

Organization of peribronchial fibrin was found in 10 of the 22 autopsies
in which peribronchial fibrinous pneumonia had been found. Fibroblasts
have invaded the fibrin and newly formed capillaries have penetrated
into it. In some instances the interalveolar septa are thickened and
infiltrated with lymphoid and plasma cells, and in 7 instances there was
chronic pneumonia with thickening and mononuclear infiltration of the
interstitial tissue about the bronchi and blood vessels, and elsewhere.
The duration of the fatal illness in 12 instances with no organization
was usually from ten days to two weeks, though in 3 instances there was
no organization although the respiratory disease had lasted from
seventeen to nineteen days (average duration with no organization, 13.5
days). The duration of illness in 10 instances with organization of
fibrin was slightly less than three weeks (average 18.9 days). These
figures do not accurately represent the duration of pneumonia which
usually develops after a period of several days following onset of
influenza.

This group of instances of peribronchial fibrinous pneumonia has offered
an opportunity to study the bacteriology of pneumonia with organization
and to determine if it presents any unusual characters. The bacteriology
of autopsies with peribronchial fibrinous pneumonia with no organization
is shown in Table XLIII:

TABLE XLIII

═════════════════╤═════════════════╤═════════════════╤═════════════════
AUTOPSY │ BLOOD │ LUNG │ BRONCHUS
─────────────────┼─────────────────┼─────────────────┼─────────────────
289 │Pneum. IV │Pneum. IV │Pneum. IV, B.
│ │ │ inf., staph.
372 │ │ │
376 │S. hem. │S. hem. │S. hem., B. inf.,
│ │ │ S. aur.
409 │0 │ │
410 │ │S. hem., B. inf. │
│ │ S. aur. │
412 │Pneum. II │ │Pneum. II, B.
│ │ │ inf.
420 │S. hem. │S. hem., B. inf. │
│ │ S. aur. │
423 │S. hem. │S. hem., B. inf. │
440 │0 │B. inf., S. aur. │B. inf., S. aur.
448 │0 │0 │0
482 │0 │B. inf., Pneum. │B. inf., Pneum.
│ │ IV │ IV, S. hem.
489 │0 │Pneum. IV, B. │Pneum. IV, B.
│ │ inf. │ inf.
─────────────────┴─────────────────┴─────────────────┴─────────────────

The bacteriology of instances of peribronchial fibrinous pneumonia with
organization of the intraalveolar fibrin is shown in Table XLIV:

TABLE XLIV

═════════════════╤═════════════════╤═════════════════╤═════════════════
AUTOPSY │ BLOOD │ LUNG │ BRONCHUS
─────────────────┼─────────────────┼─────────────────┼─────────────────
283 │Pneum. IV │Staph., B. inf. │B. inf., Pneum.
│ │ │ IV, staph.
291 │0 │0 │B. inf., staph.
398 │0 │ │
419 │0 │Pneum. II, B. │Pneum. II, B.
│ │ inf. │ inf.
421 │S. hem. │Pneum. IV, S. │
│ │ hem. │
422 │0 │Pneum. II atyp., │
│ │ B. inf. │
425 │S. hem. │S. hem., B. inf.,│
│ │ S. alb. │
433 │0 │S. hem., B. inf.,│
│ │ S. aur. │
460 │S. hem. │S. hem., B. inf. │S. hem., B. inf.,
│ │ │ staph.
463 │0 │B. inf., staph. │B. inf., staph.,
│ │ │ Pneum. IV
─────────────────┴─────────────────┴─────────────────┴─────────────────

B. influenzæ has been present in the bronchi in every instance save one
in which cultures have been made, and it is probable that in this
exceptional instance cultures have remained sterile because the media
employed have been defective. The incidence of B. influenzæ in the lung
has been unusually high both with and without organization (66.7 per
cent with no organization; 77.8 per cent with organization).
Streptococci and staphylococci have been found in a considerable
proportion of all instances of peribronchial fibrinous pneumonia, but
there has been no notable preponderance of these microorganisms when
organization has occurred. Organization has been present in instances in
which pneumonia is referable to pneumococcus associated with B.
influenzæ and unaccompanied by either streptococci or staphylococci
(Autopsies 419 and 422). Wadsworth[81] found no organization after
inoculation of the lungs of dogs with pneumococcus or with
staphylococcus alone, but produced organization when he inoculated
animals with both microorganisms.

Injury to bronchi produced in part at least by B. influenzæ exposes the
bronchi and lung tissue to repeated infection with a variety of
microorganisms; absorption of fibrin and regeneration of alveolar
epithelium are prevented, resolution fails to occur and organization of
fibrin follows.

Suppurative Pneumonia With Necrosis and Abscess Formation

Three varieties of suppurative pneumonia have occurred in association
with influenza.

A. Necrosis and suppuration with formation of one or several abscesses
usually below the pleura and almost invariably caused by hemolytic
streptococci.

B. Interstitial suppurative pneumonia caused by hemolytic streptococcus.

C. Multiple abscesses in clusters caused by staphylococci.

Suppurative pneumonia with necrosis and abscess formation will be
discussed in this section. Pulmonary abscesses which occurred in 43
autopsies may be included in this group; in 4 of these autopsies abscess
and interstitial suppurative pneumonia occurred in the same individual.
These abscesses were much more frequently situated in the lower than in
the upper lobes and more often in the right than in the left lung. In
most instances there was one or several abscesses situated below the
pleura of one lobe; occasionally abscesses occurred in two lobes of the
same lung or in both lungs. The distribution was as follows: Abscess in
only one lung occurred in right upper lobe in 6 autopsies; middle lobe,
3; lower lobe, 15; left upper lobe, 2; lower lobe, 16. Abscesses
occurred in both right and left lower lobes, twice. The usual situation
was at the lower and posterior part of the lower lobe at or near the
basal edge, less frequently below the posterior border or upon the basal
surface of the lobe. These abscesses in almost every instance were found
immediately below the pleural surface, so that they appeared upon the
pleura as opaque yellow spots usually surrounded by narrow zones of
hemorrhage. In one instance (Autopsy 376) the abscess cavity was
separated from the pleural cavity by remains of the pleura which was as
thin as tissue paper and in other instances perforation had occurred
(Fig. 9). In Autopsy 480 the abscess cavity which had perforated the
pleura was in free communication with a bronchus of medium size.

In most instances of suppurative pneumonia there have been associated
lesions of bronchopneumonia which have been peribronchiolar, hemorrhagic
or lobular and have exhibited no unusual characters. The abscess or
abscesses are situated within an area of pneumonic consolidation which
is not limited by lobule boundaries and has not the characters of
bronchopneumonic consolidation. In some instances this consolidation is
limited to a zone immediately about the abscess, but often it involves
the greater part of a lobe. The tissue is laxly consolidated and flabby;
on section it has a dull, conspicuously cloudy appearance and is grayish
red, pinkish gray or gray; it is homogeneous or very finely granular.
Turbid gray fluid, which sometimes resembles thin pus, oozes from the
cut surface.

Widespread necrosis of tissue is not infrequently a conspicuous feature
of this pyogenic pneumonia (Fig. 8). Upon a cloudy gray background of
consolidation are numerous opaque yellowish gray or yellow patches,
occasionally 2 or 3 cm. across, giving a mottled character to the cut
surface. Upon the pleura these necrotic patches appear as dull opaque
yellow spots. They may be surrounded by a zone of hemorrhage. The opaque
material is at first firm but may undergo softening, becoming semisolid
and finally purulent. Necrotic patches may be scattered throughout a
lobe, but fully formed abscesses are with few exceptions immediately
below the pleura (Fig. 9).

[Illustration:

Fig. 8.—Streptococcus pneumonia with massive necrosis. Autopsy 354.
]

[Illustration:

Fig. 9.—Abscess below pleura with perforation caused by hemolytic
streptococci. Healing suppurative interstitial pneumonia indicated
by yellowish gray lines marking interlobular septa at base of lower
lobe. Autopsy 474; right lung. (See left lung, Fig. 10.)
]

The duration of illness in cases of pneumonia with abscess varied from a
week or less (11 instances) to more than four weeks. The duration of the
greater number of cases (17 instances) was between one and two weeks. In
one instance onset occurred with symptoms of influenza, pneumonia was
recognized two days later, and death occurred only four days after the
onset of illness. When the duration of the illness was less than a week
the symptoms of onset were in some instances those of pneumonia.

Table XLV shows the incidence of pneumococcus, S. hemolyticus,
staphylococcus and B. influenzæ in instances of suppurative pneumonia
with abscess formation, 4 instances of abscess with interstitial
suppurative pneumonia being excluded:

TABLE XLV

════════╤════════╤═════════════════╤═════════════════
│ NO. OF │ │ HEMOLYTIC
│CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI
────────┼────────┼────────┬────────┼────────┬────────
│ │ NO. │PER CENT│ NO. │PER CENT
│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────┼────────
Bronchus│ 24│ 5│ 20.8│ 22│ 91.6
Lung │ 36│ 9│ 25.0│ 30│ 83.3
Blood │ 37│ 6│ 16.2│ 31│ 83.8
────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════
│ │
│ STAPHYLOCOCCI │ B. INFLUENZÆ
────────┼────────┬────────┼────────┬────────
│ NO. │PER CENT│ NO. │PER CENT
│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────
Bronchus│ 12│ 50.0│ 18│ 75.0
Lung │ 14│ 35.6│ 8│ 22.2
Blood │ │ │ │
────────┴────────┴────────┴────────┴────────

In over 80 per cent of instances of pulmonary abscess hemolytic
streptococcus has been found in blood, lungs and bronchus and, when
cultures have been made, in the inflamed pleural cavity as well.
Streptococci have been found in immense number in sections from the
necrotic lung tissue and the abscesses which have been formed. It is
evident that hemolytic streptococci have caused suppurative pneumonia
and death, being found in the blood of the heart just as frequently as
in the lungs (83 per cent). The relative unimportance of pneumococci is
indicated by their low incidence in the blood (16.2 per cent) when
compared with that of lobar pneumonia (65.5 per cent) or of
bronchopneumonia (31.4 per cent). B. influenzæ has been found in
three-fourths of these autopsies in the bronchus, but its incidence in
the lungs has been much smaller.

In 3 instances of suppurative pneumonia with abscess formation no
hemolytic streptococci were found; they are as follows:

=Autopsy 380.=—Bronchopneumonia with gray and red lobular
consolidation in right upper and lower lobes; peribronchiolar
nodules of consolidation in left lower lobe; abscess, 1.5 cm.
across, below the pleura of the posterior border of the left lower
lobe near its base; fibrinopurulent pleurisy (300 c.c.) on right
side; serous pleurisy (200 c.c.) on left. Pneumococcus III was found
in cultures from the blood of the heart from the right lung and with
B. influenzæ from the right pleural cavity. No culture was made from
the left lung which contained the abscess. In sections of the
abscess gram-positive streptococci in chains of 4 to 8 cocci were
numerous.

=Autopsy 406.=—Acute lobar pneumonia with red hepatization of
greater part of right lung; patch of consolidation in lower lobe of
left lung containing an abscess cavity 2.5 x 1.5 cm.; localized
seropurulent pleurisy (375 c.c.) on left side. Pneumococcus IV was
obtained from the blood of the heart; a culture from the lung was
contaminated. Tissue from the abscess was not saved for histologic
examination.

=Autopsy 416.=—Suppurative pneumonia with necrosis and abscess
formation in right lower lobe; fibrinous pleurisy on right side.
Pneumococcus IV was obtained from the blood, right lung and right
main bronchus. No streptococci were found in sections from the
abscess in the right lung.

The foregoing observations demonstrate that suppurative pneumonia with
abscess formation following influenza is with few exceptions caused by
S. hemolyticus.

The autopsies (Table XLVI) in which pneumococci have been found in
association with hemolytic streptococci in the blood or lungs indicate
that pneumococci have had a part in the production of fatal pneumonia.

TABLE XLVI

═════════════════╤═════════════════╤═════════════════╤═════════════════
AUTOPSY │ CULTURE FROM │ CULTURE FROM │ CULTURE FROM
│ BLOOD │ LUNGS │ BRONCHUS
─────────────────┼─────────────────┼─────────────────┼─────────────────
258 │S. hem. │S. hem., Pneum. │
│ │ IV B. inf. │
282 │S. hem., Pneum. │S. hem., Pneum. │S. hem., B. inf.
│ II │ II │ Pneum. II,
│ │ │ staph.
345 │ │S. hem., Pneum. │
│ │ II, staph. │
378 │Pneum. atyp. II │S. hem., Pneum. │S. hem., B. inf.,
│ │ atyp. II │ Pneum. atyp. II
381 │S. hem. │S. hem., Pneum. │
│ │ II Pneum. IV, │
│ │ staph. │
383 │Pneum. III │S. hem., Pneum. │
│ │ III B. inf. │
387 │S. hem. │Pneum. II, │S. hem., pneum.,
│ │ staph., B. inf.│ staph., B. inf.
─────────────────┴─────────────────┴─────────────────┴─────────────────

These autopsies, notably those in which pneumococci have been found in
the blood, suggest that infection with pneumococci has preceded
suppurative pneumonia caused by hemolytic streptococci. In a small
number of instances the sputum was examined in life after onset of
pneumonia.

TABLE XLVII

═══════╤═══════════════════════════════╤═══════════════════════════════
AUTOPSY│ SPUTUM │CULTURES FROM BLOOD, LUNGS AND
│ │ BRONCHUS
───────┼───────────────────────────────┼───────────────────────────────
282 │Pneum. IV. B. inf. │S. hem., Pneum. II, staph., B.
│ │ inf.
288 │S. hem., B. inf. │S. hem., B. inf.
376 │(No S. hem., Oct. 8) │S. hem., staph., B. inf. (Oct.
│ │ 11)
───────┴───────────────────────────────┴───────────────────────────────

In 2 of these 3 cases infection with hemolytic streptococcus occurred
subsequent to the onset of pneumonia.

Several observations help to explain the occurrence of abscess in
association with the pneumonia of influenza. The fissures which will be
described in association with bronchiectasis represent traumatic
ruptures of the bronchial wall consequent upon weakening by necrosis and
over distention. They expose the injured bronchial wall and the alveolar
tissue adjacent to it to infection by the microorganisms contained
within the lumen of the inflamed bronchus. Occasionally a favorable
microscopic section demonstrates the relation of pulmonary necrosis and
consequent suppuration to injuries of the bronchial wall. Peribronchial
fibrinous pneumonia occurs about the bronchi of which the epithelial
lining has been destroyed, and when a fissure penetrates the bronchial
wall fibrinous pneumonia is almost invariably found in a zone about the
tear; it doubtless tends to limit the extension of the process.
Occasionally, wide areas of necrosis occur within consolidated tissue
near the site of the fissure (Autopsy 312 with S. hemolyticus and B.
influenzæ, p. 254). Accumulation of polynuclear leucocytes between
living and dead tissue may form a line of demarcation (Autopsy 387);
finally, fairly large, irregularly formed, abscess cavities are found.

Necrosis and beginning suppuration in contact with the lumen of the
bronchus will be described in association with bronchiectasis (Autopsies
312, Fig. 24, and 423, p. 256). In the following autopsies upon
individuals who have died with pulmonary abscesses, favorable
microscopic sections have demonstrated abscess formation in contact with
lesions which have penetrated the walls of small bronchi. They help to
explain the pathogenesis of abscess in association with influenza.

=Autopsy 376.=—H. M., white, aged twenty-four, a fireman, resident
of Oklahoma, had been in military service one month. Onset of
illness occurred October 1, ten days before his death; he was
admitted to the base hospital on the fourth day of his illness with
the diagnosis of bronchopneumonia.

=Anatomic Diagnosis.=—Acute bronchopneumonia with patches of lobular
and confluent lobular consolidation in both lungs and hemorrhagic
peribronchiolar consolidation in right upper lobe; abscess in right
upper lobe below pleura; fibrinopurulent pleurisy on right side;
purulent bronchitis; bronchiectasis at base of left lobe.

An irregular abscess, 2 x 1 cm., filled with creamy purulent fluid
is separated from the interlobular surface of the right upper lobe
by a thin membrane representing the pleura. The right pleural cavity
contains 200 c.c. of turbid yellow fluid in which is soft fibrin.
The bronchi contain purulent fluid in great abundance. The bronchi
at the base of the left lower lobe are widely dilated, so that many
small bronchi with no cartilage in their wall measure from 3 to 5
mm. in diameter.

Cultures show the presence of hemolytic streptococci in the blood of
the heart and in three plates from the lung; B. influenzæ and S.
aureus were found in the left bronchus.

The bronchi have wholly or partially lost their epithelium and there
is deep erosion of the walls. Cavities containing polynuclear
leucocytes occur within the alveolar tissue; in some instances pus
containing cavities are surrounded by alveolar tissue, but in other
places it is evident, that they have had their origin in bronchi. In
a short segment of the circumference the wall of the preexisting
bronchus is preserved and consists of squamous epithelium, vascular
connective tissue and smooth muscle. The remainder of the bronchus
has disappeared and a cavity is produced. The very irregular wall of
the cavity is formed by partially destroyed alveoli filled with
fibrin and leucocytes.

=Autopsy 387.=—C. M., white, aged twenty-one, laborer, resident of
Mississippi, had been in military service twenty-one days. Illness
began on September 22, nineteen days before death, and the patient
was admitted to the hospital on the same day with a diagnosis of
bronchitis; a diagnosis of bronchopneumonia was made on October 2,
nine days before death. The leucocytes on October 3 numbered 8000
(small mononuclear, 36 per cent; large mononuclear, 5 per cent;
polynuclear, 59 per cent).

=Anatomic Diagnosis.=—Acute bronchopneumonia with consolidation in
right upper lobe and hemorrhagic peribronchiolar consolidation in
left lower lobe; abscess below pleura in left lower lobe; purulent
pleurisy on both sides; edema of mediastinum; purulent bronchitis;
bronchiectasis.

There is advanced bronchiectasis, and bronchi with no visible
cartilage are dilated to from 4 to 8 mm. in diameter; they contain
purulent fluid which wells up from the cut surface. About dilated
bronchi there is in places dull red or grayish red consolidation
forming an encircling zone. Situated below the pleural surface
within an area of consolidation at the posterior border of the left
lower lobe there is a spot 3 cm. across where the tissue is yellow
and has in places undergone purulent softening. Several smaller
abscesses occur nearby.

Cultures from the blood of the heart and from the edematous
mediastinum contain hemolytic streptococci. From the abscess are
grown S. albus, Pneumococcus II and B. influenzæ. The purulent
contents of a small bronchus contains S. hemolyticus, B. influenzæ,
S. aureus and a few pneumococci.

Microscopic examination shows that the epithelium of dilated bronchi
has disappeared and the denuded surface is covered by fibrin and
polynuclear leucocytes; fissures extend from the lumen through the
bronchial wall into the surrounding alveolar tissue. A zone of
fibrinous pneumonia surrounds these bronchi and fissures in the
bronchial wall penetrate into this zone. One dilated bronchus 2.4
mm. in diameter with no cartilage in its wall has vascular
connective tissue covered by epithelium on one side, whereas the
remainder of the circumference is formed by exposed alveoli filled
with fibrin, the bronchial wall having disappeared. A section
through a part of the abscess which has been mentioned shows a very
irregularly formed cavity approximately 1 x 0.7 cm. Remains of
bronchial wall, consisting of very vascular tissue covered by flat
epithelium in several layers, indicate the origin of the cavity.
Between these remnants of bronchi deep pockets extend into the
pulmonary tissue which in the margin of the cavity is the site of
fibrinous pneumonia. In one place, in contact with the cavity, a
wide area of consolidated tissue has undergone necrosis and both
alveolar walls and their contents have lost their nuclei. Leucocytes
which are accumulating at the margin of the necrotic patch form a
line of demarcation between living and dead tissue.

Abscess may be the result of the profound changes which occur in the
bronchi as the result of influenza. Necrosis caused by bacteria within
the bronchi weakens and in places destroys the wall. Bacteria penetrate
into the surrounding tissue and hemolytic streptococci (or
staphylococci) may produce localized abscesses. These abscesses are
usually situated near the pleural surface of the lung, because
destructive changes causing rupture of the bronchial wall occur more
frequently in the smaller peripheral bronchi than in the larger bronchi
containing cartilage. Abscesses occur more frequently at the bases of
the lungs, because the most severe changes in the bronchi occur in the
dependent part. (See “Bronchiectasis,” p. 240.)

=Healing of Abscess.=—The following autopsy is of interest in relation
to the treatment of pulmonary abscess and associated empyema.

=Autopsy 467.=—P. C., white, aged twenty-five, a farmer from
Missouri, had been in military service three months. Illness began
September 27, thirty days before death, and the patient was admitted
the day following onset with headache, backache and cough. Pneumonia
with consolidation in the right lower lobe was recognized on the
sixth day of illness. On the ninth day 500 c.c. of fluid were
withdrawn from the right pleural cavity; there were cyanosis and
dyspnea. On the eleventh day 700 c.c. of fluid were withdrawn. On
the twelfth day thoracotomy was performed and 100 c.c. of greenish
fluid were removed. The patient’s condition improved for a time, but
on the twenty-sixth day 1,000 c.c. of straw colored fluid were
aspirated from the left pleural cavity and on the twenty-eighth day
the same amount of seropurulent fluid was withdrawn.

=Anatomic Diagnosis.=—Healing abscess of right lower lobe
communicating with the pleural cavity; acute purulent pleurisy with
closed thoracotomy wound on the right side; purulent pleurisy on the
left side; acute bronchopneumonia with lobular consolidation in the
left lung; purulent bronchitis; bronchiectasis with formation of
spherical bronchiectatic cavities; acute splenic tumor.

At the base of the right chest is a closed thoracotomy wound 2 cm.
in length; the right pleural cavity contains 200 c.c. of thick
creamy pus and the cavity is lined by a thick tough membrane. The
left pleural cavity contains 800 c.c. of white purulent fluid
thinner than that on the right side. The right lung is compressed
into the posterior and inner part of the chest. The upper lobe is
pink and air containing; the posterior and lower part of the lower
lobe is red and atelectatic, and fibrous septa are more conspicuous
than elsewhere. The pleura of the external surface near the basal
edge, in an area 2 cm. across, is depressed and yellowish gray in
color. In the center of this area is a small opening communicating
with a pocket 0.5 cm. across within the substance of the lung.

In the lower lobe beneath the interlobular surface are two spherical
bronchiectatic cavities, each about 1.5 cm. across, with smooth
lining in continuity with two branches of the same bronchus of
medium size.

Bacteriologic examination showed the presence of S. hemolyticus in
the blood of the heart. No growth was obtained from the left lung;
the left pleural cavity contained hemolytic streptococci and S.
aureus, the latter in small number. S. hemolyticus and B. influenzæ
were grown from the left main bronchus.

A microscopic section through the abscess and its communication with
the pleura shows that its cavity contains polynuclear leucocytes and
the wall is formed by granulation tissue covered by fibrin. Some
alveoli outside the abscess contain compact balls of fibrin
containing a few fibroblasts; this fibrin stains deeply with
hematoxylin as if it contained calcium. The surface of the lung is
covered by fibrin in process of organization.

In the foregoing instance a pulmonary abscess on the right side has
ruptured into the pleura and, completely separated from the adjacent
lung by a wall of newly formed tissue, is in process of healing. It
shows that these pulmonary abscesses below the pleura may heal provided
drainage is established by rupture into the pleural cavity and
subsequent evacuation of pleural exudate. It is noteworthy that in this
instance empyema extended from the right to the left pleural cavity,
both S. hemolyticus and S. aureus were found at autopsy. The thoracotomy
wound on the right side was closed at autopsy.

Interstitial Suppurative Pneumonia

A second type of suppurative pneumonia is characterized by acute
inflammation of interstitial tissue between the secondary lobules of the
lung and by acute lymphangitis; suppuration involves the interstitial
septa and the walls of the lymphatics. The lesion is designated by
Kaufmann,[82] Beitzke[83] and others acute interstitial pneumonia.
_Pneumonia dissecans_ in which solution of interstitial tissue isolates
sections of lung tissue is said to be a consequence of the lesion. Many
text books of pathology, overlooking the occurrence of this lesion,
limit the consideration of interstitial pneumonia to chronic processes
in which the interlobular and interalveolar fibrous tissue is increased.

Acute inflammation and edema of the interlobular septa of the lung with
no suppuration is often found with both lobar and bronchopneumonia and
is occasionally so far advanced that it can be recognized on gross
examination of the lungs. In a small area interlobular septa are
conspicuous as yellowish lines of edematous appearance which may be 1 to
1.5 mm. in thickness and sometimes form a network with rectangular or
polygonal meshes. The gelatinous appearance of the edematous fibrous
tissue does not suggest suppuration. Microscopic examination shows that
the tissue is distended by edema and contains fibrin and polynuclear
leucocytes; the lymphatics are distended and contain a network of fibrin
within which leucocytes are numerous. Inflammatory edema of the
interstitial tissue has been recognized at autopsy four times in
association with bronchopneumonia (Autopsy 253 with Pneumococcus II;
Autopsy 335, with Pneumococcus IV and S. viridans; Autopsy 477 with S.
hemolyticus and Autopsy 498 with S. viridans); twice with lobar
pneumonia (Autopsy 343 with Pneumococcus IV and Autopsy 353 with
atypical Pneumococcus II); twice with combined lobar and broncopneumonia
(Autopsy 273 with S. hemolyticus and Pneumococcus IV and Autopsy 357
with Pneumococcus IV). Edema of interstitial septa was recognized at
autopsy in the immediate neighborhood of an abscess three times
(Autopsies 277 and 278 with hemolytic streptococci and Autopsy 282 with
hemolytic streptococci and Pneumococcus II). In these instances of
inflammation and edema the lymphatics are found distended by fibrinous
thrombi, and it is probable that occlusion of lymphatics determines the
occurrence of inflammatory edema within the surrounding tissue.
Inflammation has not proceeded to suppuration.

With interstitial suppurative pneumonia, interlobular connective tissue
is marked by conspicuous yellow lines, 1 to 3 or even 5 mm. in
thickness, forming a network with polygonal meshes which represent
secondary lobules (Figs. 10 and 11). The distended septa not
infrequently have bead-like enlargements at intervals and from the cut
surface it is often possible to scrape away creamy yellow pus. These
lines of suppuration invariably extend up to the pleura and are often
broadest immediately below it. Adjacent septa which have not undergone
suppuration are much thickened and have the yellowish gray appearance
produced by edema.

[Illustration:

Fig. 10.—Interstitial suppurative pneumonia; interstitial septa are
the site of suppuration and lymphatics are distended with purulent
fluid; empyema. Autopsy 474, left lung. (See right lung) Fig. 9.
]

[Illustration:

Fig 11.—Suppurative interstitial pneumonia; the left lower lobe is the
site of almost uniform consolidation and here interstitial septa and
their lymphatics are distended with pus. There is more extensive
interstitial suppuration in the upper lobe where consolidation is
absent. The cloudy appearance of the consolidated lung is well
shown. Autopsy 452.
]

Suppurative interstitial pneumonia frequently occurs in association with
bronchopneumonic consolidation which may be peribronchiolar, hemorrhagic
or lobular, but there is in addition consolidation of the pulmonary
tissue between the inflamed septa which may affect part of a lobe, an
entire lobe, or parts of several lobes; it does not exhibit the
characters of confluent lobular pneumonia.

In approximately half of the cases consolidation, associated with
interstitial suppuration, has been lobar in distribution (Fig. 11). The
tissue is laxly consolidated, finely granular, and has a cloudy red or
gray appearance. The coarsely granular surface of lobar pneumonia is
absent. The affected lung may weigh 1,500 or 1,650 grams. Occasionally,
interstitial septa of air containing lung tissue is the site of
suppurative inflammation or edema. In Autopsy 452 the lower lobe, save a
small part at the base, is laxly consolidated; interstitial septa in the
consolidated area are yellow, 1.5 to 2 mm. in thickness, beaded and
exude purulent fluid on pressure. In the adjacent part of the upper lobe
there is a patch of consolidation, and a network of yellow thickened
septa extends from it far into the surrounding air containing tissue.
The weight of the right lung is 635 grams; of the left, 1,650 grams.

The distribution of interstitial suppuration in 21 instances, including
4 in which the lesion has occurred in the same lungs with abscess
formation, has been as follows: right upper lobe, 9 instances; middle
lobe, 4; lower lobe, 5; left upper lobe, 7; left lower lobe, 6. In 6 of
these autopsies more than one lobe of the same lung has been affected by
the lesion; in 2 autopsies parts of both lungs have been affected.
Localized abscess of the lung is more common in the lower than in the
upper lobes, but suppuration of the interstitial tissue is more often
found in the upper lobes.

The duration of illness with interstitial suppurative pneumonia has
varied from six days to five weeks. In over half of the cases death has
occurred during the second week of illness.

The bacteriology of these cases is shown in Table XLVIII.

TABLE XLVIII

════════╤════════╤═════════════════╤═════════════════
│ NO. OF │ │ HEMOLYTIC
│CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI
────────┼────────┼────────┬────────┼────────┬────────
│ │ NO. │PER CENT│ NO. │PER CENT
│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────┼────────
Bronchus│ 10│ │ │ 9│ 90.0
Lung │ 20│ 1│ 5.0│ 17│ 85.0
Blood │ 21│ 2│ 9.5│ 17│ 81.0
────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════
│ │
│ STAPHYLOCOCCI │ B. INFLUENZÆ
────────┼────────┬────────┼────────┬────────
│ NO. │PER CENT│ NO. │PER CENT
│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────
Bronchus│ 5│ 50.0│ 10│ 100.0
Lung │ 5│ 25.0│ 7│ 35.0
Blood │ │ │ │
────────┴────────┴────────┴────────┴────────

S. hemolyticus has been almost invariably present in lungs, heart’s
blood and bronchi. In 16 of 21 autopsies hemolytic streptococci have
been obtained from the blood in pure cultures, in one instance
associated with pneumococcus. With associated empyema, pericarditis or
peritonitis, the same microorganism has been found in the pleural
cavities, pericardium or peritoneum. Furthermore, microscopic
examination has demonstrated the presence of chains of streptococci in
the affected interlobular tissue and in much greater abundance in the
distended lymphatics.

Nevertheless in 2 instances no streptococci have been found. These cases
are as follows:

=Autopsy 330.=—Illness began with symptoms of influenza ten days
before death; signs of pneumonia were recognized three days before
death. There is firm, gray red consolidation of the entire left
upper lobe; the interlobular septa are here indicated by yellow
lines of obvious suppuration and thick puslike fluid exudes from the
cut surface of the consolidated tissue. The upper half of the left
lower lobe has undergone gray hepatization, but here there is no
distention of the interlobular septa. There is fibrinopurulent
pleurisy on the left side with accumulation of 400 c.c. of fluid.
Pneumococcus IV is obtained from the blood of the heart and from the
lung. In the suppurating tissue diplococci which stain by Gram’s
method are present in large number; there are a few short chains.

=Autopsy 379.=—Illness began seven days before death with influenza;
signs of pneumonia were first recognized the day before death. The
middle lobe of the right lung is firmly consolidated; on section
there is mottling of deep red and pinkish red and the cut surface is
coarsely granular. The interstitial septa are distended by fluid and
are grayish yellow. There is fibrinopurulent pleurisy on the right
side with accumulation of 600 c.c. of fluid. Pneumococcus atypical
II is obtained from the blood of the heart. A large bacillus
unstained by Gram’s method is obtained from the right lung and from
the right main bronchus. In the bronchus are a few influenza
bacilli. In the suppurating and necrotic tissue of the interstitial
septa are found diplococci and chains of 4 to 6 cocci in great
number; a few large Gram-negative bacilli are found.

In both these autopsies consolidation had the characters of lobar
pneumonia, and pneumococci were obtained from the blood of the heart. It
is possible that streptococci failed to grow or while present elsewhere
were absent at the spot where cultures were made.

It is noteworthy that B. influenzæ was found in the bronchi in every
instance (10) in which cultures were made, but was obtained much less
frequently from the lung. In one instance (Autopsy 474) this
microorganism was found in the blood in association with hemolytic
streptococci. There was suppurative interstitial pneumonia in the left
lung and abscess in the right lower lobe with rupture into the cavity
and empyema. Hemolytic streptococci and B. influenzæ were found in the
bronchus, right pleural cavity and blood of the heart.

In 4 instances (Autopsies 251, 259, 295 and 474) interstitial
suppurative pneumonia has been associated with abscess formation. In one
instance (Autopsy 251) the right middle lobe has been the site of
interstitial suppuration and abscess formation; in another (Autopsy 295)
the left lower lobe has been the site of both lesions, but in the other
2 instances suppurative interstitial pneumonia and abscess formation
have occurred in opposite lungs. In all 4 autopsies hemolytic
streptococci have been found in the blood of the heart and in lungs or
bronchi.

Empyema has been present in all but 3 of 21 instances of interstitial
suppurative pneumonia.

[Illustration:

Fig. 12.—Suppurative interstitial pneumonia, showing an immensely
dilated lymphatic containing purulent exudate, a short distance
below the pleura. Autopsy 474.
]

Histologic examination of lungs with interstitial suppuration shows that
the interlobular septa are distended by serum and contain a conspicuous
network of fibrin. Polynuclear leucocytes are present in varying number,
and at times densely infiltrate the distended tissue; it is not uncommon
to find a zone of densely crowded polynuclear leucocytes along each edge
of the septum, whereas the central part contains comparatively few.
Occasionally, there is hemorrhage into the distended connective tissue.

Within the distended septa occur greatly dilated lymphatics filled with
polynuclear leucocytes (Figs. 12 and 13). Thrombosis of the distended
lymphatics has usually occurred, and a conspicuous network of fibrin in
which are polynuclear leucocytes plugs the lumen. Streptococci in chains
of variable length are found in the inflamed interstitial tissue, but
are present in far greater number within the distended lymphatics.

[Illustration:

Fig. 13.—Suppurative interstitial pneumonia showing a dilated
lymphatic. Autopsy 428.
]

Necrosis of the cells which fill the lymphatics occurs in spots, usually
in the center of the thrombus, and occasionally affects the entire
contents of the lymphatic; polynuclear leucocytes have lost their nuclei
or in some the nucleus has undergone fragmentation. In these spots the
network of fibrin has disappeared. Not infrequently the wall of the
lymphatic in a small sector or throughout the circumference has
undergone necrosis, and spots of necrosis may occur in the interlobular
septa distended by inflammatory exudate. Wherever necrosis has occurred,
chains of streptococci are present in immense number.

Accumulation of polynuclear leucocytes, necrosis of these cells,
solution of fibrin at first in the centers of the lymphatic thrombus and
later throughout, occasionally with necrosis of the wall of the vessel,
result in the formation of an abscess at the site of the distended
lymphatic. These lymphatics, dilated by purulent fluid, may have a
diameter from 2 to 3 mm. and may cause considerable compression and
collapse of immediately adjacent alveoli. Lymphangitis, distention of
lymphatics, thrombosis and finally suppuration may occur in the
lymphatic vessels encircling the blood vessels and in those situated in
the adventitia of the bronchi of medium size.

The alveoli adjacent to the distended septa are filled by inflammatory
products; edema is almost invariably present and the alveoli may contain
serum and desquamated epithelial cells; fibrin is often present, but
more frequently polynuclear leucocytes are predominant. Not
infrequently, abscess formation, recognized microscopically, has
occurred in contact with septa most often immediately below the pleura.
Polynuclear leucocytes are present in immense number and alveolar septa
have disappeared; occasionally, with abscess formation there is more or
less widespread necrosis of tissue, cells both of the exudate and of the
alveolar walls having lost their nuclei.

Lymphatics in many places are distended and plugged by fibrinous
thrombi, whereas elsewhere softening of the thrombus has been brought
about by suppuration. Suppuration, both within the lymphatic and in
adjacent alveoli, appears to be secondary to lymphatic obstruction. In
some instances the lymphatic appears to have undergone distention after
the thrombus has formed, for between the thrombus and the wall of the
lymphatic a channel is occasionally found containing uncoagulated lymph.

[Illustration:

Fig. 14.—Endophlebitis occurring in association with suppurative
pneumonia; the intima contains lymphoid cells in great number; at
one spot there is a small thrombus adherent to the intima. Autopsy
325.
]

Acute endophlebitis has been repeatedly observed in association with
interstitial suppurative pneumonia (Fig. 14). The lesion usually occurs
in veins situated within the septa which are the site of intensely acute
inflammation associated with necrosis. The wall of the vein appears to
be so injured by the surrounding changes that polynuclear leucocytes and
small mononuclear cells accumulate below the endothelium. Throughout the
circumference of the veins, often 0.5 to 1 mm. in diameter, the
endothelium is separated from the underlying media by polynuclear
leucocytes which form a conspicuous zone encircling the lumen. Some
cells of lymphoid type are usually present among the polynuclear
leucocytes. Polynuclear leucocytes are often adherent to the endothelial
lining of the vessel and are not infrequently fixed in the process of
passing through the endothelium. The lesion may be more severe (Autopsy
325), so that the endothelium has disappeared, and upon the exposed
surface fibrin is deposited; within this fibrin polynuclear leucocytes
are numerous and nuclear fragmentation has occurred. The middle coat of
the vessel usually contains few cells; some polynuclear leucocytes
within it may be stretched out as if in process of wandering through the
wall.

In other instances the accumulation of cells below the endothelium is
almost wholly mononuclear. Cells of the type of lymphocytes occur, but
more abundant are slightly larger cells with more abundant cytoplasm.
These cells may form a thick zone below the intima throughout the entire
circumference of the lesion. It seems probable that these cells, like
the polynuclear leucocytes, are derived from circulating blood within
the lumen of the vessel, for small cells of the type of lymphocytes are
not infrequently found adherent to the lumen and occasionally one is
fixed in process of passing through the endothelium.

This endophlebitis appears to be the result of changes outside the
vessel; there is usually necrosis of the adjacent tissue and the
production of the lesion is favored by lymph stasis; as the result of
injury to the vessel wall, polynuclear leucocytes in response to
chemotaxis, or with milder irritation, mononuclear cells, wander through
the endothelium and accumulate below it perhaps on account of the
greater impermeability of the middle coat to the passage of cells.

The lesion described does not occur exclusively with interstitial
suppurative pneumonia caused by hemolytic streptococci, but has been
found in association with abscess formation (Autopsies 354 and 383)
caused by hemolytic streptococci or (Autopsy 322) caused by
staphylococci. In 1 instance it has been found with lobar pneumonia
(Autopsy 320) caused by atypical Pneumococcus II and in 2 instances with
combined lobar and bronchopneumonia (Autopsy 357 with Pneumococcus IV;
Autopsy 392 with Pneumococcus II). In these 3 instances there has been
interstitial inflammation, edema and lymphangitis without suppuration.

Interstitial suppurative pneumonia of long standing may occasionally be
accompanied by chronic changes which bring about thickening of the
interlobular tissue. In the following autopsy acute suppurative
inflammation in the left lung has been associated with conspicuous
thickening of interlobular septa in the right lung.

=Autopsy 474.=—I. H., white, aged twenty-one, was a native of
Oklahoma and had been in military service one month. His illness
began with influenza thirty-six days before death; he was admitted
to the base hospital thirty-one days before his death with signs of
pneumonic consolidation of the right lower lobe. Evidence of fluid
in the right pleural cavity was obtained two weeks before death, and
from 100 to 700 c.c. of thick purulent fluid were aspirated on five
occasions. Hemolytic streptococci were found in the aspirated fluid.

=Anatomic Diagnosis.=—Interstitial suppurative pneumonia in left
lung; abscess of right lower lobe with rupture into pleural cavity;
thickening of interlobular septa of right lower lobe; double
purulent pleurisy with thoracotomy on right side; serofibrinous
pericarditis.

The right pleural cavity contains 85 c.c. of thick purulent fluid; the
right lung (Fig. 9) is collapsed and pushed to the median line, being
bound by firm adhesions to the pericardium. Over the external and basal
surfaces is a localized cavity walled off by adhesions. An abscess
cavity in the lower part of the lower lobe communicates through a
perforation in the basal surface of the lung with the pleural cavity and
is in free communication with a small bronchus. About the abscess the
lung is red and laxly consolidated, but elsewhere air containing;
throughout the lower half of the lower lobe, the interlobular septa are
marked by conspicuous yellowish gray lines about 1 mm. in thickness.
Between these thickened septa the lung tissue contains air. The lung
weighs 600 grams. The left lung (Fig. 10) is voluminous and heavy,
weighing 1,320 grams. The surface is everywhere covered by thickened
pleura and fibrin, the pleural cavity containing 150 c.c. of thick
purulent fluid. The lung is consolidated varying in color from a fleshy
red to yellowish gray. The surface is very conspicuously marked by
yellow lines 2 or 3 mm. thick, corresponding to the interlobular septa
which have undergone suppuration. The septa have bead-like swellings
along their course, and when pus escapes from the cut surface small
cavities remain at the site of these swellings.

Bacteriologic examination has shown hemolytic streptococci in the blood,
left lung, right and left pleural cavities, and right bronchus. B.
influenzæ has been found in the bronchus, in the right pleura and in the
heart’s blood. A few colonies of S. aureus have been found on the plate
from the right pleural cavity (site of thoracotomy).

Microscopic examination of the right lower lobe shows that the
interstitial septa are much thickened by young fibrous tissue
infiltrated with lymphoid and a few plasma cells. Large mononuclear
cells with granular cytoplasm are very numerous. A lymphatic is much
distended and contains a few polynuclear leucocytes and many lymphoid
and large mononuclear cells. There is no suppuration. Sections from the
right lung show suppurative lymphangitis with suppurative inflammation
of interstitial tissue.

The right lung is the site of a healing lesion of the interstitial
tissue which has developed simultaneously with acute interstitial
suppurative pneumonia in the left lung. Both lesions are doubtless
caused by S. hemolyticus. This healing lesion exhibits little similarity
to the interstitial bronchopneumonia described by several observers with
both measles and influenza.

The following autopsy furnishes further evidence that interstitial
suppurative pneumonia exhibits a tendency to heal. Proliferation of
endothelial cells lining the inflamed lymphatics gives rise to
phagocytic cells which aid in removing the accumulated leucocytes.

=Autopsy 397.=—N. P., white, aged twenty-one, farmer, a native of
Oklahoma, had been in military service twenty-one days. Illness
began twenty-two days before death, the patient being admitted on
the day following onset with influenza, pharyngitis and bronchitis.
A diagnosis of lobar pneumonia was made fourteen days before death.
The left pleural cavity was aspirated twelve days later and 800 c.c.
of thick yellow pus were withdrawn. Hemolytic streptococci were
found in the sputum five days before death.

=Anatomic Diagnosis.=—Interstitial suppurative pneumonia in left
upper lobe; acute bronchopneumonia with lobular consolidation in
right upper lobe; localized purulent pleurisy on left side with
compression and atelectasis of left lung; compensatory emphysema of
right lung; purulent bronchitis; beginning serofibrinous
pericarditis; chronic passive congestion of liver, spleen and
kidneys.

The right lung is very voluminous, free from coal pigment and bright
pink save over lobular patches of consolidation which have a bluish
red color; the bronchi contain mucopurulent material. The anterior
surface of the left lung is bound to the chest wall by firm
adhesions, but over the external and posterior surfaces of the lung
there is a localized cavity containing 1,100 c.c. of turbid fluid.
The left lung is collapsed and airless with deep fleshy red color.
In the upper lobe there are scattered patches of consolidation 1.5
to 2.5 cm. across where the tissue is grayish red and coarsely
granular. In the adjacent tissue interstitial septa are thickened to
1 or 2 mm. and are conspicuous as gray bands. Along their course
occur bead-like swellings from which purulent fluid can be scraped.
These septa at one point reach the anterior surface of the lung
where the pleural cavity is in large part obliterated by adhesions;
here there is an encapsulated pocket 4 x 1.5 cm. containing thick
creamy pus.

Bacteriologic examination of the blood shows the presence of
hemolytic streptococci; cultures from the lungs contain hemolytic
streptococci and B. influenzæ.

Microscopic examination shows that interlobular septa are thickened
and infiltrated with plasma cells in large number. Leucocytes in the
center of much dilated lymphatics have undergone necrosis and have
lost their nuclear stain. About the periphery of the lumen and
evidently derived from the swollen endothelial cells which surround
it, are numerous large mononuclear cells. They act as phagocytes and
ingest polynuclear leucocytes. Multinucleated giant cells, derived
from these cells, occur. In several places thrombosed lymphatics in
process of organization occur; the lumen is filled with compact
fibrin which is invaded by fibroblasts and newly formed capillaries.

The process just described is analogous to that which occurs whenever an
unopened abscess heals; mononuclear cells accumulate and act as
phagocytes ingesting polynuclear leucocytes.

The following instance of streptococcus empyema is noteworthy because no
suppurative pneumonia has been found in association with it.
Nevertheless the character of the changes present in the lung indicate
that the organ has been the site of an interlobular inflammation which
has healed.

=Autopsy 499.=—J. H. M., white, aged twenty-four, a farmer from
Arkansas, had been in military service five months. Onset of illness
began two weeks before his admission to the hospital on November 15
with cough, fever, headache and malaise; on admission there was
acute bronchitis. Thirteen days after admission the patient
developed parotitis (mumps?); five days later and five days before
death pleurisy was recognized on the right side and pneumonia was
suspected. Death occurred thirty-six days after onset. The
temperature on admission was 103.2° F. and remained elevated during
one week falling by lysis; from this time until the pleurisy was
recognized it was normal and later it remained approximately 103° F.

=Anatomic Diagnosis.=—Fibrinopurulent pleurisy on right side;
fibrinous pleurisy on left side; fibrinopurulent pericarditis;
chronic interstitial (interlobular) pneumonia in process of healing;
purulent bronchitis; acute splenic tumor; parenchymatous
degeneration of kidneys.

The right pleural cavity contains 1,650 c.c. of grayish yellow fluid
containing an abundant sediment of softened fibrin. Part of this
fluid, more opaque than the remainder is confined in a localized
pocket between the inner surface of the lung and the pericardium.
The apex and anterior surface of the right upper lobe, over an area
about 7 cm. across, is held by fibrinous adhesions to the chest
wall; when this adhesion is broken a pocket is exposed 6.5 x 2.5 cm.
containing fibrin and fluid. The pericardial cavity is distended by
350 c.c. of turbid yellow seropurulent fluid. The pericardial
surfaces are covered by shaggy, tough gray fibrin.

The right lung is collapsed; the lower and posterior part of the
upper lobe is deep red and atelectatic. Throughout the upper lobe
the interlobular septa are thickened, often 1 mm. across and very
conspicuous; in the lower and anterior tip of the lobe is an area
where tissue is firm grayish red and heavier than water. The lower
and posterior half of the right lower lobe is firm and airless, and
the tissue is reddish gray or gray and in places finely granular on
section; interlobular septa are conspicuous. Although the lung is
cut into thin sections, no abscesses are found. Bronchi throughout
the lung contain mucopurulent fluid.

The left lung over its lower half is covered by a thin layer of
fibrin. The tissue is crepitant throughout and moderately edematous.
Bronchi contain mucopurulent fluid.

Hemolytic streptococci in pure culture are obtained from the blood
of the heart, right pleural cavity and pericardium. No growth is
obtained on a plate inoculated with material from the right lower
lobe. The right bronchus contains hemolytic streptococci and B.
influenzæ.

The pleural surface of the right lung is covered by a thick layer of
fibrin which has undergone advanced organization. Fibrous septa
within the lung are much thickened by the presence of newly formed
fibrous tissue; the interstices of the tissue are distended and
contain fibrin into which fibroblasts and new blood vessels have
penetrated. Some lymphatics are plugged with fibrin and contain
polynuclear leucocytes, lymphoid and large mononuclear cells. In
several places organization of these thrombi is beginning. About the
blood vessels are thrombosed lymphatics in which polynuclear
leucocytes and mononuclear cells are equally abundant. Alveoli
immediately adjacent to blood vessels and to fibrous septa often
contain fibrin, and alveoli elsewhere contain desquamated cells in
abundance.

In association with hemolytic streptococci in the blood, pleura and
pericardium, there has been inflammation of the interlobular septa of
the lungs with acute lymphangitis; there has been no suppuration and the
lesion is in process of healing with new formation of fibrous tissue. It
is evident that this lesion, as well as pleurisy with advanced
organization, preceded the exacerbation of the patient’s illness which
occurred five days before death. The advanced chronic changes found at
autopsy indicate that the pulmonary and pleural lesions had their origin
during the illness which was present at the time of admission to the
hospital. Interstitial pneumonia caused by hemolytic streptococci was of
mild character and did not produce suppuration within the lung;
nevertheless, hemolytic streptococci which reached the pleura caused
empyema.

Suppurative Pneumonia with Multiple Clustered Abscesses Caused by
Staphylococci

In the preliminary report of this commission published in _The Journal
of the American Medical Association_, _loc. cit._, pg. 111, we described
suppurative pneumonia with multiple abscesses caused by staphylococci
and cited 4 instances of the lesion which followed influenza. Chickering
and Park[84] published in a subsequent number of the same journal an
account of staphylococcus pneumonia, a lesion which has heretofore
attracted very little attention.

In a small group of cases abscesses in the lungs have had characters
which serve to distinguish them from the abscesses previously described.
Small, sharply circumscribed yellow nodules, which in their centers have
undergone suppurative softening, form a cluster upon a red, airless
background (Figs. 15 and 16). One or more of these groups several
centimeters across, occur in the lungs. It is usually evident that the
abscesses are clustered about a medium-sized bronchus, but occasionally
with increase in the size of the small cavities the lung tissue assumes
a honey-combed appearance.

These clustered abscesses occur in association with bronchopneumonia and
have been in all instances associated with purulent bronchitis. The
mucosa of the small bronchi may be destroyed so that the surface is
eroded. These small clustered abscesses are seen as conspicuous yellow
spots immediately below the pleura, but there has been no associated
empyema. In 2 instances these abscesses were accompanied by fibrinous
pleurisy, but in the remaining autopsies the pleura has been normal. The
infrequency of empyema is in contrast with its almost invariable
presence when a streptococcus abscess is found below the pleura.

=Autopsy 280.=—Onset of illness with malaise, headache, cough and
fever was on September 24, eight days before death. At autopsy there
were hemorrhagic peribronchiolar and lobular bronchopneumonia,
clustered foci of suppuration in right lung, purulent bronchitis and
fibrinous pleurisy. Hemolytic streptococci were obtained from the
consolidated lung and from a bronchus. A culture from the right lung
was contaminated. In the bronchus were found B. influenzæ and a few
staphylococci. Microscopic examination of the abscesses shows that
they contain Gram-staining cocci grouped into staphylococcus-like
colonies.

=Autopsy 286.=—Duration of illness, which began September 25 with
symptoms of influenza, was nine days. At autopsy there were lobular
and confluent patches of bronchopneumonia, clustered abscesses in
the right lung below the pleura, purulent bronchitis, and
serofibrinous pleurisy localized in the neighborhood of the
abscesses. Pneumococcus IV was obtained from the blood of the heart,
and Pneumococcus IV, staphylococci and B. influenzæ from the right
main bronchus; growth failed to occur on plates from right and left
lungs. Microscopic examination shows the presence of clumps of cocci
with staphylococcus grouping in the centers of the small abscesses.
Section through one abscess shows its continuity with the wall of a
bronchus; along one side of the abscess is epithelium composed of
flattened epithelial cells in multiple layers continuous with that
of the bronchus; the remainder of the abscess wall is formed by
disintegrated lung tissue.

[Illustration:

Fig. 15.—Abscesses in two clusters caused by S. aureus in upper part
of right upper lobe; confluent lobular consolidation in lower part
of lobe. Autopsy 333.
]

[Illustration:

Fig. 16.—Abscesses in cluster caused by S. aureus at apex of right
upper lobe. Autopsy 322.
]

=Autopsy 322.=—The patient was admitted with influenza eight days
before death; signs of pneumonia appeared two days later, and on the
following day Pneumococcus IV was obtained from the sputum. At
autopsy there were bronchopneumonia with lobar consolidation,
abscesses clustered about a bronchus in the right upper lobe and
purulent bronchitis. The blood was sterile; S. aureus was obtained
from the consolidated part of the left lung; S. aureus and
Pneumococcus III from the abscesses of the right lung. Microscopic
examination of sections of abscesses showed the presence of
Gram-staining cocci in staphylococcus-like colonies, surrounded by
necrotic material and polynuclear leucocytes; Gram-negative bacilli
resembling B. influenzæ were seen. (See Fig. 16.)

=Autopsy 333.=—The onset of influenza was fifteen days before death;
a diagnosis of pneumonia was made seven days before death. At
autopsy there were confluent bronchopneumonia, clustered abscesses
in the right lung and purulent bronchitis (no pleurisy). The blood
contained Pneumococcus II atypical. S. aureus and Pneumococcus II
atypical were obtained from the abscesses; S. hemolyticus, from the
consolidated left lung; S. aureus, B. influenzæ and a few hemolytic
streptococci, from the bronchus. (See Fig. 15.)

=Autopsy 370.=—The patient was admitted seventeen days before death
and signs of pneumonia were noted three days after admission. At
autopsy there were lobular and confluent bronchopneumonia and small
abscesses clustered about bronchi and situated within the gray
consolidated lung; purulent bronchitis and patches of atelectasis,
with distention of the lungs, so that they failed to collapse on
removal. No growth was obtained from the heart’s blood; S. aureus in
pure culture was obtained from the abscesses of the right lung; S.
aureus, Pneumococcus IV and B. influenzæ were obtained from a small
bronchus on the left side.

=Autopsy 425.=—Illness began with influenza twenty-nine days before
death; a diagnosis of pneumonia was made fourteen days before death.
At autopsy there were chronic bronchopneumonia with tubercle-like
nodules of consolidation with some large patches of consolidation,
multiple small abscesses giving a honey-combed appearance to part of
the right middle lobe, purulent bronchitis and bronchiectasis. S.
hemolyticus was grown from the heart’s blood; S. hemolyticus, B.
influenzæ and S. albus from the lung. Sections of an abscess contain
clumps of cocci. An abscess cavity has along one side remains of a
bronchial wall covered by squamous epithelium; a dilated bronchus,
cut longitudinally, terminates in this irregular abscess cavity.

Table XLIX shows the incidence of pneumococci, hemolytic streptococci,
staphylococci and B. influenzæ in the foregoing autopsies with abscesses
clustered about bronchi:

TABLE XLIX

════════╤════════╤═════════════════╤═════════════════
│ NO. OF │ │ HEMOLYTIC
│CULTURES│ PNEUMOCOCCI │ STREPTOCOCCI
────────┼────────┼────────┬────────┼────────┬────────
│ │ NO. │PER CENT│ NO. │PER CENT
│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────┼────────
Bronchus│ 4│ 2│ 50.0│ 2│ 50.0
Lung │ 6│ 2│ 33.3│ 3│ 50.0
Blood │ 6│ 2│ 33.3│ 2│ 33.3
────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════
│ │
│ STAPHYLOCOCCI │ B. INFLUENZÆ
────────┼────────┬────────┼────────┬────────
│ NO. │PER CENT│ NO. │PER CENT
│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────
Bronchus│ 4│ 100.0│ 4│ 100.
Lung │ 4│ 66.7│ 2│ 33.3
Blood │ │ │ │
────────┴────────┴────────┴────────┴────────

Staphylococcus shows in the lung the same tendency to produce localized
abscesses which it exhibits in other tissues of the body; it invades the
lung by way of the bronchi, but shows no ability to invade lymphatics,
and in the cases we have examined rarely enters the pleura or the blood.
In all of these cases B. influenzæ has been found in the bronchi and
perhaps precedes the staphylococcus as an invader of the lower
respiratory passages. Pneumococci atypical II, Types III and IV have
been found in over half of these cases. The significance of this
organism is emphasized by the 2 cases in which it has been found in the
heart’s blood at autopsy. It appears not improbable that S. aureus has
invaded the lung already the site of bronchopneumonia caused by
pneumococci.

Notwithstanding the small number of autopsies, the figures in Table
XLIX, showing the incidence of pneumococci, streptococci, staphylococci
and B. influenzæ, are cited so that they may be compared with the
corresponding figures for the usual type of streptococcus abscess (p.
203). The incidence of hemolytic streptococci is relatively low, whereas
that of staphylococci approximates 100 per cent. S. aureus was present
in great number in the lung of Autopsies 322 and 333 and in pure culture
in the abscess of Autopsy 370. Microscopic examination of sections from
the abscesses which have been described, demonstrated the presence of
Gram-staining cocci in characteristic staphylococcus-like clumps within
the exudate of the abscesses; scattered chains of streptococci were not
found. In those instances (Autopsies 280 and 286) in which cultures
failed to demonstrate staphylococci, microscopic examination
demonstrated staphylococcus-like clumps of bacteria within the abscess
cavity. Cultures were usually made from the consolidated lung near the
abscess where the pleural surface could be seared, rather than from the
pus, so that in some instances the microorganism has doubtless escaped
detection although present.

In association with the multiple abscesses which have been described,
injury to the bronchi and bronchopneumonia have been invariably present.
Purulent bronchitis has been present in all instances of this lesion; in
2 instances there has been dilatation of the bronchi, and in 1 instance
in which the onset of influenza was twenty-nine days before death, there
has been advanced bronchiectasis.

Microscopic examination shows that the epithelium of the bronchi is
partially or completely destroyed and that destruction of the underlying
tissue, with acute suppurative inflammation, penetrates to a greater or
less depth into the wall. When the epithelium of the bronchus is wholly
destroyed and the lumen is filled and distended with polynuclear
leucocytes, a cross section of the tube has the appearance of a small
abscess; but more careful examination often shows that the engorged
mucosa is still intact. Occasionally, a network of fibrin forms a layer
covering the denuded mucosa. Disintegration of the superficial tissue
may extend to the muscularis or through it, and may penetrate the wall
of the bronchus. The tissue in contact with the exposed surface contains
many polynuclear leucocytes and blood vessels plugged with fibrinous
thrombi, but deeper in the tissue lymphoid and plasma cells are more
numerous. In 2 instances (Autopsies 286 and 425) favorable sections have
demonstrated that the wall of an abscess on one side consists of the
remains of a bronchus, covered by epithelium composed of squamous cells,
Whereas the remainder of the wall, here very irregular, is formed by
partially destroyed alveoli plugged with fibrin. The suppurative process
has penetrated the wall of the bronchus on one side and extended into
the surrounding alveolar tissue. In other instances, abscess cavities
occur within the alveolar tissue of the lung and their relationship to
bronchi is not evident. In the mass of polynuclear leucocytes which fill
the abscess cavity, are clumps of staphylococci in great abundance,
usually forming characteristic colonies which are conspicuous with the
low power of the microscope.

Empyema, Pericarditis and Peritonitis

No sharp line can be drawn between nonpurulent and purulent pleurisy. A
diagnosis of empyema has been made when the fluid in the chest has
become opaque and fibrin has undergone softening or solution. The lesion
has been designated seropurulent when there has been abundant thin,
opaque, gray fluid. Pleurisy has been designated fibrinopurulent when
the cavity has contained opaque fluid and ragged soft white or yellowish
fibrin adherent to the chest wall; this fibrin is evidently in process
of disintegration and there may be numerous shreds and flakes of fibrin
which subside to the bottom of the fluid. The amount of fluid in the
cavity may occasionally exceed 1,700 c.c.; that in both pleural cavities
may exceed 2,500 c.c. The lesion has been designated purulent when
fibrin has almost wholly disappeared and the cavity contains thick
yellowish white fluid. In 4 of 5 instances in which thoracotomy had been
performed, empyema has assumed this otherwise uncommon type.

Some inflammation of the pleura is almost constantly found in
association with all forms of pneumonia, but in many instances is so
slight that it has no noteworthy significance. Table L shows the
incidence of various types of pleurisy.

TABLE L

═══════════════════╤═════════╤════════════════╤═══════════╤════════════
│ LOBAR │BRONCHOPNEUMONIA│SUPPURATIVE│INTERSTITIAL
│PNEUMONIA│ │ PNEUMONIA │SUPPURATIVE
│ │ │ WITH │ PNEUMONIA
│ │ │ ABSCESS │
───────────────────┼────┬────┼────────┬───────┼─────┬─────┼──────┬─────
„ │No. │ % │ No. │ % │ No. │ % │ No. │ %
───────────────────┼────┼────┼────────┼───────┼─────┼─────┼──────┼─────
No pleurisy noted │ 30│46.9│ 44│ 55│ 1│ 2.6│ 1│ 5.9
Serous pleurisy │ 5│ 7.8│ 9│ 11.2│ │ │ │
Fibrinous pleurisy │ 10│15.6│ 5│ 6.2│ 1│ 2.6│ │
Serofibrinous │ 12│18.2│ 14│ 17.5│ 3│ 7.7│ │
pleurisy │ │ │ │ │ │ │ │
Seropurulent │ │ │ │ │ 9│ 23.1│ 1│ 5.9
pleurisy │ │ │ │ │ │ │ │
Fibrinopurulent │ 7│10.9│ 5│ 6.2│ 17│ 43.6│ 12│ 70.6
pleurisy │ │ │ │ │ │ │ │
Purulent pleurisy │ │ │ 3│ 3.7│ 8│ 20.5│ 3│ 17.6
───────────────────┼────┼────┼────────┼───────┼─────┼─────┼──────┼─────
Total │ 64│ │ 80│ │ 39│ │ 17│
───────────────────┴────┴────┴────────┴───────┴─────┴─────┴──────┴─────

Empyema has occurred, on the one hand, in 12.4 per cent of instances of
lobar pneumonia and in 9.9 per cent of instances of bronchopneumonia
alone. It has occurred, on the other hand, in 87.2 per cent of instances
of suppurative pneumonia with abscess formation and in 94.1 per cent
instances of interstitial suppurative pneumonia. These suppurative
lesions are caused by hemolytic streptococci, and when cultures are made
from the pleural exudate this microorganism is isolated.

Of 16 instances in which empyema has occurred in association with lobar
pneumonia or bronchopneumonia unaccompanied by suppuration in 6 there
has been infection with hemolytic streptococci. Empyema has occurred in
the absence of hemolytic streptococci only 10 times.

=Empyema Caused by Hemolytic Streptococci.=—When necrosis preceding
abscess formation has occurred in the lung, streptococci are found in
immense numbers in the dead tissue. The pleura overlying the abscess
undergoes necrosis and occasionally streptococci are particularly
numerous upon the pleural surface of the necrotic tissue. In Autopsy 376
a membrane thin as tissue paper, representing the pleura, separated an
abscess containing thick pus from the pleural cavity which was the site
of empyema. The abscess may rupture into the pleural cavity and at the
same time may be in free communication with a bronchus (Autopsy 480). In
one (Autopsy 467) instance an abscess which had ruptured into the
pleural cavity had completely discharged its contents and was in process
of healing, newly formed fibrous tissue being abundant in its wall.

With few exceptions empyema has accompanied subpleural abscess caused by
hemolytic streptococci, being found on the side corresponding to the
abscess. Among 39 instances of pulmonary abscess, empyema has been
limited to the side of the abscess in 23; it has been present on the
opposite side as well in 10 instances. In 2 instances there have been
abscesses in both lungs; in one (Autopsy 385 A) there has been double
empyema, and in the other (Autopsy 487) empyema only on the left side.
In one instance abscess has been recognized by microscopic examination
and its location is not recorded. In 5 instances of abscess formation
there has been no empyema. In Autopsy 383 there has been no pleurisy
noted; in Autopsy 416 there has been fibrinous pleurisy and in Autopsies
277, 290 and 380, serofibrinous pleurisy.

Empyema has been almost invariably found in association with
interstitial suppurative pneumonia. This lesion extends by way of the
lymphatics up to the pleural surface and is often more conspicuous just
below the pleura than elsewhere. Empyema has been absent in only 3 of 21
examples of the lesion and in one of these there has been serous
effusion. In 12 instances interstitial suppuration has occurred only on
one side and empyema has been limited to this side; in 5 instances with
interstitial suppuration on one side there has been empyema on both
sides; in 2 instances with interstitial suppuration in both lungs there
has been double empyema.

The amount of fluid in the pleural cavity has varied from less than 100
to 1,500 c.c. The fluid has occasionally been seropurulent or yellow,
thick and purulent, but in most instances the exudate is best described
as fibrinopurulent. There is yellow or yellowish gray purulent fluid
containing flakes of soft ragged fibrin.

The foregoing study has shown, on the one hand, that empyema is a
frequent complication of streptococcus pneumonia and, on the other hand,
that empyema following influenza with relatively few exceptions is
caused by hemolytic streptococci. Empyema caused by this microorganism
exhibits in some instances characters not seen with other varieties of
pleural inflammation. The tissue between sternum and pericardium is
often edematous and the adjacent fat has a firm brawny consistence. In
some instances the exudate contains blood, and hemolysis has occurred so
that the fluid has a diffuse red color. The occurrence of multiple
pocketed collections of purulent fluid within the pleural cavity is
peculiar to streptococcus empyema. These pockets have been found 6 times
in association with abscess and 5 times with interstitial suppurative
pneumonia. In the presence of an exudate within the pleural cavity, some
part of the lung, usually the anterior surface behind the sternum and
costal cartilages, is glued by fibrinous adhesions to the parietal
pleura. Here occur pockets containing thin purulent fluid and softened
fibrin or thicker creamy pus walled off by fibrin about the edges of the
pocket. At the site of the lesion the lung, after it is separated from
the chest wall, is marked by a shallow depression surrounded by the
fibrin which has walled in the pocket. The little cavity thus formed,
varying much in size, is usually oval, the long diameter being from 1 to
3 cm. These pleural pockets may occur over the external surface of the
lung (Autopsies 452, 455, and 472) or between the internal surface and
pericardium (Autopsy 452). Occasionally with partial fibrinous adhesion
between the pleural surfaces there are both scattered pockets containing
purulent fluid and a larger encapsulated collection of fluid; in Autopsy
455 the pleural surfaces were adherent and there was 100 c.c. of
purulent fluid encapsulated in a space over the external surface of the
lung, 12 × 8 cm. In Autopsy 452 the lower part of the pleural cavity was
encapsulated and contained 650 c.c. of fluid. This tendency of empyema
caused by S. hemolyticus to form encapsulated pockets is doubtless of
considerable importance in the treatment of the condition.

Stone, Bliss and Phillips[85] have described these encapsulated pockets
as “subcostosternal pus pockets” and have maintained that they are
formed about the sternal lymphatic nodes. We have found them so widely
scattered that this relation seems improbable.

=Pneumococcus Empyema.=—Empyema occurred in association with pneumonia
referable to pneumococci 10 times, once with Pneumococcus II; 6 times
with Pneumococcus atypical II; once with Pneumococcus III and twice with
Pneumococcus IV. The lesion was seropurulent once; fibrinopurulent 8
times and purulent once. Fibrin in several instances was somewhat
voluminous. In the following instance voluminous masses of fibrin had an
important influence upon the attempted treatment.

=Autopsy 473.=—A. D. P., white, aged twenty-one, a student from
Missouri, had been in military service two weeks. He was admitted to
the hospital with influenza twenty-eight days before his death, and
four days after admission there were signs of pneumonia.
Paracentesis was performed on the right side on the eleventh day
after admission; 4 c.c. of cloudy fluid which contained Pneumococcus
III were obtained at this time and later in the day 800 c.c. were
withdrawn. On the thirteenth day attempted withdrawal of fluid from
both pleural cavities failed. On the eighteenth day aspiration of
the right pleural cavity yielded only 30 c.c. of fluid. On the
nineteenth day 400 c.c. of purulent fluid were withdrawn from the
right pleural cavity. On the twenty-fifth day there was cyanosis and
delirium. Shortly before death aspiration of the right pleural
cavity was attempted, but only 4 c.c. of fluid were obtained.

=Anatomic Diagnosis.=—Chronic bronchopneumonia with lobular and
peribronchiolar consolidation in left lung; fibrinopurulent pleurisy
on both sides; purulent bronchitis and bronchiectasis.

On removal of the sternum, encysted purulent pleurisy is found
between the inner surface of the right lung and the pericardium;
there is here 450 c.c. of very thick creamy, greenish yellow pus
entirely separated from the remainder of pleural cavity. The
external part of the cavity contains 1,450 c.c. of fluid and
voluminous masses of firm fibrin which placed in a measuring
cylinder occupy 450 c.c. The left pleural cavity contains 400 c.c.
of seropurulent fluid in which there is abundant sediment of
fibrinous particles.

The right lung is compressed; the bronchi exude purulent fluid. The
left lung is voluminous; in the upper and lower lobes there are
small yellowish gray nodules of consolidation, grouped in clusters,
and gray patches of lobular consolidation occur. Bronchi are dilated
and filled with purulent fluid.

Bacteriologic examination shows the presence of Pneumococcus III
obtained in pure culture from the blood of the heart and from the
right pleural cavity. S. viridans is grown from the left lung; a
plate from the right bronchus contained B. influenzæ, S. viridans
and a few colonies of staphylococcus and M. catarrhalis.

The foregoing case is particularly noteworthy because aspiration failed
repeatedly to yield more than a few cubic centimeters of fluid,
doubtless because the voluminous masses of fibrin present in the cavity
prevented escape of fluid. Aspiration was attempted shortly before
death, but only 4 c. c. of fluid were obtained; nevertheless, at autopsy
the right pleural cavity contained 2,350 c.c. of exudate. Another factor
of much importance in relation to treatment is the encapsulation of 450
c.c. of purulent fluid between the inner surface of the right lung and
the pericardium. It is possible that free drainage might have emptied
the main cavity and perhaps even freed the encapsulated fluid.

=Pericarditis.=—Among 241 autopsies on individuals with pneumonia
following influenza, pericarditis occurred 23 times; these lesions were
classified as follows: Serous pericarditis, 1; serofibrinous
pericarditis, 9; seropurulent pericarditis, 1; fibrinopurulent
pericarditis, 10; purulent pericarditis, 2.

It is noteworthy that in 12 of 23 instances of pericarditis the lesion
was associated with S. hemolyticus infection of the lung and whenever in
these instances cultures were made (Autopsies 434, 485, 499 and 504)
hemolytic streptococci were obtained from the pericardial exudate in
pure culture.

The tendency of interstitial suppurative pneumonia to produce
pericarditis is especially evident. Among 21 instances of interstitial
suppurative pneumonia pericarditis occurred 6 times (28.6 per cent);
among 39 instances of suppurative pneumonia with abscess formation,
pericarditis occurred twice (5.1 per cent); whereas among all other
autopsies, namely, 181, the lesion occurred 15 times (8.3 per cent).

Pericarditis occurred in association with pneumonia referable to
Pneumococcus I, once, (Pneumococcus I isolated from the pericardium); to
Pneumococcus II, once; to atypical Pneumococcus II, 5 times (twice
isolated from the pericardium); and to Pneumococcus IV, twice (once
isolated from the pericardium).

=Peritonitis.=—Purulent peritonitis occurred only twice, in both
instances in association with pneumonia caused by hemolytic
streptococci. Purulent peritonitis was part of a general serositis
involving both pleural cavities, pericardium and peritoneum in 2
noteworthy instances:

=Autopsy 465.=—J. K., white, aged twenty-two, farmer from Oklahoma,
had been in military service one month. He was admitted to the
hospital with influenza, sore throat and bronchitis twenty-four days
before his death. Signs of pneumonia were recognized thirteen days
later and at the same time there was otitis media on the right side.
Empyema and pericarditis were found three days before death and two
days later 1000 c.c. of cloudy fluid were withdrawn from the chest.

=Anatomic Diagnosis.=—Suppurative pneumonia with consolidation and
abscess in right lower lobe below pleura; purulent pleurisy on
right, seropurulent pleurisy on left side; beginning serofibrinous
pericarditis; fibrinopurulent peritonitis; purulent bronchitis.

The body is emaciated. The right pleural cavity contains 350 c.c. of
thick, creamy yellow pus in which are flakes of fibrin; the right
lung is collapsed and lies at the back and inner side of the cavity.
The left pleural cavity contains 500 c.c. of turbid, yellow,
seropurulent fluid in which is soft fibrin. The lower lobe of the
right lung is consolidated throughout, flabby, gray red and finely
granular on section. Below the pleura of the posterior border is a
wedge-shaped cavity with its base 1.5 cm. across, in contact with
the pleural surface. About the cavity consolidated tissue has an
opaque, yellow color. Bronchi in both lungs contain mucopurulent
fluid. The pericardial cavity contains 20 c.c. of turbid fluid; the
left auricular appendage is bound by a thin layer of fibrin to the
parietal pericardium.

The peritoneal cavity contains 100 c.c. of thick, creamy, yellow,
purulent fluid. Between the diaphragm and liver is a layer of
fibrin, in places 1.5 cm. in thickness; fibrin is present upon the
peritoneum overlying the kidneys and base of mesentery.

Bacteriologic examination shows the presence of hemolytic
streptococci, obtained in pure culture from the blood of the heart,
right pleural cavity and peritoneum. From the right bronchus are
grown S. hemolyticus, B. influenzæ and a few colonies of S. viridans
and staphylococcus.

=Autopsy 504.=—G. R. C., white, aged twenty-eight, farmer from
Alabama, had been in military service three months. Onset of illness
occurred six days before death, and two days later he entered the
hospital with fever (103.4° F.), pains in the abdomen and vomiting.
Consolidation at the bases of the lung was recognized on the day
following admission and on the day before death 900 c.c. of greenish
brown fluid were aspirated from the left pleural cavity.

=Anatomic Diagnosis.=—Interstitial suppurative pneumonia with
consolidation in left lower lobe; purulent pleurisy on both sides;
purulent pericarditis; purulent peritonitis; parenchymatous
degeneration of kidneys; acute splenic tumor.

The body is that of a large well-nourished man. The left pleural
cavity contains 975 c.c. of creamy, yellow fluid; right pleural
cavity contains 425 c.c. of purulent fluid thinner than that on the
left side. The left lung is collapsed; the posterior and lower half
of the lower lobe is consolidated, flabby, deep red and fleshy in
appearance. The interstitial septa are yellow, thickened with
bead-like enlargements and contains creamy purulent fluid which
flows away and leaves small cavities. This interstitial suppuration
is more advanced below the outer surface of the lobe than elsewhere.

The pericardial cavity contains 25 c.c. of creamy, yellow, purulent,
fluid; the epicardium is dull, covered in a few places by a small
amount of fibrin and below it are ecchymoses.

The peritoneal cavity contains 100 c.c. of thick, yellow pus; the
peritoneal surfaces are injected and between the liver and diaphragm
is fibrin.

Bacteriologic examination shows the presence of S. hemolyticus in
pure culture from the blood of the heart, the lower lobe of the left
lung, pericardium and peritoneum. The right main bronchus contains
the same microorganism, B. influenzæ and a few staphylococci.

General serositis has been caused by hemolytic streptococci which in one
instance have entered the pleura from a subpleural abscess, and in the
other from the suppurating interstitial tissue of the lung. In one of
these cases the patient entered the hospital with symptoms suggestive of
acute peritonitis.

Bronchiectasis

Acute dilatation of the bronchi is a common result of the bronchitis of
influenza, and its frequent occurrence is an index of the severity of
the changes in the bronchial wall. In some instances the smaller bronchi
in well-localized areas are uniformly dilated; in other instances, large
cavities, several centimeters in diameter, are formed and all
transitions between the two extremes occur.

The occurrence of bronchiectasis following influenza is mentioned by
Leichtenstern[86]. He states that evidence of bronchiectasis can persist
for weeks or months and nevertheless end with complete restitution of
the lungs to normal. Lord[87] has described instances of bronchiectasis
occurring in association with infection by B. influenzæ and Boggs[88]
has recorded similar observations.

We have had abundant opportunity to observe early stages in the
production of bronchiectasis and to study the much discussed
pathogenesis of the condition.

The following figures show the predilection of bronchiectasis for the
left lung and for the lower lobes: Bronchiectasis occurred 30 times in
the left lung alone, 9 times in the right lung alone and 13 times in
both lungs, the total being 52. Among 30 instances in which the lesion
occurred only in the left lung, in 24 it was limited to the lower lobe,
and in 15 of these 24 instances to the base of the lower lobe. Among 9
instances in which dilatation of bronchi occurred only in the right
lung, it was limited to the lower lobe in 4 instances and to the base of
the lower lobe in 2 of these 4 instances.

When the lesion is limited to the base of the lower lobes small bronchi
with no recognizable cartilage in their wall are dilated to a diameter
of from 3 to 6 cm. and are distended with thick mucopurulent fluid. The
tenacious character of the bronchial contents and the action of gravity
doubtless have a part in the production of the dilatation. In several
instances dilatation of the bronchi was limited to the basal parts of
both upper and lower lobes.

When bronchiectasis occurs throughout a whole lung, usually the left, or
in both lungs, the lesion is more advanced and conspicuous (Fig. 26).
There is diffuse dilatation of small and medium-sized bronchi. Dilated
bronchi with deeply injected mucosa and filled with yellow mucopurulent
fluid, are seen throughout the sectioned lung. A bronchus cut
longitudinally may have a nearly uniform diameter of from 5 to 9 mm. for
a distance of 5 or 6 cm., maintaining this diameter to within 1 cm. of
the pleural surface, where normally only small bronchi occur.

More advanced bronchiectasis is represented by the occurrence of
spherical bronchiectatic cavities, having a diameter from 1 to 2.5 cm.
In some instances there have been two or three of these cavities but
occasionally there may be many. Cylindrical dilatation of the bronchi
usually occurs widely distributed in the lungs. In Autopsy 440 a small
bronchus, cut longitudinally, was dilated to a diameter of 5 mm. for a
distance of 5 cm. and terminated in a spherical cavity 2 cm. in
diameter; there was another smaller spherical cavity nearby and dilated
bronchi occurred elsewhere. In Autopsy 467, in the upper part of the
lower lobe, two spherical cavities 1 and 1.5 cm. in diameter
communicated with a bronchus of medium size.

Autopsies with bronchiectasis are listed in the order of the duration of
illness to show the parallel increase in the severity of the lesion
(Table LI). In 2 instances (Autopsies 244 and 314) bronchiectatic
cavities surrounded by firm fibrous tissue have evidently existed before
the onset of the fatal illness, which has lasted in one instance
approximately four and in the other six days; these autopsies have been
omitted from the table.

The table shows that bronchiectasis observed within twelve days after
onset of illness with symptoms of influenza is moderately advanced and
almost invariably limited to the left lower lobe and usually to the base
of the lobe. Advanced dilatation, indicated by the formation of
spherical or cylindrical cavities, occurs with increasing frequency as
the duration of the respiratory disease increases.

Bronchiectasis has been almost invariably associated with purulent
bronchitis. The dilated bronchi contain mucopurulent material and
throughout the lungs the same condition is usually widespread. Among 137
instances of purulent bronchitis bronchiectasis consequent upon
influenza has been present in 50.

TABLE LI

═══════╤════════╤═════════════╤══════════════╤══════════════╤═══════════
NO. OF │DURATION│ TYPE OF │ LOCATION OF │ CHARACTER OF │BACTERIA IN
AUTOPSY│ OF │ PNEUMONIA │BRONCHIECTASIS│BRONCHIECTASIS│ BRONCHUS
│ILLNESS │ │ │ │
│IN DAYS │ │ │ │
───────┼────────┼─────────────┼──────────────┼──────────────┼───────────
394│ 5 ?│Broncho │Rt. base │Dilatation │
359│ 7 +│Lobar and │Lt. lower lobe│Dilatation │
│ │ broncho │ │ │
322│ 8│Abscess │Lt. base │Dilatation │
│ │ (staph.) │ │ │
325│ 8│Interst. │Lt. base │Dilatation │S. hem., B.
│ │ suppuration│ │ │ inf.,
│ │ │ │ │ staph.
352│ 8│Lobar and │Lt. lower lobe│Advanced │
│ │ broncho │ │ dilatation │
429│ 8 ?│Broncho │Rt. base │Dilatation │
288│ 10│Abscess │Lt. base │Dilatation │S. hem., B.
│ │ │ │ │ inf.
374│ 10│Lobar and │Rt. and lt. │Advanced │
│ │ broncho │ lungs │ dilatation │
376│ 10│Abscess │Lt. base │Dilatation │S. hem.
437│ 11│Lobar │Rt. lower lobe│Advanced │
│ │ │ │ dilatation │
482│ 11│Broncho │Lt. base │Dilatation │B. inf.,
│ │ │ │ │ Pneum.
│ │ │ │ │ IV, S.
│ │ │ │ │ hem.
489│ 11│Lobar and │Lt. lung │Dilatation │B. inf.,
│ │ broncho │ │ │ Pneum.
│ │ │ │ │ IV.
287│ 12│Lobar and │Lt. lower lobe│Advanced │Pneum. IV.,
│ │ broncho │ │ dilatation │ B. inf.,
│ │ │ │ │ staph.
289│ 12│Broncho │Lt. lower lobe│Advanced │Pneum. IV.,
│ │ │ │ │ B. inf.
│ │ │ │ │ staph.
295│ 12│Interst. sup.│Rt. lung │Advanced │S. hem., B.
│ │ and abscess│ │ dilatation │ inf.
336│ 12│Broncho │Lt. base │Dilatation │
375│ 12│Broncho │Rt. and lt. │Dilatation │
│ │ │ bases │ │
422│ 12 ?│Lobar and │Lt. base │Dilatation │
│ │ broncho │ │ │
381│ 13│Abscess │Lt. base │Spherical │
391│ 13│Lobar and │Lt. lung │Dilatation │
│ │ broncho │ │ │
401│ 14 ?│Lobar and │Rt. and lt. │Spherical │
│ │ broncho │ lungs │ │
402│ 14│Chronic │Rt. lower lobe│Dilatation │
│ │ broncho │ │ │
410│ 14 ?│Abscess │Rt. upper lobe│Dilatation │
333│ 15│Abscess │Lt. upper lobe│Dilatation │S aur., B.
│ │ (staph.) │ │ │ inf. S.
│ │ │ │ │ hem.
389│ 15│Interst. │Lt. lung │Advanced │
│ │ suppuration│ │ dilation │
412│ 15│Lobar and │Lt. lower lobe│Cylindrical │
│ │ broncho │ │ │
398│ 16│Broncho │Rt. and lt. │Advanced │
│ │ │ lungs │ dilatation │
423│ 16│Broncho │Lt. base │Dilation │
488│ 16│Abscess │Lt. lower lobe│Dilatation │S. hem.,
│ │ │ │ │ Pneum.
│ │ │ │ │ atyp. II.
312│ 17│Broncho │Rt. and lt. │Dilatation │S. hem., B.
│ │ │ lungs │ │ inf.
│ │ │ │ │ staph.
372│ 17│Broncho │Rt. lung │Dilatation │
385 C│ 17│Interst. │Lt. base │Dilatation │
│ │ suppuration│ │ │
448│ 17│Broncho │Lt. lung │Dilatation │
460│ 17│Abscess │Lt. lower lobe│Spherical │S. hem., B.
│ │ │ │ │ inf.,
│ │ │ │ │ staph.
291│ 18│Broncho │Lt. base │Advanced │B. inf.,
│ │ │ │ dilatation │ staph.
296│ 18│Abscess │Lt. base │Dilatation │S. hem., B.
│ │ │ │ │ inf.,
387│ 19│Abscess │Rt. and lt. │Advanced │S. hem., B.
│ │ │ lungs │ dilatation │ inf., S.
│ │ │ │ │ aur.
│ │ │ │ │ Pneum.
│ │ │ │ │ II.
421│ 19│Chronic │Rt. lung │Advanced │
│ │ broncho │ │ dilatation │
440│ 19│Chronic │Rt. and lt. │Spherical │B. inf., S.
│ │ broncho │ lungs │ │ aur.
419│ 20│Broncho │Rt. lung │Dilatation │Pneum. II,
│ │ │ │ │ B. inf.
463│ 20│Chronic │Rt. and lt. │Spherical │B. inf.,
│ │ broncho │ lungs │ │ staph.,
│ │ │ │ │ Pneum. IV
431│ 23│Chronic │Lt. base │Dilatation │
│ │ broncho │ │ │
468│ 23 ?│Lobar and │Lt. lung │Dilatation │S. aur., B.
│ │ broncho │ │ │ inf., S.
│ │ │ │ │ vir.
465│ 25 ?│Broncho │Lt. base │Dilatation │S. hem., B.
│ │ │ │ │ inf.,
│ │ │ │ │ staph.,
│ │ │ │ │ S. vir.
445│ 27│Broncho │Lt. lower lobe│Spherical │S. aur.
449│ 27│Abscess │Rt. and lt. │Spherical │S. hem., B.
│ │ │ lungs │ │ coli.
378│ 28│Abscess │Lt. base │Cylindrical │S. hem., B.
│ │ │ │ │ inf.,
│ │ │ │ │ Pneum.
│ │ │ │ │ atyp. II.
473│ 28│Chronic │Lt. lung │Advanced │B. inf., S.
│ │ broncho │ │ dilatation │ vir.,
│ │ │ │ │ staph.,
│ │ │ │ │ M.
│ │ │ │ │ catarr.
425│ 29│Abscess │Rt. and lt. │Cylindrical │
│ │ (staph.) │ lungs │ │
467│ 30│Abscess │Rt. lower lobe│Spherical │S. hem., B.
│ │ │ │ │ inf.
472│ 37│Chronic │Rt. and lt. │Advanced │B. coli
│ │ broncho │ lungs │ dilatation │
487│ 55│Abscess │Rt. and lt. │Cylindrical │B. inf. S.
│ │ │ lungs │ │ hem.
───────┴────────┴─────────────┴──────────────┴──────────────┴───────────

The bacteriology of autopsies with bronchiectasis is shown in Table LII.

TABLE LII

════════╤════════╤═════════════════╤═════════════════
│ NO. │ │
│EXAMINED│ PNEUMOCOCCUS │ S. HEMOLYTICUS
────────┼────────┼────────┬────────┼────────┬────────
│ │ NO. │PER CENT│ NO. │PER CENT
│ │POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────┼────────
Bronchus│ 29│ 9│ 31.0│ 15│ 51.7
Lung │ 37│ 16│ 43.2│ 18│ 48.6
Blood │ 50│ 12│ 24.0│ 22│ 44.0
────────┴────────┴────────┴────────┴────────┴────────

════════╤═════════════════╤═════════════════
│ │
│ STAPHYLOCOCCUS │ B. INFLUENZÆ
────────┼────────┬────────┼────────┬────────
│ NO. │PER CENT│ NO. │PER CENT
│POSITIVE│POSITIVE│POSITIVE│POSITIVE
────────┼────────┼────────┼────────┼────────
Bronchus│ 16│ 55.2│ 23│ 79.3
Lung │ 10│ 27.0│ 19│ 51.4
Blood │ │ │ │
────────┴────────┴────────┴────────┴────────

Comparison of the percentage incidence of the organisms which have to be
found associated with bronchiectasis and with purulent bronchitis
unaccompanied by bronchiectasis shows that there is no noteworthy
difference in the occurrence of pneumococci, hemolytic streptococci or
B. influenzæ within the bronchi. When allowance is made for the
difficulty of demonstrating B. influenzæ in the presence of a large
number of other microorganisms, it is not improbable that this organism
has been constantly present in the purulent contents of the bronchi with
purulent bronchitis, with and without bronchiectasis. Pneumococci,
streptococci and staphylococci are each present in the bronchi in about
one-half of the instances of bronchiectasis and mixed infections are
very common, S. viridans, B. coli and M. catarrhalis being occasionally
found in the bronchi. The table shows that pneumococci, streptococci and
staphylococci show no greater tendency to enter the lungs and blood when
bronchiectasis and purulent bronchitis coexist than with purulent
bronchitis alone.

Moderate dilatation of the small bronchi at the base of the left lung
was found in several instances eight days after onset of symptoms
referable to the respiratory passages. Advanced, diffuse dilatation of
the bronchi was seldom seen before the lapse of two weeks, and
bronchiectasis with formation of spherical or cylindrical cavities was
found with few exceptions three weeks after onset of the fatal illness.
Long continued, purulent bronchitis does not necessarily produce
dilatation of the bronchi. It is noteworthy that the average duration of
the fatal illness in 137 instances of pneumonia and purulent bronchitis
with no bronchiectasis was 12.5 days, whereas the average duration of 49
instances of pneumonia with purulent bronchitis and bronchiectasis was
only 16.5 days.

Bronchiectasis is almost invariably associated with purulent bronchitis
in which tenacious mucopurulent fluid accumulates in the bronchi. It
begins at the bases of the lower lobes and is usually more advanced here
than elsewhere. Mechanical distention of the small bronchi by viscid
fluid, expelled with difficulty, brings about their dilatation and
gravity appears to have a part in accentuating the process. Histologic
examination of the changes accompanying bronchitis show that lesions
which penetrate into the muscular layer and presumably weaken the
bronchial wall are not uncommon and partial or complete destruction of
the wall may result. To what extent infiltration of the muscular wall by
polynuclear leucocytes or by lymphoid and plasma cells is accompanied by
changes which weaken the wall may be questioned. When the epithelial
lining of the bronchus is destroyed coagulative necrosis of the
underlying tissue occurs and may extend a variable distance into the
bronchial wall, not infrequently penetrating into or entirely through
the muscular layer. These changes furnish an explanation of the
occurrence of bronchiectasis following influenza.

[Illustration:

Fig. 17.—Acute bronchiectasis showing fissures penetrating into
bronchial wall and at one place entering surrounding alveolar
tissue; the surrounding alveoli are filled with fibrin. Autopsy 425.
]

Acute bronchiectasis may be found following influenza after the illness
has lasted eight or ten days. There is no increase of fibrous tissue.
Small bronchi with no cartilage, which in normal lungs have a diameter
approximating 1 mm., are dilated to 3 mm. or more. The surface
epithelium is wholly or partially lost. Necrosis occurs in places and
extends deep into the tissue, destroying muscle and often penetrating
the entire thickness of the wall which in these small bronchi consists
in large part of fibrous tissue containing greatly engorged blood
vessels. In this necrotic material nuclei are absent and the tissue
containing fibrin stains deeply with eosin. In it occur fissures or
tears which extend from the lumen a variable distance, very frequently
penetrating the entire thickness of the wall and entering adjacent
alveoli (Figs. 17 and 19). Alveoli thus exposed almost invariably
contain plugs of dense fibrin. Where these rents have occurred, adjacent
edges of the bronchial wall, held together by underlying lung tissue,
have separated from one another, so that the circumference of the
bronchus has been increased (Fig. 18). These breaks in the continuity of
the wall may occur in several places, so that a fourth or a third of the
circumference may be formed by exposed alveolar tissue which has become
the site of fibrinous pneumonia (Fig. 20). During life, though the
inflamed bronchus is filled by mucopurulent exudate, distention of loose
alveolar tissue, uniting the interrupted bronchial wall, is doubtless
greater than it appears in the lung fixed by hardening fluids.

[Illustration:

Fig. 18.—Acute bronchiectasis showing fissures in the bronchial wall
extending into neighboring alveoli which in zone about are filled
with fibrin; one fissure has separated widely; peribronchial
fibrinous pneumonia (fibrin is black). Autopsy 425.
]

Recently dilated bronchi have an irregularly stellate lumen as the
result of clefts penetrating at intervals into or through the bronchial
wall (Fig. 26). Longitudinal fissures mark the lining of these dilated
bronchial tubes.

When the fatal illness has lasted more than two weeks, abundant new
formation of fibrous tissue occurs in a zone surrounding the dilated
bronchus. Adjacent alveolar walls are thickened by young fibrous tissue.
Alveoli, much diminished in size, are filled by hyaline fibrin into
which fibroblasts and newly formed blood vessels have penetrated. These
changes are limited to a wide zone in immediate contact with the dilated
bronchus, whereas at a greater distance alveolar walls have undergone no
thickening and alveoli contain no fibrin.

[Illustration:

Fig. 19.—Acute bronchiectasis; the bronchial wall indicated by
engorged mucosa shows a varying degree of destruction, fissures
extending into and through the bronchial wall. Autopsy 352.
]

[Illustration:

Fig. 20.—Acute bronchiectasis; with destruction of bronchial wall
exposing alveoli filled with fibrin; peribronchial fibrinous
pneumonia is seen about several bronchi present in the section; Gram
Weigert fibrin stain. Autopsy 425.
]

This stage is well represented by Autopsy 421 after an illness of
nineteen days. Bronchiectatic cavities, from 3 to 6 mm. in diameter, are
numerous in sections of the lung; their lumina are irregular in outline
and often irregularly stellate. Microscopic examination shows the
presence of clefts which interrupt the bronchial wall at intervals
throughout its entire circumference. The original wall is well indicated
by the very richly vascularized connective tissue containing scattered
muscle bundles and is infiltrated with lymphoid and plasma cells in
great number. Where fissures have occurred the adjacent edges of the
interrupted wall have separated from one another, leaving a wide
interval where underlying alveolar tissue is exposed. Two changes tend
eventually to render the fissures inconspicuous, namely, regeneration of
epithelium and new formation of fibrous tissue. Exposed alveoli filled
with fibrin are in process of organization and epithelium which has
assumed a squamous type has grown down over the exposed surfaces of the
interrupted bronchial wall. It has begun to cover or in some instances
has completely covered the surface of rents entering alveoli plugged
with fibrin (Fig. 21). In the periphery of the bronchus alveolar walls
are thickened and infiltrated with lymphoid and plasma cells. The same
changes affect bronchi containing cartilage which is undergoing atrophy.

The reinforcement of the fissured bronchial wall by new formation of
fibrous tissue, by thickening of the interalveolar walls and by
organization of fibrin within the alveoli is well shown after four weeks
(Autopsy 425; Fig. 28). There are spherical bronchiectatic cavities more
than a centimeter in diameter surrounded by a dense fibrous wall in
which are atrophied alveoli lined by epithelium of cubical form.
Occasionally, the fibrous wall is interrupted and alveoli, plugged with
organizing fibrin, are in immediate contact with the lumen. When these
plugs of fibrin which are slowly absorbed disappear, evidence of
preexisting rents in the bronchial wall are lost, and there are in this
lung bronchiectatic cavities of which the wall is a continuous circle of
dense fibrous tissue.

[Illustration:

Fig. 21.—Bronchiectasis with fissures extending through the bronchial
wall into alveolar tissue which is the site of fibrinous pneumonia;
epithelium has grown down into these fissures and has covered the
exposed surfaces. Autopsy 463.
]

[Illustration:

Fig. 22.—Regeneration of epithelium over fissures which have been
formed in the wall of a bronchus; the epithelium in the neighborhood
of and within the fissure is squamous.
]

Epithelium lining the dilated bronchi is at times completely destroyed
(Fig. 28), but more frequently it persists in part. That which remains
has almost constantly the character of squamous epithelium (Figs. 22 and
23). The lowermost cells are cubical; those above them are polygonal,
tending to become flatter as the surface is approached; upon the surface
are cells often much flattened and occasionally they have lost their
nuclei and stain deeply with eosin as the result of superficial
necrosis. The change should not be regarded as metaplasia, for the
epithelium assumes this squamous type when the superficial columnar
cells have been lost. Actual necrosis of superficial ciliated columnar
cells is occasionally seen (Autopsy 352); injured cells have separated
from one another and desquamated into the lumen of the bronchus. The
epithelium which remains after the superficial cells are lost consists
of cells which become flatter from base to surface, but the
intercellular bridges characteristic of the epithelium of the skin are
not found. When epithelium is in process of regeneration, a layer
gradually diminishing in thickness extends over the denuded surface, the
advancing edge being formed by very flat cells in a single layer. The
epithelium growing into fissures which have penetrated the bronchial
wall may completely cover the exposed alveolar tissue. The newly formed
epithelium may follow a fissure into an alveolus which has been opened
and come into contact with the fibrin which fills the alveolus.

[Illustration:

Fig. 23.—Squamous epithelium growing over the defect in the bronchial
wall shown in Fig. 22 more highly magnified; squamous epithelium is
present above and columnar epithelium below.
]

Bronchiectasis usually affects the small bronchi with no cartilage. It
is not uncommon to find greatly dilated bronchi with no cartilage in
close proximity to cartilage containing bronchi of smaller caliber. In
one instance (Autopsy 421) a bronchus of medium size with cartilage
measured 3 mm. in diameter, whereas two bronchi with no cartilage were
dilated to 4 and 6 mm., respectively. Nevertheless, larger bronchi are
occasionally the site of superficial loss of epithelium, necrosis
extending into the bronchial wall, formation of fissures and stretching
of the wall at the spot which is weakened. In association with these
changes atrophy of the cartilage may occur (Autopsies 421, 425, 440,
463). Plates of cartilage in process of atrophy are readily recognized
by their irregularly indented outline and often by their small size. The
fibrous tissue surrounding the cartilage is the site of chronic
inflammation and is densely infiltrated with lymphoid and plasma cells
among which polynuclear leucocytes are scant. Nevertheless, polynuclear
leucocytes are abundant in immediate contact with the cartilage and
appear to have an important part in the solution of its matrix, for
about them occur indentations of the edge. Leucocytes penetrate into the
cartilage.

The necrosis and tears which occur in the wall of the bronchus are not
always limited to the bronchus, but may extend deeply into the
surrounding tissue. In Autopsies 312 (Fig. 21) and 423 wide areas of
necrosis have penetrated deeply into the tissue about the bronchi.

=Autopsy 312.=—Illness began with influenza on September 26,
seventeen days before death; a diagnosis of lobar pneumonia with
consolidation of the right lower lobe was made ten days after onset
and Pneumococcus IV, B. influenzæ and S. hemolyticus were found in
the sputum. At autopsy there was bronchopneumonia with red and gray
lobular and confluent lobular patches of consolidation and right and
left serofibrinous pleurisy; there was purulent bronchitis; no
abscesses were seen. Small bronchi throughout both lungs were
dilated and often surrounded by a zone of hemorrhage.

Hemolytic streptococci were found in the heart’s blood, in the
pleural exudate, consolidated lung and bronchus; B. influenzæ was
found in the lung and in a small bronchus, and staphylococci in the
contents of a small bronchus.

[Illustration:

Fig. 24.—Acute bronchiectasis with fissures extending through
bronchial wall which is marked by great engorgement of blood
vessels; at one point a fissure has penetrated deep into the
alveolar tissue and formed a small cavity containing purulent
exudate and surrounded by fibrinous pneumonia. Autopsy 312.
]

Bronchi which are the site of acute inflammation have lost their
epithelium wholly or in part, and deep fissures penetrate the entire
thickness of the bronchial wall, extending into the surrounding lung
tissue which is the site of fibrinous pneumonia. In some instances
plugs of fibrin within the alveoli are bisected by these tears.
There is some superficial necrosis along the edge of each fissure,
in several places extending outward from defects in the walls of
small bronchi dilated to approximately 1.5 mm. There are wide
patches of necrosis affecting both alveolar walls and contents of
alveoli and extending 2 mm. into the lung tissue. When a fissure has
penetrated from the lumen of the bronchus into necrotic tissue (Fig.
21), polynuclear leucocytes have accumulated within the necrotic
tissue, disintegration of tissue occurs, and a small cavity
communicating with the bronchus is formed.

=Autopsy 423.=—C. H., white, aged twenty-five, resident of Oklahoma,
had been in military service one month. Death occurred sixteen days
after onset of influenza.

=Anatomical Diagnosis.=—Chronic bronchopneumonia with
peribronchiolar consolidation throughout right lung and in left
lower lobe; right purulent pleurisy; purulent bronchitis;
bronchiectasis at base of left lung.

The right lung weighs 1,260 grams; in the upper lobe are yellowish
gray nodules having the appearance of tubercles clustered about
small bronchi; in places similar nodules occur upon a background of
pinkish gray consolidation occupying the greater part of the lower
lobe. Bronchi contain purulent fluid. The left lung weighs 760
grams; it is edematous and small, yellowish gray nodules of
consolidation in the lower lobe are clustered about terminal
bronchi. Bronchi at the base of the lower lobe are dilated.

Bacteriologic examination shows the presence of hemolytic
streptococci in the blood of the heart; hemolytic streptococci and
B. influenzæ in the lung.

Microscopic examination shows that the walls of the bronchi are
infiltrated with lymphoid and plasma cells; these cells are very
numerous in peribronchiolar patches of consolidation. A small
bronchus 1 mm. in diameter has squamous epithelium along one side;
on the opposite side, the wall is completely absent and there is
superficial necrosis of exposed alveoli filled with fibrin. A deep
fissure passes from the bronchus into the consolidated tissue; its
edges are necrotic and it is filled with polynuclear leucocytes. A
small cavity in contact with the bronchus has been formed. In
another part of the lung a distended bronchus has lost its
epithelium on one side, and here alveoli filled with fibrin form the
wall of the bronchus which is filled with leucocytes. Extending
outward from the eroded wall is a focus of necrosis where both
alveolar walls and contained exudate have lost their nuclei.

The necrosis which has had its origin in the bronchi is soon followed by
accumulation of polynuclear leucocytes, softening and disintegration of
tissue. Discharge of the disintegrated tissue through the bronchi
results in the formation of a small cavity continuous with the bronchus.
These changes are well illustrated by the bronchiogenic abscesses which
have been described elsewhere (Autopsies 376, p. 206, and 387, p. 206).
When disintegrated tissue is discharged by way of the bronchi no
accumulation of pus occurs, but cavities will be formed, in part by
dilation of bronchi, in part by erosion of the adjacent lung tissue.
Histologic examination shows that these changes have produced the
advanced bronchiectasis found in Autopsy 445 (Fig. 25).

=Autopsy 445.=—W. F., white, aged twenty-three, from Mississippi,
had been in military service one month. His illness began September
22, twenty-seven days before death, with severe coryza, weakness,
nausea and vomiting; great pain in bones, cough and sore throat. He
was admitted to the base hospital one week later with diagnosis of
influenza and bronchitis. On October 3, sixteen days before death,
signs of consolidation were found on the left side over the back and
a diagnosis of lobar pneumonia was made. On October 18 there was
severe headache, pupils were dilated, and there was rigidity of
neck; lumbar puncture was made and pneumococci were found in the
fluid obtained. Death occurred on the following day.

=Anatomic Diagnosis.=—Bronchiectasis with unresolved pneumonia
limited to the left lower lobe; acute bronchopneumonia with
peribronchiolar consolidation in right lung; purulent bronchitis,
peribronchial hemorrhage and organizing bronchiolitis in right lung;
adherent pleura on left side; purulent meningitis.

The left upper lobe is crepitant throughout. The outer and posterior
two-thirds of the left lower lobe is riddled with cavities often
rounded and varying in diameter from 0.5 to 3 cm. but not
infrequently irregular in shape and in communication with adjacent
cavities (Fig. 25). In places cavities pass in a tortuous course
from pleura to the midpart of lung. The lining of these cavities is
usually smooth, but in places is covered by gray necrotic material.
Communication between the cavities and medium-sized bronchi is
occasionally found. The lung tissue between the cavities is in part
grayish red and consolidated, in part pink and air containing. The
right lung is edematous throughout; the bronchi in the lower part of
the right lung contain purulent fluid and are in places surrounded
by zones of hemorrhage.

The spleen is very large (14 × 11 × 5 cm.) and firm.

The spinal fluid is cloudy and blood vessels over the lumbar
enlargement and lower thoracic region are congested; in the upper
thoracic region the cord is covered by purulent exudate.

Bacteriologic examination demonstrates the presence of hemolytic
streptococci in the blood of the heart; plates from the left lung
contain a few colonies of S. aureus and Pneumococcus IV; plates from
the right main bronchus contain S. aureus and a large bacillus which
does not stain by Gram’s method. Three plates from the spinal
meninges contain Pneumococcus IV.

[Illustration:

Fig. 25.—Advanced bronchiectasis throughout lower left lobe. Autopsy
445.
]

Microscopic examination shows that the cavities which have been
described are lined by very vascular connective tissue containing
many cells; there is no epithelial lining and the surface is in
places covered by fibrin. On the surface polynuclear leucocytes are
numerous, but immediately below, large mononuclear cells occur and
frequently contain one or several ingested polynuclear leucocytes.
None of the structures peculiar to the bronchi can be identified in
the wall of these cavities, and in many places it is evident that
lung tissue has undergone destruction, for in places the lining of
vascular connective tissue is interrupted and an extension of the
cavity penetrating into the lung substance is surrounded by alveoli
filled with fibrin; in contact with the cavity there is some
necrosis.

The cavities communicate with the bronchi and are lined in part by
vascular connective tissue which may in part represent preexisting
bronchial walls, but no epithelium is present and the relation to the
bronchi cannot be established with certainty. These cavities have
extended by necrosis which has broken the vascular connective tissue of
their wall and penetrated into adjacent lung tissue. Death has been the
result of purulent meningitis caused by pneumococcus, and the histologic
changes in the walls of the cavities suggest that the activity of the
inflammatory reaction here is subsiding, for large mononuclear cells are
numerous and are ingesting polynuclear leucocytes. The changes described
would, if continued, result in the formation of cavities lined by
fibrous tissue and resembling many of those formed as the result of
dilatation of the bronchi.

A study of the progress of the changes which result in the formation of
bronchiectatic cavities has shown how the inflammatory irritant within
the bronchus destroys the epithelium of the bronchus, penetrates into
the deeper tissues and produces fissures which extend through the entire
thickness of the bronchial wall at one or usually several places. These
longitudinal fissures, which at first often give a stellate outline in
cross section to the cavity of the affected bronchus, permit the
separation of the edges of the fissure, so that an increase in the
circumference occurs. The base of the fissure is formed by surrounding
alveolar tissue and its edges are the site of necrosis. Tears may extend
into the surrounding alveolar tissue, thus permitting further stretching
of the bronchial wall. The consequences of rupture of the small bronchi
into the adjacent alveoli are to some extent overcome by the
inflammatory reaction which plugs the adjacent alveoli with fibrin.

Compression of the lungs by forced expiration, even though the glottis
were closed as in coughing, would not dilate the bronchi, because
pressure outside and within the bronchi would be equally elevated
(Thornton and Pratt[89]). The pressure within the bronchi does not
differ greatly from atmospheric pressure, whereas the negative pressure
within the pleural cavity may vary from approximately 6 mm. of mercury
during quiet inspiration to 30 mm. with forced inspiration. Excess of
pressure upon the inner surface of the bronchial walls will vary with
coughing and other respiratory efforts, between these limits depending
upon the readiness with which pressure is equalized within and without
the bronchi by penetration of air into the alveoli. The presence of
viscid mucopurulent fluid within bronchioles will obstruct these tubules
and retard the entrance of air into alveoli.

Weakening of the bronchial wall by the changes which have been described
will cause lasting dilatation of the bronchi. Whatever increases
pressure within the bronchi will increase the tendency to dilatation;
the bronchi being filled with mucopurulent exudate dilatation usually
appears first at the bases of the lung, since gravity increases
intrabronchial pressure here. New formation of fibrous tissue within the
wall of the bronchus, thickening of adjacent alveolar walls, and
organization of fibrin reinforce the weakened bronchial wall and limit
the dilatation which follows injury to the wall. Regeneration of
epithelium covering the dilated tube will further obscure the early
changes which have made dilatation possible. The changes which weaken
the bronchial wall permit dilatation at a time when there is no new
formation of fibrous tissue. When the bronchial lesion has persisted
several weeks, chronic pneumonia is associated with it. It has been
suggested that the contraction of newly formed fibrous tissue within the
substance of the lung might cause bronchi to be enlarged by traction
upon their walls. Newly formed connective tissue is most abundant in the
wall of the bronchiectatic cavity, and here contraction would tend to
diminish the size of the cavity.

Unresolved Bronchopneumonia

Chronic bronchopneumonia is characterized by changes similar to those
associated with chronic inflammation in other parts of the body, namely,
by thickening of the interstitial tissue of the lung, by accumulation of
mononuclear cells, by proliferation of fibrous tissue and by
organization of exuded fibrin. In a few instances these changes have
begun at the end of two weeks after onset of influenza, but they have
been little advanced until three weeks has elapsed; advanced chronic
inflammation has occurred after from four to eight weeks. Chronic
inflammation primarily affects those structures which are most severely
injured by the acute lesion and is most conspicuous in immediate
proximity to the small bronchi and bronchioles; the perivascular and
interlobular connective tissue are secondarily involved. Corresponding
to each of the lesions of the alveolar tissue which have been found with
bronchopneumonia, namely, peribronchiolar, hemorrhagic peribronchiolar,
lobular and peribronchial consolidation, there is a chronic lesion which
develops when pneumonia has failed to resolve.

The term interstitial bronchopneumonia has been used by MacCallum to
designate a lesion which he has found in association with measles at
Fort Sam Houston. This name he states does not describe accurately the
early stage of the lesion, for its interstitial character is not evident
at first. In his monograph on “Epidemic Pneumonia in the Army Camp,”
published in 1919, MacCallum describes and pictures instances of the
lesion which we have designated interstitial suppurative pneumonia and
classifies them as interstitial bronchopneumonia. We have shown that
this lesion, which is the result of infection of the lymphatics with S.
hemolyticus, bears no necessary relation to the lesion which is
characterized in its early stage by peribronchiolar pneumonia and in its
later stages by chronic inflammation with mononuclear infiltration and
proliferation of the peribronchial, perivascular and interalveolar
tissue. At Fort Sam Houston, nearly every patient with measles was
infected with hemolytic streptococci; we observed, following influenza,
similar prevalence of hemolytic streptococci in certain wards in the
base hospital at Camp Pike. Among the cases at Fort Sam Houston there
were doubtless instances both of interstitial suppurative pneumonia
caused by hemolytic streptococcus and of chronic bronchopneumonia not
referable to this microorganism.

Studying pneumonia following influenza at Camp Lee, Va., and later at
Camp Dix, N. J., during the fall of 1918, MacCallum reached the
conclusion that “interstitial bronchopneumonia” following influenza was
caused by B. influenzæ of Pfeiffer. This lesion attributed to B.
influenzæ differed from that previously referred to hemolytic
streptococcus in the following characters: the lymphatic channels in the
bronchial walls and widened interlobular septa are inconspicuous and
none are found distended with exudate; there is no intense infection of
the pleura, and polynuclear leucocytes are inconspicuous in the alveolar
exudate and in the walls of the bronchi. It seems probable these
differences are explained by the absence of hemolytic streptococci which
tend to invade lymphatics and produce severe inflammatory changes in the
pleura.

=Chronic Bronchitis.=—The earliest changes in the bronchial wall with
bronchitis of influenza are hyperemia, leucocytic infiltration and
hemorrhage, and they may occur even though the lining epithelium remains
intact. Epithelium frequently undergoes partial or complete destruction,
and with this severe injury the influence of the inflammatory irritant
may extend directly through the wall of the bronchus, for in some
instances there is hemorrhage into all the alveoli in a zone encircling
the bronchus. Since these alveoli have only indirect communication with
the affected bronchus through alveolar tissue not involved in the
inflammatory process, it is evident that the surrounding hemorrhage is
secondary to the lesion of the bronchus. Fibrinous inflammation in other
instances, similarly localized in a zone of alveoli encircling a
bronchus, is doubtless the result of direct extension of the
inflammatory process through the bronchial wall. After the disease has
existed during two or three weeks inflammation is still active
immediately below the inner surface of the bronchus; here polynuclear
leucocytes are numerous whereas in the deeper parts of the mucosa and
about the muscularis leucocytes are scant but lymphoid and plasma cells
are very numerous. The severity of the inflammatory reaction may be
judged by the abundance and extent of this cellular reaction and is in
close relation to the intensity of the changes affecting the mucous
membrane of the bronchus. Infiltration of the entire bronchial wall with
lymphoid and plasma cells is almost invariable when the primary injury
to the bronchus has destroyed the epithelial lining, and this
infiltration is not limited to the bronchial wall but extends outward
into the contiguous alveolar septa which are thickened by it. The sheath
of the pulmonary artery which accompanies the bronchus exhibits a
similar change, and the alveolar septa, as a fringe about it, are
thickened and infiltrated with mononuclear cells. Interlobular septa
continuous with the bronchus often show some infiltration.

A later phase in this series of changes is represented by new formation
of fibrous tissue. The bronchial walls and interalveolar septa are
thickened by proliferating fibrous tissue, young fibroblasts and newly
formed collagen fibrils being abundant (Fig. 28; also Fig. 30). This
increase of fibrous tissue is especially noteworthy immediately
surrounding the walls of the small bronchi, which are often considerably
dilated, and about the smaller of those bronchi which have cartilage;
with thickening of alveolar walls immediately adjacent to the bronchus
every stage in the obliteration of the alveoli may be found. Their walls
are thickened and their lumina are diminished in size and often
flattened in a direction concentric with the bronchus. Such atrophied
alveoli lined by cubical epithelial cells occurring within the thickened
peribronchial fibrous tissue give evidence that this tissue has replaced
alveoli. Alveoli surrounding and within the new fibrous tissue are
frequently filled with fibrin, and organization indicated by penetration
of fibroblasts and capillaries into the fibrin may be far advanced.
There is some increase of perivascular and interlobular tissue. The
bronchiectasis which is almost invariably found with unresolved
bronchopneumonia has been described. Squamous transformation of
epithelium (page 251) is frequently found in association with the
chronic bronchitis of unresolved pneumonia.

=Organizing Bronchitis and Bronchiolitis.=—When the bronchial epithelium
is destroyed, fibrin is deposited upon the denuded surface and may
partly or completely fill the lumen of the bronchial tube. The plug of
fibrin is adherent to the underlying tissue wherever epithelium is lost
but is separated from the bronchial wall by a well-defined space where
epithelial lining is still intact. Fibroblasts promptly migrate from the
wall of the bronchiole into this fibrin, and fibroblasts, fixed during
ameboid movement, are irregularly elongated in a direction toward the
fibrin.

Organization of fibrin occurs within the smallest bronchi (diameter 0.3
to 0.5 mm.) or within respiratory bronchioles. It has been found in 8
autopsies. In one instance it has been present eleven days after the
onset of influenza, but usually it is seen three or four weeks after
onset of symptoms of respiratory disease. In the early stages of the
lesion a plug of fibrin within the lumen of the bronchus or bronchiole
is invaded by fibroblasts, plasma cells and newly formed capillaries.
These capillaries have their origin in the wall of the tube and enter
the fibrin at points where in consequence of loss of epithelium fibrin
is continuous with the connective tissue. When the bronchiole is cut
longitudinally, partially or completely organized fibrin may be found
adherent at several places with intact epithelium, sometimes beautifully
ciliated, between the sites of attachment. The fibrin is finally
replaced completely and the lumen of the bronchiole contains a mass of
organized fibrous tissue in which young fibroblasts and plasma cells are
numerous.

The lesion has been associated with chronic bronchopneumonia in 6 of 8
instances. In Autopsy 445, p. 257, organizing bronchitis and
bronchiolitis occurred in the right lung unassociated with other chronic
lesion, although there was advanced bronchiectasis with fibrous
induration in the left lung. In Autopsy 499 (p. 224) organizing
bronchiolitis occurred in association with chronic changes which appear
to have followed interstitial suppurative pneumonia caused by S.
hemolyticus. Other severe lesions of the bronchi have accompanied
organizing bronchitis and bronchiolitis. Purulent bronchitis has been
present in 7 of 8 instances; bronchiectasis in 5 of 8 instances.

The bacteriology of autopsies with organizing bronchitis and
bronchiolitis is shown in Table LIII.

The bacteriology of these cases presents no constant feature. Invasion
of the blood by S. hemolyticus has been present in a large proportion of
cultures, namely, in 5 of 7 (71.4 per cent). In one of the 2 instances
in which hemolytic streptococci have been found, neither in the blood
nor lungs, Pneumococcus III has been found in the blood and S. viridans
in the lungs and bronchus; in the other, S. aureus has been found in the
lung and bronchus. Staphylococci have been found frequently in the
bronchi (60 per cent) and in the lungs (50 per cent). B. influenzæ has
been present in the bronchi in the usual proportion of instances (80 per
cent). The lesion has occurred in the presence of B. influenzæ combined
with streptococci or staphylococci.

TABLE LIII

═══════════╤══════════════╤══════════════╤══════════════╤══════════════
AUTOPSY │ DURATION OF │ BLOOD │ LUNGS │ BRONCHUS
│ ILLNESS │ │ │
───────────┼──────────────┼──────────────┼──────────────┼──────────────
420 │11 days │S. hem. │S. hem., B. │
│ │ │ inf., S. │
│ │ │ aur. │
402 │14 days │Pneum. IV, │ │
│ │ S.hem. │ │
370 │17 days │ │S. aur. │S. aur.,
│ │ │ │ Pneum. IV,
│ │ │ │ B. inf.
457 │17+ days │ │ │Pneum. IV, B.
│ │ │ │ inf.
421 │19 days │S. hem. │Pneum. IV, S. │
│ │ │ hem. │
445 │27 days │S. hem. │Pneum. IV, S. │S. aur.
│ │ │ aur. │
473 │28+ days │Pneum. III │S. vir. │B. inf., S.
│ │ │ │ vir.,
│ │ │ │ staph., M.
│ │ │ │ catarr.
499 │36 days │S. hem. │ │S. hem. B.
│ │ │ │ inf.
───────────┴──────────────┴──────────────┴──────────────┴──────────────

Thrombosis of lymphatics in the wall of bronchi adjacent to blood
vessels and in interlobular septa occurs, and occasionally organization
of the fibrinous plug within the lymphatic is in progress (Autopsies
283, 425 and 463). Fibroblasts and capillaries penetrate from the wall
of the lymphatic into a mass of hyaline fibrin which fills the lumen.

=Unresolved Bronchopneumonia.=—The most common type of pneumonic lesion
following influenza is characterized by acute inflammation of the
alveoli immediately adjacent to the bronchioles and the lesion is
associated in many instances with hemorrhage or edema. If this lesion
persists unresolved during several weeks, evidences of chronic
inflammation are found. Peribronchial, perivascular and interlobular
connective tissue is thickened and richly infiltrated with lymphoid and
plasma cells, large mononuclear cells and many young fibroblasts.
Interalveolar septa adjacent to the walls of bronchi and between alveoli
surrounding inflamed bronchioles are implicated in the process.
Interstitial changes characterize the lesion only in its late stage. It
appears undesirable to give the name “interstitial pneumonia” to the
early stage of a lesion which begins and in most instances terminates as
an acute relatively superficial inflammation of the bronchi, bronchioles
and peribronchiolar alveoli.

Chronic bronchopneumonia is often overlooked at autopsy because newly
formed connective tissue is not present in sufficient quantity to
attract attention (Fig. 26). When the lesion is advanced conspicuous
gray white patches of fibrous tissue may be seen about the bronchi
(Autopsy 487; Fig. 27) and interlobular septa may be obviously thickened
(Autopsy 472). The most distinctive feature of the lungs is the presence
of small, firm, gray or yellowish gray nodules of consolidation which
resemble miliary tubercles. They represent the peribronchiolar patches
of bronchopneumonia present during the acute stage and have assumed the
well-defined outline and firm consistence of tubercles because
polynuclear leucocytes and red blood corpuscles have in large part
disappeared, interstitial tissue is increased, and exudate is in process
of organization. These nodules are grouped in clusters about the small
bronchi.

With unresolved bronchopneumonia the lungs are very voluminous and fail
to collapse after they are removed from the chest and in some instances
even after incision. The air containing tissue is usually dry. In our
autopsies the lungs have been pink in color and often free from coal
pigment, because those suffering with pneumonia have been in
considerable part men from rural districts. Thick mucopurulent material
exudes from the small bronchi which have been cut across; purulent
bronchitis has been present in 20 of 21 instances of chronic
bronchopneumonia. Bronchiectasis has been present in 13 instances;
dilatation is often advanced, so that throughout the lungs are found
bronchi with no cartilage distended to a diameter of 0.5 cm. In addition
to the firm peribronchiolar tubercle-like nodules of consolidation there
are scattered patches of gray lobular or confluent lobular
consolidation. Yellowish nodules, grouped about bronchi and resembling
those found elsewhere in air containing tissue, are occasionally seen
scattered upon the cut surface of a patch of gray, confluent lobular
consolidation (Autopsies 421, 423, 431).

[Illustration:

Fig. 26.—Unresolved bronchopneumonia with tubercle-like nodules of
peribronchiolar consolidation best seen in lower lobe;
bronchiectasis. Autopsy 425.
]

Microscopic examination demonstrates the presence of those changes which
have been described in association with chronic bronchitis and
bronchiectasis. There is abundant new formation of fibrous tissue about
the bronchi of small and medium size, thickening of adjacent
interalveolar walls and incorporation of alveoli into the thickened
bronchial wall (Figs. 27, 28, 30, and 31). In half of the instances of
chronic bronchopneumonia there has been peribronchial fibrinous
pneumonia, and organization of fibrin within the alveoli is usually well
advanced. In one instance (Autopsy 487; Figs. 27 and 28) after an
illness of fifty-five days this process has resulted in the formation of
conspicuous patches of firm, grayish white fibrous tissue surrounding
dilated bronchi. Organization of fibrinous exudate within the lung has
not been limited to the alveoli but has occurred in the bronchioles as
well. Organizing bronchiolitis has been present in 5 instances
(Autopsies 370, 402, 457 and 473).

Increase of fibrous tissue occurs about the blood vessels and in the
septa between the lobules, which are infiltrated with mononuclear
wandering cells and fibroblasts. Dilatation and thrombosis of the
lymphatic vessels have occurred in both situations, and in 3 instances
(Autopsies 283, 425 and 463) organization of these fibrinous thrombi has
occurred.

[Illustration:

Fig. 27.—Unresolved pneumonia with peribronchial formation of fibrous
tissue; bronchiectasis. Autopsy 487.
]

[Illustration:

Fig. 28.—Unresolved pneumonia with bronchiectasis showing new
formation of fibrous tissue about a greatly dilated bronchus of
which the epithelial lining has been lost. Autopsy 487.
]

Thickening, cellular infiltration and fibrosis of the bronchial walls
with interstitial inflammation and fibrosis of immediately adjacent
alveolar septa are found about the ramifications of the bronchial tree
and may be followed to the smallest bronchi. When the respiratory
bronchioles are reached it will be found that the alveoli which stud
their walls are implicated in the change. The fibrin which they contain
is infiltrated with lymphoid and plasma cells, and with progress of the
lesion is invaded by fibroblasts and capillaries. Infiltration and
fibroid thickening extends from the bronchiolar wall to the alveolar
septa continuous with it (Fig. 31 with measles). Similar changes occur
about the alveolar ducts, and about the orifices of the tributary
infundibula (Fig. 32), peribronchiolar foci of acute inflammation having
assumed the characters of a chronic inflammatory process. Fibrin within
the alveoli contains round cells and fibroblasts. With thickening of
alveolar walls the alveolar lumina may be much diminished in size and
often persist as spaces lined by cubical cells. Polynuclear leucocytes
are usually numerous within the alveolar duct and in a few alveoli
immediately adjacent to it, but elsewhere throughout the focus of
inflammation round cells are predominant. The changes which have been
described correspond with the transformation of ill-defined, gray or
reddish gray spots of consolidation grouped about the terminal bronchi
into firm sharply defined grayish white nodules having the consistence
and appearance of miliary tubercles.

One of the most constant characters of pneumonia following influenza is
its hemorrhagic character. In the earlier stages of pneumonia
phagocytosis of red blood corpuscles by large mononuclear cells is
frequently seen. In association with the chronic changes which have been
described, large mononuclear cells filled with brown pigment, doubtless
formed from red corpuscles, are often found within the alveoli. These
pigment containing cells are similar to those commonly associated with
chronic passive congestion of the lungs.

In one instance (Autopsy 457) hemorrhagic peribronchiolar pneumonia has
been found in process of organization. The bronchioles and alveoli
adjacent to them contain polynuclear leucocytes, but intervening alveoli
almost uniformly contain blood and are the site of new formation of
connective tissue. Interalveolar septa are thickened and alveoli which
are lined by cubical epithelium are often diminished in size. In many
places fibroblasts have penetrated in considerable number into the blood
within the alveoli and occasionally newly formed capillaries are found
within them.

Lobular patches of pneumonia are often found in process of organization
(Autopsies 370, 421, 423, 433, 463, 472 and 473). Microscopic
examination shows that whole lobules well defined by thickened septa are
the site of chronic interalveolar inflammation and intraalveolar
organization of exudate, whereas adjacent lobules are air containing and
relatively normal. In the earlier stages of the process fibrin present
within the alveoli is invaded by fibroblasts, mononuclear wandering
cells and blood vessels but in the later stages fibrin has disappeared;
the lumina of the alveoli are occupied by cellular fibrous tissue and in
places the thickened alveolar walls and intraalveolar fibrous tissue
have been fused to form wide patches of new tissue.

With chronic bronchopneumonia confluent lobular consolidation
occasionally has a gray ground upon which are scattered small yellow
spots clustered about the small bronchi (Autopsies 421, 423 and 431).
Microscopic examination has shown that the yellowish spots correspond to
dilated bronchioles filled with purulent exudate and surrounded with
alveoli containing many polynuclear leucocytes. In the interstitial
tissue about the bronchiole and between adjacent alveoli plasma cells
are often present in great number. Between these spots of subacute
bronchiolar inflammation lung tissue is the site of interalveolar
proliferation of fibrous tissue and intraalveolar organization of
exudate.

In all instances of chronic bronchopneumonia there has been
peribronchial pneumonia in a zone encircling small bronchi with no
cartilage and the smallest of the bronchi which have cartilage in their
wall; thickening of interalveolar septa, organization of peribronchial
fibrinous pneumonia and partial disappearance of alveoli have been
described. In the following autopsy peribronchial fibroid pneumonia has
been so advanced that conspicuous patches of gray white tissue
surrounding bronchi have replaced in some parts of the lung a
considerable part of the lung substance.

=Autopsy 487.=—W. C., white, aged twenty-seven years, a farmer from
Mississippi had been in military service twenty-one days. Illness
began on September 17, fifty-five days before death, with chill,
fever, cough, backache, pain in the chest and coryza. The patient
was admitted two weeks after onset with the diagnosis of influenza.
Eight days later his sputum was blood tinged and there were signs of
bronchopneumonia. One month after admission the patient developed a
rash and a diagnosis of scarlet fever was made.

=Anatomic Diagnosis.=—Chronic bronchopneumonia with peribronchial
fibroid induration; bronchiectasis; purulent bronchitis; abscesses
at the bases of both lungs; seropurulent pleurisy on the left side.

The body is much emaciated. The left pleural cavity contains 650
c.c. of opaque, dull yellow, thin, purulent fluid. The surface of
the left lung is covered in spots by white partially organized
fibrin.

On section of the right lung (Fig. 27) the tissue is found in great
part air containing but there are numerous firm, gray patches,
irregular in shape and from 1 to 2 cm. across. In these spots the
tissue is tough and resembles fibrous tissue; within them are much
dilated bronchi. In the central part of the upper lobe is a group of
cavities with smooth wall, the largest of these cavities being 12
mm. in diameter; immediately adjacent are dilated bronchi. Between
and surrounding these cavities is gray tissue, like that described
above. Below the outer surface of the upper lobe is an extensive
area 7 cm. from above downward, thickly studded with bronchiectatic
cavities, in the walls of which there is tough fibrous tissue. In
the middle lobe are several dilated bronchi, the largest of which is
7 mm. in diameter, and elsewhere occur dilated bronchi with
thickened walls. At the base of the lung below the pleura are two
abscesses, which are yellow in the center and surrounded by
hemorrhagic tissue. At the posterior part of the lower lobe there
are numerous firm, nodular, yellowish spots grouped in clusters upon
a background of red, air containing tissue. The bronchi throughout
the lung contain mucopurulent fluid.

In the left lung patches of fibrous tissue are more numerous than on
the right side and are irregular in shape, from 1 to 2 cm. across
and most abundant in the center of the upper lobe. This fibrous
tissue is in great part gray but in places it has a yellowish tinge.
The bronchi everywhere are moderately dilated. At the base of the
lung below the pleura is an abscess.

The other organs show no noteworthy change.

=Bacteriologic Examination.=—The fluid in the left pleura and right
main bronchus contain S. hemolyticus. B. influenzæ is found in the
right lung and right main bronchus.

Microscopic examination shows that the patches of dense fibrous
tissue seen at autopsy almost invariably surround dilated bronchi
with no cartilage in their walls (Fig. 28) and with a diameter of
from 1 to 2 or more millimeters. These bronchi have lost their
epithelial lining; they contain polynuclear leucocytes, and their
wall in contact with the lumen is infiltrated to a varying distance
with the same cells. Their inner surface is very irregular, and
superficial necrosis occurs. The limits of the preexisting bronchial
wall is no longer recognizable in the dense surrounding fibrous
tissue richly infiltrated with lymphoid and plasma cells. In contact
with the bronchus, often in a wide zone, all traces of alveoli have
been destroyed, but further outward alveoli are represented by
spaces lined by cubical epithelium. At the periphery of the zone of
fibroid induration alveolar walls are much thickened and richly
infiltrated with mononuclear wandering cells; the lumina of the
alveoli contain plugs of organized fibrous tissue often covered by
flat or cubical epithelium. In the surrounding tissue a few small
bronchi are lined by columnar epithelium; there is scant new
formation of fibrous tissue but the alveolar walls are thickened and
infiltrated with cells. Epithelium of the larger bronchi with
cartilage in their walls is usually intact and there is about them
little peribronchial inflammation.

Advanced induration about the bronchioles represents a late stage of
chronic peribronchiolar pneumonia. A bronchiole cut transversely is
found in the center of a focus of induration situated within relatively
normal air containing lung tissue. Next the bronchiole which in some
instances has wholly or partly lost its epithelium there is very
cellular fibrous tissue; further from the bronchiole alveoli are much
diminished in size, lined by flat or cubical epithelium and separated by
thick cellular walls. Plugs of cellular fibrous tissue sometimes fill
the alveolar duct. In favorable sections, cut in a plane which shows the
alveolar duct opening out into infundibula, it is found that newly
formed fibrous tissue surrounds the alveolar duct and extends into the
walls of its tributary alveoli; alveoli may be obliterated by this
fibrous tissue. Induration of alveolar walls is evident along the
proximal part of the infundibula which are readily demonstrable because
they are much dilated. (See Fig. 32.) The distal parts of the
infundibula are surrounded by alveoli with delicate walls.

One bronchus retains along one side part of its epithelium which has
assumed a squamous form. In other places the wall has undergone necrosis
which at one spot extends deeply into the surrounding tissue. Necrotic
tissue in another part of the circumference is infiltrated with
polynuclear leucocytes and separated from the surrounding tissue by a
space filled with leucocytes. An abscess communicating with the bronchus
is thus formed.

The foregoing instance is an example of the chronic fibroid pneumonias
with bronchiectasis which occur as sequelæ of the epidemic of influenza.
It is not improbable that a considerable number of those who suffer with
chronic bronchitis and bronchiectasis following influenza have less
extensive lesions similar to those which have been described.

=Bacteriology of Unresolved Bronchopneumonia.=—Bacteria found in the
bronchi in 10 instances of chronic bronchopneumonia have been as
follows:

BACTERIA IN BRONCHI WITH CHRONIC BRONCHOPNEUMONIA

B. coli 1
B. influenzæ and pneumococcus 1
B. influenzæ and S. hemolyticus 2
B. influenzæ and staphylococcus 1
S. hemolyticus and B. coli 1
B. influenzæ, pneumococcus and staphylococcus 3
B. influenzæ, S. viridans and M. catarrhalis 1

Bacteria found in the lungs in 17 instances of chronic bronchopneumonia
were as follows:

BACTERIA IN LUNGS WITH CHRONIC BRONCHOPNEUMONIA

B. influenzæ 1
Staphylococcus 1
S. viridans 1
B. influenzæ and pneumococcus 1
B. influenzæ and S. hemolyticus 3
B. influenzæ and staphylococcus 3
Pneumococcus and S. hemolyticus 1
S. hemolyticus and B. coli 2
B. influenzæ, S. hemolyticus and staphylococcus 3
No organism found 1

A noteworthy feature of these lists is the multiplicity of microorganism
found, namely, B. influenzæ, S. hemolyticus, pneumococcus,
staphylococcus, S. viridans, B. coli, and M. catarrhalis. More than one
microorganism is usually found in both bronchus and lung. In the one
instance (Autopsy 472) in which B. coli alone has been found in the
bronchus, B. coli and S. hemolyticus have been found in the lung and
hemolytic streptococcus in the blood; it is evident that B. coli alone
has not been responsible for the lesion. In one instance (Autopsy 487)
B. influenzæ alone has been found in the lung but hemolytic streptococci
have been found in the bronchus, pleura and blood of heart; with S.
aureus alone in the lung (Autopsy 370), S. aureus, Pneumococcus IV and
B. influenzæ have been found in the bronchus. With S. viridans alone in
the lung (Autopsy 473), Pneumococcus III has been found in the pleura
and in the blood of the heart and has doubtless had an important part in
the production of pneumonia; S. viridans, M. catarrhalis and B.
influenzæ have been found in the bronchus in this instance.

No single microorganism is associated with the lesions but combinations
of B. influenzæ with hemolytic streptococci or staphylococci are common
(over 50 per cent). In Autopsy 422 B. influenzæ and Pneumococcus
atypical II have been present in the lungs. Among 10 instances in which
cultures have been obtained from the bronchus B. influenzæ is found 8
times, and in the 2 instances in which it has not been identified B.
coli has been present. B. influenzæ has seldom been found (Table XXVII)
in the presence of B. coli, and it is not improbable that B. coli
outgrows and obscures the presence of B. influenzæ.

Table LIV shows the per cent incidence of pneumococci, hemolytic
streptococci, staphylococci and B. influenzæ in the bronchus, lung and
heart’s blood with chronic bronchopneumonia and serves as an index of
the readiness with which each of these microorganisms passes from
bronchus to lung and from lung to the blood in this disease.

TABLE LIV

═══════════╤══════════════╤══════════════╤══════════════╤══════════════
│ PNEUMOCOCCUS │ HEMOLYTIC │STAPHYLOCOCCUS│ B. INFLUENZÆ
│ PER CENT │STREPTOCOCCUS │ PER CENT │ PER CENT
│ POSITIVE │ PER CENT │ POSITIVE │ POSITIVE
│ │ POSITIVE │ │
───────────┼──────────────┼──────────────┼──────────────┼──────────────
Bronchus │ 40.0│ 30.0│ 50.0│ 80.0
Lung │ 12.5│ 56.2│ 37.5│ 68.7
Blood │ 16.6│ 55.6│ 0│ 0
───────────┴──────────────┴──────────────┴──────────────┴──────────────

Comparison of Table LIV with the analogous figures for acute
bronchopneumonia shows little noteworthy difference. Pneumococci are
less frequently found in the lung (12.5 per cent) and in the blood (16.6
per cent) with chronic bronchopneumonia than with acute bronchopneumonia
(lung 43.9 per cent; blood, 40.3 per cent). Hemolytic streptococci and
staphylococci are not more frequently found with unresolved than with
acute bronchopneumonia and failure to resolve cannot be referred to
either or to both microorganisms, for bronchopneumonia not infrequently
remains unresolved in their absence. B. influenzæ is present in the
bronchi in at least 80 per cent of instances and perhaps in all; it is
usually combined both in the lungs and in the bronchi with one of the
pyogenic cocci.

The severity of the injury to the walls of bronchi resulting in
continued infection with a variety of bacteria, appears to be the factor
determining failure of resolution and the persistence of
bronchopneumonia.

=The Relation of Unresolved Bronchopneumonia to Interstitial Suppurative
Pneumonia Caused by Hemolytic Streptococci.=—Hemolytic streptococci have
been present in a considerable proportion of those who have had
unresolved bronchopneumonia and its occurrence in the bronchi, lung and
blood of the heart indicates that it has had an important part in
causing death. Unresolved bronchopneumonia, following measles,
designated by MacCallum “interstitial bronchopneumonia” in a series of
autopsies at Fort Sam Houston in the spring of 1918, was constantly
associated with hemolytic streptococci. Among the lesions described as
interstitial bronchopneumonia was at least one which was evidently what
we have designated interstitial suppurative pneumonia. Lymphangitis was
not infrequently found with “interstitial bronchopneumonia” following
measles. At Camp Lee and Camp Dix, following the epidemic of influenza,
MacCallum found “interstitial bronchopneumonia” with no hemolytic
streptococci and noted that lymphatics in the interstitial septa were
inconspicuous and that none was found distended with exudate; empyema
was not present.

We have shown that interstitial suppurative pneumonia is an acute lesion
caused by hemolytic streptococci. Unresolved bronchopneumonia is
accompanied by chronic pneumonia and has no necessary relation to this
microorganism.

In a foregoing section we have described instances of interstitial
suppurative pneumonia unaccompanied by chronic changes, and in the
present section we have described instances of unresolved
bronchopneumonia with no infection by hemolytic streptococci. We have
pointed out that the incidence of streptococcus infection with
unresolved bronchopneumonia does not materially differ from that with
acute bronchopneumonia even though the greater duration of the disease
gives more opportunity for infection. In some of the autopsies made by
MacCallum at Fort Sam Houston, lesions of streptococcus infection
doubtless coexisted with unresolved bronchopneumonia.

In the 3 autopsies described below, interstitial suppurative pneumonia
with empyema caused by hemolytic streptococcus occurs in association
with unresolved bronchopneumonia.

=Autopsy 420.=—J. E. S., white, aged thirty-two years, born in
England and resident of Los Angeles, Cal., had been in military
service one month. Onset of illness began on October 3, eleven days
before his death. He was admitted to the hospital on the following
day with the diagnosis of influenza and acute bronchitis. Pneumonia
believed to be lobar was recognized eight days after admission.

=Anatomic Diagnosis.=—Unresolved bronchopneumonia with hemorrhagic
peribronchiolar consolidation in right lung; interstitial
suppurative pneumonia with consolidation in left upper lobe;
fibrinopurulent pleurisy; purulent bronchitis.

The left pleural cavity contains 200 c.c. of turbid yellow fluid in
which are flakes of fibrin. In the inner and upper part of the left
upper lobe there is an area of consolidation where the tissue has a
cloudy, pinkish gray color and is finely granular on section. Here
the interstitial septa are distended by edema, so that they are in
places 0.5 c.c. across; in some spots they have a bright yellow
color. In the posterior parts of the middle and lower lobes there is
flabby consolidation where the tissue has a cloudy, red color with
scattered ill-defined yellow spots.

Bacteriologic examination shows the presence of hemolytic
streptococci in the blood of the heart; hemolytic streptococci with
B. influenzæ and S. aureus in the left lung and S. hemolyticus with
S. aureus in the right lung.

Microscopic examination shows that bronchi, bronchioles, alveolar
ducts and the greater part of the infundibula are filled with
polynuclear leucocytes, whereas the alveoli surrounding these
structures contain fibrin. The walls of the small bronchi are
thickened and contain mononuclear cells; the adjacent alveolar walls
are similarly infiltrated and thickened and the fibrin within them
is undergoing organization, being invaded by plasma cells,
fibroblasts and newly formed blood vessels. In some sections
interstitial septa are distended by edema and contain fibrin in
abundance; in places the tissue contains polynuclear leucocytes
closely packed together. There are lymphatics greatly distended by
polynuclear leucocytes with some fibrin, lymphocytes and red blood
corpuscles.

=Autopsy 428.=—D. B., white, aged twenty-five, a farmer from
Oklahoma, had been in military service three weeks. Onset of illness
was on September 21, twenty-five days before death, with fever,
cough and mucopurulent expectoration. The patient was admitted with
the diagnosis of acute bilateral bronchitis. Four days later
bronchopneumonia was recognized, and subsequently there was otitis
media and empyema; 600 c.c. of thin, purulent fluid were aspirated
from the right chest three days before death.

=Anatomic Diagnosis.=—Unresolved bronchopneumonia; suppuration of
interstitial tissue of upper right and lower left lobes; purulent
bronchitis; fibrinopurulent pleurisy; thoracotomy wound at the base
of the right chest; collapse of both lungs; serofibrinous
pericarditis.

The left pleural cavity contains 550 c.c. of turbid seropurulent
fluid in which are numerous flakes of soft fibrin. The right pleural
cavity contains 150 c.c. of similar fluid. The mediastinum is
edematous. The pericardial cavity contains 50 c.c. of yellow fluid.

The right lung is moderately collapsed. In the upper and lower lobes
are small patches of red, lobular consolidation. The upper third of
the upper lobe is laxly consolidated and near its inner surface the
interstitial septa are thickened to from 1 to 1.5 mm. in width, and
at intervals occur bead-like swellings from which creamy purulent
fluid exudes upon the cut surface. In the left lung small patches of
gray consolidation occur throughout the lower lobe and here the
interstitial septa are thickened, beaded and contain purulent fluid.

Bacteriologic examination shows that the blood contains S.
hemolyticus; from the right lung and from the right main bronchus
hemolytic streptococci and B. influenzæ are grown.

Microscopic examination shows that the epithelium of the bronchi has
undergone hypertrophy; the wall is infiltrated with lymphoid and
plasma cells and thickened by new formation of fibrous tissue; there
is similar thickening of adjacent alveolar septa and alveoli, often
lined by cubical cells, are diminished in size. Connective tissue
about the blood vessels and the interstitial septa are thickened and
infiltrated with mononuclear cells. In parts of the lung the
interstitial septa are edematous and contain polynuclear leucocytes,
in some places in great number. Lymphatics are greatly dilated and
filled with polynuclear leucocytes which in the center of some
lymphatics have undergone necrosis. In one place a small abscess is
in contact with a distended lymphatic. Lymphatics contain
Gram-staining cocci in pairs and short chains, present in immense
number where necrosis has occurred.

=Autopsy 433.=—B. J., white, aged twenty-seven, from Arkansas, has
been in military service one month. Onset of illness was on
September 28, nineteen days before death, with cough and
expectoration. Pneumonic consolidation was recognized two days later
and 20 c.c. of cloudy fluid were aspirated from the left chest on
the same day. Hemolytic streptococci were found in a culture from
the throat nine days before death.

=Anatomic Diagnosis.=—Unresolved bronchopneumonia with
peribronchiolar and confluent lobular consolidation; interstitial
suppuration of the right lower lobe; purulent bronchitis;
fibrinopurulent pleurisy.

The right pleural cavity contains 700 c.c. of yellowish gray
purulent fluid containing flakes of fibrin. The left pleural cavity
contains seropurulent fluid localized over the external part of the
lung.

The right lung is voluminous and free from consolidation save at the
lower and posterior part of the lower lobe where the tissue is deep
red and studded with firmer spots of yellow color clustered about
the bronchi. In places the interstitial septa are thickened and
yellow. Surrounding some of the bronchi near the apex of the left
lung are red patches of consolidation.

Culture from heart’s blood remained sterile. S. hemolyticus was
grown from right pleural cavity, and S. hemolyticus and B. influenzæ
were grown from the right lung. Culture from the left lung contained
S. aureus and contaminating microorganisms.

Microscopic examination shows the presence of peribronchiolar
patches of pneumonia in which there are few polynuclear leucocytes
and many lymphoid and plasma cells; the alveolar walls are thickened
and infiltrated with mononuclear cells. In some sections the tissue
is wholly consolidated and the site of advanced organizing
pneumonia. Interlobular septa and connective tissue about blood
vessels are thickened and cellular. Small bronchi have lost their
epithelial lining, their walls are thickened and there is
peribronchial organizing pneumonia. In some sections the lymphatics
are immensely dilated and distended with polynuclear leucocytes.
There is necrosis of the walls of the lymphatics and of the
polynuclear leucocytes within the lumen.

In the discussion of acute bronchopneumonia it has been shown that S.
hemolyticus is not infrequently a secondary invader of a pneumonic
lesion perhaps caused by pneumococci. With progress of the disease
hemolytic streptococci persist. In the autopsies with unresolved
pneumonia just described, hemolytic streptococci have found their way
into the lymphatics and produced suppurative lymphangitis with
inflammation of the interstitial septa of the lung.

CHAPTER V
SECONDARY INFECTION IN THE WARD TREATMENT OF MEASLES

JAMES C. SMALL, M.D.

A study of 979 cases of measles was made in the base hospitals of Camps
Funston and Pike from July to December, 1918, with the purpose of
establishing any existing relation between the prevalence of the
hemolytic streptococci and the incidence of the graver complications of
measles, especially the pneumonia following measles. The greater number
of these cases occurred at Camp Pike coincidently with the influenza
epidemic, so that the picture is modified during this period by a
summation of the after effects of the two diseases.

The work undertaken includes:

(a) Routine throat cultures on admission of all patients with measles.

(b) Separation and treatment in separate wards of the patients harboring
hemolytic streptococci and those free from such streptococci.

(c) Investigation of the bacteriology of all cases under treatment, by
weekly throat cultures during the period in the hospital.

(d) Bacteriologic study of the complications of measles during life and
at autopsy.

(e) Study of the throat bacteriology of men on duty in the camp, to
establish the prevalence of hemolytic streptococci and of B. influenzæ
in normal individuals.

The work is further divided into that done at Camp Funston during the
latter part of July and throughout August, and that done at Camp Pike
during September, October, November and December, 1918.

=Studies at Camp Funston.=—The work done at Camp Funston is limited
strictly to the identification of hemolytic streptococci in the throats
of all patients with measles coming into the base hospital at Ft. Riley
and to the same study of a group of normal men on duty. During the
period of study hemolytic streptococci were identified by throat culture
in about 1 in 5 of all the normal men examined. Two instances of otitis
media represent the only complications developing in the 112 cases of
measles. Cultures from both patients showed staphylococci. The entire
absence of streptococcus complications appears the more surprising in
view of the fact that the prevalence of hemolytic streptococci among
patients under treatment in the ward was for a time as great as that
among the normal men. No special hospital management was instituted on
the basis of the findings in throat culture. S. hemolyticus carriers
remained in the wards and were treated alongside the “clean” cases. The
sheet cubicle system was used for bed patients. Face masks were not
worn. Convalescent patients were not segregated, and they assisted in
the care of the bed patients and in the ward kitchen. After the initial
throat culture on admission, the throats were gargled with argyrol and
afterwards sprayed with the same solution three times a day. This
solution was also employed to relieve the discomfort caused by the
conjunctivitis during the acute stage of the disease.

=Throat Culture and Identification of Hemolytic Streptococci.=—In
general the methods for the isolation and identification of hemolytic
streptococci as adopted by the Medical Department of the Army were used.
All organisms were isolated in pure culture, grown in broth, examined
microscopically and subjected to tests for hemolysis, (a 5 per cent
suspension of sheep corpuscles being employed), and for bile solubility.

Beef infusion broth and beef infusion agar constituted the two basic
media used. They were prepared so that the finished product titrated
about 0.3 per cent acid to phenolphthalein.

Broth tubes were carried to the bedside. In swabbing, the attempt was
made to produce gagging. This causes the tonsils to protrude from behind
the anterior pharyngeal pillars and places a slight tension on the
capsule which tends to squeeze material from the crypts. The surfaces of
the tonsils thus protruding toward the midline were brushed quickly with
a small cotton swab which was lastly touched to the posterior pharyngeal
wall and withdrawn so as to avoid touching any other parts. The swab was
immediately introduced into a tube of broth, twirled freely under the
surface of the liquid and discarded. The material thus washed into the
broth was carried to the laboratory and kept in the ice box until
plating, which was accomplished with as little delay as possible.

Tubes of melted agar containing 12 c.c. cooled below 45° C., after
receiving 0.6 c.c. of sterile defibrinated horse blood, were inoculated
with a loopful of this broth. Thorough mixing and pouring into Petri
dishes (10 cm. diameter) followed. After cooling, a second loopful was
streaked over the surface of one half of the plate. Deep and superficial
planting were thus effected on the same plate.

This method was found to be very useful. It can be used with advantage
provided one is not called upon to make a great number of cultures when
its time consuming factor is a great inconvenience. Another disadvantage
is the difficulty of picking single colonies for subculture. In spite of
the most careful selection and fishing of a deep colony, subcultures are
less likely to be pure than when surface colonies are chosen. By careful
regulation of the amount of agar in the tubes, the addition of a
measured amount of blood to each enabled one to pour standard blood agar
plates. Uniform thorough mixing of the blood is essential so that the
plate may present the desired “silky” rather than a “curdled” appearance
when viewed by transmitted light.

The plates were incubated eighteen to twenty-four hours when subcultures
in broth were made from the hemolytic colonies. After growing these for
a similar period the additional tests were carried out as indicated
above.

=Hemolytic Streptococci with Measles.=—The incidence of hemolytic
streptococci in the throats of patients with measles admitted to the
base hospital at Ft. Riley was found to be remarkably small.

TABLE LV

HEMOLYTIC STREPTOCOCCI WITH MEASLES IN ALL PATIENTS ADMITTED TO THE
WARDS AT CAMP FUNSTON

═══════════════╤════════╤═══════════╤════════╤════════════╤════════════
│ │APPROXIMATE│ NO. OF │ NO. WITH │ PER CENT
│DAYS IN │ DAY OF │PATIENTS│ HEMOLYTIC │ WITH
│HOSPITAL│ DISEASE │CULTURED│STREPTOCOCCI│ HEMOLYTIC
│ │ │ │ │STREPTOCOCCI
───────────────┼────────┼───────────┼────────┼────────────┼────────────
First Culture │ 0 to 1│ 1 to 8│ 112│ 3│ 2.67
Second Culture │ 3 to 10│ 4 to 16│ 86│ 11│ 12.79
Third Culture │ 8 to 23│ 12 to 26│ 58│ 14│ 24.14
───────────────┴────────┴───────────┴────────┴────────────┴────────────

The first culture represents the findings on admission, in a series of
112 cases; 86 patients being cultured twice; 58 patients three times.

Of the 112 cases examined on admission only 3, or 2.67 per cent were
found to carry hemolytic streptococci. Those patients who were
recultured after from three to ten days in the hospital showed an
incidence of 12.8 per cent. A third culture including patients from
eight to twenty-three days in the hospital, showed an incidence of 24.1
per cent.

=Hemolytic Streptococci in the Throats of Normal Men.=—A total of 274
throat cultures from normal men on duty at Camp Funston (Table LVI)
shows that 21.9 per cent carried hemolytic streptococci at a time when
there were few upper respiratory infections in the camp. A small group
of men resident in the hospital shows a slightly higher prevalence of
hemolytic streptococci (29.3 per cent).

The figures in Table LVI are in sharp contrast with those for measles
patients on admission to the hospital.

TABLE LVI

INCIDENCE OF HEMOLYTIC STREPTOCOCCI, CAMP FUNSTON.

════════════════════════════════════╤════════╤════════════╤════════════
│ │ │ PER CENT
│ │ HEMOLYTIC │ WITH
│ NUMBER │STREPTOCOCCI│ HEMOLYTIC
│EXAMINED│ PRESENT │STREPTOCOCCI
────────────────────────────────────┼────────┼────────────┼────────────
(_a_) White Men: │ │ │
70th Infantry │ 24│ 4│ 16.7
210th Engineers, Co. C │ 26│ 6│ 23.1
164th Depot Brigade, Co. 15 │ 50│ 10│ 20.0
164th Depot Brigade, Co. 18 │ 51│ 13│ 25.5
164th Depot Brigade, Co. 28 │ 50│ 13│ 26.0
────────────────────────────────────┼────────┼────────────┼────────────
Total │ 201│ 46│ 22.9
│ │ │
(_b_) Colored Men, Detention Camp │ │ │
No. 2: │ │ │
164th Depot Brigade, Prov. Co. 22 │ 25│ 6│ 24.0
3d Development Battalion, Co. A │ 24│ 3│ 12.5
3d Development Battalion, Co. D │ 24│ 5│ 20.8
────────────────────────────────────┼────────┼────────────┼────────────
Total │ 73│ 14│ 19.2
│ │ │
(_c_) Men resident in the hospital: │ │ │
Laboratory workers │ 10│ 3│ 30.0
Patients in surgical ward │ 14│ 4│ 28.6
────────────────────────────────────┼────────┼────────────┼────────────
Total │ 24│ 7│ 29.3
────────────────────────────────────┴────────┴────────────┴────────────

Two organizations from which normal men were chosen for examination
furnished a considerable number of cases of measles and offer data
(Table LVII, A and B) for further comparison.

TABLE LVII

A. HEMOLYTIC STREPTOCOCCI WITH MEASLES IN 164TH DEPOT BRIGADE, COMPANY
28.

═══════════════════════════╤════════╤════════╤════════════╤════════════
│ │ │ │ PER CENT
│ │ NO. OF │ NO. WITH │ WITH
│DAYS IN │PATIENTS│ HEMOLYTIC │ HEMOLYTIC
│HOSPITAL│CULTURED│STREPTOCOCCI│STREPTOCOCCI
───────────────────────────┼────────┼────────┼────────────┼────────────
First Culture │ 0 to 1│ 23│ 0│ 0
Second Culture │ 3 to 9│ 23│ 4[90]│ 17.4
Third Culture │10 to 21│ 21│ 4│ 19.05
Normal men of Co. 28 │ │ 50│ 13│ 26.00
───────────────────────────┴────────┴────────┴────────────┴────────────

B. HEMOLYTIC STREPTOCOCCI WITH MEASLES IN SEVENTIETH INFANTRY

───────────────────────────┬────────┬────────┬────────────┬────────────
First Culture │ 0 to 1│ 38│ 0│ 0
Second Culture │ 5 to 9│ 25│ 1│ 4.0
Third Culture │ 8 to 17│ 12│ 2│ 16.7
Normal men on duty with │ │ │ │
70th Infantry │ │ 24│ 4│ 16.7
───────────────────────────┴────────┴────────┴────────────┴────────────

No one of the 61 cases of measles from the two organizations was found
to be positive on admission to the hospital. Yet among normal men in one
of these organizations the incidence of hemolytic streptococci was 26
per cent and in the other, 16.7 per cent. In both organizations the
incidence among normal individuals compares closely with that of the
patients after a period in the measles wards of the hospital.

=Discussion.=—Three features of the data collected at Camp Funston are
noteworthy. First, the small percentage of S. hemolyticus carriers among
the men admitted to the hospital with measles as compared with the
percentage found in normal men in the camp. Second, the increase in the
number of S. hemolyticus carriers among patients during their stay in
the hospital, the increase continuing until it approaches that of the
normal men on the outside. Third, the prevalence of hemolytic
streptococci in normal throats.

In comparing men arriving at the hospital acutely ill with measles with
normal men in the organization from which they came, only one variable
can be found on which to base the differences observed in the two
groups. This is the advent of the acute disease. The figures seem to
suggest a temporary disappearance of hemolytic streptococci from the
throats of patients acutely ill with measles, at least, to such an
extent that the same cultural methods fail to identify the organisms.

The increase in the S. hemolyticus carriers among patients with measles
after a period in the hospital might depend upon two factors: First, the
exposure to contact infections in the hospital ward, depending on the
length of time in the ward as well as on the character of the ward
management; second, the passing of the acute stage of measles with a
return of the bacterial flora of the throat to the condition existing
before the onset of the acute disease. The first appears the more
probable. The second has only the support of the observation that the
streptococci were absent from the throat during the acute stage of
measles or were much less frequently found in patients with measles than
in normal men and later their incidence approached that in normal
individuals. The rather high incidence of hemolytic streptococci in
normal men at Camp Funston may have been due to the very recent
assembling of the 10th Division which now occupied the camp. It is
probable that the housing of large numbers of men in barracks is
attended by the same contact dissemination of mouth organisms that
occurs in hospital wards.

=Measles at Camp Pike.=—All cases of measles coming into the base
hospital at Camp Pike between September 15 and December 15, 1918, a
total of 867 cases, are included in the report. Upon the arrival of the
commission at Camp Pike early in September, a plan for the separation of
cases carrying hemolytic streptococci and those free from these
organisms was put into operation. The preliminary arrangements included
the allotment of suitable wards for treatment of the different classes
of cases; a throat culture survey of all patients with measles under
treatment at the time; their separation in accordance with the results
of bacteriologic examination, and the transfer of each group of patients
to its designated ward. By September 15 these preliminary arrangements
had been completed. Cases of measles admitted on this date and
afterwards were held in an observation ward pending the report upon a
throat culture before they were transferred to the treatment wards.

Beginning September 15 the following system of handling measles cases
was maintained in the wards of the base hospital.

All patients were received in an observation ward where they remained
until the results of a throat culture for hemolytic streptococci could
be reported back to the ward. Cases reported positive or negative were
immediately transferred to their respective treatment wards. All
patients in the treatment wards were cultured at intervals of one week
and cases found positive were transferred from the “clean” treatment
wards to a treatment ward for cases carrying hemolytic streptococci. The
ward personnel attending patients in the “clean” treatment wards was
examined by throat cultures from time to time with the purpose of
eliminating S. hemolyticus carriers. Patients segregated in the
streptococcus wards remained there, if uncomplicated, throughout their
hospital treatment even though subsequent repeated throat cultures
showed that the carrier condition had disappeared. Two wards were
provided to care for the pneumonia following measles. One received only
patients whose throat cultures were negative for hemolytic streptococci;
the other, those positive. It is essential that the throat culture on
which this differentiation is made be taken as soon as the complication
is reported and that transfer be made promptly on receipt of the report
of the culture. To facilitate this transfer, cases of pneumonia
complicating measles were reported to the laboratory as soon as
diagnosed and cultures were taken at once. The case remained in the
measles ward during twenty-four hours, isolated as well as possible,
awaiting report of culture before transfer. Within the positive ward for
measles pneumonias, distinction was made between streptococcus
pneumonias and nonstreptococcus pneumonias harboring hemolytic
streptococci in their throats. The two classes of cases were treated in
separate sections of the ward.

Ear complications were seen and treated by medical officers from the
otological service. These patients remained in the measles wards while
in the acute stage of measles, but later were transferred to the service
of otology whenever further surgical treatment became necessary.

Within the individual wards for treatment of measles and measles
pneumonias, precautions for minimizing the dangers of contact infections
were carried out as well as possible. Throughout the study we had the
hearty cooperation of the base hospital authorities and earnest,
well-directed effort to perfect ward management on the part of the ward
surgeons and their staffs. Difficulties encountered during the emergency
created by the sudden explosion of the influenza epidemic, in spite of
the best efforts of all, did much to disrupt the plan which had been
instituted for the control and study of the complications of measles.
Scarcely had wards been designated and all measles patients on hand
differentially allotted to them, when the influenza epidemic appeared
and quickly filled the hospital beyond its capacity. Measles wards were
taken over for the care of influenza patients. Measles patients, of
which there were not a great number at the time, were necessarily
crowded together, so that compartments of wards instead of separate
wards had to be used in maintaining our separation of the two groups of
patients. While the base hospital was yet filled with patients with
influenza and influenza pneumonia, admission of patients with measles
increased, so that one ward after another was reclaimed for the care of
this disease. During this period the measles wards were at times
overcrowded and the strictest ward technic could not be practiced. Again
new wards were, on occasions, partly filled by admission and transfer
before they were properly equipped to receive patients. This
disorganization was directly due to the necessity of treating a rapidly
increasing number of measles patients before the hospital was cleared of
patients with influenza and pneumonia. After this emergency, the system
of ward management was rapidly readjusted, and admissions were limited
to the normal capacities of the wards.

The cubicle system was used in all wards. Bed patients were not required
to wear masks, but the mask was strictly enforced upon all patients
leaving the cubicle. All attendants were required to wear gowns, caps
and masks while in the wards. An attempt was made to prevent the
congregating of convalescents. Guards were posted at the latrine doors
to limit admission to the capacity of the latrine. Borrowing and lending
of any materials between patients were strictly forbidden. Paper sputum
cups were provided, kept clean and covered. In the measles pneumonia
wards hand disinfectant solutions were provided for use by attendants
when they passed from one patient to another. The ward floors were
scrubbed at intervals with lysol in water. Dry sweeping of the wards in
the morning is regrettable.

=Bacteriologic Methods Used in the Study.=—The methods used for the
identification of hemolytic streptococci here were essentially the same
as those used at Camp Funston and described above, the one exception
being the use of surface cultures on blood agar instead of the combined
surface and deep culture. Blood agar plates containing 5 per cent
defibrinated horse blood were poured and used while fresh. The throat
swabs were carried to the laboratory in sterile test tubes. The plates
were inoculated by touching the swab lightly to the surface of the agar
plate at two places, one near either extremity of a given diameter of
the plate. On touching the swab to the agar, the swab stick was rolled
between the fingers so as to turn it through one revolution and thereby
bring all points of the circumference of the cotton swab in contact with
the agar surface.

The material thus inoculated on the plates was spread by means of a
platinum wire slightly turned over at the end in “hockey stick” fashion.
The wire was passed back and forth several times over the point of
inoculation and then multiple streaks and cross streaks were made over
the agar surface. The initial contact of the wire with the point of
inoculation was not repeated. The cross streaking serves to spread and
distribute this material evenly over the surface. Well seeded plates by
this multiple streak method are the rule and the uniform distribution of
well separated colonies over the surface makes it very easy to pick pure
cultures, and renders plate reading easy.

Very early in the course of our study of throat cultures at Camp Pike,
the great frequency of abundant growths of B. influenzæ was observed.
Consequently, the throat cultures of all measles patients examined from
September 15 to October 20 were studied for the identification of B.
influenzæ. In all cases identification was based on the cultural,
staining and morphologic characteristics. Tests for growth on hemoglobin
free media were not made as a routine.

=Relation of Measles and Pneumonia Following Measles to the Influenza
Epidemic.=—The influenza epidemic at Camp Pike was recognized on
September 23 because of an alarming increase of hospital admissions. It
ran its brief course, and ten days later, October 3, the decline began.
The first four days of October rank highest in admissions of patients
with pneumonia following influenza. The onset of 20 scattered cases of
measles occurred before September 25, and later the number slowly
increased reaching its height about the middle of October; after this
time a gradual decline began, and continued during about three weeks
before the preepidemic level was reached. During this period of six
weeks following September 25, 709 cases of measles occurred.

TABLE LVIII

ONSET OF MEASLES AND OF PNEUMONIA FOLLOWING MEASLES BY WEEKS FROM
SEPTEMBER 11 TO DECEMBER 11, 1918

═══════════════════════╤═══════════════════════╤═══════════════════════
DATES │ MEASLES │ PNEUMONIA FOLLOWING
│ │ MEASLES
───────────────────────┼───────────────────────┼───────────────────────
Sept. 11 to 17 │ 18│ 0
Sept. 18 to 24 │ 20│ 0
Sept. 25 to Oct. 1 │ 74│ 0
Oct. 2 to 8 │ 143│ 13
Oct. 9 to 15 │ 178│ 9
Oct. 16 to 22 │ 158│ 16
Oct. 28 to 29 │ 100│ 6
Oct. 30 to Nov. 5 │ 56│ 3
Nov. 6 to 12 │ 38│ 4
Nov. 13 to 19 │ 23│ 1
Nov. 20 to 26 │ 29│ 1
Nov. 27 to Dec. 3 │ 22│ 1
Dec. 4 to 10 │ 8│ 1
Dec. 11 │ 0│ 1
───────────────────────┴───────────────────────┴───────────────────────

Pneumonia following measles began to appear on October 5, and within the
week following 16 cases occurred. An equal number of cases appeared each
week during about three weeks and fewer scattered cases occurred
throughout November and December. Table LVIII shows date of onset of
measles and measles pneumonia cases.

Chart 3 presents the occurrence of measles and of the pneumonia
following measles by weeks of onset compared with that of epidemic
influenza.

[Illustration:

Chart 3.—Shows the relation of the epidemic of measles to that of
influenza at Camp Pike, and the relations of the pneumonia following
measles to both measles and influenza. The large incomplete curve
represents influenza; the intermediate curve, measles; the small
curve, pneumonia following measles.
]

It will be noted from the overlapping of the two curves in Chart 3 that
a considerable portion of the measles cases appeared before the
influenza had subsided in Camp Pike. This occurrence of the two
epidemics at the same time makes it impossible to separate the parts
played by each disease in producing the pneumonias and other
complications following measles. Analysis of the chart, however, shows
that the pneumonia with measles occurred in large part during the first
half of the measles epidemic. This is of particular significance since
it was during this period that the effects of the influenza wave were
felt most severely.

In Table LIX the cases of measles are grouped into fifteen day periods
according to their dates of onset and the pneumonias arising from each
group are tabulated. This tabulation shows very clearly that the
pneumonia complications developed in large part in patients with measles
entering the hospital during the influenza period, that is, late in
September and during the first half of October.

TABLE LIX

PATIENTS WITH MEASLES AND WITH SUBSEQUENT PNEUMONIA

═════════════════╤═════════════════╤═════════════════╤═════════════════
DATES │ TOTAL CASES OF │ TOTAL CASES │ OF PER CENT
│ MEASLES DURING │ PNEUMONIA FROM │ INCIDENCE OF
│ INTERVALS OF 15 │ SAME │ PNEUMONIAS
│ DAYS │ │
─────────────────┼────────┬────────┼────────┬────────┼────────┬────────
Sept. 11 to 30 │ 86│ 433│ 14│ 42│ 16.28│ 9.7%
Oct. 1 to 15 │ 347│ „ │ 28│ „ │ 8.07│ „
─────────────────┼────────┼────────┼────────┼────────┼────────┼────────
Oct. 16 to 31 │ 270│ 434│ 8│ 14│ 2.96│ 3.2%
Nov. 1 to 15 │ 91│ „ │ 2│ „ │ 2.2│ „
Nov. 16 to 30 │ 56│ „ │ 4│ „ │ 7.15│ „
Dec. 1 to 15 │ 17│ „ │ 0│ „ │
─────────────────┴────────┴────────┴────────┴────────┴─────────────────

The high incidence of pneumonia among measles patients coming into the
hospital prior to, with, or immediately following the height of the
influenza epidemic is very striking. It so happens that half of the
total number of measles cases considered, date their onsets prior to
October 15. From the 433 cases included in this first half, 42 cases of
pneumonia arose, while from the 434 cases arising during the two months
following October 15, only 14 or one-third as many cases of pneumonia
developed. These figures very strongly suggest that influenza played a
large part in the production of the pneumonia with measles in this group
of cases.

Again the 9.7 per cent incidence of pneumonia in the first half of cases
considered, approaches the 12 per cent incidence of pneumonia following
influenza observed in the epidemic at Camp Pike, while the incidence of
3.2 per cent in the second half of the cases conforms more nearly to
figures for pneumonia following measles in the army prior to the
pandemic of influenza.

It has been shown that the prevalence of B. influenzæ at Camp Pike
increased with the passing of the wave of influenza (p. 40) and that
this increase applied to the measles admissions. For a time the
separation of measles patients carrying B. influenzæ as identified by
throat culture on admission, from those free from it, was practiced. All
cases were then followed up by weekly throat cultures, and cases in
negative wards on being identified as positives were transferred.

This practice was discontinued as impractical when it became apparent
that about 80 per cent of patients with measles would be found positive
for B. influenzæ when repeated throat cultures were made during their
hospital treatment. The dissemination of B. influenzæ through the wards
from which we were attempting to exclude it took place much faster than
we could follow its spread by cultural methods. When this became
evident, the practice of separating the two groups of patients with
reference to B. influenzæ was discontinued and the great inconvenience
of repeated transfer of patients was largely eliminated.

Table LX gives the findings in 426 cases of measles cultured for B.
influenzæ during the period when the practice of separating measles
patients carrying B. influenzæ from those not carrying the organisms was
followed.

TABLE LX

RESULTS OF REPEATED THROAT CULTURES FOR B. INFLUENZÆ ON 426 CASES OF
MEASLES, CAMP PIKE, SEPT. 15 TO OCT. 20, 1918.

═══════════╤════════╤═════════╤═════════════════════════════════════
│ │ │
│ │ │
│ │GROUP NO.│
│ TOTAL │NEGATIVE │
GROUPS │ NUMBER │ FOR B. │ RESULTS OF CULTURES TO DATE
│CULTURED│INFLUENZÆ│
│IN GROUP│ ON │
│ │ADMISSION│
│ │ │
│ │ │
───────────┼────────┼─────────┼───────┬───────┬───────┬───────┬─────
│ │ │ │ │ │ │ NO.
„ │ „ │ „ │ 1ST │ 2ND │ 3RD │ 4TH │ IN
│ │ │CULTURE│CULTURE│CULTURE│CULTURE│EACH
│ │ │ │ │ │ │CLASS
───────────┼────────┼─────────┼───────┼───────┼───────┼───────┼─────
I │ │ │ │ │ │ │
1st culture│ │ │ │ │ │ │
on │ 426│ ——│ − │ │ │ │ 274
admission│ │ │ │ │ │ │
„ │ „ │ „ │ + │ │ │ │ 152
───────────┼────────┼─────────┼───────┼───────┼───────┼───────┼─────
II │ │ │ │ │ │ │
1st and 2nd│ │ │ │ │ │ │
culture, │ │ │ │ │ │ │
after one│ 201│ 143│ − │ − │ │ │ 75
week in │ │ │ │ │ │ │
hospital │ │ │ │ │ │ │
„ │ „ │ „ │ − │ + │ │ │ 68
„ │ „ │ „ │ + │ + │ │ │ 29
„ │ „ │ „ │ + │ − │ │ │ 29
───────────┼────────┼─────────┼───────┼───────┼───────┼───────┼─────
III │ │ │ │ │ │ │
1st, 2nd │ │ │ │ │ │ │
and 3rd │ │ │ │ │ │ │
cultures │ 94│ 69│ − │ − │ − │ │ 22
after two│ │ │ │ │ │ │
weeks in │ │ │ │ │ │ │
hospital │ │ │ │ │ │ │
„ │ „ │ „ │ − │ − │ + │ │ 18
„ │ „ │ „ │ − │ + │ − │ │ 13
„ │ „ │ „ │ − │ + │ + │ │ 16
„ │ „ │ „ │ + │ + │ + │ │ 8
„ │ „ │ „ │ + │ − │ + │ │ 6
„ │ „ │ „ │ + │ + │ − │ │ 4
„ │ „ │ „ │ + │ − │ − │ │ 7
───────────┼────────┼─────────┼───────┼───────┼───────┼───────┼─────
IV │ │ │ │ │ │ │
1st, 2nd, │ │ │ │ │ │ │
3rd and │ │ │ │ │ │ │
4th │ │ │ │ │ │ │
cultures │ 25│ 19│ − │ − │ − │ − │ 4
after │ │ │ │ │ │ │
three │ │ │ │ │ │ │
weeks in │ │ │ │ │ │ │
hospital │ │ │ │ │ │ │
„ │ „ │ „ │ − │ − │ − │ + │ 3
„ │ „ │ „ │ − │ − │ + │ + │ 3
„ │ „ │ „ │ − │ − │ + │ − │ 2
„ │ „ │ „ │ − │ + │ + │ + │ 2
„ │ „ │ „ │ − │ + │ − │ + │ 2
„ │ „ │ „ │ − │ + │ + │ − │ 2
„ │ „ │ „ │ − │ + │ − │ − │ 1
„ │ „ │ „ │ + │ + │ + │ + │ 2
„ │ „ │ „ │ + │ − │ − │ + │ 1
„ │ „ │ „ │ + │ − │ + │ + │ 1
„ │ „ │ „ │ + │ + │ + │ − │ 1
„ │ „ │ „ │ + │ − │ − │ − │ 1
───────────┴────────┴─────────┴───────┴───────┴───────┴───────┴─────

═══════════╤════════╤══════════╤════════╤═════════
│ │ GROUP OF │ │GROUP PER
│ │POSITIVES │ │ CENT OF
│ GROUP │DEVELOPING│PER CENT│POSITIVES
│ NO. │TO DATE IN│OF GROUP│ TO DATE
GROUPS │POSITIVE│ CASES │POSITIVE│ AMONG
│ FOR B. │ NEGATIVE │ FOR B. │ CASES
│INF. TO │ FOR B. │INF. TO │NEGATIVE
│ DATE │ INF. ON │ DATE │ FOR B.
│ │ADMISSION │ │ INF. ON
│ │ │ │ADMISSION
───────────┼────────┼──────────┼────────┼─────────
│ │ │ │
„ │ „ │ „ │ „ │ „
│ │ │ │
│ │ │ │
───────────┼────────┼──────────┼────────┼─────────
I │ │ │ │
1st culture│ │ │ │
on │ 152│ ————│ 35.6│ ————
admission│ │ │ │
„ │ „ │ „ │ „ │ „
───────────┼────────┼──────────┼────────┼─────────
II │ │ │ │
1st and 2nd│ │ │ │
culture, │ │ │ │
after one│ 126│ 68│ 62.7│ 47.5
week in │ │ │ │
hospital │ │ │ │
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
───────────┼────────┼──────────┼────────┼─────────
III │ │ │ │
1st, 2nd │ │ │ │
and 3rd │ │ │ │
cultures │ 72│ 47│ 77.7│ 68.1
after two│ │ │ │
weeks in │ │ │ │
hospital │ │ │ │
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
───────────┼────────┼──────────┼────────┼─────────
IV │ │ │ │
1st, 2nd, │ │ │ │
3rd and │ │ │ │
4th │ │ │ │
cultures │ 21│ 15│ 84│ 79.
after │ │ │ │
three │ │ │ │
weeks in │ │ │ │
hospital │ │ │ │
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
„ │ „ │ „ │ „ │ „
───────────┴────────┴──────────┴────────┴─────────

On admission 35.6 per cent of the patients were found positive for B.
influenzæ. Repeated throat cultures were not confined to those appearing
negative on this initial culture, but were made on all patients without
regard to their being previously positive or negative. By a summation of
the results of the weekly cultures of all patients, the percentage of
patients carrying B. influenzæ rises from 35.6 per cent on admission, to
62.7 per cent after one week; to 77.7 per cent after two weeks; to 84
per cent after three weeks in the hospital.

To gain some idea of the rate of spread of B. influenzæ in wards
receiving only patients whose throat cultures were negative for B.
influenzæ on admission, a similar summation of the results of repeated
throat cultures on patients in negative wards shows weekly increases
from 47.5 per cent after one week, to 68.1 per cent after two weeks; to
79 per cent at the end of three weeks.

These results demonstrate quite clearly that the measles wards were
saturated with B. influenzæ during the period of the influenza epidemic.
Conditions within the measles wards with regard to B. influenzæ were not
at all different from those in the camp community during this period.
While no clinical methods could be relied upon to diagnose influenza in
the presence of an acute attack of measles, there is every reason to
believe that the occurrence of clinical influenza with measles was no
less frequent than was its incidence in the camp at large, that is,
about 20 to 25 per cent. That influenza played a large part in
determining predisposition to the complications of measles in this
series seems evident.

Hemolytic Streptococci with Measles at Camp Pike

Between September 15 and December 15, 1918, 867 cases of measles,
admitted to the wards of the base hospital, were studied and handled
according to the system outlined above. About one half of these cases
appeared during the first month of the study. During this month
hemolytic streptococci played a very insignificant rôle. This
microorganism did not appear with alarming prevalence until after the
wards had been thoroughly overcrowded. After the emergency, when better
ward conditions were provided, S. hemolyticus carriers continued to
develop in the wards and were removed when identified. The first S.
hemolyticus carriers to develop in the wards were identified on October
8. The first case of streptococcus pneumonia developed on October 17,
while streptococcus otitis as a complication of measles did not begin
until a little later. During the latter two months of the study, S.
hemolyticus became rampant in the wards. The streptococcus complications
date their onset at some time during these two months.

Table LXI shows the number of admissions to the measles wards by weeks
and the patients among them found to be carrying hemolytic streptococci.
It also shows the number of S. hemolyticus carriers developing each week
among patients under treatment in the “clean” wards, as identified by
throat cultures repeated at weekly intervals. For purposes of
orientation, the number of cases developing streptococcus pneumonia and
otitis media with its subsequent mastoiditis are given for each week
during the period of observation.

An admission to the measles ward can generally be regarded as an acute
case of measles. There are a few exceptions to this statement and these
are cases of measles treated in barracks and afterwards transferred to
the base hospital. A relatively small number of such cases furnished 16
of the cases positive for hemolytic streptococci on admission to the
measles ward.

TABLE LXI

S. HEMOLYTICUS CARRIERS IDENTIFIED BY THROAT CULTURE AMONG ADMISSIONS; THOSE
DEVELOPING AMONG PATIENTS UNDER TREATMENT IN THE STREPTOCOCCUS “CLEAN”
MEASLES WARDS; S. HEMOLYTICUS COMPLICATIONS ACCORDING TO THEIR DATES OF ONSET

════════╤══════════════════════╤══════════════════════╤══════════════════════
GROUPING│ │HEMOLYTIC STREPTOCOCCI│ PRINCIPAL
OF CASES│ ADMISSION CASES │ HOSPITAL CASES │ COMPLICATIONS DUE TO
BY WEEKS│ │ DEVELOPING │ HEM. STREP.
────────┼────────┬──────┬──────┼────────┬──────┬──────┼──────┬──────┬────────
„ │ │ NO. │ PER │ │ NO. │ PER │ │ │
│ NO. │ POS. │ CENT │ NO. │ POS. │ CENT │ │ │MASTOID-
│ CASES │ HEM. │ POS. │ CASES │ HEM. │ POS. │PNEUM.│OTITIS│ ITIS
│CULTURED│STREP.│ HEM. │CULTURED│STREP.│ HEM. │ │ │
│ │ │STREP.│ │ │STREP.│ │ │
────────┼────┬───┼───┬──┼──────┼────────┼──────┼──────┼──────┼──────┼────────
Sept. 15│ │ │ │ │ │ │ │ │ │ │
to │ 23│252│ 1│ 3│ 1.2│ 0│ 0│ 0│ 0│ 0│ 0
Sept. │ │ │ │ │ │ │ │ │ │ │
21 │ │ │ │ │ │ │ │ │ │ │
Sept. 22│ │ │ │ │ │ │ │ │ │ │
to │ 25│ „ │ 1│„ │ „ │ 23│ 0│ 0│ 0│ 0│ 0
Sept. │ │ │ │ │ │ │ │ │ │ │
29 │ │ │ │ │ │ │ │ │ │ │
Sept. 30│ │ │ │ │ │ │ │ │ │ │
to │ 95│ „ │ 0│„ │ „ │ 24│ 0│ 0│ [91]1│ 0│ 0
Oct. 6│ │ │ │ │ │ │ │ │ │ │
Oct. 7 │ │ │ │ │ │ │ │ │ │ │
to │ 109│ „ │ 1│„ │ „ │ 121│ 4│ 3.3│ 0│ 0│ 0
Oct. │ │ │ │ │ │ │ │ │ │ │
13 │ │ │ │ │ │ │ │ │ │ │
────────┼────┼───┼───┼──┼──────┼────────┼──────┼──────┼──────┼──────┼────────
Oct. 14 │ │ │ │ │ │ │ │ │ │ │
to │ 223│494│ 7│19│ 3.8│ 175│ 8│ 4.6│ 1│ 0│ 0
Oct. │ │ │ │ │ │ │ │ │ │ │
20 │ │ │ │ │ │ │ │ │ │ │
Oct. 21 │ │ │ │ │ │ │ │ │ │ │
to │ 156│ „ │ 5│„ │ „ │ 451│ 35│ 7.7│ 2│ 3│ 0
Oct. │ │ │ │ │ │ │ │ │ │ │
27 │ │ │ │ │ │ │ │ │ │ │
Oct. 28 │ │ │ │ │ │ │ │ │ │ │
to │ 71│ „ │ 6│„ │ „ │ 333│ 29│ 8.7│ 1│ 12│ 1
Nov. 3│ │ │ │ │ │ │ │ │ │ │
Nov. 4 │ │ │ │ │ │ │ │ │ │ │
to │ 44│ „ │ 1│„ │ „ │ 263│ 45│ 17.1│ 3│ 8│ 11
Nov. │ │ │ │ │ │ │ │ │ │ │
10 │ │ │ │ │ │ │ │ │ │ │
────────┼────┼───┼───┼──┼──────┼────────┼──────┼──────┼──────┼──────┼────────
Nov. 11 │ │ │ │ │ │ │ │ │ │ │
to │ 31│117│ 4│13│ 11.1│ 149│ 46│ 30.8│ 0│ 5│ 5
Nov. │ │ │ │ │ │ │ │ │ │ │
17 │ │ │ │ │ │ │ │ │ │ │
Nov. 18 │ │ │ │ │ │ │ │ │ │ │
to │ 41│ „ │ 4│„ │ „ │ 93│ 7│ 7.5│ 0│ 2│ 2
Nov. │ │ │ │ │ │ │ │ │ │ │
24 │ │ │ │ │ │ │ │ │ │ │
Nov. 25 │ │ │ │ │ │ │ │ │ │ │
to │ 19│ „ │ 0│„ │ „ │ 48│ 7│ 14.6│ 0│ 3│ 2
Dec. 1│ │ │ │ │ │ │ │ │ │ │
Dec. 2 │ │ │ │ │ │ │ │ │ │ │
to │ 26│ „ │ 5│„ │ „ │ 52│ 12│ 23.1│ 0│ 3│ 0
Dec. 8│ │ │ │ │ │ │ │ │ │ │
────────┼────┼───┼───┼──┼──────┼────────┼──────┼──────┼──────┼──────┼────────
Dec. 9 │ │ │ │ │ │ │ │ │ │ │
to │ 4│ │ 2│ │ │ 47│ 12│ 25.5│ 1│ 0│ 0
Dec. │ │ │ │ │ │ │ │ │ │ │
15 │ │ │ │ │ │ │ │ │ │ │
────────┴────┴───┴───┴──┴──────┴────────┴──────┴──────┴──────┴──────┴────────

An admission to the measles ward does not indicate admission to the
hospital, because a considerable number of cases of measles developed
from time to time among patients under treatment in the hospital for
other conditions. Since these patients remained in other wards not
subject to the same ward management and with no distinction between
those positive and those negative for hemolytic streptococci, they
cannot be included in figures to show the incidence of hemolytic
streptococci in patients with measles at the time of admission to
hospital from the camp. Two classifications of the 37 cases, positive
when first observed, are necessary.

1. Division of cases according to days in the hospital before first
culture was taken:

Days in Hospital No. of cases
0–1 (admission) 15 (2 not acute)
2–7 10
More than 7 12

2. Classification according to stage of the disease:

During acute stage 21 cases
After acute stage 16 cases

The first classification shows only 13 cases positive when cultured on
admission to the hospital and also during the acute stage of the
disease; the incidence of S. hemolyticus in patients on admission is
very low (1.76 per cent).

The second classification shows a slightly higher incidence for cases
during the acute stage of the disease, regardless of whether they were
admitted to the measles service from camp or from another service of the
hospital (2.4 per cent). These findings conform with those at Fort Riley
in a smaller series of cases and support the opinion that the hemolytic
streptococci temporarily disappear from the throat during the acute
onset of measles. Unfortunately controls among normal men in Camp Pike
were not taken at intervals throughout the period of three months
represented by this study of measles, but all controls taken show a
higher incidence than that found among measles patients on admissions
over a period of time comparable to that of the control series.

The gradual increase in the percentage of patients developing hemolytic
streptococci in their throats in wards receiving only streptococcus free
cases demonstrates that the admission culture and the subsequent weekly
cultures, with the separation of all patients identified as carriers,
did not suffice to control the spread of streptococcus in this group of
cases. It is interesting to note that the greatest incidence of
streptococcus carriers among these patients occurred three weeks after
the height of the measles epidemic, when it became about four times that
observed at the height of the measles epidemic.

When we consider the time relations of the streptococcus complications,
it is noteworthy that they begin to appear somewhat after the appearance
of streptococcus carriers and then increase parallel with the increase
in the numbers of carriers. The relative number of complications
developing among the first carriers which were identified is less than
that among the carriers appearing later. This suggests an increase in
virulence of hemolytic streptococci attending their wider dissemination.

Tables LXII and LXIII are introduced for the purpose of showing to what
extent duration of stay in the hospital increases the individual’s
chances of acquiring hemolytic streptococci. Table LXII includes all
cases admitted to and treated in the measles wards. On repeated
cultures, previous positives and negatives were cultured alike and the
total positives reported for each week.

Table LXIII includes only those cases treated in the “clean” wards and
known to be negative on previous culture.

TABLE LXII

INCIDENCE OF HEMOLYTIC STREPTOCOCCI IN THROATS OF MEASLES CASES WITH
REFERENCE TO PERIOD IN HOSPITAL

(All cases treated in the wards)

═════════════════╤═════════════════╤═════════════════╤═════════════════
PERIOD IN MEASLES│ NO. CASES │NO. POSITIVE FOR │PER CENT POSITIVE
WARD │ CULTURED │ HEMOLYTIC │ FOR HEMOLYTIC
│ │ STREPTOCOCCI │ STREPTOCOCCI
─────────────────┼─────────────────┼─────────────────┼─────────────────
(Admission) │ 867│ 37│ 4.2
1 week│ 768│ 84│ 10.9
2 weeks│ 479│ 109│ 22.8
3 weeks│ 240│ 63│ 26.2
4 weeks│ 133│ 44│ 33.1
5 weeks│ 82│ 26│ 31.7
6 weeks│ 53│ 14│ 26.4
7 weeks│ 25│ 8│ 32.0
8 weeks│ 13│ 1│ 7.7
9 weeks│ 9│ 1│ 11.1
10 weeks│ 6│ 0│ 0
11 weeks│ 5│ 0│ 0
─────────────────┴─────────────────┴─────────────────┴─────────────────

TABLE LXIII

WEEKLY DEVELOPMENT OF HEMOLYTIC STREPTOCOCCI IN THROATS OF PATIENTS
TREATED IN “CLEAN” WARDS

═════════════════╤═════════════════╤═════════════════╤═════════════════
PERIOD IN MEASLES│ NO. CASES │NO. POSITIVE FOR │PER CENT POSITIVE
WARD │ CULTURED │ HEMOLYTIC │ FOR HEMOLYTIC
│ │ STREPTOCOCCI │ STREPTOCOCCI
─────────────────┼─────────────────┼─────────────────┼─────────────────
1 week│ 738│ 67│ 9.1
2 weeks│ 424│ 74│ 17.4
3 weeks│ 195│ 34│ 17.4
4 weeks│ 92│ 16│ 17.4
5 weeks│ 46│ 7│ 15.2
6 weeks│ 26│ 4│ 15.4
7 weeks│ 14│ 3│ 21.4
8 weeks│ 8│ 0│
9 weeks│ 5│ 0│
10 weeks│ 4│ 0│
11 weeks│ 3│ 0│
─────────────────┴─────────────────┴─────────────────┴─────────────────

A comparison of Tables LXII and LXIII gives some indication of what
might have been expected if the carriers had not been removed from the
treatment wards at weekly intervals. With the carriers removed from the
“clean” cases and segregated in a separate ward so as to be removed
effectively as sources of spread of the S. hemolyticus infection to
clean cases, the percentage incidence with all cases considered rose to
a point nearly twice as high as that ever reached in the wards where
clean cases alone were allowed to remain. Had these carriers not been
separated, and remained in contact with cases free from hemolytic
streptococci, they would have served as just so many more sources of
infection, and an incidence of at least twice that recorded for all
cases combined, or four times that of the treatment wards, might have
been expected. These results indicate that the weekly separation of
carriers from clean cases did, to a considerable extent, lower the
individual’s danger of acquiring S. hemolyticus infection while in the
hospital.

Complications of Measles

In Table LXIV the complications developing in the measles patients under
observation at Camp Pike are tabulated. In the division of the
complications developing in “carriers” and “noncarriers” of the
hemolytic streptococci, reference is made only to the records of the
throat cultures. The division is therefore not dependent upon the
bacteriology of the complications. For example, only 9 of the 12 cases
of pneumonia developing in “carriers” were streptococcus pneumonias. On
the other hand, the cases of mastoiditis following otitis media were
almost invariably due to hemolytic streptococci. Of the 10 otitis cases
occurring in “noncarriers,” 4 developed mastoiditis and 3 of these
showed hemolytic streptococci on culture from the mastoid cells at
operation. Missed cases of identification of S. hemolyticus by throat
culture in cases which develop S. hemolyticus complications may arise
from a number of causes. It is desired here only to direct attention to
these discrepancies.

=Pneumonia Following Measles.=—Fifty-six cases of pneumonia following
measles occurred during the period of observation in this group of 867
cases of measles. Of these, 9 were streptococcus pneumonias. This gives
an incidence for streptococcus pneumonias of 1.04 per cent, while that
for all the pneumonia is 6.4 per cent. There were 8 cases of lobar and
48 cases of bronchopneumonia. Seventeen fatal cases occurred giving a
mortality rate of 30.4 per cent for the group. Five of these fatal cases
occurred among the 9 streptococcus pneumonias. The mortality rate for
the streptococcus pneumonia thus was 55.5 per cent; that for the
nonstreptococcus group was 25.5 per cent. All 9 cases of streptococcus
pneumonia developed empyema. In 7 cases it was diagnosed clinically; in
2 at autopsy only. No cases of empyema developed in the group of
nonstreptococcus pneumonias.

TABLE LXIV

COMPLICATIONS DEVELOPING IN 867 CASES OF MEASLES AT CAMP PIKE. DISTRIBUTION
OF COMPLICATIONS BETWEEN 242 “CARRIERS” AND 625 “NONCARRIERS” OF HEMOLYTIC
STREPTOCOCCI FROM SEPTEMBER 15 TO DECEMBER 15, 1918

═════════════╤═════════════════════════════╤══════╤══════════════════════════
NAME OF │ │TOTAL │
COMPLICATION │ NUMBER OCCURRING IN │NUMBER│ PER CENT IN
─────────────┼──────────┬─────────┬────────┼──────┼─────┬──────────┬─────────
„ │ │ │ CASES │ │ │ │
│ │ │WITH IN-│ │ │ │
│ │ │COMPLETE│ │ │ │
│ │ “NON- │ RECORD │ │ │ │ “NON-
│“CARRIERS”│CARRIERS”│ OF │ │ │ HEM. │CARRIERS”
│ OF HEM. │ OF HEM. │ THROAT │ │ ALL │ STREP. │ OF HEM.
│ STREP. │ STREP. │CULTURES│ „ │CASES│“CARRIERS”│ STREP.
─────────────┼──────────┼─────────┼────────┼──────┼─────┼──────────┼─────────
Pneumonia │ 12│ 44│ 0│ 56│ 6.4│ 5.0│ 7.0
Otitis media │ 31│ 11│ 6│ 48│ 5.5│ 12.8│ 1.8
Mastoiditis │ │ │ │ │ │ │
(following │ │ │ │ │ │ │
otitis │ │ │ │ │ │ │
media) │ 15│ 4│ 4│ 23│ 2.6│ 6.2│ 0.6
Local │ │ │ │ │ │ │
meningitis │ │ │ │ │ │ │
(extension │ │ │ │ │ │ │
from │ │ │ │ │ │ │
mastoid) │ 2│ 0│ 0│ 2│ │ │
Frontal │ │ │ │ │ │ │
sinusitis │ 1│ 0│ 0│ 1│ │ │
Ethmoidal │ │ │ │ │ │ │
sinusitis │ 0│ 1│ 0│ 1│ │ │
Suppurative │ │ │ │ │ │ │
arthritis │ 1│ 0│ 0│ 1│ │ │
Cervical │ │ │ │ │ │ │
adenitis │ 1│ 0│ 0│ 1│ │ │
Acute │ │ │ │ │ │ │
bronchitis │ 4│ 2│ 0│ 6│ │ │
Acute │ │ │ │ │ │ │
tonsillitis│ 4│ 1│ 0│ 5│ │ │
Acute │ │ │ │ │ │ │
laryngitis │ │ │ │ │ │ │
and aphonia│ 1│ 0│ 0│ 1│ │ │
Acute │ │ │ │ │ │ │
pleurisy │ 2│ 1│ 0│ 3│ │ │
Erysipelas of│ │ │ │ │ │ │
face │ 0│ 1│ 0│ 1│ │ │
Epidemic │ │ │ │ │ │ │
meningitis │ 0│ 1│ 0│ 1│ │ │
─────────────┴──────────┴─────────┴────────┴──────┴─────┴──────────┴─────────

Note.—The percentages of incidence of pneumonia and otitis media in the
“carrier” and “noncarrier” groups are at direct variance. It would appear
from these findings that streptococci very readily invade the middle ear from
the throat and set up grave disorders. The invasion of the lung from the
throat occurs with less frequency. Hemolytic streptococci perhaps never
initiate the pneumonic processes and can be regarded as more or less
accidental secondary invaders.

The relation of these pneumonias following measles, to the influenza
epidemic has been discussed. The time relations between the onsets of
measles and that of the subsequent pneumonia vary widely. There appears
to be nothing constant in the length of time between the onset of
measles and that of the pneumonia. In 30 of the cases this period is
less than ten days; in the remaining 26 cases, it ranges from ten to
thirty-two days (Chart 4).

In the ward treatment of these cases of pneumonia, they were divided
into three groups according to their clinical characters and according
to the results of throat and sputum cultures.

(_a_) Streptococcus pneumonias 9 cases
(_b_) Pneumonia with hemolytic streptococci in the throat
without symptoms referable to the streptococcus 13 cases
(_c_) Pneumococcus pneumonias not carrying hemolytic
streptococci 34 cases

The streptococcus-free cases were treated in a separate ward. Cases were
admitted to this ward directly from the “clean” measles wards, but only
after a throat culture taken prior to their transfer had been negative
for the hemolytic streptococcus.

The other two groups were treated together in another ward, but in
strictly separate compartments of it. This precaution was carried out on
the assumption that patients with an acute streptococcus pneumonia were
real sources of danger in the ward because of a heightened virulence of
the organism causing the grave symptoms. The pneumonias subsequently
developing hemolytic streptococci in their throats, without their
presence modifying the course of the pneumonia, came to be regarded as
being in the same class with uncomplicated cases of measles carrying
hemolytic streptococci, in so far as their being potential sources of
danger in a ward is concerned.

[Illustration:

Chart 4.—Shows the time interval between the onset of measles and the
onset of the subsequent pneumonia in the 56 cases of pneumonia
following measles at Camp Pike. Each case is represented by one of
the small blocks measured along the ordinate. The onset of measles
in all cases is represented by the line at the extreme left of the
chart. The onset of pneumonia in each case is indicated by the limit
of the block marked off in days to the right of this line.
]

(_a_) =Streptococcus Pneumonias.=—Nine cases of streptococcus pneumonia
developed. Of the 867 cases of measles studied, 242 showed throat
cultures positive for the hemolytic streptococci at some period of their
stay in the hospital. It appears then that 3.7 per cent of the patients
carrying hemolytic streptococci in their throats developed streptococcus
pneumonia. Thirty-seven cases had positive throat cultures when first
observed on admission to the measles wards. It is significant to note
that not a single case of pneumonia of any kind developed among these
cases.

MEASLES PNEUMONIA; STREPTOCOCCUS GROUP

Case 98, O. McN. Onset of measles, Sep. 19; admitted to hospital
Sep. 21; onset of bronchopneumonia, Oct. 21; of empyema, Oct. 23.
Recovered from pneumonia; convalescent in empyema ward.

_Bacteriology._—1. Throat culture for: (_a_) S. hem.: Sep. 21, −;
28, −; Oct. 9, −; 20, −; 23, +; Nov. 2, −; 9, −; 15, −; (_b_) B.
influenzæ: Sep. 21, +; 28, −; Oct. 9, +. 2. Pleural fluid (culture)
S. hem. Oct. 23, +.

Case 141, J. G. G. Autopsy No. 438. Onset of measles, Sep. 28;
admitted to hospital, Oct. 1; onset of bronchopneumonia, Oct. 6; of
otitis media (bilateral), Oct. 12; died, Oct. 18.

_Bacteriology._—1. Throat culture for: (_a_) S. hem., Oct. 2, −; 6,
−; 8, −; (_b_) B. influenzæ, Oct. 2, −; 6, +; 8, +. 2. Autopsy
cultures: Heart blood, negative; left lung, Pneumococcus II
atypical, B. influenzæ and S. viridans; right lung, S. hem. and B.
influenzæ; right bronchus, S. hem. and B. influenzæ.

Case 147, S. W. Autopsy No. 442. Onset of measles, Oct. 1; admitted
to hospital, Oct. 2; onset of bronchopneumonia, Oct. 17, with chill
and rapid development; died, Oct. 18.

_Bacteriology._—1. Throat culture for: (_a_) S. hem., Oct 2, −; 9 −;
15, −; 18, +; (_b_) B. influenzæ, Oct. 2, −; 9, −; 15, −; 18, −. 2.
Autopsy cultures: Heart blood, S. hem.; right main bronchus, S. hem.
and B. influenzæ.

Case 281, T. M. Onset of measles, Oct. 6; admitted to hospital Oct.
9; onset of bronchopneumonia, Oct. 21; of empyema, Oct. 23;
recovered from pneumonia; convalescent in empyema ward.

_Bacteriology._—1. Throat culture for: (_a_) S. hem., Oct. 10, −;
20, −; 24, +; Nov. 2, +; 9, +; 15, +; (_b_) B. influenzæ, Oct. 10,
−; 20, +. 2. Culture from pleural fluid, Oct. 23, S. hem.

Case 285, J. H. Onset of measles, Oct. 4; admitted to hospital, Oct
9; onset of lobar pneumonia, Oct. 29; of empyema, Nov. 9;
convalescent in empyema ward.

_Bacteriology._—1. Throat cultures for: (_a_) S. hem., Oct. 11, −;
20, −; 24, +; 29, −; Nov. 2, −; 9, −; (_b_) B. influenzæ, Oct. 11,
−. 2. Cultures from pleural fluid, Nov. 9 and 13, S. hem.

Case 714, W. H. Onset of measles, Oct. 26; admitted to hospital,
Oct. 28; otitis media, Nov. 8; onset of bronchopneumonia, Nov. 9; of
empyema, Nov. 17; convalescent in pneumonia ward.

_Bacteriology._—1. Throat cultures for: S. hem., Oct. 28, −; Nov. 4,
−; 12, +; 23, +; 30, +; Dec. 7, +; 12, −. 2. Sputum: Nov. 10,
Pneumococcus II atypical, S. hem. and B. influenzæ.

Case 730, W. S. Autopsy No. 491. Onset of measles, Oct. 26; admitted
to hospital, Oct. 29; onset of bronchopneumonia, Nov. 10; of
empyema, Nov. 11; of cervical adenitis, Nov. 5; died, Nov. 15.

_Bacteriology._—1. Throat culture for: S. hem., Oct. 30, −; Nov. 4,
+. 2. Sputum: Nov. 10, S. hem. 3. Pleural fluid: Nov. 11, S. hem.
Autopsy bacteriology: Heart blood, S. hem.; right main bronchus, B.
influenzæ, B. coli; right lung, S. hem. and B. influenzæ; right
pleura, S. hem.; peritoneum, S. hem.

Case 751, P. B. Autopsy No. 492. Entered hospital, Oct. 19; onset of
measles, Oct. 30; of bronchopneumonia, Nov. 5; of right empyema,
Nov. 12; died, Nov. 16.

_Bacteriology._—1. Throat cultures for: S. hem., Nov. 1, −; 4, +;
15, +. 2. Sputum: Nov. 13, B. influenzæ and S. hem. 3. Autopsy
cultures: Heart blood, S. hem.; right lung, S. hem., Pneumococcus
IV, B. influenzæ, B. coli; pericardium, negative; right pleura, S.
hem.; peritoneum, S. hem.

Case 880, B. McN. Autopsy No. 507. Onset of measles, Nov. 30;
entered hospital, Dec. 3; onset of bronchopneumonia, Dec. 11; of
empyema, Dec. 14; died, Dec. 14.

_Bacteriology._—1. Throat cultures for: S. hem., Dec. 3, −; 5, −;
12, +. 2. Cultures from pleural fluid, Dec. 14, S. hem. 3. Autopsy
cultures: Heart blood, S. hem.; right main bronchus, S. hem., B.
influenzæ, staphylococcus (a few); left lung, S. hem.; left pleura,
S. hem.

The average period in the hospital before the development of the
streptococcus pneumonia is about two weeks. Cases 98 and 285 were in the
hospital thirty and twenty days respectively before the onset of
pneumonia. There is a record of from one to four negative throat
cultures on each case before streptococcus was found in the throat. This
enables us to fix the onset of the pneumonia with reference to the
appearance of the streptococcus in the throat.

Case 141 stands alone as representing a class in which S. hemolyticus
was implanted upon a pneumococcus pneumonia during its course. In this
instance two throat cultures on alternate days after the onset of the
pneumonia were negative for hemolytic streptococci. Unfortunately the
last record of a throat culture is for one taken ten days before the
fatal termination of the case, and it can only be stated that the S.
hemolyticus infection was implanted within the last ten days of the
course of the pneumonia, perhaps on or about October 12 when bilateral
otitis media developed.

In Cases 285 and 730 hemolytic streptococci were found in the throats
five and six days respectively before the onset of pneumonia. They
represent the 2 cases of pneumonia which developed in patients isolated
in the streptococcus “carrier” ward. Case 285 is of particular interest
for several reasons. It is the only case of lobar pneumonia in the group
and happens also to be the only case from which B. influenzæ was not
obtained. S. hemolyticus was found only once on throat culture, i.e.,
five days before the onset of the pneumonia. Three throat cultures after
the onset of the pneumonia were negative. The case ran the course of a
lobar pneumonia. Eleven days after the onset (November 9) a small amount
of pleural fluid was diagnosed. Aspirated fluid on this date and again
four days later showed many streptococci in smears and pure cultures of
S. hemolyticus.

The remaining 6 cases belong to a group in which hemolytic streptococci
were first identified in the throats after the cases had been reported
to the laboratory as pneumonia suspects to be examined by culture before
transfer from the measles ward. In all these cases the culture taken at
this time was positive while all cultures taken before were negative. In
some cases, _e. g._, Cases 98, 147, and 281, throat cultures taken only
one or two days before the onset of the pneumonia were negative. In
these cases the onset of the pneumonia and the appearance of the
streptococcus in the throats appear to be simultaneous.

It should be noted that the period between the appearance of the
hemolytic streptococci in the throat and the development of the
pneumonia is very short in all cases. In this small group of cases S.
hemolyticus infection which has complicated pneumonia has been acquired
at or near the time of onset of the pneumonia.

(_b_) =Pneumonia with Hemolytic Streptococci in the Throat without
Symptoms Referable to the Streptococcus.=—Thirteen cases of pneumonia
associated with measles developed into S. hemolyticus “carriers” without
having the course of the disease affected by the presence of the
organism in the throat. Cases 705, 872, and 188 are of interest in that
hemolytic streptococci were identified in the throats from one to six
days prior to the onset of the pneumonia. In spite of their presence,
the symptoms, course and outcome of the pneumonia were apparently
unaffected. One of these cases (Case 872) died. Autopsy showed lobar
pneumonia with no signs of invasion of the lung by hemolytic
streptococci. Cultures at autopsy showed that pneumonia was due to a
pneumococcus, Type II atypical. A few hemolytic streptococci were found
in culture from the right main bronchus.

Of the remaining 10 cases 1 developed S. hemolyticus in a throat culture
at the end of the first week of the pneumonia; 3 during the second week;
1 during the third week, and 5 further along in the convalescent period.
In 8 cases hemolytic streptococci appeared in the throat, at a time when
invasion of the lower respiratory tract by the streptococcus might be
expected, and yet none of them developed evidence of streptococcus
pneumonia. The 9 cases with hemolytic streptococci appearing late in
convalescence are not of particular interest, since the dangers of lower
respiratory invasion are much reduced after the acute stage of the
pneumonia has passed. Three of these cases (Cases 678, 725 and 398) did
however develop ear complications directly referable to the
streptococcus invasion of the throat. Two of them terminated in
mastoiditis with operation. These cases emphasize the greater tendency
of S. hemolyticus to invade the middle ear rather than the lung.

In 3 fatal cases of pneumococcus pneumonia in which during life no
hemolytic streptococci were found by throat culture, a few hemolytic
streptococci were found at autopsy in culture from the main bronchi,
along with predominating growths of pneumococci and B. influenzæ. In 2
instances there was frank lobar pneumonia and in the third
bronchopneumonia; there was no evidence to show that hemolytic
streptococci had any relation to the pneumonia which was found.

MEASLES PNEUMONIAS; GROUP CARRYING HEMOLYTIC STREPTOCOCCI

Case 705. Onset of measles, Oct. 25; admitted to hospital, Oct. 27;
onset of bronchopneumonia, Nov. 10; acute pleurisy, Nov. 16;
convalescent in pneumonia ward.

_Bacteriology._—1. Throat cultures for: S. hem., Oct. 27, −; Nov. 4,
−; 11, +; 15, +; 23, −; 30, −; Dec. 7, −; 12, −. 2. Sputum: Nov. 10,
Pneumococcus II atypical, S. hem. and B. influenzæ.

Case 872. Autopsy No. 508. Onset of measles, Nov. 29; admitted to
hospital, Nov. 30; onset of lobar pneumonia, Dec. 10; died, Dec. 14.

_Bacteriology._—1. Throat cultures for: S. hem., Nov. 30, −; Dec. 5,
+; 10, +; 12, +; 14, +. 2. Autopsy culture: Heart blood,
Pneumococcus II atypical; right main bronchus, Pneumococcus II
atypical, B. influenzæ, S. hem. (a few); left lung, Pneumococcus II
atypical; left pleura, Pneumococcus II atypical.

Case 188. Onset of measles, Oct. 3; admitted to hospital, Oct. 4;
onset of bronchopneumonia, Oct. 14; recovered and discharged from
hospital, Nov. 24.

_Bacteriology._—1. Throat cultures for: (a) S. hem., Oct. 5, −; 8,
+; 12, +; 19, +; 20, +; 27, −; Nov. 2, −; 9, +; 15, −; (b) B.
influenzæ, Oct. 5, −; 8, −; 12, +; 19, +.

Case 678. Onset of measles, Oct. 23; admitted to hospital, Oct. 25;
onset of bronchopneumonia, Nov. 2; of otitis media, Nov. 9; of
mastoiditis, Nov. 13; mastoid operation, Nov. 20; still under
treatment.

_Bacteriology._—1. Throat cultures for: S. hem., Oct. 25, −; Nov. 4,
−; 5, −; 12, +. 2. Sputum: Nov. 3, Pneumococcus Type IV, and B.
influenzæ. 3. Culture from mastoid bone at operation, Nov. 20, S.
hem.

Case 389. Admitted to hospital, Oct. 2, with diagnosis of influenza;
onset of bronchopneumonia, Oct. 7; onset of measles, Oct. 13;
phlebitis (right leg), Oct. 22; otitis media, Oct. 31; recovered.

_Bacteriology._—1. Throat cultures for: (a) S. hem., Oct. 16 −; 20,
−; 27, +; Nov. 2, +; 9, +; 15, −; 23, −; 30, −; Dec. 7, −; 12, −;
(b) B. influenzæ, Oct. 16, −.

Case 725. Onset of measles, Oct. 18; one week in measles barracks;
admitted to hospital, Oct. 27; onset of lobar pneumonia, Oct. 23;
otitis media, Nov. 7; mastoid operation, Nov. 20; still under
treatment.

_Bacteriology._—1. Throat cultures for: (_a_) S. hem., Oct. 29, −;
Nov. 1, −; 5, −; 12, +; (_b_) B. influenzæ, Oct. 29, +. 2. Sputum:
Nov. 2, Pneumococcus II atypical. B. influenzæ. 3. Culture from
mastoid at operation, Nov. 20, S. hem.

(_c_) =Pneumococcus Pneumonias not Carrying Hemolytic
Streptococci.=—Thirty-four cases of pneumonia following measles went
through their entire course in the hospital with no throat culture
positive for hemolytic streptococci. In some of these cases there are
records of twelve negative throat cultures. Eleven fatal cases occurred
in this group. Autopsy findings and bacteriology showed in each instance
that S. hemolyticus was not the cause of the pneumonia.

=Measles During the Course of Pneumonia.=—Eleven cases of pneumonia
which developed measles during the course of the pneumonia came under
observation. Hemolytic streptococci appeared in the throats of 3 of
these patients during convalescence, but there was no evidence that it
invaded the lung. In one fatal case autopsy showed that there was no
streptococcus pneumonia; pneumonia followed influenza and the onset of
measles occurred three days after the onset of bronchopneumonia.

=Bacteriology of Pneumonia Following Measles.=—When observations made
during life are combined with the results of postmortem cultures, the
bacteriology of 35 of the 56 cases is available and is as follows:
Pneumococcus Type II atypical in 36 per cent, Type IV in 22.9 per cent,
Type I in 2.8 per cent, Type III in 2.8 per cent, hemolytic streptococci
in 22.4 per cent, and B. influenzæ in 88.6 per cent of these cases.

=Otitis Media and Mastoiditis Complicating Measles.=—The occurrence of
otitis media and mastoiditis complicating measles in patients harboring
hemolytic streptococci in their throats has already been presented
(Table LXIV). The bacteriology of these complications was not studied by
this commission. The records of the base hospital laboratory at Camp
Pike contain reports of twenty-nine cultures made at operation from pus
in the middle ear and the mastoid bone. Hemolytic streptococci were
found in 22 of these cases. Throat cultures were in accord with these
positive findings in all except a few instances. The throat culture
serves as a fairly reliable index of the bacterial nature of these
complications. By combining our records of throat cultures with the
results of the cultures from the lesions, hemolytic streptococci were
obtained from 37 of the 48 cases of otitis media. In 23 cases of
mastoiditis following the otitis media, hemolytic streptococci were
demonstrated in all except 2. It is evident that the great majority of
these complications were due to hemolytic streptococci.

The relation between the appearance of hemolytic streptococci in the
throat and the onset of the otitis is recorded in all except 4 of the 31
instances of otitis media occurring in patients with throat cultures
positive for hemolytic streptococci. These four patients had positive
throat cultures when first observed and represent the only patients who
carried hemolytic streptococci when admitted to measles wards and
developed complications.

The first of these patients had been under treatment in an otologic ward
during a month before measles developed. Measles caused a recurrence of
disease of the ear with double mastoiditis requiring bilateral
operation. Two other patients had been in the hospital ten and eleven
days respectively before they were admitted to the measles ward; on
admission to the ward otitis media was present in one patient and in the
other it developed six days later. The fourth patient was admitted to
the measles wards directly from the camp, and culture from the throat on
the day of admission showed the presence of S. hemolyticus. Two weeks
later at the time of onset of otitis media, culture from the throat
contained no hemolytic streptococci. Repeated cultures during the next
three weeks were negative. No complications of otitis media developed
and no direct cultures from the ear are recorded.

[Illustration:

Chart 5.—Shows the time relation between the identification of
hemolytic streptococci in the throats and the development of otitis
media in 27 cases shown to be due to hemolytic streptococci. The
onset of otitis media is represented by the ordinate marked ○. The
number of days before or after the onset of the otitis, within which
the throat culture which proved positive for hemolytic streptococci
was taken, is marked off along abscissæ to the left and right of
ordinate ○ respectively. On the curve plotted these symbols are
used: A circle represents a throat culture positive for hemolytic
streptococci in a case of otitis media without extension to mastoid.
The plus sign represents a throat culture positive for hemolytic
streptococci in a case of otitis media with mastoiditis and
osteitis.

]

In this series of cases (Chart 5) the appearance of S. hemolyticus in
the throat and the onset of otitis media are very closely associated in
those patients in whom further extensions of the streptococcus infection
occurred. In instances in which appearance of streptococci and of otitis
media are separated by an interval of more than seven days, no further
extension occurred. In 8 cases in which this interval is seven days or
less there has been no further extension of the infection.

The Dissemination of Hemolytic Streptococci in Wards

Beginning October 24 cultures for the identification of carriers of
hemolytic streptococci were made from all patients in a ward and
repeated at intervals of one week. Prior to this time individual
patients had been examined at intervals of one week, so that an entire
ward was never studied on any particular day. This system did not
identify and remove all “carriers” in a ward at a given time and was
abandoned because it failed to show the conditions present.
Investigation of wards as units proved much more satisfactory.

The studies made in four of the double wards used for the care of
patients with measles are presented in Table LXV. During the time of
this study hemolytic streptococci were more prevalent than at an earlier
period.

Cultures from the throats of all patients entering these wards were
negative for S. hemolyticus on admission. The table showing the
incidence of “carriers” of hemolytic streptococci each week in these
wards demonstrates:

1. The separation of “carriers” and “noncarriers” by throat culture made
on admission does not prevent the increase of streptococcus “carriers”
in wards.

2. Removal of all “carriers” found by cultures on admission and at
weekly intervals is inadequate.

TABLE LXV

WARD CONDITIONS WITH REFERENCE TO HEMOLYTIC STREPTOCOCCUS INFECTION

═══════╤════════╤════════╤═════════╤═════════════╤═════════════════════
DATE OF│ NO. │ NO. │PER CENT │COMPLICATIONS│
CULTURE│PATIENTS│POSITIVE│POSITIVE │ ASSOCIATED │
│CULTURED│ HEM. │ HEM. │ WITH HEM. │ REMARKS
│ │ STREP. │ STREP. │ STREP. WITH │
│ │ │ │ DATES OF │
│ │ │ │ ONSET │
───────┼────────┼────────┼─────────┼─────────────┼─────────────────────
Ward 57│ │ │ │ │
11–3 │35 │1 │2.8 │ │
11–10 │13 │2 │15.5 │None │
11–17 │16 │6 │37.5 │ │
───────┼────────┼────────┼─────────┼─────────────┼─────────────────────
Ward 58│ │ │ │ │Wards 57 and 58
│ │ │ │ │ served by same ward
│ │ │ │ │ staff.
11–3 │38 │7 │18.4 │Otitis media:│ „
11–10 │11 │4 │36.4 │11–8 1 case │Members of staff
│ │ │ │ │ cultured on 11–5,
│ │ │ │ │ 11–12 and 11–19. No
│ │ │ │ │ positives
11–17 │6 │2 │33.0 │11–7 1 case │ „
───────┼────────┼────────┼─────────┼─────────────┼─────────────────────
Ward 49│ │ │ │ │
│ │ │ │Otitis media:│
10–25 │37 │7 │18.9 │10–25 2 cases│
11–1 │31 │3 │9.7 │10–26 1 case │
11–8 │35 │9 │25.7 │10–28 1 case │
11–15 │32 │18 │56.3 │11–15 1 case │
11–22 │16 │7 │43.8 │11–18 1 case │
│ │ │ │11–27 1 case │
───────┼────────┼────────┼─────────┼─────────────┼─────────────────────
Ward 50│ │ │ │ │Wards 49 and 50
│ │ │ │ │ served by same ward
│ │ │ │ │ staff.
10–25 │29 │2 │3.4 │Otitis media:│ „
11–1 │43 │2 │4.6 │11–8 1 case │Ward staff cultured:
│ │ │ │ │ 11–5 1 positive
│ │ │ │ │ 11–12 1 positive
│ │ │ │ │ 11–26 2 positives
11–8 │32 │3 │9.4 │11–13 1 case │ „
11–15 │20 │11 │55.0 │11–22 1 case │ „
11–22 │11 │0 │0.0 │ │ „
───────┼────────┼────────┼─────────┼─────────────┼─────────────────────
Ward 41│ │ │ │ │Case of pneumonia
│ │ │ │ │ developing on 11–9
│ │ │ │ │ was transferred to
│ │ │ │ │ the “clean”
│ │ │ │ │ pneumonia ward
│ │ │ │ │ without a throat
│ │ │ │ │ culture to warrant
│ │ │ │ │ its transfer; last
│ │ │ │ │ culture 11–4
│ │ │ │ │ negative; culture
│ │ │ │ │ 11–12 in pneumonia
│ │ │ │ │ ward positive
10–28 │45 │4 │8.9 │Streptococcus│ „
│ │ │ │pneumonia: │
11–4 │34 │9 │26.5 │(11–9 1 case)│ „
11–11 │12 │8 │66.6 │11–10 1 case │ „
Ward closed—No patients. │Otitis media:│ „
11–21 │13 │0 │0.0 │10–29 1 case │ „
11–28 │8 │4 │50.0 │11–4 1 case │ „
12–5 │12 │4 │33.3 │11–5 1 case │ „
12–12 │4 │3 │75.0 │11–11 1 case │ „
│ │ │ │11–27 1 case │ „
│ │ │ │12–3 1 case │ „
───────┼────────┼────────┼─────────┼─────────────┼─────────────────────
Ward 42│ │ │ │ │Wards 41 and 42
│ │ │ │ │ served by same ward
│ │ │ │ │ staff.
│ │ │ │Streptococcus│ „
│ │ │ │pneumonia: │
10–28 │32 │0 │0 │11–10 1 case │ „
11–4 │43 │7 │16.3 │12–11 1 case │ „
Ward closed—No patients. │Otitis media:│Ward staff cultured:
│ │ 11–5 2 positive
│ │ 11–12 2 positive
│ │ 11–26 2 positive
│ │ 12–2 1 positive
10–21 │16 │4 │25.0 │10–29 1 case │ „
11–28 │12 │1 │12.5 │12–3 1 case │ „
12–5 │20 │10 │50.0 │12–6 1 case │ „
12–12 │14 │7 │50.0 │ │ „
───────┼────────┼────────┼─────────┼─────────────┼─────────────────────
Ward 59│ │ │ │ │The 3 cases of
│ │ │ │ │ streptococcus
│ │ │ │ │ pneumonia acquired
│ │ │ │ │ S. hemolyticus
│ │ │ │ │ infection while
│ │ │ │ │ patients in the 16
│ │ │ │ │ bed south section
│ │ │ │ │ of this ward
│ │ │ │Streptococcus│ „
│ │ │ │pneumonia: │
10–24 │37 │6 │16.2 │10–17 1 case │ „
10–31 │27 │5 │18.5 │10–21 1 case │ „
11–7 │9 │3 │33.3 │10–29 1 case │Case developing 10–29
│ │ │ │ │ was removed from
│ │ │ │ │ section a few days
│ │ │ │ │ before onset of
│ │ │ │ │ pneumonia
11–12 │7 │1 │14.3 │Otitis media:│ „
│ │ │ │11–1 1 case │ „
───────┼────────┼────────┼─────────┼─────────────┼─────────────────────
Ward 60│ │ │ │ │Wards 59 and 60
│ │ │ │ │ served by same ward
│ │ │ │ │ staff.
│ │ │ │Streptococcus│ „
│ │ │ │pneumonia: │
10–24 │22 │1 │4.5 │10–21 1 case │Ward staff cultured:
│ │ │ │ │ 11–5 0 positive
│ │ │ │ │ 11–12 1 positive
│ │ │ │ │ 11–19 0 positive
10–31 │17 │2 │11.7 │Otitis media:│ „
11–7 │8 │1 │12.5 │10–31 1 case │ „
11–12 │6 │1 │16.6 │ │ „
───────┴────────┴────────┴─────────┴─────────────┴─────────────────────

When the streptococcus complications are traced back to the wards in
which the streptococcus infection of the throat was acquired, it is
found that with the exception of Case 141 (already cited) all the
streptococcus pneumonias arose from two double wards. Wards 41 and 42
furnished 4 cases at times when streptococcus was rampant in them and 3
of these cases arose within a period of a few days. Wards 59 and 60
furnished 4 cases, very closely associated. In 3 cases the streptococcus
infection was acquired in a section of Ward 59 containing 16 beds. These
patients were in beds, of which the positions are represented by numbers
2, 5, and 7, along one side of the ward. The fourth instance of
pneumonia appeared at the same time in Ward 60, which was attended by
the same ward personnel, but no other connection can be established
between this case and the other three.

The otitis media appeared in patients scattered throughout those wards
for measles in which the weekly incidence of “carriers” was rising
rapidly. This relation is illustrated by Wards 58, 50, and 41. The same
observation applies to streptococcus pneumonia arising in Wards 41 and
42. In Ward 41 the weekly percentage of carriers are October 28, 8.9,
November 4, 26.5 and November 11, 66.6. On November 9 and 10 the first 2
cases of streptococcus pneumonia arising from this ward developed. At
the same time, November 10, a third case appeared in another part of
this same ward unit (Ward 42) where the spread of hemolytic streptococci
had been very active. These observations suggest that hemolytic
streptococci may build up its virulence as the result of rapid
dissemination to such a degree that it is capable of causing grave
complications.

The relation of complications to “carriers” in Wards 59 and 60 is
different from that in the wards just cited. Wards 59 and 60 were opened
on October 9 and before October 17; when the first case of fulminating
streptococcus pneumonia occurred, only three “carriers” had been found
in them. From October 17 to 24 when the record in Table LXV begins eight
“carriers” were removed. The appearance of a case of severe
streptococcus pneumonia in an unusually clean ward was followed by the
rapid development of “carriers,” and the appearance within twelve days
of 3 other cases of streptococcus pneumonia, 2 of which were in beds
close to the first case. This sequence suggests focal dissemination of a
streptococcus from a case in which it had suddenly assumed high
virulence.

An outbreak of infection with S. hemolyticus was recognized on November
12 in a measles-pneumonia ward which had been opened for several weeks
and had continued free from streptococcus. In three patients hemolytic
streptococci were found by throat cultures. Inquiry revealed that a
nurse in this ward, recognized as a streptococcus “carrier” the week
before, had been retained on duty. Two patients well advanced in the
course of their pneumonias, had acquired S. hemolyticus demonstrated by
throat examination. Both patients developed otitis media with mastoid
extension requiring operations. Cultures from both at operation showed
hemolytic streptococci.

The third patient, with acute pneumonia, had been sent into the ward on
November 11 from Ward 42, which at the time was a highly infected ward;
no culture of the throat was made before transfer. This patient
developed streptococcus pneumonia with empyema requiring subsequent
operation.

=Discussion.=—At Camp Funston, where the prevalence of S. hemolyticus in
the measles wards did not rise above that among normal men in the camp
at large, 112 consecutive cases of measles were treated without a single
complication due to hemolytic streptococci.

At Camp Pike, the investigation began at the onset of a small epidemic
of measles at a time when hemolytic streptococci were an almost
negligible factor. The epidemic of measles was followed throughout its
course; and, with the passing of the epidemic, there was an increase in
the prevalence of hemolytic streptococci which assumed alarming
importance in the production of complications.

The epidemic of measles was in part superimposed upon the epidemic of
influenza, so that deductions concerning complications strictly due to
measles became impossible. It is evident that influenza played a
considerable part in producing the complications of measles at Camp
Pike.

The dissemination of hemolytic streptococci through measles wards was
controlled only in part by the methods used. This partial control may
have served to limit the incidence of streptococcus pneumonia, nine
instances occurring among 867 cases of measles.

In the ward treatment of measles effort should be directed to prevent
the exposure of patients free from hemolytic streptococci to S.
hemolyticus “carriers.” By this means the rate of development of S.
hemolyticus “carriers” may be reduced.

Measures which should be adopted are as follows:

1. Adequate wards should be prepared in advance for the treatment of
measles. The rather gradual onset of epidemics of measles makes this
provision possible.

2. The separation of S. hemolyticus “carriers” from other patients
should be enforced. Observation wards, where strict technic to prevent
transfer of infection is practiced and where throat cultures are made on
admission, are essential. Those wards should be promptly evacuated to
wards for the care of S. hemolytic “carriers” on the one hand and for
“noncarriers” on the other. As far as possible patients should be
admitted to a ward until it is filled and then another ward should
receive consecutive cases in the same manner. It is desirable to have
all cases in each treatment ward in the same stage of the disease. With
this system of ward rotation convalescent wards are necessary, so that
cases requiring a period of hospitalization longer than the average may
be segregated, thus rendering treatment wards available for another levy
of acute cases.

3. Strict ward technic elaborated to prevent transfer of bacterial
infection from one patient to another must be employed.

4. Throat culture for identification of “carriers” is laborious but
essential. An accurate method for identifying and reporting “carriers”
as speedily as possible must be employed. A competent bacteriologist is
essential. A twenty-four hour interval between culture and its report is
desirable. The following scheme is recommended:

(_a_) A culture from the throat made on admission to the observation
ward (first day in hospital).

(_b_) A culture made on the first day in the treatment ward (third day
in hospital).

(_c_) A culture made one week later (tenth day in hospital).

If the ward incidence of hemolytic streptococci reaches 10 per cent,
especially in a filled ward, the cultures should be repeated on the
thirteenth day in the hospital. If the incidence of “carriers” of
hemolytic streptococci increase rapidly, cultures on alternate days
should be made so that “carriers” may be removed from the ward. Wherever
possible, culturing of the treatment wards as units should be practiced.

5. Patients developing acute symptoms in any way suggestive of infection
with S. hemolyticus should be immediately isolated; culture from the
throat should be made at once and final disposal of the patient should
depend upon its result.

Carriers of Hemolytic Streptococci

During the winter of 1917–18, with the establishment of the army camps,
it very soon became evident that in many of the serious and fatal
complications of measles and other respiratory diseases, hemolytic
streptococci were playing a very important rôle. The epidemic prevalence
of hemolytic streptococci among hospital cases, and later among men on
duty in the camps, was established by bacteriologic studies. Prior to
this time in civil life, hemolytic streptococci under epidemic
conditions had been studied in milk-borne epidemics of septic sore
throat, such as are reported from Chicago in 1911–13[92]; from Boston in
1911[93]; and from Baltimore in 1911–12[94]. Contact air-borne infection
has not been emphasized in considering the dissemination of hemolytic
streptococci. Smillie[95] reports a few cases of hemolytic streptococcus
throat infections which he attributes to contact infection. Conditions
within the army camps were such as to suggest the dissemination of
hemolytic streptococci by contact air-borne infection. Some knowledge of
the percentage of individuals showing positive throat cultures became
desirable at the very beginning of studies of contact dissemination of
hemolytic streptococci.

Smillie found that only one of 100 normal throats harbored the Beta
hemolytic streptococci of Smith and Brown. Levy and Alexander[96] report
the presence of hemolytic streptococci in 83.2 per cent of healthy men
at Camp Taylor, and hemolytic organisms (not definitely identified as
streptococci) in 14.8 per cent of recruits arriving at Camp Taylor.
Irons and Marine[97] found hemolytic streptococci among 70 per cent of
healthy men at Camp Custer.

Among measles patients on admission to the hospital at Fort Sam Houston,
Cole and MacCallum[98] report 11.4 per cent and Cummings, Spruit and
Lynch,[99] 35 per cent of throat cultures positive for hemolytic
streptococci. At Camp Taylor, Levy and Alexander report 77.1 per cent
positive among 388 cases of measles on admission to the hospital.

The spread of hemolytic streptococci in measles wards was shown by Cole
and MacCallum when on admission 11.4 per cent of cases had positive
throat cultures, 38.6 per cent after from three to five days, and 56.8
per cent after from eight to sixteen days in the ward. In our study of
hemolytic streptococci with measles at Camp Funston, 2.6 per cent of the
cases had positive throat cultures on admission, 12.8 per cent after
three to ten days, and 24.1 per cent after eight to twenty-three days in
the hospital. In a similar study at Camp Pike we found 1.7 per cent
positive on admission; 10.9 per cent after one week; 22.8 per cent after
two weeks; 26.2 per cent after three weeks; and, 33.1 per cent after
four weeks in the hospital.

=Hemolytic Streptococci in the Throats of Normal Men.=—The percentage of
normal individuals harboring hemolytic streptococci in their throats was
investigated in three distinct classes of men, classified according to
the degree of exposure to contact infection.

The first group includes men largely from country districts, cultured
within an hour after being assembled by their local draft board. The
laboratory car “Lister” was sent to Hot Springs, Ark. to meet the
November draft of men to be sent to Camp Pike. These men were returned
to their homes when the armistice was signed, so that there was no
opportunity to study them after they had lived under camp conditions.

The second group includes men on duty in Camps Funston and Pike. These
men, while largely from country districts, had been living crowded
together in the camp for a period varying from a few weeks to several
months.

The third group includes normal men resident in the base hospitals at
Ft. Riley and Camp Pike. This group includes at Camp Pike the medical
personnel of the measles and measles pneumonia wards and represents
individuals most exposed to contact infection with hemolytic
streptococci. On the other hand, the group includes doctors, nurses and
seasoned medical detachment men who are perhaps less susceptible to
respiratory infections than are raw recruits.

The results of studies of these groups are presented in Tables LXVI and
LXVII.

TABLE LXVI

HEMOLYTIC STREPTOCOCCI IN THROATS OF NORMAL MEN NOT RESIDENT IN THE
BASE HOSPITAL

═════════════╤═══════╤════════╤════════╤═══════════════════════════════
PLACE OF │NO. OF │ NO. │PER CENT│ REMARKS
STUDY │ CASES │POSITIVE│POSITIVE│
DATE │ │FOR HEM.│FOR HEM.│
│ │ STREP. │ STREP. │
─────────────┼───────┼────────┼────────┼───────────────────────────────
Camp Funston,│ 274│ 60│ 21.9│Men on duty in camp including
Kan., │ │ │ │ 201 white and 73 colored; in
Aug., 1918.│ │ │ │ great part newly drafted men
─────────────┼───────┼────────┼────────┼───────────────────────────────
Camp Pike, │ 337│ 25│ 7.4│Largely white men on duty in
Ark., │ │ │ │ camp
Nov. 5 to │ │ │ │
Dec. 10, │ │ │ │
1918 │ │ │ │
─────────────┼───────┼────────┼────────┼───────────────────────────────
Hot Springs, │[100]64│ 0│ 0.0│Men from country districts,
Ark., │ │ │ │ assembled by the local draft
Nov. 12, │ │ │ │ board
1918 │ │ │ │
─────────────┴───────┴────────┴────────┴───────────────────────────────

TABLE LXVII

HEMOLYTIC STREPTOCOCCI IN THROATS OF NORMAL MEN RESIDENT IN THE BASE
HOSPITAL

═════════════╤═══════╤════════╤════════╤═══════════════════════════════
PLACE OF │NO. OF │ NO. │PER CENT│ REMARKS
STUDY │ CASES │POSITIVE│POSITIVE│
DATE │ │FOR HEM.│FOR HEM.│
│ │ STREP. │ STREP. │
─────────────┼───────┼────────┼────────┼───────────────────────────────
Ft. Riley, │ 24│ 7│ 29.2│14 convalescent patients in a
Kan., │ │ │ │ surgical ward; 10 laboratory
Aug., 1918 │ │ │ │ workers
─────────────┼───────┼────────┼────────┼───────────────────────────────
Camp Pike, │ 153│ 22│[101]7.5│Personnel of measles wards
Ark., │ │ │ │
Sept. 10 to│ │ │ │
Nov. 30, │ │ │ │
1918. │ │ │ │
─────────────┴───────┴────────┴────────┴───────────────────────────────

The group of men studied at Hot Springs represents individuals among
whom there was little chance for contact dissemination of hemolytic
streptococci. It is a control series of men from outlying districts
examined before their throat bacteriology has been complicated by the
interchange of mouth organisms which occurs when a group of men are
crowded into close quarters. The entire absence of hemolytic
streptococci by the throat culture method is noteworthy. By multiplying
the chances of identifying hemolytic streptococci by making parallel
cultures from the saliva, and from the peritoneal exudates of mice
inoculated with saliva, hemolytic streptococci were found, in small
numbers, in 3 instances. The findings in this group were only three
throats lightly infected with hemolytic streptococci. They are in direct
contrast with the findings among individuals living in camps under
crowded conditions and are in accord with the findings among recruits
arriving in camp as recorded by Levy and Alexander.

In the second group, men living for a time in camp, the findings at Camp
Funston and at Camp Pike show rather striking differences. The lower
percentage incidence at Camp Pike is the more remarkable since the
studies were made soon after the influenza epidemic had swept the camp
and made necessary the hospitalization of about 20 to 25 per cent of the
camp population.

In the third group, namely, individuals resident in the hospital,
percentage rates at Camp Funston are slightly higher than for men
resident in camp. This difference disappears for the entire group at
Camp Pike if we consider a single throat culture, as we must for the
sake of comparison. The majority of these individuals at Camp Pike
served in measles wards from which patients carrying hemolytic
streptococci were removed at weekly intervals. Seven and one-half per
cent of the ward personnel were positives when first cultured. An
additional 7.5 per cent acquired the streptococcus while under
observation.

=Duration of the “Carrier” State.=—Unfortunately there are very few
observations with regard to the duration of the “carrier” state which
can be determined only by repeated cultures at short intervals. We have
made no observations of the duration of the “carrier” state in healthy
men. Two hundred and forty-two individuals carrying hemolytic
streptococci were identified in the ward treatment of measles. All
except 37 of these cases were “noncarriers” when first observed. The
remaining 205 include 166 contact “carriers” and 39 patients with acute
symptoms of infection by hemolytic streptococci.

The complete record of throat cultures on these cases is presented in
Table LXVIII.

=Group I= includes 37 cases positive for hemolytic streptococci on
admission.

(_a_) Twenty-two of these remained positive throughout the period of
observation. Four patients became negative after one or two weeks and
later showed positive findings, leaving the hospital as positives. These
are classified as “irregular.” The results of culture were as follows:
Cultured once only, 7; positive after one week, 7; positive after two
weeks, 6; positive after three weeks, 2; irregular, 4.

TABLE LXVIII

RESULTS OF THROAT CULTURES IN 242 HOSPITAL PATIENTS IDENTIFIED AS “CARRIERS” OF
HEMOLYTIC STREPTOCOCCI; CULTURES TAKEN AT WEEKLY INTERVALS

═════╤════╤════╤════╤════╤════╤════╤════╤════╤════╤════╤════╤════╤═══════╤═════
GROUP│1st │2nd │3rd │4th │5th │6th │7th │8th │9th │10th│11th│12th│No. of │ No.
│Cul-│Cul-│Cul-│Cul-│Cul-│Cul-│Cul-│Cul-│Cul-│Cul-│Cul-│Cul-│Contact│with
│ture│ture│ture│ture│ture│ture│ture│ture│ture│ture│ture│ture│ “Car- │Acute
│ │ │ │ │ │ │ │ │ │ │ │ │riers.”│Hem.
│ │ │ │ │ │ │ │ │ │ │ │ │ │Strep.
│ │ │ │ │ │ │ │ │ │ │ │ │ │Com-
│ │ │ │ │ │ │ │ │ │ │ │ │ │pli-
│ │ │ │ │ │ │ │ │ │ │ │ │ │ ca-
│ │ │ │ │ │ │ │ │ │ │ │ │ │tions
─────┼────┼────┴────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
=I=│=37=│ =Cases= │ │ │ │ │ │ │ │ │ │ │
─────┼────┼────┬────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ +│ │ │ │ │ │ │ │ │ │ │ │ 7│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ +│ + │ │ │ │ │ │ │ │ │ │ │ 7│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ +│ + │ + │ │ │ │ │ │ │ │ │ │ 6│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ +│ + │ + │ + │ │ │ │ │ │ │ │ │ 2│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ +│ − │ │ │ │ │ │ │ │ │ │ │ 8│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ +│ − │ − │ │ │ │ │ │ │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ +│ − │ − │ − │ − │ │ │ │ │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ +│ + │ − │ │ │ │ │ │ │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ +│ − │ + │ │ │ │ │ │ │ │ │ │ 2│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ +│ − │ − │ − │ − │ + │ + │ + │ │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ +│ + │ − │ − │ + │ + │ + │ │ │ │ │ │ 1│
─────┼────┼────┴────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
=II=│=67=│ =Cases= │ │ │ │ │ │ │ │ │ │ │
─────┼────┼────┬────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ + │ │ │ │ │ │ │ │ │ │ │ 26│ 3
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ + │ + │ │ │ │ │ │ │ │ │ │ 12│ 5
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ + │ + │ + │ │ │ │ │ │ │ │ │ 2│ 2
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ + │ − │ │ │ │ │ │ │ │ │ │ 9│ 1
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ + │ − │ − │ │ │ │ │ │ │ │ │ 0│ 1
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ + │ + │ − │ │ │ │ │ │ │ │ │ 2│ 1
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ + │ + │ + │ + │ − │ − │ + │ − │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ + │ − │ + │ │ │ │ │ │ │ │ │ 2│
─────┼────┼────┴────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
=III=│=74=│ =Cases= │ │ │ │ │ │ │ │ │ │ │
─────┼────┼────┬────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ + │ │ │ │ │ │ │ │ │ │ 38│ 5
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ + │ + │ │ │ │ │ │ │ │ │ 5│ 3
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ + │ + │ + │ │ │ │ │ │ │ │ 4│ 1
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ + │ + │ + │ + │ │ │ │ │ │ │ 0│ 2
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ + │ − │ − │ − │ │ │ │ │ │ │ 0│ 1
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ + │ − │ │ │ │ │ │ │ │ │ 4│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ + │ + │ − │ − │ − │ − │ │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ + │ + │ − │ │ │ │ │ │ │ │ 0│ 2
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ + │ + │ − │ − │ − │ │ │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ + │ + │ + │ + │ − │ │ │ │ │ │ 0│ 1
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ + │ − │ + │ │ │ │ │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ + │ − │ + │ + │ │ │ │ │ │ │ 2│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ + │ − │ + │ + │ + │ │ │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ + │ − │ − │ + │ + │ │ │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ + │ + │ + │ − │ − │ + │ │ │ │ │ 1│
=IV=│=34=│ =Cases= │ │ │ │ │ │ │ │ │ │ │
─────┼────┼────┬────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ + │ │ │ │ │ │ │ │ │ 12│ 4
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ + │ + │ │ │ │ │ │ │ │ 5│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ + │ + │ + │ │ │ │ │ │ │ 4│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ + │ − │ │ │ │ │ │ │ │ 3│ 1
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ + │ − │ − │ │ │ │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ + │ + │ − │ │ │ │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ + │ + │ + │ − │ │ │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ + │ − │ − │ + │ + │ │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ + │ + │ − │ − │ − │ − │ − │ │ │ 0│ 1
─────┼────┼────┴────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
=V=│=16=│ =Cases= │ │ │ │ │ │ │ │ │ │ │
─────┼────┼────┬────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ + │ │ │ │ │ │ │ │ 1│ 1
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ + │ + │ │ │ │ │ │ │ 1│ 1
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ + │ − │ │ │ │ │ │ │ 3│ 1
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ + │ − │ − │ │ − │ │ │ │ 0│ 2
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ + │ − │ − │ − │ − │ − │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ + │ + │ − │ │ │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ + │ − │ + │ │ │ │ │ │ 2│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ + │ + │ − │ │ + │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ + │ + │ − │ − │ − │ + │ │ │ 1│
─────┼────┼────┴────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
=VI=│ =7=│ =Cases= │ │ │ │ │ │ │ │ │ │ │
─────┼────┼────┬────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ − │ + │ │ │ │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ − │ + │ + │ │ │ │ │ │ 2│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ − │ + │ − │ │ │ │ │ │ 3│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ − │ + │ − │ − │ │ │ │ │ 1│
─────┼────┼────┴────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
=VII=│ =4=│ =Cases= │ │ │ │ │ │ │ │ │ │ │
─────┼────┼────┬────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ − │ − │ + │ │ │ │ │ │ 2│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ − │ − │ + │ + │ │ │ │ │ 1│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ − │ − │ + │ − │ − │ − │ − │ − │ 1│
─────┴────┼────┴────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
=VIII= =3=│ =Cases= │ │ │ │ │ │ │ │ │ │ │
─────┬────┼────┬────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ − │ − │ − │ + │ │ │ │ │ 2│
─────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼────┼───────┼─────
│ −│ − │ − │ − │ − │ − │ − │ + │ + │ + │ │ │ 1│
─────┴────┴────┴────┴────┴────┴────┴────┴────┴────┴────┴────┴────┴───────┴─────

(_b_) Eleven of the patients entering as positives became negative, 10
after one week and 1 after two weeks.

This group of cases furnishes no data concerning the duration of the
“carrier” state, since all cases were positive when first observed. In
30 per cent of instances, hemolytic streptococci disappeared within the
first two weeks of observation.

=Groups II to VIII= include 205 patients who became positive at some
time during their stay in the hospital. The arrangement in groups
depends upon the length of time the patients remained in the hospital
before acquiring S. hemolyticus. Ninety-five of these patients had no
further cultures after the initial positive culture. Fourteen appear as
“irregular,” as defined above. These two classes of cases are omitted in
the following summary of these groups. The initial positive culture is
arbitrarily considered the day of infection and subsequent cultures mark
off weekly intervals.

(_a_) Thirty-nine patients had acute infections due to hemolytic
streptococci. Thirteen of these patients passed from observation after
their initial positive culture. The cases with repeated cultures after
initial positive may be summarized as in Table LXIX.

TABLE LXIX

═════════════════════════════╤═════════════╤═════════════╤═════════════
│NO. PATIENTS │NO. BECOMING │ PER CENT
│ CULTURED │ NEGATIVE │ BECOMING
│ │ │ NEGATIVE
─────────────────────────────┼─────────────┼─────────────┼─────────────
Recultured after one week │ 26│ 7│ 26.9
Recultured after two weeks │ 14│ 8│ 57.1
Recultured after three weeks │ 7│ 4│ 57.1
Recultured after four weeks │ 2│ 2│ 100.0
─────────────────────────────┴─────────────┴─────────────┴─────────────

The records within this small group of cases indicate that hemolytic
streptococci tend to disappear with the passing of the acute infection.

(_b_) One hundred and sixty-six contact “carriers” are included in
Groups II to VIII. Eighty-two of these passed from observation after
their initial positive culture and 14 appear as “irregular.” The cases
with repeated throat cultures after the initial positive are summarized
in Table LXX.

TABLE LXX

═════════════════════════════╤═════════════╤═════════════╤═════════════
│NO. PATIENTS │NO. BECOMING │ PER CENT
│ CULTURED │ NEGATIVE │ BECOMING
│ │ │ NEGATIVE
─────────────────────────────┼─────────────┼─────────────┼─────────────
Recultured after one week │ 70│ 26│ 37.1
Recultured after two weeks │ 22│ 9│ 40.9
Recultured after three weeks │ 5│ 5│ 100.0
Recultured after four weeks │ 4│ 4│ 100.0
─────────────────────────────┴─────────────┴─────────────┴─────────────

These records indicate that contact carriers in great part harbor
hemolytic streptococci during short intervals. A longer period of
observation after the disappearance of hemolytic streptococci would have
been desirable in many instances. Some patients were followed with
consistently negative cultures during three, four and five weeks after
hemolytic streptococci had disappeared.

It is difficult to explain those instances in which negative cultures
are interposed between positives. Where one negative interrupts positive
cultures, it is possible that the throat culture failed to demonstrate
hemolytic streptococci which were present. Such cases in this series
fall within the limits of the percentage error of throat culture
identification. Where two or three, or even four negative cultures
intervene, reinfection is not impossible.

=Relation of S. Hemolyticus “Carriers” to the Complications of Acute
Respiratory Diseases.=—In the present study of measles it has been shown
that pneumonia following measles has been no more common in “carriers”
than in “noncarriers.” Nevertheless, pneumonia occurring in badly
infected wards has been modified by streptococcus complications.

More cases of otitis media have appeared in “carriers” than in
“noncarriers.” The possibility that mild otitis media, which would
ordinarily pass unnoticed, might become evident as the result of
streptococcus invasion must be considered. Levy and Alexander have made
an important contribution to our knowledge of the rôle of hemolytic
streptococci in measles. They find that “carriers” of hemolytic
streptococci among measles patients are especially predisposed to
complications following measles.

Their cases were drawn from a camp population highly saturated with S.
hemolyticus “carriers.” In the organization from which 89 per cent of
their patients with measles came, there were 83 per cent hemolyticus
“carriers” among men on duty. Among patients with measles, throat
cultures were positive for hemolytic streptococci on admission in 77 per
cent. It is evident that all patients with measles have been exposed to
hemolytic streptococci during the first day or two after admission.
Failure to carry streptococcus would appear to be dependent upon ability
to resist it rather than upon lack of opportunity for acquiring it. Of
388 cases observed by Levy and Alexander only 79 were “noncarriers” of
hemolytic streptococci on admission, and of these, 27 became positive
while under observation; only 52 remain as “noncarriers” of hemolytic
streptococci. This small group must be regarded as a highly selected
one, composed of individuals more than ordinarily resistant to hemolytic
streptococci and perhaps to all complications of measles. The chances
are that these 52 cases placed under any circumstances might very well
have been among the large number of measles cases in which no
complications develop.

Furthermore, it is not unlikely that any complication of measles may be
modified by a streptococcus secondarily when about 85 per cent of the
cases show S. hemolyticus in the throat. The complications in the cases
of Alexander and Levy appear to have been caused in large part by
streptococcus, but a complete bacteriologic study of them is not
recorded. Complications among streptococcus “carriers” are not identical
with complications due to the streptococcus, and it is desirable to know
what percentage of complications actually due to hemolytic streptococci
occurred among the 85 per cent of patients with measles who carried
hemolytic streptococci.

=Summary.=—No hemolytic streptococcus complications occurred in 112
cases of measles observed at Ft. Riley, among which streptococcus
“carriers” rose from 2.6 per cent on admission to 24.1 per cent before
discharge from the hospital. The percentage of “carriers” of hemolytic
streptococci among normal men in the camp supplying these cases was
about 25.5 per cent.

The influenza epidemic and a small epidemic of measles occurred in part
simultaneously at Camp Pike during September and October, 1918. The
complications following measles at Camp Pike were to a considerable
extent dependent upon the combined effects of influenza and measles.

Thirty-five per cent of the measles patients showed throat cultures
positive for B. influenzæ on admission to the hospital. On repeated
cultures, this rose to 84 per cent before discharge.

Ward separation of cases of measles carrying hemolytic streptococci in
their throats and cases not carrying these organisms were practiced in
handling this epidemic. Of 867 cases of measles treated in this manner,
37 were positive for hemolytic streptococci on admission, and 205
developed positive throat cultures for these organisms during their
period of observation in the hospital.

At Camp Pike, the percentage incidence of S. hemolyticus “carriers,” on
admission to the measles wards, was 4.2 per cent. In cases recultured
after one week, it was 10.9 per cent; after two weeks 22.8 per cent;
after three weeks 26.2 per cent; and after four weeks 33.1 per cent. The
weekly development of “carriers” in the “clean” treatment wards was
during the first week 9.1 per cent; during the second week 17.4 per
cent; during the third week 17.4 per cent; and during the fourth week
17.4 per cent.

The principal complications of these 867 cases of measles at Camp Pike
were: pneumonia, 56 cases; otitis media, 48 cases, with subsequent
mastoiditis in 23 cases, 2 of which had extensions to the meninges and
brain. The greater part of the pneumonia occurred early in the period of
observation, while most of the otitis media occurred later. Incidence of
hemolytic streptococci was low during the pneumonia period and high
during the prevalence of otitis media.

Hemolytic streptococci complicated 9 of these pneumonias; caused a large
percentage of otitis (bacteriology incomplete), and 21 of the 23 cases
of mastoiditis.

The bacteriology of 35 of the 56 pneumonias showed: Pneumococcus Type II
atypical, in 36 per cent, Type IV in 22.9 per cent, Type I in 2.8 per
cent and Type III in 2.8 per cent; hemolytic streptococci in 22.4 per
cent; and B. influenzæ in 88.6 per cent.

The culturing of wards as units revealed widespread contact
dissemination of hemolytic streptococci, at times 25 to 50 per cent of
the patients in a ward becoming “carriers” within the period of a week.
Streptococcus pneumonias, otitis media and its complications were
furnished in large part by wards in which active dissemination occurred.

Streptococcus complications did not occur among 37 patients who were
“carriers” of hemolytic streptococci when admitted to the hospital.

The epidemic dissemination of hemolytic streptococci occurs in measles
wards, and is a serious danger. Many, patients whose throats become
infected, develop no symptoms. In some instances streptococcus invades,
and renders much more serious lesions caused by other microorganisms.

Methods to prevent transfer of infection within the ward and separation
of “carriers” from “noncarriers” in different wards are efficient in
keeping epidemic dissemination of hemolytic streptococci under control.
Frequent throat cultures and prompt report of the results of cultures
are essential.

The dissemination of B. influenzæ in patients with measles was not
controlled by segregation of “carriers” and “noncarriers” of this
organism as identified by throat cultures in separate wards.

CHAPTER VI
THE PATHOLOGY AND BACTERIOLOGY OF PNEUMONIA FOLLOWING MEASLES

EUGENE L. OPIE, M.D.; FRANCIS G. BLAKE, M.D.; JAMES C. SMALL, M.D.; AND
THOMAS M. RIVERS, M.D.

Among 18 autopsies upon men who have died with pneumonia following
measles there are pulmonary lesions representing almost every type of
pneumonia which has been found in association with influenza. In most
instances pneumonia made its appearance during the second week of
measles and death occurred during the third week. Of 16 instances in
which the record is definite, pneumonia had its onset during the first
week of measles in 4 instances, during the second week in 11 instances,
and in one instance (Autopsy 390) perhaps not referable to measles in
the fifth week. The duration of pneumonia varied from three to
thirty-two days; in 10 instances it did not exceed one week, in 5
instances it was between one and two weeks and in one instance,
thirty-two days. When the duration of pneumonia exceeded ten days some
evidence of chronic pulmonary disease was found at autopsy.

The same lack of correspondence between clinical diagnosis and pulmonary
lesions noted with influenza was found following measles. In accordance
with the prevailing opinion concerning the character of pneumonia
following measles, the diagnosis of bronchopneumonia was made in 13
instances and in all of these cases bronchopneumonia was found at
autopsy. The diagnosis of lobar pneumonia was made 5 times and was
correct only once. Nevertheless, lobar pneumonia was present 4 times,
but was recognized only once (Autopsy 486.) Failure to recognize lobar
pneumonia, was doubtless due in part at least to its association with
purulent bronchitis and peribronchiolar pneumonia (Table LXXI).

TABLE LXXI

=Changes in Bronchi.=—The changes in the bronchi do not differ in
character from those associated with pneumonia following influenza.
Purulent bronchitis recognized at autopsy by the presence of
mucopurulent material in the small bronchi was found in a much larger
proportion of instances in this group of autopsies occurring in 13 of 18
instances (72.2 per cent), whereas it was present in only 55.6 per cent
of autopsies on individuals with pneumonia following influenza. There
was peribronchial hemorrhage recognizable on gross examination in 3
autopsies and microscopically in 3 additional instances.

Bronchiectasis was present in a considerable proportion of these
autopsies, dilatation of bronchi being noted in 7, but it was usually
moderately advanced and at times limited to the bases of the lungs. The
short duration of respiratory disease perhaps explains the infrequency
of advanced bronchiectasis. The incidence of the lesion is greater with
measles (43.7 per cent) than with influenza (22.4 per cent).

Microscopic changes in the bronchi do not differ from those found after
influenza. Evidence of acute inflammation, often hemorrhagic in
character, is found within the lumen of the bronchus and in the tissues
immediately in contact with the lumen. Not infrequently the epithelium
is lost; there is superficial necrosis and deposition of fibrin upon the
surface and within the tissue. In the deeper tissues of the bronchial
wall there is infiltration with lymphoid and plasma cells, which in the
larger bronchi is particularly advanced about the mucous glands of which
the acini exhibit degenerative changes. With the onset of chronic
changes new formation of fibrous tissue occurs in the wall of the
bronchus and in the contiguous interalveolar walls. The lining
epithelium often loses its columnar cells and assumes a squamous type.

Changes in the bronchi with bronchiectasis have been similar to those
following influenza. Weakening of the wall permitting dilatation is
brought about by necrosis extending outward from the lumen a varying
distance into the bronchial wall and permitting the formation tears
which diminish resistance to intrabronchial pressure.

=Lobar Pneumonia.=—Lobar pneumonia following measles occurred in 4
instances. Onset in these cases was on approximately the 9th, 10th,
11th, or 14th day of measles; the onset of bronchopneumonia bore a
similar time relation to the onset of measles, the average interval
being nine days. Hepatization with lobar pneumonia was in 1 instance
red, in 3 instances gray, and in all save 1 instance the consolidation
was firm and coarsely granular on section. In the exceptional instance
the greater part of the right upper lobe was laxly consolidated and
rather finely granular but the microscopic appearance was in all
instances that of lobar pneumonia. Lobar pneumonia in 2 of these cases
was associated with purulent bronchitis present in parts of the lung
that had not undergone consolidation, whereas in the other 2 instances
there were acute bronchitis and peribronchiolar pneumonia recognized by
microscopic examination.

In one instance hepatization of the lung presented some noteworthy
features.

=Autopsy 450.=—G. D., white, aged twenty-one, a farmer, resident of
Arkansas, had been in military service twenty-nine days. Onset of
illness began on October 2, nineteen days before death, and on
admission on the same day the diagnosis of measles was made. Signs
of pneumonia, regarded as bronchopneumonia, were recognized five
days before death. Three days later there was otitis media and
paracentesis was performed. On October 3 and 10 neither S.
hemolyticus nor B. influenzæ was found in the sputum; on October 17
and 20 S. hemolyticus was not found but B. influenzæ was present.

=Anatomic Diagnosis.=—Acute lobar pneumonia with gray and red
hepatization in right upper and lower lobes; edema and peribronchial
hemorrhage in left lung.

[Illustration:

Fig. 29.—Lobar pneumonia following measles, showing extension of
gray hepatization from lower to upper lobe through a defect in the
septum separating the two lobes. Autopsy 450.
]

The entire lower lobe of the right lung (Fig. 29) with the exception
of a narrow air-containing zone in contact with basal surface is
firmly consolidated. The greater part of the consolidated tissue is
yellowish gray, firm and coarsely granular. The uppermost part of
the consolidated tissue is softer than elsewhere as if it has
undergone autolysis. The lowermost part of the consolidated tissue
in a zone from 2.5 to 3.5 cm. in breadth is firmly consolidated but
deep red. The bronchi contain stiff plugs of fibrin. In the upper
lobe continuous with the consolidated part of the lower is a
semicircular patch of yellowish gray consolidation. It overlies the
line of the interlobular cleft at the site of a break in its
continuity. Consolidation appears to have spread from the lower lobe
into the upper at the site where the alveolar tissue of the two
lobes is continuous but is absent from that part of the upper lobe
separated from the lower by the interlobular cleft. This
semicircular patch of yellowish gray consolidation is separated from
air containing tissue of the upper lobe by a zone of red
hepatization about 1 cm. in thickness.

Bacteriologic examination showed the presence of Pneumococcus IV in
the blood of the heart; B. influenzæ alone was obtained from the
right lower lobe and B. influenzæ and staphylococcus from the left
main bronchus.

The distribution of lobar pneumonia in the foregoing autopsy indicates
that it has spread like a wave from the upper part of the lower lobe
(Fig. 32) penetrating into the upper where the alveolar tissue of the
two lobes is in contact; gray hepatization is everywhere separated from
air containing tissue by an advancing zone of red hepatization.

It may be assumed that lobar pneumonia was caused by Pneumococcus II
atypical in 3 instances although it was recovered from the lungs only
twice, for in the third instance (Autopsy 486) it was found in the
bronchus and in the inflamed pleural cavity; pneumococci were doubtless
previously present in the lung, but had disappeared at least from that
part from which the culture was made. Pneumococcus IV was evidently the
cause of pneumonia in 1 instance (Autopsy 450), for it was found in the
blood of the heart although it was absent in the culture from the lung.

Little significance can be attributed to the observation that B.
influenzæ was present in pure culture in the lungs from Autopsies 450
and 486, for the presence of Pneumococci IV in the blood of the heart in
Autopsy 450 and of Pneumococcus II atypical in the pleura in Autopsy 486
furnishes evidence in view of the occurrence of lobar pneumonia that
pneumococci had disappeared from the lungs. B. influenzæ was found both
in the lungs and bronchus or in the bronchus alone in 3 of these 4
cases.

The relation of hemolytic streptococci to the lesion is of interest. In
3 of 4 instances of lobar pneumonia this microorganism had entered the
bronchi but was not found in the lungs or in the heart’s blood; and
gross and histologic examination showed none of the lesions which are
usually caused by it. In 1 instance (Autopsy 508) hemolytic
streptococci, absent from the throat when the patient was admitted to
the hospital with measles sixteen days before death, appeared in a
culture made five days later and was subsequently found three times; it
had penetrated into the bronchus but failed to reach the lung.
Observations made upon lobar pneumonia following influenza have shown
the relative insusceptibility of lobar pneumonia with gray hepatization
to secondary infection with hemolytic streptococci (p. 160). Autopsy 508
demonstrates that occurrence of hemolytic streptococci in the sputum of
a patient with pneumonia does not furnish conclusive proof of the
existence of streptococcus pneumonia.

=Bronchopneumonia.=—Bronchopneumonia has been found in every instance of
pneumonia following measles save 3, namely in Autopsy 486, Autopsy 505
with lobar pneumonia and Autopsy 507 with interstitial suppurative
pneumonia. It is not improbable that further histologic study might have
demonstrated small patches of peribronchiolar pneumonia, for purulent
bronchitis was present in the two autopsies with lobar pneumonia. This
small group of cases has reproduced all of the important features of
bronchopneumonia following influenza. Hemorrhagic peribronchiolar
consolidation characterized by the presence of small gray spots
clustered about terminal bronchi upon a homogeneously red background has
been found in 5 of 18 instances of pneumonia with measles. Pfeiffer
regarded this lesion as characteristic of the pneumonia of influenza.
Peribronchiolar patches of consolidation with no surrounding hemorrhage
were found in 14 instances, being recognized first by microscopic
examination in half of this number. Lobular consolidation occurred in 11
autopsies and peribronchial fibrinous pneumonia was present in a third
of the autopsies on patients with pneumonia of measles.

Bronchial, peribronchial and intraalveolar hemorrhage is much more
commonly associated with the pneumonias of influenza than with the more
familiar types of acute bronchopneumonia. Exuded blood may undergo
absorption; and with bronchopneumonia which, persisting unresolved, has
assumed the characters of a chronic lesion, it is common to find
mononuclear cells often in great abundance filled with brown pigment
derived from the hemoglobin of red blood corpuscles.

Autopsy 439 is an example of acute hemorrhagic bronchopneumonia; there
are red lobular and confluent lobular patches of consolidation which
upon the pleural surface have a blue or purplish color. In the dependent
part of the left lung occupying a large part of the lower lobe there is
lax, red consolidation marked by gray or yellowish gray spots of
peribronchiolar pneumonia and in this lobe bronchi are encircled by
zones of hemorrhage. Pneumococcus II atypical was obtained from the
lung. In Autopsy 444 the lesion has the same hemorrhagic character
although lobular patches are in a stage of grayish red hepatization.
Pneumococcus II atypical has been found in the heart’s blood, and with
B. influenzæ in lungs and bronchus. Autopsy 441 is an example of the
occurrence of conspicuous nodules of peribronchiolar consolidation in
some parts of the lungs with the same lesion in other parts on a
background of hemorrhage. B. influenzæ and S. aureus have been found in
both lungs and bronchi.

Steinhaus[102] states that the pneumonia of measles is never lobular
inflammation but occurs in small patches several of which may be found
in a single lobule.

Chronic fibroid pneumonia following measles characterized by cellular
infiltration and proliferation of the interstitial tissue of the lung
has been described by Bartels,[103] Steinhaus,[104] Hart,[105]
MacCallum[104] and others.

[Illustration:

Fig. 30.—Unresolved bronchopneumonia with measles showing new
formation of fibrous tissue about a bronchus and in immediately
adjacent alveolar walls; partially obliterated alveoli occur in the
peribronchial fibrous tissue. Autopsy 481.
]

[Illustration:

Fig. 31.—Unresolved bronchopneumonia with measles showing a nodule of
chronic fibrous pneumonia surrounding a respiratory bronchiole.
Autopsy 481.
]

The incidence of unresolved bronchopneumonia among instances of
bronchopneumonia following measles is higher than that among
bronchopneumonias following influenza. There have been 6 instances of
chronic or unresolved bronchopneumonia among 18 pneumonias following
measles, namely 33.3 per cent. The incidence of unresolved
bronchopneumonia among 241 autopsies on pneumonia following influenza
has been 21, namely 8.7 per cent. The essential features of this chronic
lesion have been as follows: (_a_) chronic peribronchiolar pneumonia
indicated by the presence of firm nodules of peribronchiolar
consolidation which have considerable resemblance to miliary tubercles.
Induration of the nodule occurs because the walls of alveoli surrounding
and adjacent to a respiratory bronchiole (Fig. 31) become thickened and
infiltrated with cells and there is organization of exudate within the
alveoli. New formation of fibrous tissue (Fig. 32) occurs where the
acute inflammatory reaction of peribronchiolar consolidation is most
advanced (p. 169 and compare with Figs. 3 and 4), namely, about the
respiratory bronchiole, alveolar duct and the proximal parts of the
infundibula, disappearing as the distal half of the infundibulum is
approached. Distention of the alveoli explaining the distention of the
lung and its failure to collapse on section is a noteworthy feature of
the lesion. (_b_) Chronic peribronchial inflammation (Fig. 30) with new
formation of fibrous tissue about the smaller and medium-sized bronchi
extending into immediately adjacent alveolar walls and often associated
with organization of peribronchial fibrinous pneumonia. (_c_) Chronic
lobular inflammation with changes similar to those just cited,
distributed throughout entire lobules. (_d_) Moderate thickening of
interlobular septa. Bronchiectasis may be associated with the chronic
lesion (Autopsies 443, 481, 484, 492 and 496) but with one exception
(Autopsy 443) has been only moderately advanced. Suppurative pneumonia
with abscess formation has occurred twice (Autopsies 438 and 492).

[Illustration:

Fig. 32.—Unresolved bronchopneumonia with measles showing chronic
pneumonia about a respiratory bronchiole and alveolar duct; alveoli
about the proximal parts of three distended infundibula are filled
with polynuclear leucocytes, whereas inflammatory changes disappear
as the distal parts of the infundibula are approached. Autopsy 481.
]

With acute bronchopneumonia following measles the average duration of
pneumonia, determined by the date upon which physical signs of pneumonia
were first recognized and in consequence subject to some error, was
seven days; in instances of chronic bronchopneumonia the average
duration of pneumonia has been fifteen days.

The bacteriology of acute bronchopneumonia following measles is shown in
Table LXXII.

TABLE LXXII

════════════╤═══════╤═══════════════╤════════════════╤═════════════════
WITH NO │SPUTUM │ BACTERIA IN │ BACTERIA IN │ BACTERIA IN
SUPPURATION │IN LIFE│BLOOD OF HEART │ LUNGS │ BRONCHI
────────────┼───────┼───────────────┼────────────────┼─────────────────
Autopsy 390│ │Pneum. II atyp.│ │
439│ │0 │Pneum. II atyp. │B. coli
│ │ │ S. aur. │
441│ │0 │B. inf., S. aur.│B. inf., S. aur.
444│B. inf.│Pneum. II atyp.│Pneum. II atyp. │Pneum. II atyp.
│ │ │ B. inf. │ B. inf.
453│ │Pneum. I │Pneum. I │Pneum. I, B. inf.
With │ │ │ │
suppuration:│ │ │ │
442│S. hem.│S. hem. │ │B. inf., S. hem.
491│S. hem.│S. hem. │S. hem., B. coli│B. inf., B. coli
507│S. hem.│S. hem. │S. hem., S. aur.│S. hem., B. inf.,
│ │ │ │ S. aur.
────────────┴───────┴───────────────┴────────────────┴─────────────────

It is noteworthy that pneumococci have been recovered from the heart’s
blood or lung in all but 1 (Autopsy 441) of 5 instances of acute
bronchopneumonia with no suppuration and is doubtless the cause of this
pneumonia. Pneumococcus II atypical has been found in 3 of 4 instances
of lobar pneumonia following measles and is present in 3 of these 5
instances of bronchopneumonia.

Where suppuration has been found, hemolytic streptococci have been
present in the sputum, in the heart’s blood and either in the lungs
(Autopsy 491) or in the bronchi (Autopsy 442) or in both (Autopsy 507).
In these instances pneumococci have not been found, though in view of
the readiness with which pneumococci disappear from the lungs it is
possible that they have been the primary cause of bronchopneumonia.

The bacteriology of 6 instances of unresolved bronchopneumonia following
measles is given in Table LXXIII.

TABLE LXXIII

════════════╤═══════╤═══════════════╤════════════════╤═════════════════
WITH NO │SPUTUM │ BACTERIA IN │ BACTERIA IN │ BACTERIA IN
SUPPURATION │IN LIFE│BLOOD OF HEART │ LUNGS │ BRONCHUS
────────────┼───────┼───────────────┼────────────────┼─────────────────
Autopsy 443│ │0 │B. coli │B. inf., B.coli
481│ │0 │B. inf. │B. inf., Pneum.
│ │ │ │ II, atyp., S.
│ │ │ │ hem.
484│Pneum. │0 │0 │B. inf.,
│ IV., │ │ │ diphtheroids
│ B. │ │ │
│ inf. │ │ │
496│Pneum. │0 │0 │B. inf.
│ IV., │ │ │
│ B. │ │ │
│ inf. │ │ │
With │ │ │ │
Suppuration:│ │ │ │
Autopsy 438│B. inf.│0 │Pneum. II atyp.,│S. hem., B. inf.
│ │ │ S. vir. B. │
│ │ │ inf. S. hem. │
492│St. │S. hem. │S. hem., Pneum. │
│ hem.,│ │ IV, B. coli, │
│ B. │ │ B. inf. │
│ inf. │ │ │
────────────┴───────┴───────────────┴────────────────┴─────────────────

Whereas with acute bronchopneumonia death has been accompanied and
perhaps caused by bacterial invasion of the blood by pneumococci or
streptococci in 5 of 7 instances, with unresolved or chronic
bronchopneumonia, bacteriemia has been present only once, namely, in
Autopsy 492 in which with suppurative pneumonia hemolytic streptococci
have entered the blood. It is probable that pneumococci have likewise
had an important part in the causation in these instances of
bronchopneumonia which have run a chronic course but in all save 2 cases
(Autopsies 438 and 492) have disappeared from the lungs. Pneumococcus II
atypical has been found twice.

B. influenzæ has been found in association with acute bronchopneumonia
in the lungs in 1 of 6 examinations and in the bronchi in 5 of 6
examinations. These figures indicate that it is present in small numbers
if at all in the consolidated lung tissue but is relatively abundant in
the bronchi. With chronic bronchopneumonia B. influenzæ has been found
in every instance, in half of the examinations of lungs and in all of
the examinations of bronchi. In 1 instance (Autopsy 481) B. influenzæ
has been found in pure culture in the lung; Pneumococcus II atypical has
been found in the bronchus and has perhaps disappeared from the
pneumonic lung, since this microorganism is often destroyed in the late
stages of pneumonia so that its demonstration at autopsy is no longer
possible. In 1 instance B. influenzæ found in the bronchus has been the
only microorganism isolated at autopsy, although the sputum during life
contained B. influenzæ and Pneumococcus IV.

=Suppurative Pneumonia.=—Suppurative pneumonia with formation of
abscesses has occurred in 2 autopsies with pneumonia following measles
(Autopsies 438 and 492), both instances of chronic bronchopneumonia. In
Autopsy 438 the lower and posterior part of the left lower lobe has been
consolidated and has had on section a cloudy, grayish red color; within
this area of consolidation and immediately below the pleural surface
there have been opaque, yellow spots where the tissue has been softer
than elsewhere. Microscopic examination shows that the tissue has here
undergone widespread necrosis so that all nuclear stain has disappeared;
at the edges of the necrotic tissue polynuclear leucocytes are often
present in large numbers, but necrosis is much more conspicuous than
suppuration. In the necrotic tissue and at its edges streptococci are
present in vast numbers. Hemolytic streptococci have been grown both
from the lung and from the bronchus, but these have not been the only
microorganisms present, for Pneumococcus II atypical and S. viridans
have been obtained from the lungs and B. influenzæ from lungs and
bronchus.

In Autopsy 492 with chronic bronchopneumonia the posterior half of the
right lower lobe is laxly consolidated, deep red in color and with the
cloudy appearance often associated with streptococcus pneumonia; upon
this background are peribronchiolar spots of yellow color, in places
well seen below the pleura; in the corresponding part of the left lower
lobe similar nodules have been converted into small abscesses by central
suppuration. There is empyema on the right side, fibrinopurulent
pericarditis, and purulent peritonitis. Hemolytic streptococci had been
found in the sputum three times, the first examination being thirteen
days before death. This microorganism is found in pure culture in the
blood of the heart and with Pneumococci IV, B. coli and B. influenzæ in
the lung. Hemolytic streptococci were found in the right pleural exudate
and peritoneum.

The pneumonias following measles give opportunity to consider the
relationship of suppurative interstitial pneumonia to unresolved or
chronic bronchopneumonia, which is characterized by infiltration and
proliferation of the fibrous tissue of the lungs. A number of those who
have studied the pneumonia of measles have recognized that this chronic
interstitial lesion is a common sequela of measles. MacCallum has
designated the lesion “interstitial bronchopneumonia,” and has included
under this name its acute stage in which the interstitial character of
the lesion is not more evident than with other forms of acute
bronchopneumonia. He has regarded S. hemolyticus as the cause of
“interstitial bronchopneumonia” following measles. A review of the
autopsies which he has described shows that he has included under the
same designation typical instances of interstitial suppurative pneumonia
associated with suppurative lymphangitis. Instances of unresolved,
chronic or “interstitial” bronchopneumonia and of interstitial
suppurative pneumonia which we have observed after measles, demonstrate
that the two lesions are distinguishable both by their anatomic
characters and by their etiology.

Three instances of suppurative interstitial pneumonia occurred among the
pneumonias following measles (Autopsies 442, 491 and 507). The lesion is
characterized by suppuration of the interlobular septa and particularly
noteworthy is the occurrence of suppurative lymphangitis, lymphatics
being immensely dilated and distended with purulent fluid so that their
irregularly dilated, beaded appearance is recognizable upon the section
of the lung. In the group of pneumonias following measles this lesion
has not been associated with unresolved or chronic bronchopneumonia; no
nodular tubercle-like foci of bronchopneumonia have been found at
autopsy, and there has been no thickening of the interstitial tissue.
The lesion has accompanied confluent lobular pneumonia in 2 instances
(Autopsies 442 and 491). In the third instance (Autopsy 507) there was
in the neighborhood of the suppurative lesions diffuse consolidation
which had the cloudy, gray red color of streptococcus pneumonia, but
this consolidation was not lobular in distribution.

The etiology of interstitial suppurative pneumonia established by study
of instances following influenza is confirmed by Table LXXII (p. 345)
showing the bacteriology of instances of acute bronchopneumonia
following measles. Pneumococci are almost invariably found in
uncomplicated instances of bronchopneumonia and hemolytic streptococci
have been absent, whereas in 3 instances of suppurative interstitial
pneumonia hemolytic streptococci have been found in the sputum during
life, in pure culture in the blood of the heart and in the lungs and
bronchus (missed in the bronchus in one instance, Autopsy 507). In the 3
instances of the disease B. influenzæ has been found in the bronchi.

Table LXXIII shows that suppuration has accompanied unresolved
bronchopneumonia (“interstitial bronchopneumonia”) in 2 instances
(Autopsies 438 and 492), but in these instances the interlobular tissue
of the lung has not been the site of suppuration and there has been no
suppurative lymphangitis. Localized abscesses have been formed;
hemolytic streptococci, as with abscesses following influenza, have been
found.

Empyema has occurred only 5 times in association with pneumonia
following measles and in these 5 instances has been associated with
suppurative pneumonia caused by hemolytic streptococci. In Autopsy 492
there was fibrinopurulent pleurisy on both sides. Aspiration had been
performed 3 times and at autopsy the right pleural cavity contained 150
c.c. of purulent fluid. In small pockets, corresponding to shallow oval
depressions upon the anterior surface of the lung, fluid was walled off
from the general cavity. The pericardial cavity contained 25 c.c. of
turbid yellow fluid containing yellow flakes of fibrin and the
peritoneal cavity contained thick purulent fluid. Hemolytic streptococci
present in the heart’s blood and lung were recovered from the right
pleural cavity and from the peritoneum. Among 3 instances of empyema
accompanying interstitial suppurative pneumonia, in 1 (Autopsy 491)
there were walled off pockets of fluid similar to those just described.
Aspiration of the right pleural cavity had been performed 3 times; at
autopsy 100 c.c. of fibrinopurulent fluid was found on the right side
and 450 c.c. on the left. There was general purulent peritonitis and the
peritoneal cavity contained 350 c.c. of thick yellow pus. Hemolytic
streptococci were obtained from the heart’s blood, right lung, right
pleural cavity and peritoneum.

Among 4 instances of lobar pneumonia following measles there was
serofibrinous pleurisy 3 times; in 1 instance there is no record of
pleural change. In 1 instance of lobar pneumonia (Autopsy 505) the right
pleural cavity contained 800 c.c. of serofibrinous exudate and the
pericardial cavity contained 510 c.c. of opaque, yellow seropurulent
fluid; Pneumococcus II atypical in pure culture was obtained from the
blood, lung and pleural and pericardial exudates. Among 9 instances of
bronchopneumonia following measles there was fibrinous pleurisy 3 times,
serofibrinous 3 times, and no recorded lesion of the pleura 3 times.
Empyema, like suppurative pneumonia following measles, is in most
instances, but not constantly, caused by invasion of hemolytic
streptococci.

The foregoing study has shown that pneumonia which has followed measles
has reproduced all of the lesions usually found after influenza. There
is no pulmonary lesion peculiar to measles. Lobar pneumonia follows the
disease in some instances, but bronchopneumonia with purulent bronchitis
is more common. The same tendency to hemorrhagic inflammation found with
the pneumonia of influenza is seen after measles. Unresolved pneumonia
with chronic inflammatory changes in the interstitial tissue of the lung
has all of the characters of the similar lesion following influenza but
has been found in a larger proportion of the pneumonias of measles.

B. influenzæ has been found in the bronchi in 14 of 16 examinations,
namely in 87.5 per cent of fatal instances of pneumonia. In 1 instance
in which B. influenzæ has not been found at autopsy, it has been
isolated from the sputum during life. It is not improbable that B.
influenzæ has been constantly present in the inflamed bronchi both after
influenza and measles. It is noteworthy that the outbreak of pneumonia
following measles has been in part coincident with, in part slightly
subsequent to, an epidemic of influenza which has exposed every
individual in the camp to infection with this disease.

B. influenzæ has been found in the lung with the pneumonia of measles in
7 of 17 examinations, namely, in 41.2 per cent of instances. The
microorganism with measles, as with influenza, is found in the inflamed
lung only half as frequently as in the bronchi. It appears to be
peculiarly adapted for multiplication within the bronchial tubes, and
its isolation from the inflamed lung in less than half of the cases of
pneumonia is perhaps referable to its presence in the small bronchi and
bronchioles. The presence of B. influenzæ in the lungs in pure culture
in 3 instances at first sight suggests that the microorganism produces
pneumonia, but a more intimate survey of these cases gives little
support to this view. In Autopsy 450 B. influenzæ has been found in pure
culture in the lung, but Pneumococcus IV has been isolated from the
blood of the heart and has been with little doubt the cause of typical
lobar pneumonia present in this instance. In Autopsy 486 the condition
is almost identical, for in the presence of lobar pneumonia B. influenzæ
has been found in the lung in pure culture, but Pneumococcus II atypical
has been isolated from the pleural cavity and from the bronchus; in both
autopsies the pneumococci which have caused lobar pneumonia have
disappeared from that part of the consolidated lung from which a culture
has been made; and here doubtless its invasion has been effectively
resisted although it is still present in other organs. In Autopsy 481 in
which B. influenzæ has been isolated from the lung in pure culture, the
part of pneumococci in the production of the fatal disease is less
evident; in this instance, Pneumococcus II atypical, S. hemolyticus and
B. influenzæ have been isolated from the bronchus.

The presence of microorganisms which have a well-established etiologic
relation to pneumonia explains the occurrence of pneumonia and makes
unnecessary the assumption that B. influenzæ, which is present in the
lungs in less than half of the instances examined, is essential to the
production of the pneumonic consolidation. In view of the
well-recognized etiology of lobar pneumonia we may conclude that this
lesion is referable to the pneumococci (Pneumococcus II atypical in 3
instances and Pneumococcus IV in 1 instance) isolated from the autopsies
in which this lesion occurred. Pneumococcus (Pneumococcus II atypical in
3 instances and Pneumococcus I in 1 instance) has been isolated from the
lungs or heart’s blood in 4 of 5 instances of acute bronchopneumonia
unaccompanied by suppuration. With unresolved bronchopneumonia with no
suppuration, pneumococci have been in no instance found in the lungs or
blood though their presence in the washed sputum during life or in the
bronchus at autopsy suggests the possibility that they may have
disappeared from the lungs.

In all instances in which suppuration has occurred hemolytic
streptococci have been found in the lungs or blood, or in both. The
occurrence of pneumococci in the lungs in 2 of 5 instances of
suppurative pneumonia indicates that infection with S. hemolyticus is in
some instances at least superimposed upon acute bronchopneumonia caused
by pneumococci. Bronchopneumonia in 3 instances has the character of
that caused by pneumococci. It is probable that the sequence of
infection frequently observed after influenza, namely, bronchial
infection by B. influenzæ, followed by pneumonia caused by pneumococci,
followed in turn by infection by hemolytic streptococci with necrosis or
suppuration, is not uncommon after measles.

=Pneumonia Associated with Acute Infectious Diseases Other than
Influenza and Measles.=—A small group of autopsies have been excluded
from the list of those which accompanied the epidemic of influenza,
because pneumonia has been associated with an acute infectious disease
to which it is perhaps secondary. These few instances of pneumonia, like
those following measles reproduce characters of the pneumonia following
influenza and may be in part referable to influenza which has attacked
an individual suffering with typhoid fever, mumps or scarlet fever.

In 2 instances pneumonia followed typhoid fever and appeared on
September 23 and 26 shortly after the epidemic of influenza had become
evident. In the following autopsy there was acute lobar pneumonia which
appeared ten days after onset of typhoid fever.

=Autopsy 245.=—O. H., white, aged twenty-one, a farmer, resident of
Oklahoma, had been in military service twenty-one days. Onset of
illness was on September 13 with chill, headache, cough and nausea.
The patient was admitted two days later with the diagnosis of acute
bronchitis. On September 20 the abdomen was tense, the spleen was
enlarged and rose spots were present. Signs of lobar pneumonia were
found September 23. Death occurred September 25, twelve days after
onset of typhoid fever and two days after recognition of pneumonia.

=Anatomic Diagnosis.=—Typhoid fever with necrotic ulcers in lower
ileum and in colon; hyperplasia of ileocecal lymphatic nodes; acute
splenic tumor; parenchymatous degeneration of liver and kidneys;
acute lobar pneumonia with gray hepatization in left lower lobe and
red hepatization and edema in left upper lobe and in right lung;
serofibrinous pleurisy on left side.

The left pleural cavity contains 75 c.c. of yellowish gray turbid
fluid. Over the left lower lobe there is a layer of fibrin. The
upper half of the lobe is firmly consolidated, pinkish gray and
coarsely granular; the bronchi contain plugs of fibrin. The lower
and posterior part of the lower lobe is consolidated deep red and
edematous. The left upper lobe is edematous and a layer in the
lowermost part in contact with the lower lobe is deep red and
consolidated. The left lung weighs 1,490 grms. The lower half of the
right upper lobe and the posterior border of the lower is
consolidated deep red and edematous; the lung weighs 970 grms.

Bacteriologic examination shows that the blood of the heart contains
Pneumococcus II atypical.

The foregoing autopsy is of interest because typical lobar pneumonia
appears to have spread from the left lower lobe, where consolidation is
firm and gray, to the adjacent part of the upper lobe where
consolidation is red and edematous.

The second instance of pneumonia following typhoid fever is an instance
of suppurative pneumonia caused by S. aureus.

=Autopsy 329.=—J. B., white, aged twenty-two, laborer, resident of
Oklahoma, had been in military service two days before onset of
symptoms of typhoid fever. He was admitted to the hospital on August
27 and B. typhosus was found in cultures from the blood on September
2 and 3. Acute bronchitis appeared on September 26 when the epidemic
of influenza had almost reached its height. A diagnosis of
bronchopneumonia was made on the day preceding death, which occurred
forty-one days after onset of typhoid fever and eleven days after
onset of bronchitis.

=Anatomic Diagnosis.=—Typhoid ulcers of ileum; acute splenic tumor;
acute bronchopneumonia with red hemorrhagic peribronchiolar and
lobular consolidation in right lung; multiple abscesses forming a
circumscribed group in left upper lobe; purulent bronchitis.

The pleural cavities contain no excess of fluid. The lungs are
voluminous and there is interstitial emphysema. Below the pleura are
bluish red spots of lobular consolidation; in the right upper lobe
is a large patch of red consolidation marked by yellowish gray spots
in clusters. In the external and upper part of the left upper lobe
is a patch of gray consolidation within which, beneath the pleura,
there are small abscesses grouped to form a cluster 1.5 cm, across.

Bacteriologic examination demonstrates no microorganisms in the
blood of the heart; of two cultures from the left lung one contains
S. aureus in pure culture, the other S. aureus and a few colonies of
Pneumococcus IV. Cultures from the left main bronchus and from the
mucopurulent exudate in a small bronchus both contain B. influenzæ,
S. aureus and Pneumococcus IV.

In the foregoing case bronchitis has appeared thirty days after onset of
typhoid fever on September 26, immediately preceding the height of the
epidemic of influenza. In association with hemorrhagic bronchopneumonia
there is suppurative pneumonia with small abscesses forming a
circumscribed group below the pleura; there is no empyema. The lesion
has the characters of the staphylococcus abscesses following influenza,
and S. aureus is found in association with the lesion; B. influenzæ is
identified in two cultures from the bronchi.

In 2 instances pneumonia was associated with parotitis which was
diagnosed mumps.

=Autopsy 403.=—C. T., colored, aged twenty-five, a laborer, resident
of Arkansas, had been in military service one month. Illness began
September 27 with swelling of face behind jaw and difficult
mastication; the patient was admitted to the hospital on the same
day with the diagnosis of mumps. Pneumonic consolidation was
recognized on October 8. Death occurred October 13, sixteen days
after onset of illness and six days after recognition of pneumonia.

=Anatomic Diagnosis.=—Acute lobar pneumonia with red and beginning
gray hepatization of lower and parts of upper and middle right
lobes; acute bronchopneumonia with lobular consolidation in left
lung; purulent bronchitis; bronchiectasis in left lung.

The lower lobe of the right lung with the exception of the anterior
and basal edge is firmly consolidated; the posterior part of the
middle lobe and a small corner at the posterior and lower part of
the upper lobe is similarly consolidated. The consolidated tissue is
gray and coarsely granular on section. The remainder of the lung is
dry and voluminous, and the bronchi contain purulent fluid. The left
lung contains red and gray patches of consolidation, from 0.2 to 3
cm. across. Bronchi contain purulent fluid and in the lowermost
parts of both upper and lower lobes are moderately dilated.

Bacteriologic examination shows that the blood of the heart contains
Pneumococcus III.

It is noteworthy that there was in this case, as in many instances of
influenza, both lobar and bronchopneumonia. Purulent bronchitis was
present and there was bronchiectasis throughout one lung.

In the following case the diagnosis of mumps may be questioned since the
lesion of the parotid has characters of terminal suppurative parotitis.

=Autopsy 417.=—H.W.D., white, aged twenty-four, a farmer, resident
of Oklahoma, had been in military service one month. He said that he
had had pneumonia four times. He was admitted to the hospital
delirious and the diagnosis of lobar pneumonia was made. Parotitis
regarded as mumps appeared five days before death and suppuration
occurred on the right side of the face. Death of the patient
occurred thirteen days after admission to the hospital.

=Anatomic Diagnosis.=—Acute bronchopneumonia with lobular
consolidation in both lungs; suppurative pneumonia with necrosis and
beginning abscess formation in left lung; purulent pleurisy in left
side; purulent bronchitis; bronchiectasis; acute parotitis.

The left pleural cavity contains 100 c.c. of purulent fluid of
creamy consistence. The left lung is voluminous and bound to the
chest wall in places. There are numerous patches of lobular
consolidation. At the apex of the lung there is a large area of
consolidation, 7 cm. across, where the tissue is cloudy gray and
soft in consistence. In the upper lobe is a well-defined patch of
grayish yellow color, 6 by 2 cm., with opaque yellow edges; purulent
fluid escapes from the cut surface. Bronchi throughout the lung are
widely dilated and contain purulent fluid. The right lung is
voluminous and contains lobular patches of consolidation; bronchi of
this lung are widely dilated.

Bacteriologic examination shows the presence of hemolytic
streptococci in the blood of the heart; hemolytic streptococci and
B. influenzæ in the lung, and hemolytic streptococci, B. influenzæ
and S. aureus in a main bronchus.

In association with bronchopneumonia there have been necrosis and
beginning abscess formation with empyema, the suppurative lesions being
caused by hemolytic streptococci which had finally entered the blood
stream. There was purulent bronchitis, and the lungs had the voluminous
character often associated with this lesion; there was beginning
bronchiectasis. B. influenzæ was obtained both from the lung and from
the bronchus.

In 2 instances (Autopsies 323 and 335) the diagnosis of scarlet fever
was made in patients suffering with pneumonia following influenza. These
lesions have been included in the list of influenzal pneumonias. In the
following instance the patient was admitted with scarlet fever, later
developed acute follicular tonsillitis, and finally suppurative
pneumonia caused by hemolytic streptococcus.

=Autopsy 311.=—E. J., white, aged twenty-two, a tinsmith and
automobile repairer, resident of Arkansas, had been in military
service three months. Onset of illness was on September 18 with
headache and sore throat. The patient was admitted September 24 with
the diagnosis of scarlet fever; two days later there was acute
follicular tonsillitis. Pneumonic consolidation on the right side
was recognized October 2, three days before death.

=Anatomic Diagnosis.=—Acute suppurative pneumonia with three small
abscesses below pleura of right lower lobe; acute fibrinopurulent
pleurisy on both sides; serous pericarditis.

The right pleural cavity contains 1500 c.c. of turbid, dirty yellow
fluid containing masses of fibrin; the left cavity has 500 c.c. of
similar contents. The pericardium contains 30 c.c. of turbid fluid
containing a small quantity of fibrin; there are ecchymoses below
the epicardium. The right lung is collapsed and in the lower lobe
contains three small subpleural abscesses, the largest of which is
1.5 cm. across.

Bacteriologic examination shows the presence of hemolytic
streptococci in pure culture in the blood of the heart and in the
right lung. From the right main bronchus are obtained hemolytic
streptococci, B. influenzæ, Pneumococcus IV and a few staphylococci.

In this instance there has been infection with streptococcus which is a
common sequela of scarlet fever. In the absence of evidence of
bronchopneumonia there has been abscess formation below the pleura with
empyema and pericarditis. B. influenzæ has been found in the bronchus.

The pneumonias found in association with measles reproduce the
characters of the pneumonias described in association with influenza.
Particularly noteworthy is the occurrence of lobar pneumonia,
hemorrhagic peribronchiolar pneumonia, interstitial suppurative
pneumonia, severe bronchitis with bronchiectasis and unresolved
bronchopneumonia. In the presence of an epidemic of influenza attacking
more than one fourth of the population of a camp, those suffering with
diseases, such as measles, typhoid fever, mumps, etc., are unlikely to
escape entirely, and it is probable that the tendency to the occurrence
of pneumonia present in association with these diseases will be
increased. The close resemblance between the pneumonias which we have
found with the diseases mentioned, on the one hand, and the pneumonias
of influenza on the other, both being characterized by the occurrence of
hemorrhagic, suppurative and chronic pulmonary lesions, indicates that
influenza has had a part in the production of the pneumonia found with
measles and some other infectious diseases during the progress of the
epidemic of influenza.

CHAPTER VII
SUMMARY OF THE INVESTIGATION AND CONCLUSIONS REACHED

EUGENE L. OPIE, M.D.

There is no reason for believing that the influenza which prevailed in
this country differed in any essential feature from that of previous
epidemics and particularly of the pandemic of 1889–90. Our studies have
shown that an organism with the morphologic and cultural characters of
B. influenzæ of Pfeiffer has been constantly found in association with
the disease, and so frequently demonstrated in association with its
pulmonary complications that there is little doubt of its constant
presence. The bronchial and pulmonary complications of influenza present
characters which, while varied, are not usually observed in the absence
of epidemic influenza, and in this pandemic agree with those of the
former pandemic so far as it is possible to determine from the
descriptions available.

Especially noteworthy is the severity of the changes within the
bronchial passages. Clinical studies have shown that purulent bronchitis
has occurred in 36 per cent of instances of influenza. The sputum with
this condition has contained B. influenzæ in all instances, but although
there were no signs of pneumonia it has been constantly associated with
other microorganisms, namely, pneumococci (in 11 of 13 instances), S.
hemolyticus, S. viridans, M. catarrhalis, etc.

Identification of the bacteria which have been present in the bronchi of
those dead with pneumonia following influenza have determined what
microorganisms have penetrated into the lower respiratory passages. B.
influenzæ has been found so frequently (80 per cent) that there is good
reason to believe that it has been constantly present and has not been
isolated in every instance because it has been overgrown by other
microorganisms on the plates or after long continued illness has
disappeared from the bronchi. Mixed infections of B. influenzæ and other
microorganisms are constantly found in the inflamed bronchi;
combinations of B. influenzæ and pneumococci, B. influenzæ and hemolytic
streptococci or these combinations with staphylococci or the four
organisms together are common. Other microorganisms such as B. coli, S.
viridans, M. catarrhalis and diphtheroid bacilli are not infrequently
associated with those which have been mentioned.

Purulent bronchitis has been found in 137 of 241 autopsies; its
bacteriology differs in no respect from that which has just been
described and indeed no line can be drawn between this condition and the
bronchitis invariably present with the pneumonias of influenza. Other
evidence of profound injury to the bronchi is the frequent occurrence of
hemorrhage in a zone ensheathing the smaller bronchi, and the common
occurrence of bronchiectasis when the fatal disease has lasted more than
two or three weeks.

Microscopic study demonstrates that the changes in the bronchial walls
are such as destroy the defences against invasion by microorganisms. The
bronchial epithelium undergoes destruction which is not infrequently
limited to the superficial ciliated cells, but often complete loss of
epithelium occurs. The mucous glands of the larger bronchi exhibit a
special susceptibility to injury, and in the early stages of the lesion
profound degenerative changes are found in the secreting cells, whereas
at a later stage chronic inflammatory changes are almost invariably
present.

Pneumonia following influenza is in most instances bronchopneumonia, but
typical lobar pneumonia has been found in autopsies representing 40.7
per cent of pneumonias of influenza. Lobar pneumonia is frequently
accompanied by purulent bronchitis, and in a considerable number of
autopsies (34 of 98 with lobar pneumonia) lobar and bronchopneumonia
have occurred in the same individual.

Statistics based upon the clinical diagnosis of lobar and
bronchopneumonia following influenza are so inaccurate that they have
little if any value. Notwithstanding careful study of the symptomatology
of the disease, lobar and bronchopneumonia following influenza are not
accurately distinguishable by the means usually employed, and an
erroneous diagnosis has been recorded on the patient’s history in 36.6
per cent of 227 fatal cases with autopsy. A diagnosis of suppurative
pneumonia is rarely if ever made. The difficulties of diagnosis are in
part explained by the frequent association of lobar pneumonia with
purulent bronchitis, with bronchopneumonia or with both, and by the
occurrence of bronchopneumonia with confluent lobular consolidation
involving a large part of a lobe or whole lobes.

There are many defects in the present knowledge of the symptomatology of
the pneumonias under consideration. The symptoms of suppurative
pneumonia are not clearly defined. Many of these deficiencies might be
supplied by further application of the time-honored method of comparing
the clinical course of the disease with the changes found at autopsies,
supplemented by bacteriologic studies made during life and confirmed
after death.

With peribronchial pneumonia bronchi of medium size, on the cut surface
of the lung, are surrounded by sharply defined zones of pneumonic
consolidation perhaps 0.5 cm. in radius, and this lesion furnishes
conclusive proof that the inflammatory process can extend directly
through the bronchial wall reaching all alveoli within a limited
distance for these alveoli bear no relation to the distribution of the
terminal bronchi of the affected bronchus. This peribronchial pneumonia
is usually characterized by fibrinous exudate, and pneumococcus has been
found either in the blood of the heart or in the lung in all of 6
instances in which peribronchial consolidation has been recognized at
autopsy; in half of these autopsies Pneumococcus Type II has been
isolated and this relationship is especially noteworthy because Type II
has been uncommonly associated with the pneumonias of influenza.

=Lobar Pneumonia.=—The distribution of lobar pneumonia has repeatedly
furnished evidence that the process spreads like the peribronchial
lesion directly through the tissue of the lung and is not necessarily
disseminated by way of the bronchial tree. Pneumococci doubtless enter
the lung by way of the bronchi; the occurrence of lobar pneumonia in
frequent association with influenza which exhibits a peculiar capacity
to destroy the defences of the lower respiratory passages is in harmony
with this view. The presence of pneumococci in the blood furnishes no
evidence that infection is hematogenous, for bacterial infections,
particularly at their onset, are frequently accompanied by bacteriemia.
The wave-like spread of lobar pneumonia may be indicated by a narrow
zone of red hepatization separating a large patch of firm, gray
consolidation from engorged but air containing lung tissue. A
semicircular patch of consolidation not infrequently extends from the
left lower lobe into the upper lobe at the site where the interlobular
cleft is absent. This patch may be firm and gray in continuity with
similar consolidation in the lower lobe but surrounded over its convex
surface by a zone of red hepatization.

There is no reason to doubt that the lobar pneumonia which we have found
with influenza has been constantly caused by pneumococci. We have
encountered no instance of lobar pneumonia caused by the capsulated
bacillus of Friedländer. The incidence of different types of pneumococci
in the lung with lobar pneumonia has been as follows: Type IV, 32.4 per
cent; Type II, atypical, 26.5 per cent; Type III, 17.6 per cent; Type
II, 5.9 per cent; Type I, 2.9 per cent; no pneumococci found 14.7 per
cent. It is noteworthy that this distribution of types is in sharp
contrast with the lobar pneumonia of civil life with which Types I and
II constitute the cause of two-thirds of all instances, and is in
agreement with the etiology of the pneumonias found in an army camp
(Funston) in the absence of influenza in epidemic proportion.

=Bronchopneumonia.=—Bronchopneumonia is associated with intense
bronchitis penetrating to the finest bronchioles and is characterized by
consolidation distributed in such definite relation to the bronchial
tree that dissemination of the inflammatory irritant by way of the
bronchi is evident. Consolidation occurs (_a_) in foci affecting alveoli
in immediate proximity to the respiratory bronchioles and in consequence
clustered about the terminal bronchi, the intervening alveolar tissue
containing air; (_b_) in foci of the same character surrounded by
intraalveolar hemorrhage which occupies all alveolar tissue between
adjacent foci; (_c_) throughout whole lobules or groups of lobules,
intervening lobules being unaffected; (_d_) surrounding bronchi of
medium size like a sheath.

The lobar pneumonia of influenza is characterized by frequent
association with purulent bronchitis and bronchopneumonia. The
bronchopneumonia of influenza exhibits characters which serve to
distinguish it from other forms of bronchopneumonia; (_a_) The
associated lesions of the bronchi are unusually severe; purulent exudate
accumulates within the lumen and the lining membrane is destroyed. (_b_)
Pneumonia is frequently hemorrhagic with accumulation of blood within
the alveoli and within and surrounding the bronchi. (_c_) There is
unusual susceptibility of the injured bronchi and of the pulmonary
tissue to secondary invasion by streptococci and staphylococci with
consequent necrosis and suppuration. (_d_) Bronchiectasis frequently
accompanies bronchitis. (_e_) Bronchopneumonia frequently fails to
resolve and the lesion assumes the character of a chronic pneumonia.

With bronchopneumonia pneumococci are found with B. influenzæ in the
bronchi and lungs in nearly half and in the blood in approximately
one-third of instances of the disease, but hemolytic streptococci,
staphylococci, S. viridans, B. coli, M. catarrhalis and other
microorganisms are very frequently found in various combinations: they
undoubtedly have a part in the production of the lesion. Mixed infection
of the lung and even of the blood with pneumococci and hemolytic
streptococci is often found, and study of the sputum during life has
repeatedly shown that pneumococci alone are present shortly after the
onset of the disease, whereas hemolytic streptococci appear later or are
first discovered at autopsy. In such instances pneumococci have not
infrequently disappeared from the lung and at autopsy hemolytic
streptococci alone are demonstrable.

The part which B. influenzæ has in the production of bronchopneumonia is
of great interest. This microorganism is demonstrable by cultures in at
least three-fourths of all instances of bronchopneumonia but is obtained
from the inflamed lung tissue in less than half. In no instance of
pneumonia have we found B. influenzæ unassociated with other
microorganisms, whereas repeatedly pneumococci have been the only
microorganism demonstrable in the lung and very frequently the only
organism present in the blood. In view of the difficulty of
demonstrating the microorganism in plates overgrown by other bacteria,
it is probable that its incidence in the bronchi is much higher, if it
is not constantly present, whereas its isolation from the lung is in
part referable to its presence in the small bronchi where it can be
readily demonstrated by cultures or by microscopic preparations. We have
been almost uniformly unsuccessful in demonstrating the microorganism in
the alveoli of the lung. Goodpasture and Burnett,[106] who have devised
a special method for the demonstration of B. influenzæ in tissues, have
found few of these microorganisms in the alveoli of the lungs.

Pneumonia characterized by the occurrence of small (peribronchiolar)
spots of leucocytic pneumonia upon an almost homogeneous background of
intraalveolar hemorrhage, was regarded by Pfeiffer as the characteristic
lesion produced by his microorganism. B. influenzæ in our autopsies has
borne the same relation to this lesion which it has exhibited to other
forms of bronchopneumonia; pneumococci have been present with
approximately the same frequency and hemolytic streptococci have often
been found.

=Streptococcus Pneumonia.=—The occurrence of streptococcus pneumonia
with suppuration occurring in the trail of influenza was frequently
observed during the pandemic of 1889–90. It is now well recognized that
the streptococcus concerned is one capable of causing hemolysis.
Suppurative pneumonia referable to hemolytic streptococci is of two
types which are readily separable by their anatomic characters: (_a_)
One or several abscesses are situated below the pleura and accompanied
by empyema. Their relation to severe lesions of the bronchi is not
infrequently demonstrable, for a destructive lesion of the bronchial
wall has penetrated into the surrounding alveolar tissue so that
necrosis of tissue and subsequent abscess formation occur in continuity
with the bronchial lumen. The localization of the abscess below the
pleura is referable to the greater severity of the lesions of the small
bronchi which are most numerous at the periphery, to the greater
severity of these bronchial lesions at the bases of the lung, and to the
relation of lymphatics within the interior of the lung to those of the
pleura. It is not improbable that stasis of lymph caused by thrombosis
of the lymphatics has a part in the production of abscess. Preceding or
accompanying abscess formation, the lung tissue undergoes consolidation
and in a wide area about the abscess has a homogeneous gray cloudy
appearance occasionally mottled by opaque patches of necrosis. (_b_)
Interstitial suppurative pneumonia is a lesion not infrequently found in
association with influenza (21 times among 241 autopsies) and rarely, if
ever, seen in its absence. There are few references to this lesion in
the pathologic literature of the English language and those of German
origin in great part refer to the period of the pandemic of 1889–90. The
lesion is essentially suppurative lymphangitis, and both thrombosis and
suppuration of the lymphatics are widespread throughout the affected
lung. In proximity to the inflamed lymphatics and the surrounding
interstitial septa, lung tissue throughout parts of the lobes or even
throughout a whole (lower) lobe has undergone consolidation and has the
gray, cloudy appearance of streptococcus pneumonia.

=Staphylococcus Pneumonia.=—Abscesses produced by staphylococci differ
in anatomic characters and sequelæ from those caused by hemolytic
streptococci. Small abscesses occur in one or several localized
clusters; these abscesses are grouped about a bronchus and have their
origin in its terminal branches. This relation may be readily
demonstrated in microscopic sections. The lesion tends to remain
localized and pneumonic consolidation is limited to the immediate
neighborhood of the group of abscesses. There is no lymphangitis and the
lesion is not accompanied by empyema.

=Empyema.=—Empyema is almost invariably associated with suppurative
pneumonia caused by hemolytic streptococci. Among our autopsies purulent
fluid has been found in the pleural cavity 55 times; it occurred 15
times among 178 instances of lobar or bronchopneumonia and 50 times
among 60 instances of suppurative pneumonia referable to S. hemolyticus.
In our experience hemolytic streptococci and pneumococci are the only
microorganisms which exhibit a noteworthy capacity to penetrate from the
lung to the pleural cavity. We have not found nonhemolytic streptococci
(_e. g._, S. viridans) in association with empyema.

Staphylococcus has failed to invade the pleural cavity even when a
pulmonary abscess has been present below the pleura, and in the only
instances in which staphylococci have been isolated from the pleural
cavity thoracotomy had been performed for empyema caused by hemolytic
streptococci (2 instances) or an abscess communicating with both
bronchus and pleura. B. influenzæ has been found in the pleural cavity
with empyema only once and in this instance cannot be regarded as the
cause of the lesion, for it has accompanied hemolytic streptococci.

=Bronchiectasis.=—Bronchiectasis has been frequently found as a sequela
of the severe bronchitis of influenza and there has been abundant
opportunity to study the lesion in process of development. These
observations have furnished a satisfactory explanation of its etiology
and pathogenesis. Infection of the bronchi by B. influenzæ, accompanied
by a variety of other microorganisms, notably hemolytic streptococci and
staphylococci, has caused profound changes in the bronchial wall
beginning with destruction of the epithelial surface, and followed by
necrosis penetrating partially or completely through the wall and
occasionally extending into the surrounding alveolar tissue. The
difference between the atmospheric pressure within the bronchi and the
lower inspiratory pressure within the surrounding alveoli, accentuated
by forced inspiration at intervals and by occlusion of the bronchioles
with mucopurulent exudate, ruptures the necrotic tissue and produces
longitudinal fissures which are recognizable both macroscopically and
microscopically. In consequence of the separation of the edges of these
fissures by intrabronchial pressure the circumference is increased.
These rents in the wall are limited and partially healed by fibrinous
pneumonia about them, by new formation of fibrous tissue from the
bronchial wall, and adjacent interalveolar septa, by organization of
fibrin within adjacent alveoli and finally by growth of epithelium over
the denuded surfaces.

Bronchitis caused by B. influenzæ and pyogenic micrococci with necrosis
of the bronchi wall is the essential factor in the production of
bronchiectasis, but advanced bronchiectasis is found only in those
individuals who have survived the onset of illness during several weeks,
for dilatation under the influence of positive intrabronchial and
negative extra-bronchial pressure occurs slowly.

=Unresolved Bronchopneumonia.=—Unresolved lobar pneumonia has not been
recognized among instances of pneumonia following influenza, but
unresolved bronchopneumonia is of frequent occurrence and has well
definable gross and microscopic characters. There are purulent
bronchitis, bronchiectasis and distention of the lung tissue, so that it
fails to collapse; particularly characteristic are the indurated foci of
peribronchiolar pneumonia, which being firm and sharply defined, have
the appearance of miliary tubercles. When the process is sufficiently
long continued there are recognizable patches of fibroid pneumonia.
Microscopic examination shows that the lesion is characterized by
organization of fibrinous exudate not only within the alveoli but within
bronchioles as well, and by thickening of the alveolar walls, thickening
of fibrous tissue about the bronchi and blood vessels, and thickening of
interstitial septa. These changes may occur as peribronchiolar patches
of consolidation, producing tubercle-like nodules, or may involve areas
of hemorrhagic peribronchiolar or of lobular consolidation, or may be
limited to the immediate neighborhood of bronchi (peribronchial).

No peculiarity of the bacterial flora of the bronchi or of the lung
offers a satisfactory explanation of the failure of pneumonic exudate to
resolve. Mixed infections have been common and S. hemolyticus,
staphylococci, pneumococci, S. viridans, B. coli, etc., have been found
in association with B. influenzæ but the incidence of these
microorganisms has not been greater than with bronchitis. The lesion has
occurred in association with B. influenzæ and pneumococci unassociated
with other microorganisms. It seems probable that the severity of injury
to the bronchial and alveolar walls accompanied by recurring bacterial
invasion or by continued infection with B. influenzæ and one or several
cocci, is the factor concerned in the inhibition of resolution and the
production of chronic pneumonia. If the disease does not result in early
death, chronic pneumonia has an opportunity to manifest itself.

In this investigation of the bacteriology and pathology of influenza and
its complications, certain microorganisms have been found so frequently
that it is desirable to discuss the pathogenicity of each and to define
the character of the lesions which it causes.

=Bacillus Influenzæ.=—The microorganism has been constantly found in
association with influenza when cultures and animal inoculations have
been made from various parts of the respiratory tract within from one to
five days after the onset of the disease at a time when there have been
acute symptoms of the disease.

It is often identified with difficulty in the presence of other
microorganisms and may be overlooked when a single culture is made.
Repeated cultures from the throat alone made from the fourth to the
eighth day after admission to the hospital, at a time when temperature
had fallen to normal, have demonstrated the presence of B. influenzæ in
30.5 per cent, whereas the incidence of the microorganism in similar
cultures on admission had been 63.4 per cent. The incidence of B.
influenzæ in the present epidemic of influenza is not less than that
found by Pfeiffer in the epidemic which he studied in 1892.

Nevertheless we have found that B. influenzæ is frequently an inhabitant
of the mouth and throat of normal individuals. By inoculation of mice
with the saliva or sputum of 76 patients with influenza, the
microorganism has been found in 80.3 per cent; by inoculation of mice
with the saliva of 185 normal men at army cantonments, it was found in
41.6 per cent; by inoculation of mice with saliva from 50 recruits
immediately after they were assembled from isolated farming communities
where only a few cases of influenza had occurred, it was found in 22 per
cent. Figures for the same groups examined by a single throat culture
were as follows: 65.7 per cent, 25.9 per cent and 0 per cent.

Experiments which we have performed on monkeys show that inoculation of
the nasopharynx with B. influenzæ obtained from patients with influenza
is followed by ill-defined symptoms associated with the presence of B.
influenzæ within the throat. After from two to eleven days the symptoms
and the microorganism disappear. Injection of B. influenzæ into the
trachea causes bronchitis and the microorganism may be recovered from
the inflamed bronchi two or three days after inoculation.

The constant association of B. influenzæ with influenza suggests that it
is the cause of the disease. Its widespread occurrence in the throats of
normal individuals does not contradict this view, since pneumococci long
indistinguishable from those which usually cause lobar pneumonia are
commonly found in the throats of healthy men. It is possible that B.
influenzæ is a secondary invader, entering the respiratory tract when
susceptibility is increased by an unknown virus causing influenza; but
there is no convincing evidence in favor of this view. It is desirable
to determine if microorganisms having the characters of B. influenzæ
found with influenza differ in type from those found in the throats of
healthy men and if the invasion of the respiratory tract by B. influenzæ
is followed by the appearance of immunity reactions in the serum of the
patient. Experiments on monkeys demonstrate the pathogenicity of the
microorganism.

The relation of B. influenzæ to the bronchitis of influenza indicates
that it has a part in the production of the pulmonary sequelæ of
influenza. The microorganism has been found by a single culture from the
bronchial passages in 80 per cent of instances of bronchitis with fatal
pneumonia following influenza and is probably constantly present,
usually in immense number, in the bronchial mucus. It is obtained from
the pneumonic lung in only about 40 per cent of instances, and
microscopic examination of prepared tissue shows that a bacillus with
the morphology of B. influenzæ is often demonstrable in the bronchial
passages but seldom in the alveoli of the lung. The microorganism is
well adapted to multiply under conditions present in the bronchi but
doubtless readily disappears from the alveoli which are the site of an
inflammatory reaction. The microorganism has an important part in the
production of the associated mucopurulent and hemorrhagic inflammation
of the bronchi, but it is rarely if ever found in pure culture, being
associated with a considerable variety of pyogenic cocci and
occasionally bacilli. Infection of the bronchi with B. influenzæ in
immense numbers offers an explanation of the severity of the
inflammatory process within the bronchi, and of the subsequent
dilatation and other chronic changes which occur in them. The presence
of the microorganism and the accompanying injury to the ciliated
epithelium and mucous glands are important factors in lowering the
resistance of the bronchial passages to secondary bacterial infection.

We have obtained no evidence that B. influenzæ alone is capable of
causing pneumonia. Its occurrence in less than half of all pneumonic
lungs is explainable, in part at least, by its presence in the terminal
bronchi which are cut across whenever the lung is punctured for culture.
B. influenzæ alone has been found only once among 153 pneumonic lungs
from which cultures were made, and in this instance (Autopsy 487) S.
hemolyticus present in the blood of the heart, pleural cavity and
bronchus doubtless had a part in the production of the associated
pneumonia. Pfeiffer maintained that the lesion we have designated
hemorrhagic peribronchiolar consolidation was characteristic of
infection with his microorganisms. With this lesion B. influenzæ has
been found in the lungs in slightly more than half of our autopsies but
never alone, pneumococci being found in a third, hemolytic streptococci
in more than a half and staphylococci in a fourth of the lungs examined.

B. influenzæ has relatively little capacity to penetrate from the
bronchi into the lung tissue and rarely penetrates into the pleural
cavity (once with Pneumococcus III, once with S. hemolyticus and once in
pure culture), and only once has it been found in the blood of the
heart, in this instance in company with S. hemolyticus. Capacity of the
microorganism to penetrate from the bronchi into other tissues, both in
man and as our experiments have shown in the monkey, is increased by
association with pyogenic cocci.

=Pneumococcus.=—Lobar pneumonia following influenza, like lobar
pneumonia in civil life unassociated with influenza, has been caused by
pneumococci, but there is the notable difference that the pneumococci
usually found are those types which are commonly present in the mouths
of healthy men, namely, Types IV, III and atypical II and not the
so-called fixed types, namely, Types I and II, which represent the usual
cause of lobar pneumonia unassociated with influenza. It appears that
influenza increases susceptibility to lobar pneumonia, so that it is
frequently caused by microorganisms which under other conditions are
less capable of producing this lesion. The association of the
pneumococci usually found in the mouth with the lobar pneumonia of
influenza does not exclude the possibility that pneumococci transmitted
from one individual to another, when newly recruited troops are brought
together, have an important part in the production of pneumonia.

Bronchopneumonia is frequently caused by pneumococci and the types which
are recovered from the lung and blood do not differ from those found
with lobar pneumonia, those usually present in the mouth being
predominant, but the incidence of pneumococci with bronchopneumonia has
been much less than with lobar pneumonia. Both lobar and
bronchopneumonia caused by pneumococci have undergone secondary
infection with hemolytic streptococci in a large proportion of instances
and both pneumococci and streptococci are often recovered at autopsy.
Nevertheless, the bacterial flora of the bronchi and lungs is much more
varied with broncho than with lobar pneumonia, and it is evident that
microorganisms other than pneumococci are capable of causing
bronchopneumonia.

In instances of bronchopneumonia associated with pneumococci, fibrin has
been abundant in the alveolar exudate.

The pneumococcus exhibits a notable tendency to produce an inflammatory
process which extends through the bronchial walls and from one alveolus
through the alveolar walls to those adjacent, for in 6 instances in
which the bronchi were surrounded by pneumonic consolidation
recognizable at autopsy, pneumococci were uniformly the causative agent,
Pneumococcus Type II, otherwise rarely found, being present in half of
these cases.

Pneumonia caused by one type of pneumococcus does not necessarily confer
immunity from other types of pneumococci, and with somewhat limited
opportunity we have observed a number of instances in which, following
recovery from pneumonia caused by one type of pneumococcus, a second
attack of pneumonia, usually fatal, has been associated with pneumococci
of a different type. This recurring pneumonia in a considerable
proportion of the relatively small number of instances observed has been
produced by Pneumococcus Type II which otherwise has been seldom found
among the cases which we have studied. The virulence of this
microorganism doubtless explains its ability to cause recurrent
pneumonia.

=Streptococcus Hemolyticus.=—Secondary infection with S. hemolyticus is
a common event during the course of lobar pneumonia following influenza.
It is noteworthy that this streptococcus infection of the lung has
almost invariably occurred in the stage of red hepatization, whereas
with gray hepatization, when the alveoli are filled with polynuclear
leucocytes, S. hemolyticus rarely invades the lung. It is possible that
infection with S. hemolyticus tends to prolong the stage of red
hepatization.

The most significant change produced in the pneumonic lung by
streptococci is necrosis. When after death with lobar pneumonia
hemolytic streptococci, usually associated with pneumococci, are found
both in the lungs and blood of the heart, the lung contains patches of
necrosis recognized microscopically, in which the alveolar walls and
exuded cells have uniformly lost their nuclei. Microscopic examination
demonstrates the presence of chains of streptococci in immense number in
these necrotic foci; elsewhere chains of streptococci occur but are much
less abundant. In some instances streptococci exhibit a tendency to
enter lymphatics and to cause acute lymphangitis with lymphatic
thrombosis and edema of the adjacent interstitial tissue.

Hemolytic streptococci have been more frequently found in association
with broncho- than with lobar pneumonia. In 24.5 per cent of instances
of lobar pneumonia, doubtless in all instances caused by pneumococci,
hemolytic streptococci have invaded the lungs and in 12.6 per cent of
instances have found their way into the blood. With bronchopneumonia
hemolytic streptococci have been obtained from the lungs in 29.8 per
cent of instances and from the blood of the heart in 34.3 per cent.

With lobar pneumonia there is little doubt that pneumococcus has been
the primary cause of pneumonia, but with bronchopneumonia pneumococci
have been less frequently found. It is difficult to determine how often
hemolytic streptococci have invaded a bronchopneumonic lesion, caused by
pneumococci because pneumococci tend to disappear. In numerous instances
in which the sputum had been studied during life, it was evident that
pneumonia was primarily referable to pneumococci, and hemolytic
streptococci made their appearance in the sputum late in the disease or
were first recognized at autopsy.

When hemolytic streptococci occur in association with bronchopneumonia,
foci of pulmonary necrosis similar to those found under the same
conditions with lobar pneumonia have been repeatedly found by
microscopic examination. In the patches of necrosis, cocci in chains are
much more abundant than in the tissue elsewhere.

In some instances of pneumonia, caused by hemolytic streptococci, opaque
gray or yellowish gray patches of necrosis occur upon a background of
flaccid homogeneous consolidation which has a peculiar cloudy, gray
color. This mottled consolidation may implicate an entire lower lobe and
has the characteristic features neither of lobar nor of
bronchopneumonia. More frequently the lesion is less widespread and
necrosis occurs in one or several spots which undergo softening so that
finally a small abscess cavity may be formed; it is surrounded by
pneumonic consolidation which is soft and has the cloudy appearance
described above. These pulmonary abscesses are almost invariably
situated below the pleural surface; the adjacent pleural cavity is
infected by streptococci and there is purulent inflammation of the
pleura.

Streptococcus infection, which has been described, doubtless has its
origin in the bronchi, for in favorable sections it is not infrequently
possible to demonstrate that necrosis extends through the bronchial
walls into the surrounding alveolar tissue and is followed by
suppuration with abscess formation. Localization of abscesses below the
pleura is in part at least referable to transmission of streptococci by
way of the lymphatics.

Streptococci in the lung, as in other tissues, often invade lymphatics
and produce an acute inflammatory reaction within and about these
vessels. The peculiar lesion which may be designated suppurative
interstitial pneumonia is a suppurative lymphangitis associated with
inflammation and edema of the interstitial tissue. Lymphatics invaded by
streptococci are the site of acute lymphangitis; occlusion by fibrinous
thrombi occurs and finally the immensely distended lymphatics, filled
with purulent fluid, take a characteristic nodular or beaded form and
pus flows from them when they are cut. Streptococci are present in vast
numbers. Suppurative inflammation may extend to the surrounding
interstitial tissue which is distended by inflammatory edema. This
interstitial suppurative pneumonia extends up to the pleural surface and
empyema is almost invariably associated with it. The lesion is seldom
seen in the absence of influenza.

One of the most significant characters of S. hemolyticus is its ability
not only to enter the bronchi and penetrate into the tissue of the lung,
but to find its way into more distant structures, namely, the pleural
cavity, pericardial sac and peritoneal cavity and to penetrate into the
blood. Among 121 examinations, hemolytic streptococci were found in the
bronchi in 47.9 per cent; among 153 examinations of the lung it was
present in approximately the same proportion, namely, 50.3 per cent;
among 218 examinations of the blood it was found in 39 per cent. In 4 of
5 fatal pneumonias in which the organism has penetrated into the bronchi
it has ultimately found its way into the blood.

=Nonhemolytic Streptococci.=—In contrast with S. hemolyticus
nonhemolytic types have rarely been encountered in association with the
pneumonias of influenza. S. viridans has been found only 5 times among
153 autopsies in which cultures have been made from the lung and has
been invariably associated with other microorganisms. In no instances
have nonhemolytic streptococci been found with empyema. In one autopsy
with lobular bronchopneumonia S. viridans has been isolated from the
blood of the heart and in this instance it has been found in the
bronchus and lung as well. This type of streptococcus is evidently
little adapted to invade the bronchi and produce lesions of the lung and
adjacent tissues.

=Staphylococci.=—Staphylococci have been very frequently isolated from
the bronchi in association with the pneumonias of influenza, being found
in approximately half of our autopsies. Their isolation in cultures from
the lung in a fourth of the autopsies examined is in part perhaps
referable to their presence in the small bronchi cut across when the
lung is punctured for cultures. S. aureus shows little ability to invade
the pleura, being found in association with empyema only 3 times; in
these autopsies there has been opportunity for entrance from the
exterior through thoracotomy wounds in 2 instances and from a bronchus
in free communication with an abscess which had ruptured into the
pleural cavity in 1 instance.

Abscesses of the lung caused by staphylococci have been found in a small
number of autopsies and have exhibited characters which differ from
those ordinarily seen in association with S. hemolyticus. Small, sharply
defined abscesses are grouped about terminal bronchi, so that they occur
in one or several isolated clusters. Microscopic examination
demonstrates that these abscesses have arisen by destruction of the
bronchial walls and extension of suppuration into the surrounding
alveolar tissue; clumps of staphylococci are found in sections through
the abscess, and cultures made from the pus within the abscess cavity
demonstrate the presence of S. aureus or albus, but the microorganism
may be missed if the culture is made from the adjacent lung tissue. It
is noteworthy that there is little tendency for the staphylococcus to
infect the pleura for even though these clusters of abscesses have been
situated just below the pleura, there has been no associated empyema.

Staphylococci have scant tendency to enter the blood and have been
obtained from the blood of the heart only once, in this instance with
hemolytic streptococci.

=Pneumonia of Measles.=—Pneumonia following measles has been responsible
for a considerable part of the deaths occurring in the United States
Army during the period of the war. The importance of measles as a factor
in the production of pneumonia is illustrated by the history of
pneumonia at Camp Funston from the establishment of the camp in
September, 1917, until September, 1918. Pneumonia following measles
occurred throughout the year; but in association with the high incidence
of measles during the second half of November and the first half of
December, 1917, there was an outbreak of related pneumonia characterized
by frequent empyema and a mortality of 45.3 per cent.

During the period of our investigation at Camp Funston there were 112
cases of measles, but no pneumonia occurred among them. At Camp Pike,
during the period of observation, there was an outbreak of measles
almost coincident with the epidemic of influenza, and among 867 cases
pneumonia occurred in 56, otitis media in 48, and mastoiditis in 23.
Pneumonia following measles was almost coincident with that of
influenza, and it is not improbable that the epidemic of influenza had
an important part in the production of pneumonia in individuals
suffering with measles.

In 9 of 56 instances of pneumonia following measles at Camp Pike, S.
hemolyticus had invaded the lung and caused pneumonia; among 48
instances of otitis media following measles a very large proportion were
caused by hemolytic streptococci, and 21 of 23 instances of mastoiditis
were caused by the same microorganism. No complication caused by S.
hemolyticus occurred among 37 patients who carried this microorganism
when admitted to the hospital.

A special study has been made to determine if those patients with
measles who carry S. hemolyticus in their throats are especially
susceptible to complications during the course of measles. The low
incidence of streptococcus “carriers” among those admitted to the
hospitals with measles was noteworthy both at Camp Funston (2.67 per
cent) and at Camp Pike (4.2 per cent). Indeed, it was found at both
places that the incidence of hemolytic streptococci in the throats of
normal men in the camp was higher (Camp Funston 21.9 per cent; Camp Pike
7.4 per cent) than that in the throats of those admitted with measles.
While in the hospital there was a gradual increase of the incidence of
S. hemolyticus, so that in three weeks it had risen to 19 per cent at
Camp Funston and to 26.2 per cent at Camp Pike. It seems not improbable
that hemolytic streptococci disappear from the throat in the early
stages of measles, so that they are not demonstrable by cultural
methods. During the course of the disease in the hospital ward the
number of those with S. hemolyticus has increased in some wards with
great rapidity, infection being apparently transmitted from one
individual to those adjacent. At Camp Funston the incidence of S.
hemolyticus in the throats of those convalescent with measles was almost
identical with that among normal men in organizations from which the
patients had come, but at Camp Funston the percentage of hemolytic
“carriers” among convalescents was much higher than that obtained among
normal men in the camp.

The demonstration of S. hemolyticus in the throat of a patient suffering
with pneumonia is not conclusive proof that the lungs have been invaded
by this microorganism. Pneumonia in individuals carrying S. hemolyticus
in the throat may pursue a favorable course and exhibit no evidence that
the microorganism has found its way into the lung. In some instances
hemolytic streptococci have been found in the bronchi at autopsy yet
none have entered the lung or blood and the lung exhibits none of the
lesions which are referable to hemolytic streptococci. Nevertheless, the
occurrence of S. hemolyticus in cultures from the throat of a patient
with pneumonia suggests the probability that he is suffering with
streptococcus pneumonia.

Pneumonia following measles studied in 18 autopsies upon patients who
died during or shortly after the epidemic of influenza, exhibited all
the characters exhibited by the pneumonias of influenza. In 4 instances
there was typical lobar pneumonia; bronchopneumonia was found in all but
3 instances, being associated with lobar pneumonia twice. All the
noteworthy features of the bronchopneumonia of influenza have been
reproduced among these instances of pneumonia with measles; there is
severe injury to the bronchi, and purulent bronchitis has been present
in 13 instances; pneumonia has frequently had a hemorrhagic character,
hemorrhagic peribronchiolar pneumonia occurring in 5 instances;
secondary infection of the pneumonic lungs with hemolytic streptococci
has been common; bronchiectasis has been associated with bronchitis (in
8 instances) when purulent bronchitis has persisted several weeks; and
unresolved bronchopneumonia has been more frequent (6 instances or
one-third of the autopsies) than with influenza.

The bacteriology of pneumonia following measles has been the same as
that of influenzal pneumonia. B. influenzæ is found with few exceptions
in the bronchi and much less frequently in the pneumonic lungs.

Pneumococci have been obtained from the blood or lungs in 5 of 13
instances of lobar or bronchopneumonia unaccompanied by suppuration;
when suppuration has been absent no hemolytic streptococci have been
found. Pneumococci concerned in the production of pneumonia of measles,
as with influenzal pneumonia, have been types usually found in the
mouth; Pneumococcus II atypical has been found 6 times, Type IV once,
Type I once.

Hemolytic streptococci have invaded the pneumonic lung in 5 instances.
They have produced subpleural abscesses accompanied by empyema in 2
instances. Interstitial suppurative pneumonia, a lesion repeatedly found
in consequence of secondary infection with S. hemolyticus following
influenza and rarely found in this country, at least in the absence of
an epidemic of influenza, has occurred 3 times among 18 instances of
pneumonia following measles.

The foregoing observations show that the pneumonia following measles,
which has occurred almost coincidentally with pneumonia accompanying
epidemic influenza has reproduced the lesions found with influenzal
pneumonia. They indicate that influenza attacking patients with measles
has had a part in the production of this pneumonia.

=The Transmission of Streptococcus Pneumonia.=—The importance of
streptococcus as a cause of pneumonia following influenza was recognized
during the pandemic of 1889–90. Patients suffering with pneumonia
following influenza or measles are susceptible to infection by S.
hemolyticus and this streptococcus pneumonia may be transmitted from one
patient to another throughout a ward in which patients with pneumonia
are assembled. There is no evidence that primary pneumonia caused by S.
hemolyticus has prevailed as an epidemic in the army or elsewhere in the
absence of preceding infection with influenza or measles.

Our autopsies demonstrate that at least half of all deaths which have
occurred at Camp Pike have been caused by hemolytic streptococci which
have invaded the lung and entered the blood. It is significant that this
mortality had its origin in the first half of the epidemic of influenza
at a time when the military and medical organization of the camp was
confronted with an unforeseen emergency which overwhelmed all agencies
for the care of disease. Curves prepared by referring cases of pneumonia
in which autopsy demonstrated the nature of the fatal infection back to
the date of the onset of influenza, demonstrate that fatal streptococcus
pneumonia was frequently acquired during the early period of the
epidemic, the maximum number of cases occurring September 23 and 24 and
became gradually less common as a sequela of the influenza which began
at a later period. Fatal pneumococcus pneumonia had its origin with
increasing frequency at a later period, the maximum incidence following
influenza which had its onset September 29 and 30. Overcrowding of
influenza patients in infirmaries, ambulances and hospital had an
important part in the dissemination of streptococcus pneumonia among
influenza patients whose disease might otherwise have pursued a benign
course.

The most important factor in the high incidence of streptococcus
pneumonia has been the spread of the disease in the hospital wards. On
September 24 the base hospital contained 2,789 patients, although it had
been planned to care for only 2,009. With the progress of the epidemic
the number of admissions increased very rapidly, so that on September 30
the hospital contained 3,587 patients and on October 5, 4,233. After
September 24 the milder cases of influenza were treated in barracks. The
pressing need of diminishing the overcrowding of the hospital was fully
recognized and adjacent barracks were transformed into hospital wards;
between October 3 and 6, 1,362 patients were transferred from the
hospital to these quarters.

In the main hospital, during the period of overcrowding 20 wards for
patients with pneumonia were added to the two which already existed.
These hastily organized and overcrowded wards have been attacked by
outbreaks of streptococcus pneumonia, which during certain periods have
been fatal to more than two-thirds of those who have been admitted with
pneumonia, whereas in the two long established wards for pneumonia
isolated cases of streptococcus infection, which have appeared, have
failed to spread to other patients and pneumococcus pneumonia with few
exceptions has been found in those who have died. In one newly
established ward 67.5 per cent of those admitted within a period of
three days have died, and in all of the 23 autopsies which have been
performed, streptococcus pneumonia has been found. In another ward 50
per cent of all who have been admitted during a period of one week have
died, and among the autopsies performed on these individuals
pneumococcus pneumonia has been found in 6 and streptococcus pneumonia
in 14. The sputum of 9 patients in this ward has been examined on
admission, and pneumococci, but no streptococci, have been found. All
these patients have died, and infection with S. hemolyticus has been
found at autopsy in 7.

=Transmission of Pneumococcus Pneumonia.=—Our study of secondary ward
infection has not only shown that patients with pneumococcus pneumonia
following influenza are susceptible to infection by S. hemolyticus, but
that patients suffering with pneumonia caused by one type of
pneumococcus may be infected with another type during the course of the
disease or after convalescence has begun, the second infection being
acquired from patients in adjacent beds. Pneumonia caused by Type IV has
ended in crisis and has been followed by a period of normal temperature;
recurrent pneumonia has been fatal and Pneumococcus Type II has been
found in the organs at autopsy. Pneumonia caused by Type I has been
followed by recurrent pneumonia caused by Pneumococcus II atypical
acquired from a patient in the next bed. These secondary pneumococcus
infections acquired within the hospital are apparently not uncommon.

=Prevention of the Transmission of Pneumonia.=—The essential factor in
the management of influenza and pneumonia is such isolation of each
patient that microorganisms cannot be transmitted from one to another or
from attendants or others to patients. This condition may be fulfilled
by the separation of patients in rooms or isolated compartments
especially constructed for the treatment of pneumonia and by the
employment of all possible means to prevent the transmission of
infection from one patient to another by physicians, nurses and
orderlies. It is desirable to examine attendants to determine if they
carry hemolytic streptococci in their mouths and to exclude those who
are found to be “carriers.”

Influenza is a self-limited disease which, in the absence of
complications implicating the lower respiratory tract, is of relatively
mild character. When death occurs as the result of influenza it is with
very rare, if any, exceptions referable to pneumonia; we have invariably
found pneumonia in those who have died in consequence of influenza. The
individual attacked by influenza may carry within his upper respiratory
passages pneumococci or hemolytic streptococci capable of invading the
bronchi and causing pneumonia, but in most instances the microorganism
which produces serious pulmonary complications is derived from others
with whom the influenza patient has come into contact. The greatest
source of danger to one with influenza is contact with patients who have
acquired pneumonia, and this danger is immensely increased when
infection with S. hemolyticus makes its appearance among pneumonic
patients. Hospital epidemics of streptococcus pneumonia will be
prevented when the disease is dreaded as much as puerperal fever or the
hospital gangrene of former years, and widespread knowledge of the
suppurative pneumonias of influenza will bring a clear recognition of
the fatal character of streptococcus infection in patients suffering
with pneumococcus pneumonia.

Overcrowding of barracks has been an important factor in the propagation
of acute respiratory disease and in the transformation of otherwise
trivial influenza into fatal pneumonia. Crowded troop trains have
doubtless had a part in disseminating infection among newly assembled
recruits. Should these dangers be recognized they may be avoided by
appropriate measures which will promote rather than retard those
military aims which must be placed foremost in time of war. It may be
possible by adequate expenditure to avoid the death of thousands of
recruits within one month of their entrance into military service.

A second factor in the increase of death rate from pneumonia is the
overcrowding and confusion of hospital facilities in the presence of an
epidemic disease. When troops are maintained in camps precautions should
be taken to provide effective safeguards against the overcrowding of the
base hospital.

Isolation of each patient with pneumonia is the most effective way of
protecting him from infection and of preventing him from becoming a
possible source of danger to others. The effectiveness of this isolation
will depend upon the separation of patients by some means more effective
than the cubicles composed of sheets heretofore employed, upon an
aseptic technic sufficiently rigid to prevent the transfer of pyogenic
infection to pneumonia patients, and upon the exclusion from the ward of
those who harbor S. hemolyticus.

Even should each patient be completely isolated from his neighbors, no
effort should be neglected to determine, as far as possible, the nature
of the infection with which he suffers. In the presence of an
overwhelming epidemic such as that which attacked our army camps, the
bacteriologic work which is required may be far beyond the facilities
which are available and in many instances it may be wholly impossible.
Nevertheless effective control of streptococcus pneumonia will depend
upon its recognition as soon as it appears, and bacteriologic
examination of the sputum offers the readiest means for its
identification. The routine performance of autopsies will furnish an
index of the success of the measures in force, and the discovery of
suppurative pneumonia will suggest the presence of imminent danger.

However perfect the organization of pneumonia wards and however accurate
the aseptic technic in force, it is desirable to separate as far as
possible those infected with streptococcus from those who are free from
this infection, so that the accuracy of the technic in force may not be
put to too severe a test. When streptococcus pneumonia has appeared in a
ward it should be closed to further admissions.

Those who are concerned in the planning and construction of military and
other similar hospitals might well give special attention to the
possibility of epidemics such as those which we have experienced, and
special provision might be made to avoid overcrowding in the presence of
a demand far in excess of the routine need for hospital facilities. In
the construction of these hospitals appropriate provision should be made
for the care of patients with pneumonia. Medical officers should receive
detailed instruction in the organization and conduct of wards designed
for the treatment of pneumonia.

APPENDIX
EXPERIMENTAL INOCULATION OF MONKEYS WITH BACILLUS INFLUENZÆ AND
MICROORGANISMS ISOLATED FROM THE PNEUMONIAS OF INFLUENZA

EUGENE L. OPIE, M.D.; ALLEN W. FREEMAN, M.D.; FRANCIS G. BLAKE, M.D.;
JAMES C. SMALL, M.D.; AND THOMAS M. RIVERS, M.D.

Experiments were undertaken at Camp Pike in December, 1918, to determine
whether bacteria freshly isolated from patients suffering with influenza
and pneumonia during the outbreak of influenza and its associated
pneumonias were capable of producing similar diseases when introduced
into the respiratory passages of monkeys. The number of animals
available for the study was limited. The attempt was made (_a_) to
determine if B. influenzæ produces in monkeys a disease comparable to
influenza of human beings, and (_b_) to determine so far as possible,
with the limited opportunity, the character of the lesions produced by
combinations of pneumococcus or S. hemolyticus with B. influenzæ and to
compare these lesions with lesions produced by pneumococcus or by
hemolytic streptococcus alone.

Pfeiffer[107] found monkeys alone susceptible to invasion by B.
influenzæ and obtained no evidence of multiplication of the
microorganism within the body of any other animal. A suspension
containing mucus from the sputum of a patient with influenza was
injected into a monkey. There was elevation of temperature and the
animal died after seven days. Lobular patches of atelectasis occurred
along the sharp edges of the lungs and the adjacent bronchial branches
contained mucus. Cultures on agar from the bronchi remained sterile.
Microscopic examination showed the presence of bacilli resembling B.
influenzæ. Death was caused, the author states, by an abscess at the
site of inoculation and not by the process in the lungs. Three monkeys
received each 0.5 c.c. of bouillon containing a blood agar culture
injected into the lung through the chest wall. There was elevation of
temperature lasting from three to five days with return to normal every
morning. There was cough but little evidence of illness. B. influenzæ
was introduced by a platinum loop into the nose of a monkey. Febrile
reaction is recorded lasting four or five days. Pfeiffer found that
guinea pigs and mice were resistant to the microorganism. Large doses
injected intravenously caused in rabbits intoxication with dyspnea and
evidence of profound muscular weakness.

Kamen[108] used a culture of B. influenzæ which was nonpathogenic for
mice, but when it was inoculated into the peritoneal cavity with
streptococcus both influenza bacilli and streptococci appeared in the
blood. Jacobson[109] found that B. influenzæ appeared in the blood and
viscera of mice killed by intraperitoneal inoculation of B. influenzæ
mixed with cultures of streptococcus either living or killed by heat. B.
influenzæ which had successively passed through mice, simultaneously
inoculated with killed streptococci, acquired such virulence that it was
capable of producing septicemia when inoculated alone.

Richie[110] introduced by lumbar puncture a suspension of two blood agar
cultures of B. influenzæ obtained from the meninges of a patient with
influenzal meningitis into the subdural space of a rhesus monkey. Death
occurred in eighteen hours and there was beginning meningitis. B.
influenzæ was present in the exudate in abundance.

In two species of monkeys Wollstein[111] produced fatal meningitis by
injecting suspensions of B. influenzæ into the subdural space by lumbar
puncture.

During the course of our investigation of pneumonia and influenza,
sputum of approximately 400 normal individuals or patients with
influenza was injected into the peritoneal cavity of mice. B. influenzæ
was found in approximately 150 instances. In only 4 instances was B.
influenzæ found in pure culture in the blood; in all other mice in which
B. influenzæ appeared in the blood it accompanied pneumococcus or S.
hemolyticus.

Before experiments were performed cultures were made from the throats of
all monkeys in order to exclude the presence of B. influenzæ. Blood agar
plates inoculated with a swab applied to the nasopharynx failed to show
in any instance B. influenzæ, pneumococci, or hemolytic streptococci.
Streptococci causing green discoloration of blood agar were usually
found.

=Inoculation of the Nose and Pharynx with B. Influenzæ.=—B. influenzæ
was introduced into the nose and pharynx of two healthy monkeys. An
actively growing culture of the microorganism made on alkaline blood
agar and sixteen hours old was used. The culture was the first
subculture from a growth obtained from the nose and throat of a patient
with influenza. A cotton swab moistened with broth was applied to the
surface of the culture. It was introduced into the nostrils and smeared
over the pharynx of the animals. A swab moistened with sterile broth was
applied to the nose and pharynx of a third monkey as a control; cultures
from this animal kept in a cage removed from those inoculated failed to
show B. influenzæ.

EXPERIMENT 1

November 21, 1918.—Small female monkey; throat culture: negative.
November 23.—10:20 A.M.—White blood corpuscles, 16,700; polynuclear
leucocytes, 68 per cent; small lymphocytes, 17.5 per cent; large
lymphocytes, 8 per cent; large mononuclears, 1 per cent;
eosinophiles, 2.5 per cent; basinophiles, 0.5 per cent. 10:30
A.M.—Mucous membranes of nose and throat were inoculated with B.
influenzæ as described above. November 25.—The animal appears sick
and is huddled in back of its cage; the nose is running. White blood
corpuscles, 13,500; polynuclear leucocytes, 44 per cent; small
lymphocytes, 30 per cent; large lymphocytes, 22 per cent; large
mononuclears, 3 per cent; eosinophiles, 1 per cent. 3:40 P.M.—Free
epistaxis occurred after culturing of nose; the swab was discolored
with old brownish blood indicating previous epistaxis. Nose culture:
B. influenzæ present in abundance; Gram-positive cocci present.
Throat culture: negative for B. influenzæ. November 28.—Monkey is
more active and appears to be fairly well. Nose and throat cultures:
negative for B. influenzæ. December 4.—Monkey is apparently well.

EXPERIMENT 2

November 21, 1918.—Small male monkey. Throat culture: negative.
November 23.—10:10 A.M.—White blood corpuscles, 10,900; polynuclear
leucocytes, 52 per cent; small lymphocytes, 18 per cent; large
lymphocytes, 25 per cent; large mononuclears, 3 per cent;
eosinophiles, 2 per cent. 10:15 A.M.—Mucous membranes of nose and
throat were inoculated by means of moist swab with 4 strains of B.
influenzæ recently isolated from acute cases of influenza. November
24.—Monkey is quiet and takes no interest in surroundings. November
25.—Animal appears sick and remains huddled at back of its cage.
Nose culture: B. influenzæ present. Throat culture: B. influenzæ
present. Swab applied to nose is stained brown with old blood
indicating previous epistaxis. November 26.—Animal is still sick;
nose is running. White blood corpuscles, 14,400; polynuclear
leucocytes, 61 per cent; small lymphocytes, 23 per cent; large
lymphocytes, 15 per cent; large mononuclears, 1 per cent. November
27.—White blood corpuscles, 11,300. November 28.—Nose culture:
negative for B. influenzæ. Throat culture: B. influenzæ present.
November 29.—Animal is active, but still appears sick. White blood
corpuscles, 19,300. December 4.—Monkey appears well. Throat culture:
B. influenzæ present.

These animals were sick two and six days following inoculation. There
was discharge from the nose. In both instances there was epistaxis. The
temperature of the animals was subject to such wide variation in
relation to external temperature that it could not be used as an index
of the progress of the disease. There was no leucocytosis, but in one
animal there was some increase in the numbers of leucocytes during
recovery. In one animal B. influenzæ present in the nose after two days
was absent after four days. In the other animal the organism was
repeatedly found in the nose and throat and was still present in the
throat eleven days after inoculation. The two animals suffered with a
self-limited disease resembling many cases of influenza.

=Introduction of Bacillus Influenzæ into the Trachea.=—In the attempt to
reproduce the bronchitis which occurs in a considerable proportion of
all cases of influenza and is almost invariably associated with B.
influenzæ, this organism was introduced into the trachea of monkeys. In
Experiment 3 a suspension containing young cultures of freshly isolated
B. influenzæ was introduced into the trachea by a silver catheter passed
through the glottis and larynx into the trachea.

Young cultures of B. influenzæ, subcultured only once after isolation
from early cases of influenza, were used. The microorganism was
recovered in abundance by throat swab two days later and again from the
bronchus at autopsy three days after inoculation. Tuberculosis of
mesenteric lymph nodes, of intestine and of liver and several small
tuberculous nodules in the lung were found at autopsy. A secondary
invasion of the lung by staphylococci had occurred. There was bronchitis
with an inflammatory infiltration of the subepithelial tissue of the
bronchi by lymphoid and plasma cells. Bronchopneumonia was present, and
the bronchi and many of the alveoli contained blood. These changes do
not differ essentially from the changes found in many instances of
pneumonia following influenza.

In three instances cultures of B. influenzæ were injected into the
trachea by means of a hypodermic syringe.

In one of these experiments (Experiment 4) intratracheal injection of 2
c.c. salt solution suspension of B. influenzæ (isolated at autopsy from
bronchus of the monkey used in Experiment 3), representing growth on 1½
blood agar plates, was made with a needle inserted into trachea just
above the suprasternal notch. On the following day a throat culture
contained B. influenzæ in abundance. Three days after inoculation the
monkey appeared to be very sick and there was profuse nasal discharge.
The animal coughed and sibilant râles were heard over the chest. There
was no leucocytosis. A throat culture contained B. influenzæ. Four days
after inoculation the monkey was still sick and weak, but appeared much
improved and was killed. The trachea and large bronchi contained thick
viscid mucus. In the middle lobe of the right lung was a patch of
grayish red, airless tissue, firmer than the lung substance elsewhere.
Cultures from the trachea, bronchus and lung contained a variety of
microorganisms, but B. influenzæ was not recovered.

In two additional experiments (Experiments 6 and 7) cultures of B.
influenzæ forty-eight hours old were injected into the trachea of
monkeys. The microorganism was recovered in cultures made from the
pharynx two days later. These animals were only slightly sick.

=Introduction of B. Influenzæ and S. Hemolyticus into the Trachea.=—In
view of the frequent association of B. influenzæ and S. hemolyticus in
the sputum of patients with streptococcus pneumonia following influenza
and in the bronchi and lungs of those who have died with this disease,
the two microorganisms were injected simultaneously into the trachea of
monkeys.

B. influenzæ and S. hemolyticus in Experiment 7 produced bronchitis and
bronchopneumonia. There was acute inflammation of the interstitial
tissue of the lung, and acute lymphangitis with numerous polynuclear
leucocytes within the lumen of the lymphatics was present. B. influenzæ
and S. hemolyticus were present in the trachea at autopsy four days
after inoculation. It is probable that part of the injected culture
entered the tissue outside the trachea, for an abscess was formed in
this situation. It is noteworthy that acute pericarditis occurred and
both S. hemolyticus and B. influenzæ were found in the pericardial
exudate. B. influenzæ not infrequently exhibits this tendency to
penetrate in association with other bacteria localities which it does
not invade independently.

In a second experiment (Experiment 8) in which B. influenzæ and S.
hemolyticus were injected into the trachea, both microorganisms were
recovered from the throat on the day following inoculation; on the fifth
day S. hemolyticus alone was recovered and on the sixth day a throat
culture was negative both for S. hemolyticus and B. influenzæ.

=Introduction of B. influenzæ and of Pneumococcus or of Pneumococcus
Alone into the Trachea.=—In two experiments B. influenzæ and
Pneumococcus Type III were simultaneously injected into the trachea.

In Experiment 9 a large male monkey was used and intratracheal injection
made with syringe and needle of 5 c.c. salt solution suspension of
Pneumococcus Type III and B. influenzæ (growth on 5 blood agar plates of
mixed cultures of Pneumococcus III and B. influenzæ). On the following
day the animal was very sick, lying on the floor of its cage, and was
dead two days after inoculation.

The dosage of bacteria in this experiment was large. The lesions in
gross appearance and microscopically resembled those seen in many
instances of pneumonia following influenza. In the trachea there was
loss of ciliated epithelium, congestion of the subepithelial tissue,
hemorrhage and infiltration with plasma cells. The lungs were
consolidated and red and there were hemorrhage and edema. B. influenzæ,
as in human cases, was abundant in the bronchi, less abundant in the
consolidated lung, being present though scant in the left lung, and
absent in cultures from the right. B. influenzæ as in Experiment 8 with
streptococcus had entered the left pericardial cavity in company in this
experiment with Pneumococcus III.

In Experiment 10 a very large monkey received by intratracheal
injection, made with syringe and needle, 5 c.c. salt solution suspension
of Pneumococcus III and 3 strains of B. influenzæ, (2 recently isolated
from cases of influenza and 1 from autopsy in a case of postinfluenzal
pneumonia). The animal died twenty-four hours later.

This simultaneous introduction of B. influenzæ and Pneumococcus III in
large quantity has produced rapidly fatal pneumonia with lobar
distribution. Hepatization was homogeneous and red, and outside the
consolidated parts of the lung there was hemorrhage and edema. The
lesion resembled that found when death has occurred within a few days
after the onset of pneumonia following influenza, but had no distinctive
characters establishing its relation to pneumonia following influenzæ.

In Experiment 11 Pneumococcus III alone in small amount was introduced
into the trachea of a small monkey. The animal was very sick, but its
condition improved and recovery seemed probable. The animal was killed
seven days after inoculation, and typical lobar pneumonia with gray
hepatization was found at autopsy.

EXPERIMENT 11

November 20, 1918.—Small monkey; throat culture: negative for B.
influenzæ, pneumococcus and S. hemolyticus. November 28 and December
6.—Nose and throat cultures again negative for B. influenzæ.
December 9—4:30 P.M.—Intratracheal injection with syringe and needle
of 0.33 c.c. of an eighteen hour broth culture of Pneumococcus Type
III. December 10.—The animal is sick, huddled up in his cage with
head down; there is rapid respiration with expiratory grunt and the
mucous membranes are moderately cyanotic. There is frequent cough.
Throat culture: Pneumococcus III present in abundance. December
15.—The animal appears to be better. Respirations are still rapid
but less labored. December 16.—The animal is improving but very weak
and emaciated.

=Autopsy.=—The pleural cavities contain no fluid. On the right side
are several strands of fibrin. The right lower lobe with the
exception of a small patch at the summit and the lower part of the
middle lobe are voluminous, have a dull gray surface covered by a
scant layer of fibrin and are firmly consolidated. On section the
consolidated tissue has a gray color and is conspicuously granular,
the granulation resembling, on a slightly smaller scale, that seen
in human lobar pneumonia. The bronchi contain a small amount of
viscid fluid.

=Bacteriology.=—Direct smears from the trachea and the lower lobe of
the left lung contain Gram-positive diplococci. Cultures from the
trachea and from the blood of the heart contain Pneumococcus III.
Cultures from the left lower lobe, from the liver and from the
spleen remain sterile.

=Microscopical Examination.=—There is abundant infiltration of the
subepithelial tissue of the trachea with plasma cells. Superficial
ciliated epithelium is in places lost. At one point is a small focus
of hemorrhage. Alveoli in the consolidated part of the lungs contain
polynuclear leucocytes and fibrin and exhibit the appearance seen in
lobar pneumonia in man.

[Illustration:

Fig. 33.—Experimental lobar pneumonia in the stage of gray
hepatization produced by injection of Pneumococcus III into the
trachea of a monkey (Experiment 11). The alveoli are uniformly
filled with plugs of fibrinous exudate.
]

In Experiment 12 B. influenzæ was injected into the trachea and two days
later identified in a culture made from the pharynx; four days after
inoculation Pneumococcus IV was injected into the trachea. The animal
was killed seven days after the first inoculation, and three days after
inoculation with pneumococcus. The lower half of the upper lobe of the
right lung and the greater part of the lower and middle lobes were
consolidated. The pleural surface of the consolidated areas was dull red
and covered by a small amount of fibrin. The lower lobe, with the
exception of a small part at the summit, was very firmly consolidated,
on section pinkish gray in the anterior part and deep red in a small
zone at the posterior border. The cut section was conspicuously
granular. The trachea and bronchi contained mucus. Cultures from the
trachea, the right lung and the right pleural cavity contained
Pneumococcus IV in pure culture. Alveoli in the consolidated part of the
lung were filled with polynuclear leucocytes and fibrin.

Lobar pneumonia has been produced by the introduction of Pneumococcus IV
into the trachea. It is doubtful if preceding inoculation of B.
influenzæ has influenced the course of the disease.

The foregoing experiments have shown that B. influenzæ introduced into
the nasopharynx or into the trachea of monkeys is capable of causing
lesions of the mucosa of these structures; the microorganism persists
within the nasopharynx or trachea and is recoverable during a variable
period of from two to eleven days after inoculation. Spontaneous
infection of monkeys with B. influenzæ has not been observed. The
animals infected with the microorganism are ill during several days, but
the experimental disease like most instances of human influenza is self
limited. Following inoculation of the nose and throat of monkeys with B.
influenzæ there is discharge from the nose, tendency to epistaxis and
absence of leucocytosis.

Bronchitis was produced by the introduction of B. influenzæ into the
trachea of monkeys, and the microorganism was recovered from the
nasopharynx two and three days following inoculation. There was no
leucocytosis. In two experiments death occurred following inoculation,
and in both instances it was found that the animal suffered with
tuberculosis which had produced only trivial lesions of the lungs. In
both animals staphylococci were obtained from the internal organs. There
was bronchitis with changes in the bronchi which, although not
characteristic, resembled those found in association with B. influenzæ
in man. It is noteworthy that B. influenzæ is usually found mixed with
other bacteria in the bronchi of those who have died with bronchitis and
pneumonia following influenza. In the experimental animals there was in
places superficial loss of ciliated epithelium, exudation of polynuclear
leucocytes, infiltration of the subepithelial tissue with plasma cells
and hemorrhage into this tissue.

In one instance simultaneous injection of B. influenzæ and S.
hemolyticus, freshly obtained from autopsy upon a man dying with
pneumonia following influenza, caused bronchitis and bronchopneumonia;
there were acute lymphangitis and infiltration of the interstitial
tissue of the lung with polynuclear leucocytes such as occurs in human
cases, but the lesion had not proceeded to suppuration.

In man B. influenzæ is usually found in greatest abundance upon the
mucosa of the respiratory passages, less frequently it invades the
alveoli of the lungs and is almost invariably found in association with
other microorganisms. In company with other microorganisms B. influenzæ
penetrates into tissues outside the lungs. In Experiment 7 it has
entered the pericardium, with streptococcus, and in Experiment 9 with
pneumococcus. When B. influenzæ and streptococcus are injected into the
peritoneal cavity of a mouse both organisms appear in the blood, whereas
in the absence of streptococcus, B. influenzæ seldom leaves the
peritoneal cavity.

Typical lobar pneumonia has been produced for the first time in monkeys
by injecting pneumococci (in quantity as small as 0.33 c.c. of
suspension) into the trachea. With the animals available it has not been
possible to adjust the dosage of the two microorganisms so that the
influence of one upon the other might be determined. Pneumococcus III,
in small quantity, introduced into the trachea has produced typical
acute lobar pneumonia in the stage of gray hepatization. A similar
lesion has been produced with Pneumococcus IV obtained from the lung of
a man dead with pneumonia.

INDEX

Abscess of lung, bacteriology of, 203
empyema with, 233
healing of, 208
measles with, 347
parotitis with, 356
pathogenesis of, 205, 375
scarlet fever with, 357
staphylococcus causing, 199, 225, 366, 377
S. hemolyticus causing, 199, 365

Autopsies, table of, 118, 120, 335

Autopsy protocols, No. 280, 226;
No. 286, 226;
No. 312, 254;
No. 322, 228;
No. 330, 214;
No. 333, 229;
No. 370, 229;
No. 376, 206;
No. 379, 215;
No. 380, 204;
No. 387, 206;
No. 397, 223;
No. 406, 204;
No. 416, 204;
No. 420, 279;
No. 425, 229;
No. 428, 280;
No. 433, 280;
No. 445, 257;
No. 465, 238;
No. 467, 208;
No. 473, 236;
No. 474, 221;
No. 487, 273;
No. 499, 224;
No. 504, 238

Bacillus influenzæ, 369
bronchi and, 178, 215, 346
bronchitis and, 153, 371
experimental inoculation with, 389
history of, 25
influenza and, 30, 42, 43, 46, 49, 76, 370
isolation of, 30, 32, 38, 44
measles with, 26, 40, 43, 295, 351
meningitis and, 26
normal men carrying, 34, 42, 45, 369
pathogenicity of, 26, 48, 370, 387, 396
pneumococcus pneumonia with, 62, 178
pneumonia with, 72, 75, 76, 173, 364, 371

Bronchi, inflammation of mucous glands of, 146

Bronchiectasis, 239, 269, 355, 367
abscess with, 254
bacteriology of, 244
bronchitis with, 245
measles with, 336
pathogenesis of, 245, 259

Bronchiolitis, organizing, 264

Bronchitis, 40, 142, 195, 359
bacteriology of, 56, 150, 164, 359, 371
bronchiectasis with, 245
chronic, 262
clinical course of, 58
measles with, 336
organizing, 264
purulent, 47, 56, 60, 63, 74, 143, 149, 153, 360

Bronchopneumonia, 60, 63, 66, 162, 360, 363
bacteriology of, 68, 163, 171, 176, 181, 184, 189, 194, 197, 345, 364
fibrin with, 182
lobar pneumonia with, 155, 157
measles with, 340
secondary infection by S. hemolyticus with, 172, 177, 181, 374

Carriers of B. Influenzæ, 46, 101, 369
of S. hemolyticus, 99, 285, 287, 298, 303, 309, 310, 315, 319, 321,
332, 379

Cartilage, atrophy with bronchiectasis of, 254

Contact infection in influenza, prevention of, 98
in measles, 289
in pneumonia, prevention of, 98

Cubicles to prevent contact infection, 98, 290

Cyanosis, 144

Empyema, 64, 67, 224, 226, 233, 304, 366
abscess of lung and, 233
encapsulated, 235
interstitial suppurative pneumonia with, 216, 234
measles with, 349
pneumococcus, 236, 350
streptococcus, 233, 350

Endophlebitis, 219

Hemorrhagic and edematous consolidation with bronchopneumonia, 188
peribronchiolar consolidation with bronchopneumonia, 163, 173, 272,
340

Hepatization with bronchopneumonia, 179, 181
with lobar pneumonia, 160

Influenza, B. influenzæ with, 30, 73
bronchitis with, 55, 56
clinical course of, 28, 53, 73, 80
coryza with, 54
cyanosis with, 54
epidemic in fall of 1918, 52, 108, 359
epidemic in spring of 1918, 47
fever with, 53
gastrointestinal symptoms with, 55
laryngitis with, 54
lobar pneumonia and, 161
measles and, 292, 319, 331, 351, 357, 380
pandemic of 1889–90, 109, 115
pandemic of 1918–19, 27, 359
pharyngitis with, 54
pneumococcus with, 33
pneumonia with, 55, 59, 74, 81, 139
pulmonary lesions of, 137
pulse with, 54
secondary infection with, 28, 45, 57, 95
sputum with, 55
S. hemolyticus with, 103

Interstitial bronchopneumonia, 261, 278, 348
suppurative pneumonia, 199, 209, 366, 376
bacteriology of, 214
chronic inflammation with, 221
empyema with, 216, 234
healing of, 222, 224
measles with, 348
pericarditis with, 237

Lobar pneumonia, 60, 63, 154, 360, 362
bacteriology of, 64, 156, 164, 339, 362
bronchopneumonia with, 155, 157
experimental production in monkeys of, 394, 397
influenza and, 161
measles with, 337
purulent bronchitis with, 60, 63, 66
secondary infection by hemolytic streptococci with, 64, 159, 340, 374
spread in lung of, 339, 354
typhoid fever with, 353

Lobular consolidation, confluent, 188, 341
with bronchopneumonia, 163, 178, 272, 341

Lymphatics, suppurative inflammation of, 217, 218, 376
thrombosis of, 217, 218

Lymphangitis, experimental production with S. hemolyticus of, 392

Masks to prevent contact infection, 98, 290

Mastoiditis, 303, 312, 332

Measles, 119, 288
B. influenzæ with, 26, 40, 43, 295
bronchiectasis with, 336
bronchitis with, 336
bronchopneumonia with, 340
complications of, 303, 378
empyema with, 349
influenza and, 292, 319, 331, 351, 357, 380
interstitial suppurative pneumonia with, 348
lobar pneumonia with, 337
pneumococcus pneumonia with, 312
pneumonia and, 292, 303, 312, 332, 334, 378
secondary infection with, 282
S. hemolyticus with, 285, 287, 297, 319, 330, 331, 353, 378
suppurative pneumonia with, 345, 347
unresolved bronchopneumonia with, 342

Methods, 29, 51, 283, 291

Mortality of pneumococcus pneumonia, 140
of pneumonia following influenza, 139
of streptococcus pneumonia, 140

Mumps, 119, 355

Necrosis with bronchopneumonia caused by S. hemolyticus, 186, 375
with lobar pneumonia caused by S. hemolyticus, 160, 374
with S. hemolyticus, 199, 200

Oedema, interstitial, 209

Organization of pneumonic exudate, 197

Otitis media, 289, 303, 312, 317, 329, 332

Peribronchiolar consolidation with bronchopneumonia, 163, 166, 267, 340

Pericarditis, 64, 237

Peribronchial consolidation with bronchopneumonia, 163, 192, 361
hemorrhage, 189

Peritonitis, 238

Phagocytosis of red blood corpuscles, 272

Pneumococcus, 372
bronchitis and, 153
bronchopneumonia with, 165, 184, 373
empyema, 236
experimental lobar pneumonia with, 393
influenza with, 33
lobar pneumonia with, 158, 372
pneumonia, 60, 75, 104
clinical course of, 62
measles and, 312, 332
mortality of, 140
secondary pneumococcus infection with, 61
secondary streptococcus infection with, 62
transmission of, 91, 383
secondary infection in pneumonia with, 91

Pneumonia, B. influenzæ causing, 72, 76, 371
bacteriology of influenza and, 60, 74, 107
bacteriology of measles and, 351
chronic fibroid, 273
clinical course of influenza with, 62
diagnosis of, 136, 334, 361
dissecans, 209
immunity following, 373
influenza with, 59, 76, 81, 109, 360
measles and, 119, 292, 303, 312, 332, 334, 378
mumps and, 119
pneumococcus, see Pneumococcus pneumonia
prevention of, 98, 319, 383
scarlet fever and, 119
secondary infection with, 83, 106
spread through lungs of, 194, 373
staphylococcus, see Staphylococcus pneumonia
streptococcus, see Streptococcus pneumonia
S. hemolyticus in throat with, 310, 329, 379

Pseudoinfluenza bacilli, 26

Scarlet fever, 119, 356

Squamous transformation of bronchial epithelium, 149, 251, 275, 336

Staphylococcus, 153, 377
pneumonia, 112, 225, 354, 366
pneumonia, pathogenesis of, 230

Streptococcus empyema, 233
hemolyticus, 374
bronchitis with, 153
dissemination in wards of, 315
experimental production of acute
lymphangitis with, 392
identification of, 283
influenza with, 103
lobar pneumonia with, 64, 159
measles with, 285, 287, 297, 330, 331, 345, 353, 378
normal men with, 285, 322
secondary infection in pneumonia with, 84, 106, 178, 204, 374
nonhemolytic, 376
peritonitis, 238
pneumonia, 60, 70, 75, 115, 307, 365
bacteriology of, 71
clinical features of, 71
measles with, 303, 305, 307, 318
mortality of, 140
transmission of, 84, 381
viridans, 377

Suppurative pneumonia, 199, 347
with measles, 345, 347

Thrombosis of capillaries with bronchopneumonia, 184

Typhoid fever, lobar pneumonia with, 353
staphylococcus pneumonia with, 354

Unresolved bronchopneumonia, 261, 266, 342, 368
bacteriology of, 276
interstitial suppurative pneumonia with, 278

-----

Footnote 1:

Report of the Surgeon General, U. S. Army to the Secretary of War,
1918, p. 44.

Footnote 2:

Stillman, F. G.: A Study of Atypical Type II Pneumococci, Jour. Exper.
Med., 1919, xxix, 251.

Footnote 3:

Opie, E. L., Freeman, A. W., Blake, F. G., Small, J. C., Rivers, T.
M.: Pneumonia at Camp Funston, Jour. Am. Med. Assn., 1919, lxxii, 108.

Footnote 4:

Vaughan, V. C., and Palmer, G. T.: Communicable Diseases in the
National Guard and National Army of the United States, Jour. Lab. and
Clin. Med., 1918, iii, 635.

Footnote 5:

Miller, J. L., and Lusk, F. B.: Jour. Am. Med. Assn., 1918, lxxi, 702.

Footnote 6:

Report of the Surgeon General to the Secretary of War, 1919, i, 637.

Footnote 7:

MacNeal, W. J.: The Influenza Epidemic of 1918 in the American
Expeditionary Forces in France and England, Arch. Int. Med., 1919,
xxiii, 657.

Footnote 8:

Pfeiffer: Ztschr. f. Hyg., 1893, xiii, 357.

Footnote 9:

Wollstein: Jour. Exper. Med., 1916, viii, 681.

Footnote 10:

Kretz: Wien. klin. Wchnschr., 1897, x, 877.

Footnote 11:

Süsswein: Wien. klin. Wchnschr., 1901, xiv, 1149.

Footnote 12:

Liebscher: Prag. med. Wchnschr., 1903, xxviii, 85.

Footnote 13:

Jehle: Ztschr. f. Heilk., 1901, xx, n. s. 2, Int. Med.

Footnote 14:

Davis: Jour. Infect. Dis., 1906, iii, 1.

Footnote 15:

Lord: Boston Med. Sur. Jour., 1905, clii, 537, 574.

Footnote 16:

Boggs: Am. Jour. Med. Sc., 1905, cxxx, 902.

Footnote 17:

Wollstein: Am. Jour. Dis. Child., 1911, i, 42.

Footnote 18:

Rosenthal: Comp. rend. Soc. Biol., 1903, lv, 1500.

Footnote 19:

Wollstein: Jour. Exper. Med., 1915, xxii, 445.

Footnote 20:

Med. Sup. October 1, 1918 also Jour. Am. Med. Assn., 1918, lxxi, 1573.

Footnote 21:

Opie, Freeman, Blake, Small, and Rivers: Jour. Am. Med. Assn., 1919,
lxxii, 108.

Footnote 22:

Vaughn and Palmer: Jour. Lab. and Clin. Med., 1918, iii, 635.

Footnote 23:

Soper: Jour. Am. Med. Assn., 1918, lxxi, 1899.

Footnote 24:

Cole and MacCallum: Jour. Am. Med. Assn., 1918, lxx, 1146.

Footnote 25:

Hammond, Rolland, and Shore: Lancet, London, 1917, ii, 41.

Footnote 26:

Abrahams, Hallows, Eyre, and French: Lancet, London, 1917, ii, 377.

Footnote 27:

Public Health Reports, U.S.P.H. Service, 1919, xxxiv, 33.

Footnote 28:

Blake: Jour. Exper. Med., 1917, xxvi, 67.

Footnote 29:

Avery: Jour. Am. Med. Assn., 1918, lxx, 17.

Footnote 30:

Dunn: Jour. Am. Med. Assn., 1918, lxxi, 2128.

Footnote 31:

Fantus: Jour. Am. Med. Assn., 1918, lxxi, 1736.

Footnote 32:

Keegan: Jour. Am. Med. Assn., 1918, lxxi, 1051.

Footnote 33:

Christian: Jour. Am. Med. Assn., 1918, lxxi, 1565.

Footnote 34:

Blanton and Irons: Jour. Am. Med. Assn., 1918, lxxi. 1988.

Footnote 35:

Hall, Stone and Simpson: Jour. Am. Med. Assn., 1918, lxxi, 1986.

Footnote 36:

Synnott and Clark: Jour. Am. Med. Assn., 1918, lxxi, 1816.

Footnote 37:

Friedlander, McCord, Sladen and Wheeler: Jour. Am. Med. Assn., 1918,
lxxi, 1652.

Footnote 38:

Brem, Bolling and Casper: Jour. Am. Med. Assn., 1918, lxxi, 2138.

Footnote 39:

Ely, Lloyd, Hitchcock, and Nickson: Jour. Am. Med. Assn., 1919, lxxii,
24.

Footnote 40:

Camp Lewis Pneumonia Unit: Jour. Am. Med. Assn., 1919, lxxii, 268.

Footnote 41:

Jour. Am. Med. Assn., 1918, lxxi, 2068.

Footnote 42:

Wolbach: Bull. Johns Hopkins Hosp., 1919, xxx, 104.

Footnote 43:

Spooner, Scott and Heath: Jour. Am. Med. Assn., 1919, lxxii, 155.

Footnote 44:

Kinsella: Jour. Am. Med. Assn., 1919, lxxii, 717.

Footnote 45:

MacCallum: Jour. Am. Med. Assn., 1919, lxxii, 720.

Footnote 46:

Pritchett and Stillman: Jour. Exper. Med., 1919, xxix, 259.

Footnote 47:

Hirsch and McKinney: Jour. Am. Med. Assn., 1918, lxxi, 1735.

Footnote 48:

Parker: Jour. Am. Med. Assn., 1919, lxxii, 476.

Footnote 49:

Opie, Freeman, Blake, Small and Rivers: Jour. Am. Med. Assn., 1919,
lxxii, 556.

Footnote 50:

See discussion on pages 115 to 118.

Footnote 51:

Isolated by blood culture on Sept. 23. Patient recovered.

Footnote 52:

Stillman: Jour. Exper. Med., 1916, xxiv, 651.

Footnote 53:

Stillman: Jour. Exper. Med., 1919, xxix, 251.

Footnote 54:

Haller and Colwell: Jour. Am. Med. Assn., 1918, lxxi, 1213.

Footnote 55:

Doust and Lyon: Jour. Am. Med. Assn., 1918, lxxi, 1216.

Footnote 56:

Held in receiving ward 40 hours because of admission of case of
meningococcus meningitis to ward by mistake.

Footnote 57:

Finkler, D.: Infectionen der Lunge durch Streptococcen und Influenza
Bacillen, Bonn, 1895.

Footnote 58:

Ribbert: Anatomische und bacteriologische Beobachtungen über
Influenza, Deutsch. med. Wehnschr., 1890, xvi, 61, 301.

Footnote 59:

Pfeiffer: Die Aetiologie der Influenza, Ztschr. f. Hyg. 1893, xiii,
357.

Footnote 60:

Leichtenstern, O.: Influenza, Nothnagel’s Specielle Pathologie und
Therapie, Wien, 1896, vol. ii, pt. 2.

Footnote 61:

Krannhals: Quoted by Leichtenstern.

Footnote 62:

Cruickshank: Brit. Med. Jour., 1895, i, 360.

Footnote 63:

Birch-Hirschfeld: Schmidt’s Jahrbücher, 1890, ccxxvi, 110.

Footnote 64:

Kuskow, N.: Zur pathologischen Anatomie der Grippe, Virchow’s Archiv.,
1895, cxxxix, 406.

Footnote 65:

Keegan, J. J.: The Prevailing Epidemic of Influenza, Jour. Am. Med.
Assn., 1918, lxxi, 1051.

Footnote 66:

Symmers, D.: Pathologic Similarity between Pneumonia of Bubonic Plague
and of Pandemic Influenza, Jour. Am. Med. Assn., 1918, lxxi, 1482.

Footnote 67:

Opie, E. L., Freeman, A. W., Blake, F. G., Small, J. C., Rivers, T.
M.: Pneumonia Following Influenza, Jour. Am. Med. Assn., 1919, lxxii,
556.

Footnote 68:

LeCount, E. R.: The Pathological Anatomy of Influenzal
Bronchopneumonia, Jour. Am. Med. Assn., 1919, lxxii, 650.

Footnote 69:

MacCallum, W. G.: Pathology of the Pneumonia Following Influenza,
Jour. Am. Med. Assn., 1919, lxxii, 720.

Footnote 70:

Lyon, M. W.: Gross Pathology of Epidemic Influenza at Walter Reed
Hospital, Jour. Am. Med. Assn., 1919, lxxii, 924.

Footnote 71:

Goodpasture, E. W. and Burnett, F. L.: The Pathology of Pneumonia
Accompanying Influenza, U. S. Naval Medical Bull., 1919, xiii, No. 2.

Footnote 72:

Wolbach: Comments on the Pathology and Bacteriology of Fatal Influenza
Cases as Observed at Camp Devens, Mass., Bull. Johns Hopkins Hosp.
1919, xxx, 104.

Footnote 73:

Cummings, J. G., Spruit, C. B., and Lynch, C.: The Pneumonias:
Streptococcus and Pneumococcus Groups, Jour. Am. Med. Assn., 1918,
lxx, 1066.

Footnote 74:

Cole, R. and MacCallum, W. G.: Pneumonia at a Base Hospital, Jour. Am.
Med. Assn., 1918, lxx, 1146.

Footnote 75:

Miller, J. L., and Lusk, F. B.: Epidemic of Streptococcus Pneumonia
and Empyema at Camp Dodge, Iowa, Jour. Am. Med. Assn., 1918, lxxi,
702.

Footnote 76:

MacCallum, W. G.: Pathology of the Epidemic of Streptococcus
Bronchopneumonia in the Army Camps, Jour. Am. Med. Assn., 1919, lxxii,
720.

Footnote 77:

Stone, W. J., Phillips, B. G., and Bliss, W. P.: A Clinical Study of
Pneumonia Based on 871 Cases, Arch. Int. Med., 1918, xxii, 409.

Footnote 78:

Opie, E. L., Freeman, A. W., Blake, F. G., Small, J. C., and Rivers,
T. M.: Pneumonia at Camp Funston, Jour. Am. Med. Assn., 1919, lxxii,
108.

Footnote 79:

Jour. Am. Med. Assn., 1919, lxxii, 556.

Footnote 80:

Miller, W. S.: Am. Rev. Tuberc., 1919, iii, 65.

Footnote 81:

Wadsworth, A. B.: A Study of Organizating Pneumonia. Jour. Med.
Research, 1918, xxxix, 147.

Footnote 82:

Kaufmann: Spezielle Pathologische Anatomie. 1909, ed. 5, p. 260.

Footnote 83:

Beitzke: Respirations Organe. Aschoff’s Path. Anat., 1913 ed. 3, Vol.
II, p. 308.

Footnote 84:

Chickering, H. T. and Park, J. H.: Staphylococcus Aureus Pneumonia,
Jour. Am. Med. Assn. 1919, lxxii, 617.

Footnote 85:

Stone, W. J., Phillips, B. G., and Bliss. W. P.: A Clinical Study of
Pneumonia Based on 871 Cases. Arch. Int. Med., 1918, xxii, 409.

Footnote 86:

Loc. cit., p. 110.

Footnote 87:

Lord, F. T.: Infections of the Respiratory Tract with Influenza
Bacilli, Boston Med. and Surg. Jour., 1905, clii, 537, 574.

Footnote 88:

Boggs, T. R.: Influenza Bacillus in Bronchiectasis, Am. Jour. Med.
Sc., 1905, cxxx, 902.

Footnote 89:

Thornton and Pratt: Bull. Johns Hopkins Hosp., 1908, xix, 230.

Footnote 90:

Two cases positive for hemolytic streptococci on this examination were
negative on next examination.

Footnote 91:

S. hemolyticus infection implanted upon a pneumococcus pneumonia.
Place in Table indicates onset of pneumonia and not appearance of
streptococcus complication.

Footnote 92:

Capps, J. A., and Davis, D. J.: Arch. Int. Med., 1914, xiv, 650;
Illinois Med. Jour., November, 1912.

Footnote 93:

Windsor, C. E. A.: Jour. Infect. Dis., 1912, x. 73.

Footnote 94:

Hamburger, L. P.: Jour. Am. Med. Assn., April 13, 1912, lviii, 1109.

Footnote 95:

Smillie, W. S.: Jour. Infect. Dis., 1917, xx, 45.

Footnote 96:

Levy and Alexander: Jour. Am. Med. Assn., 1918, lxx, 1827.

Footnote 97:

Irons and Marine: Jour. Am. Med. Assn., 1918, lxx, 687.

Footnote 98:

Cole and MacCallum: Jour. Am. Med. Assn., 1918, lxx, 1146.

Footnote 99:

Cummings, Spruit and Lynch: Jour. Am. Med. Assn., 1918, lxx, 1066.

Footnote 100:

Sputum or saliva cultures on 50 of these men yielded 1 positive for S.
hemolyticus. Sputum or saliva injected intraperitoneally into white
mice and cultures made from the peritoneal exudate of such mice,
yielded 2 additional positives in the same group of 50 men. These 3
positive cases showed very few colonies of hemolytic streptococci.

Footnote 101:

Per cent positive, on one culture only. Repeated throat cultures,
average two per person as follows:

Cultured No. Cases Positives Once 153 11 Twice 90 7 3 times 39 3
4 times 15 1

Footnote 102:

Steinhaus: Ziegler’s Beitr. 1901, xxix, 524.

Footnote 103:

Bartels: Virchows Arch. f. path. Anat.; xxi.

Footnote 104:

Loc. cit., p. 116.

Footnote 105:

Hart: Deutsch. Arch. f. Klin. Med., 1904, lxxix, 108.

Footnote 106:

Goodpasture, E. W., and Burnett, F. L.: The Pathology of Pneumonia
Accompanying Influenza, U. S. Nav. Med. Bull., 1919, xiii, No. 2, P.
21.

Footnote 107:

Pfeiffer: Ztschr. f. Hyg., 1893, xiii, 357.

Footnote 108:

Kamen, L.: Centralbl. f. Bakteriol., 1901, xxix, Erste Abt. 339.

Footnote 109:

Jacobson, G.: Arch. de méd. expér. et d’anat. path., 1901, xiii, 425.

Footnote 110:

Richie, J.: Journal Path. and Bacteriol., 1910, xiv, 615.

Footnote 111:

Wollstein, M.: Am. Jour. Dis. Child., 1911, i. 42.

------------------------------------------------------------------------

TRANSCRIBER’S NOTES

1. Silently corrected typographical errors and variations in spelling.
2. Archaic, non-standard, and uncertain spellings retained as printed.
3. Footnotes have been re-indexed using numbers and collected together
at the end of the last chapter.
4. Enclosed italics font in _underscores_.
5. Enclosed bold font in =equals=.

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