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.