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mal in from 48 to 72 hours. Persistence of a fever over a longer period of time was almost invariably indicative of a complication or an extension of the process to the lungs. With the return of the temperature to normal all symptoms disappeared, and although general weakness persisted for a week or more, the majority of the men were able to return to their organizations in from 7 to 10 days after admission to the hospital. Cases showing bronchitis ran a very similar course to those of simple influenza. The range and duration of the temperature were practically the same in either type of case. The signs of bronchitis usually persisted for a few days after the temperature had returned to normal. The cough frequently persisted for two or three weeks.
The presence of a leucopenia was noted early in the epidemic and was found to be a constant characteristic. Even with a relatively high temperature, the blood count, in the majority of cases, was found to be well under 10,000 cells to the cubic millimeter. Leucopenia did not always obtain when complications arose or when pneumonia developed. The leucopenia may be a possible factor in the frequent occurrence of complications, being indicative of a diminished resistance on the part of the individual.
Epistaxis was a not infrequent occurrence in influenza, though usually not severe, and in no instance was it found necessary to apply special therapeutic measures for its control. It was observed that cases of influenza and also of bronchopneumonia with epistaxis, ran rather a somewhat milder course than those in which expistaxis did not occur.
Hemoptysis was noted in only two instances. Bothoccurred in patients with influenzalbronchopneumonia, who presented extensive emphysema of the lungs. It was believed that thehemoptysis bore a definite relation to interstitial emphysema of the lungs where dissection of air along the blood vessels toward the hilus of the lung took place.
Tonsillitis, pharyngitis, laryngitis, and tracheitiswere of such common occurrence among ourcases as to be considered rather as integral parts of the disease thanas complications. The samewas believed to be true of bronchitis and even bronchopneumonia, that they were not truecomplications but a progressive extension of the initial process to the bronchioles or to the lung tissue, either because of a lowered resistance of the subject or because of an increased virulence of the invading organism or organisms; that the disease, influenza, in this epidemic, had a selective action on the respiratory tract, and that the development ofa simple pharyngitis in some cases and bronchopneumonia in others was merely a clinicalvariation in degree of oneand the same process.
Acute suppurative otitis media, as a complication,was not infrequent. The subjective symptoms of otitic involvement were usually very slight. Purulent discharge fromthe ear was occasionallythe first indication. In a few cases the otitis media was of the nonsuppurative type, the symptoms then being in the ear, and a slight degree of deafness. The nonsuppurative otitis usually cleared up after a few days. The suppurative type, in most cases, cleared on treatment, but in a few casesprogressed to mastoiditis requiring surgical procedures.
The mastoid cells were opened at necropsy in 20 cases where no evidence of involvement wasexhibited during life. Five of these patients showed acute
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changes in one mastoid, and changes on both sides were noted in three patients. Cultures were positive in two of these cases, in one pneumococcus Group IV being obtained, and in the other the hemolytic type of streptococcus.
Involvement of the accessory sinuses was noted in several instances, the frontal sinuses being the ones most frequently involved.
Sputum cultures and studies were made whenever possible in the bronchopneumonia patients, and in a large number of the influenza patients. During the epidemic 1,948 specimens were submitted to the laboratory for examination. Of this total 542 were found unsatisfactory because of difficulty in obtaining a specimen from the lungs. The findings in the 1,406 satisfactory specimens follow:
CHART
The above tabulation shows an interesting change in the predominance of bacterial species and varieties. The proportion of cases in which fixed types of pneumococci were present dropped sharply in October, and late in this month pneumococcus Type II (atypical) and Group IV increased. During the same period streptococci were more abundant, as were influenza bacilli. The case fatality was 2.25 percent in September, 1918, rising to 3 percent in October, but receded sharply to 0.7 percent in November, when it might have been expected to rise because of the increased prevalence of nonhemolytic streptococci, the hemolytic streptococcus being found only once in September and not again during the epidemic. Three per cent is a low case fatality for this period as judged by the rates of other camps.
It was considered very significant that the Bacillus influenzae was found in only 243 of the 1,406 specimens, an incidence of but 17.2 percent, and that when present it was associated always with the Type IV pneumococcus. From this it seemed evident that the only part Pfeiffer's bacillus played in the epidemic at this camp was that of a secondary invader.
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Although many patients admitted to the hospital during the epidemic evidently had bronchopneumonia at the first examination, it was not believed that any of the cases could be considered as primary. On the contrary, all of the bronchopneumonia cases were considered secondary and, as stated above, all cases of pneumonia seen during the epidemic were merely those which, through lowered resistance or because infected with a more virulent organism, progressed to a point of actual parenchymal involvement of lung tissue. In accordance with this view there is no sharp dividing line between a severe bronchitis, bronchiolitis, and a mild bronchopneumonia. With the methods of examination at hand it was impossible to determine when one stage of the process left off and the other began. It is inconceivable that a severe bronchitis or bronchiolitis can exist without some associated parenchymal involvement.
The clinical and physical signs of the pneumonia seen in this epidemic were atypical. The usual signs of pneumonia, as seen in young adults, were conspicuously absent. Even men showing a definite bronchopneumonia on admission had reported on sick call only because they had a bad cold or felt weak. Interrogation, however, revealed the fact that they had been feeling poorly for several days with the same train of symptoms as given in the influenza cases.
Whether bronchopneumonia was present on entry into this hospital, or developed after admission, the clinical signs were identical. The face was flushed, a dry and unproductive cough was present, and, although very uncomfortable, the majority of these patients did not appear seriously ill until the process in the lungs had become quite extensive. The respiratory rate was moderately increased, usually to 24 or 30 a minute. Unusual for pneumonia but very characteristic of the cases seen in this epidemic was the fact that, although the respiratory rate was increased, dyspnea or orthopnea was never present. Patients critically ill and having a respiratory rate of 40 to 50 a minute seemed quite as comfortable in the supine as in the reclining position.
The pulse rate was relatively slow, pratically never faster than would correspond to the rise in temperature. The quality remained good throughout the course of the disease except in those cases going to a fatal issue. In fatal cases it often became weak, thready, and irregular some 24 hours prior to death. In other patients in whom death seemed imminent there was a full bounding pulse. This observation, together with the recognized frequency of right heart dilatation and the fact that, on the average, patients having epistaxis did well, led, in a few instances, to the performance of venesection. Four to eight ounces of blood were removed at one bleeding. Although, as a rule, this did not alter the progress of the disease, there were some cases in which it was felt that this procedure alone prevented a fatal issue.
The temperature, in the milder cases, seldom exceeded 103° F., and returned to normal in from three to five days. In many fatal cases the fever did not exceed 101º F. The return of the temperature to normal was almost invariably by lysis, covering a period of from two to four days. In isolated instances there was noted a drop by crisis, similar in every respect to that seen in ordinary lobar pneumonia.
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Cyanosis was a very constant observation in cases of bronchopneumonia. This varied between the wide limits of a marked flushing of the face to the heliotrope and the dusky gray types.
The word atypical, as used in the description, applies only if the cases were considered pneumonia from the start of the symptoms of illness, as the characteristic of bronchopneumonia as a whole is its varied rather than typical symptomatology. In the early stages the fluid accumulation with little tissue response was in accord with the clinical signs above described, an asthenic state which was followed by signs of pneumonic consolidation if the patient survived a sufficient time for such changes to take place.
The physical signs in the cases of bronchopneuinonia were probably the most varied of any of the unusual characteristics of the epidemic. The diagnosis of bronchopneumonia was often very difficult. Cases showing a relatively small lung involvement occasionally went to a fatal issue, while other patients showing a tremendous involvement recovered.
From the early and rather indistinct signs the course of the disease changed rapidly. In a large majority of the patients the disease progressed no further and went on to a prompt and uninterrupted recovery. The remainder showed a rapid extension of the process, marked dullness, with markedly increased or markedly decreased breath sounds frequently appearing but a few hours after the first indefinite signs were noted.
In 152 cases analyzed it was found that the incidence of absolute accuracy of lobes involved was but 20.38 percent. The diagnosis of pneumonia was made in all but one of the fatal cases, and the diagnosis was pathologically confirmed in all cases, except in the few instances where post-mortem examinations were not made. The one fatal case which was not recognized as pneumonia occurred in a soldier who walked to the hospital at 11 a.m., became suddenly comatose at 5 p.m., and died at 8.30 p.m., with no positive diagnosis made. Necropsy revealed a bronchopneumonia of both lower lobes with a markedly dilated right heart. This makes an error of but 0.6 percent in the recognition of the presence of pneumonia when the distribution of the process is not considered.
The physical signs were occasionally those of a lobar consolidation, with marked dullness, increased fremitus, and bronchial breathing. Early in the epidemic a few errors were made at this hospital because of these signs, and lobar pneumonia was diagnosed in cases which, at necropsy, revealed the true condition to be a lobar consolidation produced by the coalescence of lobular involvement. In the 152 cases coming to necropsy lobar pneumonia was anatomically diagnosed but six times.
In three of these cases there seemed to be no good reason to doubt this diagnosis, but in the other three instances bronchopneumonia was present also, leading one to suspect that these possibly were cases of coalescent bronchopneumonia, though in the gross specimen it was not obvious. Granting, however, these were cases of true lobar pneumonia, the incidence was still less than 4 percent as judged by 152 necropsies.
Inasmuch as lobar and bronchopneumonia, pathologically, differ from each other macroscopically rather than microscopically, the macroscopic signs upon which the differentiation between lobar pneumonia and bronchopneumonia
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was based are given. The cases of bronchopneumonia showing small isolated areas of consolidation offered no special difficulty in recognition. The areas of consolidation, on cut section, stood out from the remainder of the lung tissue, were different in color, firm on palpation, and sank in water. On palpation of the lung, prior to section, they were easily felt as firm masses surrounded by soft lung tissue. When, however, large numbers of these areas coalesced, the problem of differentiating the coalescent mass from lobar consolidation was often somewhat difficult. Palpation prior to section in these cases frequently, though not always, revealed irregularities in the consolidation. This irregularity, if present, was due to variations in the stages of consolidation of the lobules, some being merely in the stage of congestion while others were in the stage of red or grey hepatization. On cut section the surface was not the even, smooth surface of lobar consolidation. It was found, on close examination, to have slightly raised areas scattered about with distinct variations in color corresponding to the stage of the involvement. Invariably, by careful dissection, small areas of air containing lung tissue could be found and dissected out as evidenced by floating the sections in water.
On microscopic examination sections taken across the interlobular septa usually showed a variation in the reactions in the two lobules quite as characteristic as the gross appearance.
In the majority of the cases of bronchopneumonia, the process was not limited to a single lobe, but usually involved two or more lobes.
In the fatal cases analyzed 51.8 percent of the patients died on or before the eighth day after admission to the hospital and only 11.8 percent lived longer than 15 days.
Blood counts were made in 71 of the 152 fatal cases. The leucopenia, so characteristic in simple influenza cases, was found frequently to pertain still when the cases had gone on to a bronchopneumonia, though usually not to so marked a degree. In most instances the white count was found to increase as the pneumonia developed, e. g., 2,320 to 11,160 per cubic millimeter. The highest white count encountered among the fatal cases was 28,800. The average white count was 10,023.
Tonsillitis, pharyngitis, laryngitis, and tracheitis occurred as complications in bronchopneumonia in the same proportion as in straight influenza. Aphonia, however, was a more frequent finding during or after the acute stage of pneumonia than was experienced in simple influenza. This aphonia was due to ulceration, inflammation, and edema of the vocal cords. Otitis media occurred in bronchopneumonia in occasional instances. Sinusitis occasionally occurred in bronchopneumonia, but was never severe and never required surgical procedures. Other complications, however, occurred which were experienced only in cases of bronchopneumonia.
Pericarditis occurred as a complication in a number of instances. Clinical recognition of fluid in the pericardium was found rather difficult, and suspected cases always were fluroscoped or radiographed for confirmation. A few cases, unsuspected clinically, were found on routine roentgenological examination. Purulent pericarditis was encountered clinically in but one instance.
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Empyema, considering the number of cases of bronchopneumonia, was rather uncommon. Lung abscess occurred as a complication in but two cases. Subcutaneous emphysema, pneumothorax, and interstitial emphysema were unusual complications encountered in some of the cases of bronchopneumonia.
Delirium, both mild and severe, was very common in the cases of bronchopneumonia.
Prolonged uterine hemorrhage occurred so constantly among the female patients that it required special mention.
The mildness and relative infrequency of serious complications indicate a low virulence of the secondarily invading organisms and are in conformity with the relatively low total case fatality rate of 3 percent in October, the month of the peak of the pandemic.
In the cultures on 152 cases pneumococcus Type I was found three times in sputum and twice at necropsy; Subgroup II, six times in sputum and twice at necropsy; Group IV, 61 times in sputum and 53 times at necropsy; pneumococcus, type undetermined, four times at necropsy; nonhemolytic streptococcus, 44 times in sputum and 44 times at necropsy; hemolytic streptococcus, once in sputum and nine times at necropsy; streptococcus viridans, 4 times in sputum and 18 times in necropsy; streptococcus mucosus, once at autopsy only; Bacillus influenzae, 15 times in the sputum and 9 times at necropsy.
During the epidemic 1,196 blood cultures were taken of which 1,170 were negative and 26 positive (2.25 percent). The organisms found in the positive cases were: Pneumococcus type undetermined, 19, Group IV. 1; streptococcus, type undetermined, 3; nonhemolytic, 1; hemolytic, 1; viridans, 1.
The infrequency of streptococcus in the blood cultures is in conformity with the low case fatality and is, in part, explanatory of it.
The urinary findings in the fatal cases were as follows: Specimens examined, 48; casts present, 2; albumin present, 7; casts and albumin present in 13. From this it would seem that some renal changes occurred in approximately 33 percent of the cases.
The gross pathological features of the fatal cases of influenzal bronchopneumonia were no less unusual or interesting than the clinical.
In the 152 cases coming to necropsy, emphysematous areas in the lung tissue were found in 47. These areas varied in size from that of a markedly distended alveolus to a large emphysematous excavation formed by the rupture of numerous adjacent alveoli. Frequently, leading off from these emphysematous excavations, there were air streaks appearing as shiny, glasslike tubes. In their course they definitely followed the blood vessels running to the hilus. In five of these patients generalized emphysema developed.
The rectus muscles were found ruptured on one or both sides in five cases. This rupture, when present, was associated with surrounding extravasation of blood and was always below the umbilicus. Several additional cases showed definite hemorrhage into the rectus muscles without rupture. In most instances it seemed that coughing was intimately associated with the rupture of the muscles; however, owing to the fact that the muscle tissue in each instance was pale and extremely friable, it is evident that the cough was but a secondary contributing factor, and that the primary factor was a degenerative process in the muscle tissue itself.
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The pathological picture of the lungs, in the cases of bronchopneumonia, has been briefly mentioned. In most instances the anatomical picture was well marked and characteristic for bronchopneumonia. Scattered areas of involvement usually were encountered in several lobes. They appeared, on cut section, as irregular, raised, firm areas of varying color, corresponding to the stage of the process. Usually several stages of infection were found in each case. In many instances several lobular areas of consolidation had become coalescent, forming a large area, not markedly dissimilar to lobar pneumonia. Careful palpation usually revealed variations in density, and dissection showed marked variations in specific gravity. In this way it was possible definitely to show that all but six of the cases were bronchopneumonia. Three specimens, on section, showed a definite greenish tinge over the areas of consolidation, and culture revealed the presence of Streptococcus viridans in each of these instances. The lungs were described as edematous or congested in 105 cases. An excess of bloody, purulent and frothy fluid came away with the knife, on scraping. The lung tissue was described as friable in but five instances. Hemorrhagic areas resembling infarcts were noted in 13 cases. Small abscesses or pus pockets were described in 15 cases, being under the sternum in 1 case, interlobar in 1 case, in the lung tissue in 8 cases, and multiple in 5 cases.
The peribronchial lymph nodes were enlarged definitely in 104 cases, being noted more frequently on the right side. They were softer than normal in 15 cases. The bronchi contained an exudate in 54 instances, frothy in 11 cases, purulent in 22, bloody in 2, and taking the form of mucous or fibrinous casts in 19. The outer surface of the lungs, usually at the bases, showed exudate in 31 cases, purulent in 5 cases and fibrinous in 26. The pleural cavity contained abnormal fluid in 99 cases. In 64 the fluid was serous, serofibrinous, flocculent or bloody, and in 35 cases was seropurulent, fibrinopurulent, or purulent. The abnormal fluid was usually small in amount. In several cases the area of lung involvement seemed too slight to be considered the cause of death.
Pathological changes in cardiac muscle were extremely frequent. The most common evidence of muscular changes was the presence of dilatation of the right heart. Dilated right heart (thin, pale, and flabby walls, and enlargement of the tricuspid ring) was found at necropsy in 100 cases, 66.4 percent. Dilatation of the left heart was much less frequent, being found in but 12 instances. Definite myocarditis was recognized anatomically in six cases. Pericarditis, although recognized clinically in but two cases, was encountered at necropsy in 10 instances. Usually the pericarditis seemed due to direct extension from an adjacent septic pleurisy. Hemorrhages into the pericardium were encountered four times. Acute endocarditis was a very rare complication, being found but three times.
The most frequent changes encountered in the liver were enlargement, 43 cases, and congestion, 67. Fatty degeneration was present in 15 instances, cloudy swelling in 18, infarct in 1, and acute hepatitis in 2 instances. An abscess was found in the liver in one instance. Jaundice was noted in 12 fatal cases.
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The spleen was enlarged in 90 cases, being markedly enlarged in 26. In 62 cases it was described as soft or friable, and was classified as acute splenitis in 35 cases. Hemorrhagic areas were noted in five cases, and definite infarcts were found in two.
The kidneys presented the usual features associated with acute infections. A large majority presented cloudy swelling, enlargement and congestion. Four cases showed hemorrhage into the kidney substance. Thirteen cases were classified as acute and four as chronic nephritis.
The adrenals were classified as normal in practically all cases. Three cases showed enlargement, and in two cases the adrenals were hemorrhagic.
The respiratory diseases at this camp throughout its duration and including the pandemic period had a relatively low case fatality rate. This low rate appears to have been due to the relatively low virulence of the secondarily infecting organisms.
Pneumococcus Group IV predominated and that group apparently had a large proportion of relatively avirulent organisms. Streptococci of the non-hemolytic variety appear to have been prevalent with Streptococcus hemolyticus practically absent. No other factor appears to explain this low case fatality. The types of pneumonia were the same as at other camps except that the interstitial variety is not described, neither do there appear to have been many deaths in the early stages before definite consolidation was present, unless in cases where, as stated by the investigators referred to, there "was a seemingly insufficient amount of pathological changes in the lung to account for death."
There are 27 protocols of necropsies on cases dying of acute respiratory disease but no lung specimens from this camp in the collections at the Army Medical Museum.
CAMP MACARTHUR, TEX.ff
Acute respiratory diseases at this camp show an epidemic incidence beginning in November, 1917, there being at first, however, relatively little pneumonia and few fatalities. The epidemic reached its peak in January, 1918, accompanied by a relatively high fatality rate, the deaths being ascribed very largely to primary pneumonia. While measles, in January, 1918, showed the highest rate for the period of the war, there was also an epidemic rise of influenza in this month, 199 cases of this disease being diagnosed. Influenza and common respiratory diseases were responsible for the peak in April during which the case fatality, as is indicated by Chart XI was very low.
The data concerning the period from the opening of the camp to the influenza pandemic are insufficient to make possible an explanation of the difference in case fatality in the two periods of high incidence. gg Empyema appears to have been more frequent in the second series and fixed type pneumococci were also more prevalent.
ff Source of information, except as otherwise indicated: Medical reports to the Surgeon General, 1917, 1918, and 1919.
gg The following statements of fact are based, in the main, on: (1) Lobar Pneumonia at a Base nospital, by Leon S. Medalia and Nathan S Schift. Journal of the American Medical Association, 1918, lxxi, No. 22,1821-1822. (2) Influenza Epidemic at Camp MacArthur: Etiology, Bacteriology, Pathology, and Specific Therapy, by Leon S. Medalia. Boston Medical and Surgical Journal 1919, clxxx, No. 12, 323-330.
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CHART XI.- The incidence and fatality of the acute respiratory diseases at Camp MacArthur
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An examination of the sputum of the very first case that appeared in this camp demonstrated the abundance of B. influenzae in the sputum and the ease with which it could be found in direct smears. Sputum smears were made, dried, fixed, and stained by a weak solution of carbol fuchsin (carbol fuchsin, 1; water 4, parts). The influenza bacilli were found in clumps varying in size. These clumps were very abundant in the vast majority of the cases that were positive. The clumps when stained by Gram's method of staining were found to consist of Gram-negative ovoid, very small bacilli agreeing in every respect with the classical description of the Pfeiffer bacillus, mixed with numerous Gram-positive cocci and diplococci.
The ease with which the influenza bacillus was demonstrated in the direct smears of the sputum suggested the possibility, in the beginning, of controlling the spread of the disease by isolating tent mates of each case as it appeared; to have these contacts sent to the laboratory, have their sputum examined, and, if found positive to isolate and treat them as carriers, while the negative contacts were to be released--in short, to handle them similarly to the handling of the diphtheria contacts.
This was carried out in 7 squads, from 5 to 8 men each, a total of 44 men, 38 of whom were found negative and 6 positive. It was soon realized, however, that the contagiousness and the spread of this infection was so rapid that the procedure became impracticable and had to be abandoned. The examination of the sputum, however, was made the basis of diagnosis of influenza in all cases that were sent to the base hospital as influenza "suspects."
Sputum examinations of 2,279 influenza "suspects" showed 76.8 per cent positive for influenza bacilli. Cases with negative laboratory findings were discharged when that was found possible clinically. The practicability of sputum smears as an aid in diagnosis was amply demonstrated in this series of examinations.
The sputums were studied also for the presence of associated organisms, more especially the pneumococci and streptococci, and for the presence of pus cells. Thus in 1,613 sputums that were found positive to B. influenzae, 861, or 53.3 percent, showed the presence of the pneumococci; 148, or 9 percent, streptococci. Out of the 552 sputums negative to B. influenzae, 296, or 53.6 percent, showed the presence of pneumococci; 26, or 4.7 percent, streptococci. The large number of pneumococci in both the positive and negative influenza sputums suggest the ever-presence of this organism generally, and explains the reason for the finding of this organism in practically all the bronchopneumonia cases complicating the influenza. The low percentage of positive findings of the streptococcus, in both those that were positive to B. influenzae and those that were negative, explain the lack of finding this organism in the bronchopneumonia cases. It also demonstrates the comparative freedom from this organism generally of the troops in this camp during this epidemic.
Cultures were obtained in a number of cases, that showed positive sputums early in the disease, from the posterior nares and tonsils. These were also found culturally positive to B. Influenzae.
It would seem fair to conclude from the foregoing that the sputum and mucous membranes of the upper respiratory tract contained B. influenzae in
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abundance. The sputum droplets in speaking, coughing, and sneezing were probably the largest, if not the only, means of conveyance of these organisms from individual to individual and the most important etiologic factor.
By far the most important problem, from a mortality standpoint, to be dealt with was the accompanying bronchopneumonia.
The type determination was made in 445 cases of this type of pneumonia with the following results: Type I, 1 case; Type IIa, 15 cases; Type II, 8 cases; Type III, 5 cases; Group IV, 378 cases; undetermined (bile insoluble), 38 cases. The other organisms, beside the pnuemococcus, noted in direct smears in 405 sputums on which the type determination was done, were B. influenzae, 54 percent; streptococcus, 15 percent. The associated organisms found in the same sputums culturally were B. influenzae, 10.6 percent; streptococcus, 15.2 percent; staphylococcus and B. mucosus capsulatus, 20 percent each. The small percentage of positive findings of B. influenzae in the sputum culturally as compared to the direct smears was due in part to the hardships encountered in cultivating this organism in culture media used in routine for the type determination. The findings were characteristic of the bacteriology of the sputum in this disease. The very large percentage (86 percent) of Group IV in these bronchopneumonia cases well illustrates the difference between secondary pneumonias and primary, such as lobar.
Blood cultures were taken in 233 cases. The usual technique was followed. Both agar plates and broth cultures were obtained in each case. The plates were made with 2 to 3 c.c. of blood to the plate while 10 c.c. were used for the broth cultures. Among the 34 positive cultures were 31 pneumococci; 20 of these pneumococci were type undetermined (being bile insoluble), and 1 of the 20 also showed B. influenzae, 7 showed Group IV, and 4 Type II a. Five of the seven with Group IV died. Four of the 20 pneumococcus type undetermined died. (One that showed B. influenzae mixed with pneumococci died.) None of those that showed the staphylococcus died. The large number of pneumococci found to be bile insoluble in this series suggests that not all the pneumococci are bile soluble.
B. influenzae was found in the blood cultures during life in two cases. In one case, B. influenzae was found in pure culture, while in another it was mixed with pneumococcus. In both these cases the broth cultures were the only ones in which the organisms were found, not in the plates.
The mortality of the 198 cases with negative cultures was 16 percent, while of the 34 positive it was 23 percent. In 12 of the positive cultures growth was present in broth only, none in the plates. The negative cultures were kept under observation for 5 days, and quite a number showed growth only after the third or fourth days.
Since the blood cultures were taken at all stages of the disease, but always before convalescence had set in, the findings under these circumstances could therefore be considered characteristic of this disease even though the cultures were not repeated excepting in a few of the cases.
During this epidemic 61 consecutive autopsies were performed on influenza-pneumonia cases, beginning with the first case that died of this disease on October 3, 1918
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Cultures were taken at time of autopsy from the heart, spleen, both pleural cavities, both lungs, and from the brain in case of meningitis. Culture media used consisted of Loeffler's blood serum, glucose agar, and blood agar. Direct smears were also made from the pleural cavities and from both lungs. The bacteriological findings in direct smears of these necropsies were as follows: Of 58 cases examined of right and left lungs, B. influenzae was found in 79 percent of each. The pneumococcus was found in 97 percent and 93 percent, respectively, while the streptococcus was found in 12 percent and 9 percent, respectively.
Direct smears of the right and left pleura in 50 cases were examined; B. influenzae was found in 62 percent and 56 percent, respectively; the pneumococcus in 78 percent and 68 percent, respectively; the streptococcus in 2 percent and 4 percent, respectively. In two cases of meningitis complicating the bronchopneumonia, B. influenzae was found in both cases, 100 per cent. One was mixed with pneumococcus.
The cultural findings in 65 influenza-pneumonia necropsies (61 consecutive and 4 additional), 3 of which were complicated with meningitis, were as follows: Among those in which the right and left lungs were cultured, 83 percent each showed B. influenzae; the pneumococcus was found in 78 percent and 85 percent, respectively; the hemolytic streptococcus in 6 percent and 5 percent, respectively. Of 62 cases in which the right and left pleurae were cultured, B. influenzae was found in 81 percent and 76 percent, respectively, the pneumococcus in 77 percent and 74 percent, respectively, while the hemolytic streptococcus was found in 5 percent each.
The high percentage (56 percent) of positive findings of B. influenzae in the heart cultures, the spleen (56 percent), and brain (66 percent), as well as in the lungs and pleural cavities is worthy of note, in view of the difference of opinion concerning the presence of the Pfeiffer bacillus in this pandemic. The low percentage of the streptococcus hernolyticus in these bronchopneumonia cases as compared with the bronchopneumonia following measles, during the preceding year, which were practically all due to the hemolytic streptococcus, is another noteworthy point.
The pneumococcus which was found in 57 of the 61 necropsies conformed to the following types: Type I, 3.5 percent; Type II a, 10.5 percent; Type II, 5.5 percent; Group IV, 63.2 percent; undetermined, 19.3 percent. The B. influenzae and the pneumococcus both in direct smears and in cultures were in some cases difficult to find, and required considerable search, due to poor preparations and scanty growth. The Loeffler's blood serum with its abundant water of condensation was found to be the best culture medium for the B. influenzae and the pneumococcus. The carrying along of body exudates onto the surface of the culture media was probably responsible to a great extent for the results obtained on this ordinary culture medium, since this same culture medium proved unsatisfactory for subcultures.
Tissues for histological specimens were obtained from all the autopsies. Paraffin sections were made from the lungs and spleen, stained by 1 to 20 carbol fuchsin for B. influenzae and by Gram-Weigert stain for the pneumococcus and associated Gram-positive organisms.
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Sections from the lungs stained by Gram-Weigert and carbol fuchsin were examined in 64 cases (61 consecutive necropsies and 3 additional); 88 percent were found positive to B. influenzae and 68 percent positive to the pneumococcus. Sections from spleen were examined in 45 cases; 69 percent were found positive to B. influenzae and 42 percent positive to pneumococcus. The streptococcus was found only in 3 cases out of the 64--all in the lungs, none in the spleen. The staphylococcus was found in 8 percent of the lung cases; none in the spleen.
In a number of the cases it required considerable search to find organisms in the tissue; especially was this true of B. influenzae.
Thus the tissues as well as the cultures of the necropsy cases showed the presence of B. influenzae and the pneumococcus as the predominating organism responsible for the disease.
The majority of the 61 consecutive cases of influenza-pneumonia that came to necropsy were in the hospital from three to seven days only, the disease lasting longer than seven days being the exception rather than the rule.
The types of pneumonia found in the 61 consecutive necropsies were 56, or 92 percent, bronchopneumonia, and only 5 cases, or 8 percent, were lobar, 4 bilateral and 1 unilateral. In over 75 percent of the cases, empyema or a bloody-sero-fibrino-purulent pleurisy was present--52 percent bilateral and 24 percent unilateral (right 13 percent, left 11 percent); 24 percent had no fluid.
The lung tissue in the majority of the cases was extensively involved, ballooned out, but not friable, having a dense tissue feel, as if filled with fluid exudate to its maximum capacity rather than with fibrin or cellular elements. The surface of the consolidated areas was of a dark red to a dark bluish red, and in the majority of the cases covered with a thin fibrinous exudate. In no case did it show the matlike appearance of the post-measles bronchopneumonia cases that obtained at this camp during the winter of 1917-18. The picture was that of a markedly congested organ. The consolidation was only rarely nodular or shotlike in feel, excepting in those lobes which showed beginning of the process; even here the unaffected parts would be crepitant or edematous, as the case may be, with a confluent patch posteriorly or centrally located.
There was only one case where the lungs presented the appearance of miliary tuberculosis; and another where the lungs were pinkish gray in color with shotlike nodules throughout and immediately under the pleural surface, giving the latter a granular appearance.
The outstanding feature of the pathological anatomy was the marked congestion. On cut section, dark fluid blood would escape from the consolidated areas as if under pressure. The surface of the cut section presented dark reddish gray areas with hemorrhagic or congested areas intervening. Distinct lobular consolidations could not be made out. In a few cases pinpoint grayish purulent droplets would escape on pressure, but those were the exception. The case that did show shotlike feel presented on section a granular surface-grayish red raised areas, with lung tissues depressed and fairly dry in appearance. The lack of purulent exudate was the outstanding
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feature which suggested a study of the leucocytosis in this condition to be referred to later.
The mucous lining of the bronchi and trachea was bright red and inflamed but not markedly swollen. In a number of cases dark fluid blood, at times frothy, would escape from the nostrils and mouth on slight pressure of thorax while handling the body.
Histologically, the early cases, those showing nodular consolidations, presented a characteristic picture of terminal bronchiolitis, conforming in all respects to the textbook description of the same. Fibrin formation was found to be the exception. In the majority of the cases that showed the confluent type of involvement, vast areas of alveoli could be seen filled with a granular appearing coagulable substance, containing loose cellular elements of red and white cells-the so-called catarrhal pneumonia was the rule. Large hemorrhagic areas of alveoli filled with red corpuscles were seen in the lung tissues of a number of cases. Areas suggesting infarcts were also encountered. The case that showed an abundance of leucocytic exudation was the exception rather than the rule.
The other organs in the 61 consecutive necropsies showed little pathologic changes. Not a single case of pericarditis or endocarditis was met with. The liver, as a rule, was congested and occasionally a case would show typical nutmeg liver, probably due to other causes rather than the bronchopneumonia. The kidneys showed congestion and only in a rare instance were there parenchymatous changes. The spleen, too, did not show more than congestion, and fluid blood would escape on section. The same was true of the stomach and intestines; very little change, if any.
It was evident from the necropsy findings of these 61 consecutive cases that the disease, as it appeared in this camp, was primarily an upper respiratory infection due to B. influenzae and pneumococcus. The rapidity with which death occurred was probably responsible for the lack of pathologic changes in any of the other organs. This contention was well borne out by later necropsies on cases that were sick from four to seven weeks in which complications such as otitis media and meningitis occurred; pericarditis and thick purulent empyemas also were found. In these cases the other organs too showed parenchymatous changes concomitant with the duration of the disease.
In order to account for the lack of purulent changes in the pathologic picture of the lungs in these bronchopneumonia cases, a study was made on 224 cases with reference to the leucocyte and differential counts. The fact that from 72 percent to 75 percent of the cases showed a leucocyte count below 15,000 fairly well explains the pathologic picture. The differential counts showed that 71 percent of the cases receiving serum had a neutrophile count between 60 percent and 80 percent, while in those not receiving serum only 56 percent had a neutrophile count between 60 percent and 80 percent. The differential count showed nothing unusual otherwise.
The technique used at this camp was such as to obtain the highest possible incidence of B. influenzae; though it is possible that the characteristic morphological and tinctorial picture in the smears was depended upon to too great an extent. It is confirmed, however, by the high percentage of positive results in
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the histopathology of the lungs, 88 percent, which exceeded the percentage found by either smear of the sputum or culture of the exudates and tissues.
Protocols and specimens from 82 cases illustrate the pathology of this camp in the collections in the Army Medical Museum. Practically every type of pulmonary lesion described is illustrated in this material, though there are no cases showing the advanced stages of universal involvement of the lungs with interstitial, suppurative pneumonia. In these tissues, as in those of other camps, the well fixed material shows minute Gram-negative organisms, morphologically influenza bacilli, while the material not well fixed and that from some cases of longer duration, are less apt to contain such organisms.
CAMP MERRITT, N. J.
This camp was an embarkation and debarkation camp, and records from which a graph could be made are not available. Troops passed through the camp from practically all the others in the United States, so that the distribution of types of respiratory affection was somewhat more varied than usually seen in any one camp with a more constant population.
The pneumonia and empyema of the period preceding the influenza epidemic of the fall of 1918 was studied in the bacteriological laboratory of the base hospital. hh
Every effort was made to have the laboratory study as complete as is possible. By hospital orders sputum from every patient, as soon as diagnosed clinically as having pneumonia, was sent to the laboratory and then without special request the white blood cells were counted on the first and tenth days of the disease. Every fluid withdrawn from the chest was sent to the laboratory for examination and again without request the white blood cells were determined on that day, the first, second, third and tenth days after operation. Throat cultures were taken on all patients admitted to the measles wards. All cultures obtained were studied and a number of patients with measles, pneumonia, and empyema received repeated injections of autogenous vaccine made from their respective cultures.
The type of pneumonia and empyema prevailing at this hospital probably represented the types found at the various camps, as troops were sent there from practically all of the camps. The material for pathological study was derived from a very small number of necropsies performed at the base hospital.
While there were many predisposing or contributing factors, the chief exciting causes appear to have been pneumococci and hemolytic streptococci. Other organisms were present, such as nonhemolytic streptococcus, influenza bacillus, and a Gram-negative bacillus. This study was concerned chiefly with the Diplococcus pneumoniae and the Streptococcus haemolyticus, for it was believed that the former produces most of the acute lobar pneumonias, such as are seen in civil life, and the latter a special variety of "bronchopneumonia," sometimes called interstitial bronchopneumonia. A few cases also were found at
hh The following statements of fact are based, in the main, on: Pneumonia and Empyema in the Late Winter of 1917-1918, by Edwin Henry Schorer, F. D. Clark, Raymond Sanderson, John D. Dickson, and Frank M. Huntoon. Medical Record, New York, 1919, xcv, No. 17, 673-680.
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necropsy where a combination of the two types of the disease occurred with a mixed infection of pneumococcus and streptococcus. It is more than likely that one or the other of the diseases was primary, producing its type, followed later by a secondary infection and subsequently developing another variety.
The lobular type of the disease, from a pathological standpoint, divided itself into three groups of cases: (1) Those with a marked bronchitis and bronchiolitis with very little consolidation. Microscopic examination showed the alveolar passages and a few contiguous air cells filled with the products of inflammation. This is sometimes called capillary bronchitis. (2) This was by far the most common and presented a disseminated bronchopneumonia. There were scattered areas of peribronchial hepatization with patches of collapse of lung tissues. Much of the lobe was still crepitant. When this type was produced by an overwhelming infection with a virulent organism there was more marked interstitial change, with hemorrhagic foci scattered throughout the lung. This has been called "interstitial bronchopneumonia," a term seemingly better expressing the more salient features of the lesion. (3) The pseudolobar form. Here the greatest part of the lobe was consolidated, though not uniformly. There were intervening areas or strands of congested lung tissue between the hepatized lobules.
The microscopical picture in lobular pneumonia was quite different from that of lobar pneumonia. The exudate was less fibrinous and not, as a rule, hemorrhagic. It consisted of mucus, leucocytes, and swollen epithelium. The walls of the bronchi were swollen and presented marked round-cell infiltration. The avenue of infection was bronchiogenic, the inflammation began in the tubes and worked downward and outward, the continuous and contiguous alveoli next to the bronchi was densely filled.
Macroscopically, in the frequently occurring interstitial or organizing bronchopneumonia the lung presented in the early stages a smooth and glistening pleural surface. It was also found to contain considerable air while at the same time might be noted the beginning formation of patches of atelectasis. Small nodular masses might be felt throughout the lungs. On section the surface was studded with gray peribronchial nodules which protruded. These nodules were surrounded by a red or gravish halo, and were many times mistaken for miliary tubercles. On close inspection the lumen of the bronchiole might be seen as a crater-like opening or it might be filled with an opaque material. The exudate in this stage was like that in the earlier stage, showing very little fibrin, but with detached and disintegrated bronchial epithelium. The walls were hyperemic and much thickened, due to the process of infiltration. Large numbers of mononuclear cells seemed to replace many leucocytes that were found in the earlier stage of the disease. The exudate in the contiguous and continuous alveoli appeared less hemorrhagic. The interlobular septa were markedly thickened and stood out very prominently as gravish yellow lines. Empyema was present in all the cases of bronchopneumonia that came to autopsy. In all these cases the Streptococcus hemolyticus was demonstrated. In the early stages the exudate was thin, turbid, and greenish in color, containing shreds of fibrin, and a thin fibrinous coating covered the lungs' surface. This
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in the early cases could be easily wiped off, but later by reason of organization it became very adherent. In many of the cases there was a very large amount of fluid accumulated, between both the parietal and visceral pleurae, and between the lobes of the lungs themselves, giving rise to what at times appeared as lung abscesses.
From February 22, 1918, to May 15, 1918, there were made 219 examinations of sputum for type of pneumococcus and the presence of hemolytic and nonhemolytic streptococci. At times other organisms, especially B. influenzae, were noted on the records, but inasmuch as the other organisms found were not noted carefully, reports on these are excluded from this study.
On the clinical records the 219 specimens of sputum examined were classified as being from the following types: Lobar pneumonia, 151 cases; bronchopneumonia, 28 cases; combined lobar and bronchopneunmonia, 2 cases; not pneumonia, 38 cases. This leaves 181 cases of clinical pneumonia to be considered.
Of these 181 cases the following organisms were found: Pneumococcus Type I alone, 8; pneumococcus Type I and hemolytic streptococcus, 17; pneumococcus Type I and nonhemolytic streptococcus, 6; pneumococcus Type II alone, 4; pneumococcus Type II and hemolytic streptococcus, 6; pneumococcus Type II and nonhemolytic streptococcus, 5; pneumococcus Type III alone, 6; pneumococcus Type III and hemolytic streptococcus, 9; pneumococcus Type 111 and nonhemolytic streptococcus, 3; pneumococcus Group IV alone, 7; pneumococcus Group IV and hemolytic streptococcus, 19; pneumococcus Group IV and nonhemolytic streptococcus, 11; hemolytic streptococcus alone, 43; nonhemolytic streptococcus alone, 24; neither pneumococci nor streptococci, 13.
Empyema was the most frequent and important complication of pneumonia. As indicated above, purulent fluid was found free and encapsulated between the parietal and visceral pleure, between the lobes, in the pericardium, the peritoneum, the mediastinum, and between the layers of fascia. During the time covered by the investigation 81 cases of empyema occurred. These were recognized from the examination of the exudate obtained at the aspiration, the operation, or at the autopsy. Operations were done on seven patients, the fluids of which were not sent to the laboratory.
Sterile chest fluids were sent in from 25 patients. Cultures obtained were studied from the fluids of 66 patients. From 56, or 84.8 per cent of these fluids, hemolytic streptococci alone were obtained, pneumococci Type I were obtained 3 times, Type II 2 times, Group IV 4 times, and Group IV and hemolytic streptococci together 1 time. The disposition and results obtained as far as the cases in which the laboratory played a part were as follows: Hemolytic streptococcus, 56 cases with 27 deaths; streptococcus not studied, 7 cases with 7 deaths; pneumococcus Type I, 3 cases with 1 death; pneumococcus Type II, 2 cases with 1 death; pneumococcus Group IV, 4 cases with 3 deaths; pneumococcus and hemolytic streptococcus, 1 case with 1 death.
The empyema complicating type pneumococcus pneumonia was more frequently caused by hemolytic streptococci than by pneumococci. In four cases the empyema was caused by type pneuniococci when no pneumococci were found in the sputum. Of 22 cases of pneumonia in the sputum of which no
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pneumococci but hemolytic streptococci were found, three had empyema caused by type pneumococci. In all but four of the empyemas complicating pneumonia, in the sputum of which hemolytic streptococci alone or together with type pneumococci were found, the empyema was caused by hemolytic streptococci. Of the chest fluids obtained from cases of hemolytic streptococcus pneumonia seven, or nearly one-third, were sterile.
Type pneumococcus pneumonia was complicated by fluid in 35.5 percent of the cases; hemolytic streptococcus pneumonia in 37.2 percent of the cases; hemolytic streptococcus and type pneumococcus pneumonia in 26.8 percent of the cases; nonhemolytic streptococcus pneumonia in 16.6 percent of the cases and mixed nonhemolytic streptococcus and type pneumococcus pneumonia in 13.8 percent of the cases. Twenty-five of the pleural fluids were sterile; 28 percent of these complicated hemolytic streptococcus pneumonia.
It was the usual custom in the hospitals in the port of embarkation, Hoboken N. J., to send to the laboratory of the base hospital at Camp Merritt, patients diagnosed clinically as having pneumonia. The laboratory then made a white blood count on that day and again on the tenth day. While there was marked variation in the initial leucocyte counts, generally in the actual cases of pneumonia the white cell count varied from 8,000 to 25,000. After 10 days in uncomplicated cases the leucocyte count was usually down to 10,000 or less. In a few cases there was no increase in the leucocyte count on the first days of the disease; these terminated unfavorably.
All fluids withdrawn from the chest were sent to the laboratory and white blood counts were made on the first, second, third, and tenth days following. In all of the empyemas there was an increase in leucocyte count. The 10-day count on the pneumonias was of value in detecting some of the empyemas, and after operation if the leucocyte count did not go down, or if it again came up on the third or tenth days, some foci had not been located and drained or new ones were being formed. The leucocyte counts were not constant for the various pneumococcus and streptococcus types in either pneumonia or empyema.
From the above details it appears that most of the pneumonias at this camp were secondary, although a few cases, as indicated by the laboratory study quoted, and by the protocols from the camp, with reason might be termed primary lobular pneumonia. At any of the periods of high incidence of pneumonia it was noted that as such incidence was prolonged, streptococcus increased in the cultures both ante mortem and post mortem. With soldiers coming to the camp from various sources in the United States it is quite reasonable that streptococci of more or less virulence should be practically constantly present.
The relatively large number of empyemas appeared to follow all of the different types of pneumonia, but more frequently the interstitial type. The streptococcus was the most important etiological agent in their production.
During the pandemic of influenza, September to November, 1918, observations as to the nature and general character of the disease and of the epidemic were made at United States Base Hospital, Camp Merritt, N. J. ii These obser-
ii The following statements of fact are based, in the main, on: The Epidemic of lnfluenza at Camp. Merritt, N.J., by Francis M. Rackemann and Samuel Brock. Archives of Internal Medicine, Chicago,1919, xxiii, No. 5, 582-602.
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vations were made with respect to (a) the clinical and pathologic picture of influenza and bronchopneumonia; (b) the importance of secondary invaders in the latter part of the epidemic, and (c) the change in character of the latter part of the epidemic consequent on the activity of these secondary invaders.
From September 19 to November 6, 1918, 4,979 cases of influenza were treated at this hospital. Of these 4,979 cases, 1,015, or 20.4 percent, developed bronchopneumonia, and of these latter 31 percent died--a mortality for all the admissions of 6.3 percent.
The clinical picture of uncomplicated influenza in the early stages was very striking. The more important points on which the diagnosis was made were: The extreme and characteristic prostration; the history of very sudden onset--from health to prostration without warning often in a few hours; the general complaint of headache, with generalized muscular pains through the trunk and limbs; the high fever and the essentially negative physical examination.
A few of the early typical cases (perhaps 10 or 15 per cent) presented a very faint pinkish macular eruption on the face, neck, and anterior chest which often simulated the early eruption of measles, but which usually cleared up in about 18 hours. The pharynx was usually red, at times showing small punctate hemorrhagic spots, but no enanthemata or true Koplik spots were ever seen. Epistaxis was frequent, often severe. The lungs showed in a small proportion of cases a few rales at the bases, but this was by no means a characteristic finding.
The clinical course was rapid. In the majority of these cases the temperature fell to normal, usually subnormal, within four days, leaving the patient still prostrated and weak. The pulse was not rapid; at the height of the disease it was full and showed a tendency to dicrotism. Immediately after the fall in temperature the bradycardia was striking; observations of as low as 50 beats per minute being not infrequent.
Blood cultures on hormone gelatin broth (10 c.c. of blood in 100 c.c. of medium) were sterile in each of the nine cases studied.
Throat cultures planted on Loeffler's blood serum gave a mixture of organisms in each of 30 cases. Similar throat cultures from the same patients streaked on defibrinated blood infusion agar plates showed nonhemolytic streptococci in 17 cases, in 2 of which they were associated with pneumococci, and in 3 others with Gram-negative influenza-like bacilli. In four cases Gram- positive diplococci predominated, and two showed only staphylococci.
Postnasal cultures were streaked on laked blood hormone agar plates and showed a mixture of organisms in 17, a predominance of Gram-negative influenza-like bacilli in 5, while in 2 there was no growth.
Total leucocytes were counted on the first day of admission in 10 cases, and averaged 9,200 cells per cubic millimeter. On the fourth day, in the same patients, they averaged 8,500, at which time none of these patients had developed pneumonia. A study of the sputum was anticipated, but these patients in the early stage of the disease did not raise suitable sputum, in spite of the fact that coughing was often a definite symptom.
Quite as typical in its clinical unity as influenza proper was the serious manifestation of this infection spoken of as "bronchopneumonia." After the
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first symptom of influenza, the average time of onset of this manifestation was 4.03 days in a series of 726 recovered cases, and 5.7 in a series of 47 fatal cases.
In the bronchopneumonia cases, the temperature maintained itself or even rose higher, the pulse became rapid, and the respiratory rate, which had been between 20 and 24, now ascended, reaching anywhere from 28 to 50 per minute; cyanosis became quite noticeable, cough more severe, and physical examination of the lungs revealed a most constant finding, namely, one or more collections of small moist rales, patchy in distribution, usually located at the bases posteriorly. At this stage, dullness to percussion and the characteristic high-pitched bronchial expiration were usually lacking. On the contrary, there was frequently a diminution or even a suppression of breath sounds in the area affected. Experience soon taught us that in the following 24 or 48 hours signs of consolidation would appear in an area so affected. The heart, pericardium, and abdomen proved uniformly negative.
The clinical picture now became characteristic. The patient was severely prostrated and apathetic: cyanosis of lips, cheeks, and finger tips, with dyspnea, was impressive, the severe cough produced a glairy mucous sputum containing a small amount of purulent material; it had not the viscid tenacity of the sputum seen in lobar pneumococcus pneumonia. Blood in the sputum was a frequent finding; it ranged from a mere streaking to a considerable amount, and was reddish or dark reddish in color, and had not the orange rusty tint seen in lobar pneumonia. Occasionally considerable amounts were expectorated, giving evidence of the hemorrhagic extravasation going on in the pulmonary tissues. Epistaxis, often seen in the earlier stages of the disease, now became quite marked, occasionally even alarming. Headache and chest pain require mention; the latter a more or less constant substernal pain, apparently due to the intense acute tracheobronchitis, the former a continuation of the pain of the milder stage, and probably due to cerebral congestion.
In from 12 to 72 hours, as the patient became more acutely ill, the cyanosis deepened and dyspnea became more marked. Symptoms of the profound intoxication now dominated the picture: abdominal distention; urinary retention; sordes on lips and teeth, and dry, parched, heavily coated tongue with foul breath appeared. Symptoms referable to the central nervous system were seen at times, as twitching of the muscles of the fingers, forearms, and face. In this connection the delirium which appeared in all of the fatal, and in a good many of the recovery cases, deserves mention. It took on the form either of an active, even maniacal occupational delirium, or more usually the low mumbling type described by the old writers as being associated with the asthenic fevers. Nausea and vomiting occasionally were seen. Jaundice was a rare symptom, probably depending on an increase in the viscidity of the bile and, therefore, obstructive in origin.
The temperature, pulse, and respiration curves differed in the fatal and recovery patients. The fatal cases had a short course; in a series of 39 such cases the duration of the pulmonary involvement averaged only 4.7 days. The temperature curve seldom assumed the sustained plateau so common in lobar pneumococcus pneumonia, but was rather of an irregular, remittent type, ranging from 99 º to 105 ° or even to 107 º F.
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The pulse rate was usually considerably slower in these primary cases than would ordinarily be expected in a lobar pneumonia of similar severity. However, a stepladder rise in the pulse rate was of serious prognostic import, the continuance of this rise for over three days almost invariably indicating a fatal outcome. Irregularity of the pulse was seldom seen. Of greater value than either the temperature or the pulse was the respiratory rate, which was always raised. Here, again, a climb in the rate, sometimes precipitous, usually more gradual, presaged death.
The systolic blood pressure was normal in the acute stage of the disease, the diastolic was at times often as low as 55. With the drop in temperature the systolic pressure also declined, the diastolic pressure remaining low. These relatively low pressures were then maintained for several days, during the period of subnormal temperature and slow pulse, when they slowly recovered. No other marked or consistent observations were made on blood pressure, nor were essentially different observations made in the fatal and recovered cases. Readings within 24 hours of death were made in several instances at a time when the pulse was very rapid, but no additional fall was seen. From these observations it may be deduced that in this disease vasomotor tone is depressed, but that the heart's strength remains good to the end.
Total leucocyte counts were made in many cases, but no consistent findings were observed except that in the cases of primary influenzal bronchopneumonia the average count was low (5,000 to 15,000 cells per cubic millimeter). The presence of the hemolytic streptococcus tended to increase this average count but slightly, although the individual counts varied from 5,000 to 30,000 or even higher. Several cases were observed with counts below 2,000 cells, all of which were fatal.
In a small series of these bronchopneumonia cases the coagulation time of the blood was determined and found normal. The urine showed, as a rule, a trace of albumin with granular and hyaline casts. Red blood cells were found frequently. No other evidences of renal insufficiency were noted.
In the patients who recovered, the following interesting facts stood forth. In a series of 25 such patients, 16, or 64 percent, had a temperature fall by "crisis"; that is, a drop from 102 ° to 105 º F. to normal in 48 hours or less, whereas 9, or 36 percent, had a defervescence by lysis. In these crisis cases a decline occurred usually on the third day of the pulmonary involvement; in the lysis cases, usually on the fourth day, in which group an average of 5.5 days then elapsed before the normal baseline was reached.
Complications and sequelae of influenzal bronchopneumonia in a series of 705 cases included otitis media, acute, 28 cases; tonsillitis, acute follicular, 15; relapse, 12; laryngitis, acute, 8; abscess, subcutaneous; parotitis, 7; phlebitis, acute, 5; sinusitis, frontal, acute, 3; emphysema, subcutaneous, 3; epistaxis, very severe, 2.
"Unresolved pneumonias" were somewhat frequent. Of 635 convalescent patients, 121, or 19 percent, showed rales with occasionally slight dullness and harsh breathing over the site of the original lung involvement, persisting for two weeks after the fall in temperature.
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Toward the end of the third week of the epidemic, as seen at this hospital, surprising changes took place. Reports from the laboratory, as noted above, showed an ever-increasing proportion of the hemolytic streptococcus in the sputum. In the early days of the epidemic it was difficult to obtain satisfactory specimens of sputum for study; the cough in the pure "influenza-bronchopneumonia" is usually unproductive of any definite purulent or mucopurulent plugs of sputum, so that washing the sputum was practically impossible, and results could be obtained only by streaking the crude material on blood agar plates.
The hemolytic streptococcus was at first present in inconsiderable numbers, but in the third and fourth weeks its curve closely approximated the curve of the total examinations. The influenza bacillus at first outnumbered the hemolytic streptococcus, but in the third week its curve fell below the curve of the latter organism and remained below throughout the epidemic.
Curiously enough, it was recognized that the streptococcus patients seemed to "do better" or at least as well as did the other patients, and, further, that the death rate in proportion to the daily admissions seemed to fall markedly. Of the patients who entered the ward in the first five-day period, 65 percent died, while at the end of the epidemic, none of the patients admitted in the last three five-day periods died. Furthermore, the individual ward was losing its homogeneous appearance. The clinical course of the individual patient was no longer true to the type described.
The sudden and remarkable change in the clinical picture, in laboratory findings, and in necropsies is to be explained by the invasion of secondary organisms and the construction of a new pathology.
Beside showing the hemolytic streptococcus in such numbers, the sputum became more profuse and purulent.
The most striking change, however, was that whereas in the influenzal type of bronchopneumonia already described, pleural effusions were never encountered, they now became comparatively common complications. Pericarditis was also noted.
EMPYEMA
By empyema here is meant the pleuritic effusion complicating bronchopneumonia, regardless of gross appearance or of bacterial flora. The bacteriology of 50 such fluids coming to the laboratory of the hospital from October 1 to November 9, 1918, was studied.
The bacteriological examination of 50 pleural fluids showed the following organisms: Hemolytic streptococcus, 52 percent; sterile, 2 percent; pneumococcus, Type I, 6 percent; Group IV, 16 percent; nonhemolytic streptococcus, 4 percent.
In the study of etiology, a comparison of the bacteriology of chest fluid with the sputum in the same patient is important. Of 27 instances in which organisms were determined in both fluid and sputum, 17, or 63 percent, showed the same organisms, while 10, or 37 percent, showed different organisms.
At the necropsy table an explanation was sought as to why the classical auscultatory signs of fluid were so often lacking. The answer to the question is believed to be that whereas, in the typical pleural effusions of tuberculosis
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or lobar pneumonia, the lung is pushed up toward the hilus by the fluid, here the tendency toward sacculation is so strong that the lung very frequently is adherent over larger or smaller areas of the parietal chest wall, and it is believed that lung tissue, so adherent and compressed by the surrounding fluid, makes an admirable conducting medium for the passage of breath and voice sounds.
The various and peculiar sacculations of the fluid at the base, between the lobes, between the pleura and pericardium, in the anterior mediastinum, etc., represent a later stage of this process of sacculation and render the localization of such fluid extremely difficult. The encapsulation of these fluids was often beautifully shown by the roentgen ray, and was found by it to be more frequent than free fluid in large amounts.
NECROPSY FINDINGS
Necropsy findings in the different periods of this influenza epidemic varied considerably. Capillary damage, with resulting hemorrhages, represented the keynote of the pathology and explained not only the wet, bloody, soggy lung seen at necropsy, but also the bleeding from nose, bowels, or kidneys which occurred clinically.
In this acute disease, the upper respiratory tract was acutely inflamed, the mucosa throughout being injected, swollen, succulent, with hemorrhages in places. The bronchial lymph glands were enlarged, and on cut section appeared injected and hemorrhagic.
Pleural effusions, except for a small amount of sanguineous fluid in a few cases, were never found, and although the visceral pleura frequently lost its glossy sheen, fibrin in any considerable amounts was absent. The lungs were the site of the most important lesions: the involved lobes, especially the lower, presented a deep blue-red appearance, and seemed bulky; while on palpation they were heavy and soggy, without, however, the solidity of pneumococcus hepatization. On section, the involved area was almost blue-black and literally dripped a frothy, bloody fluid in large amounts, in marked contrast to the "dryness" of lobar consolidation. No fibrin plugs came away with the knife. Areas of hemorrhagic infarction were fairly frequent. The anterior borders of the lungs were almost invariably emphysematous and uninvolved. A few cases showed some interstitial emphysema in the lung tissue, which led to a generalized subcutaneous emphysema in the three cases already mentioned. Pneumothorax was found once.
In the less severe cases, only parts of lobes were involved and they appeared like the areas of marked congestion seen in hypostatic pneumonia. In the slighter involvements, patches of engorged or congested lung tissue were noted.
In these early acute cases the absence of pus deserves repeated emphasis. The pericardium was normal, the heart occasionally revealed a right-sided dilatation, which, however, was rarely marked. The endocardium was normal, as was also the aorta.
The stomach and intestines occasionally revealed small areas of capillary hemorrhage in the mucosa. While the gall-bladder was normal, the viscidity of the bile therein was markedly increased in a few cases to the consistency of thin paste. It was believed that the flow of such bile can be retarded to the
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extent of producing an obstructive jaundice. Mere mention may be made of toxic degeneration in the liver, and the congestion of kidneys, spleen, and brain.
The alveoli and bronchioles contained an exudate composed mainly of red blood cells and serum; polymorphonuclear leucocytes with desquamated epithelial cells occurred to a lesser extent. Fibrin was not found.
In the areas of advanced disease, the structure of the alveolus was lost; large numbers of erythrocytes and a large amount of serum with a moderate number of leucocytes "packed" the alveoli and smaller bronchi. The capillaries were engorged and stood out. The bronchial walls were edematous.
In less-advanced stages, the same cellular elements in the same proportion were found in lesser numbers and were at times grouped about the bronchi.
The heart muscle showed but slight granular degeneration. The kidneys showed considerable albuminous degeneration of the tubular epithelium, with granular debris in the lumina. The glomeruli were frequently congested.
The liver showed varying degrees of granular degeneration, the spleen, of congestion.
With the advent of the secondary invaders, the pathology changed. Pus formation and the resemblance to post-measles bronchopneumonia were noted. The mucous membrane of the upper respiratory tract was bathed in a mucopurulent exudate, beneath which the mucous membrane was acutely inflamed. Edema of the glottis and ulceration of the vocal chords were seen.
The pleura in these cases showed the most important and most striking lesions. Larger or smaller areas of the visceral and parietal pleura were very often coated with a heavy, shaggy coat of fibrin, which by adhesions to the contiguous lung tended to form the pockets of pus which were so common. These encapsulated empyemas not infrequently were multiple, in the positions already noted. It is of interest that often different pockets contained fluids of different color and consistency, ranging from a cloudy-amber to a greenish-yellow pus, and frequently showing shreds of fibrin,
The lungs revealed a condition of bronchopneumonia which can be divided into states: First, beginning bronchopneumonia, where small reddened nodular areas stood forth on cut section, their center being a small bronchus which exuded pus, between which fairly normal crepitant lung was found; second, these same nodular areas became larger, grayish in color, and on pressure exuded considerable yellow pus from both bronchi and lung tissue; third, the spread and confluence of these areas produced a large area of consolidation-pseudolobar bronchopneumonia; and fourth, larger or smaller areas underwent necrosis with abscess formation, the affected tissue becoming soft, mushy, and losing its distinctive markings. Atelectasis and septic infarction need only be mentioned: the former common, the latter occasional.
The pericardium revealed not infrequently an acute serofibrinous inflammation: an acute vegetative endocarditis was seen but once; otherwise the heart and aorta were consistently "negative." The spleen in these areas was often enlarged, its pulp quite degenerated, mushy, and necrotic.
The other viscera revealed no pathologic changes.
In contrast to the hemorrhagic exudate of the former picture, the alveoli and bronchi in these cases of secondary bronchopneumonia contained an exudate of polymorphonuclear leucocytes and serum, whereas red blood cells were
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insignificant. The bronchial walls were edematous, infiltrated with polymorphonuclear luecocytes; their epithelium was frequently desquamated. While in less advanced areas polymorphonuclear cells were grouped about the bronchi, later this distinction was lost. In some of the specimens the number of large mononuclear (epithelioid) cells was quite astonishing; these cells equaling, if not outnumbering, the polymorphonuclear leucocytes.
While actual giant cells were rarely seen in such specimens, a distinct tendency toward their formation was not infrequently noted.
Whether the presence of these large mononuclear cells was a part of cellular resolution indicative of a strong phagocytic process is problematical; however, the presence of a good many pigment-bearing cells in certain areas led toward the belief that these mononuclear cells were capable of considerable phagocytic activity.
In certain cases edema was considerable.
A comparison of the bacteriology of the lungs between the first 15 and the last 30 of 45 autopsies gave the following results: Hemolytic streptococcus in 26.4 percent of the first and 63.7 percent of the last; influenza bacillus in 72.6 percent of the first and 57.2 percent of the last; pneumococcus in 59.5 percent of the first and 34.3 percent of the last; nonhemolytic streptococcus in 6.6 percent of the first and 9.9 percent of the last.
In the more advanced areas cells in various stages of degeneration, indicating necrosis, were found.
The kidneys and liver showed extensive acute granular degeneration; the spleen, cellular necrosis with dilatation of the lymph spaces (producing the large mushy spleen).
Between the acutely engorged hemorrhagic lung of the pure influenza-bronchopneumonia, on the one hand, and this more advanced, less acute process associated with pus formation on the other, were all stages of transformation and all combinations. In fact, in many of the cases a mixed type of lung infection was found. The invasion by the secondary organisms was in no sense invariably productive of a pure type. This was thought to account for the discrepancy found on bacteriologic examinations of sputum and chest fluids. In measles, on the other hand, the invaders were almost invariably the hemolytic streptococcus, and as a consequence a purer pathologic type of interstitial or lobular pneumonia was produced and the complicating empyema was naturally almost invariably due to the hemolytic streptococcus.
The effect of a marked increase in a number of streptococci is clearly portrayed. The fact that many of the streptococcus cases presented because the patients lived longer and gave opportunity for such infection was not appreciated.
CAMP PIKE, ARK.ii
At this camp, the total case fatality rate for all respiratory diseases was as high during the epidemic incidence of the fall and early winter of 1917 as it was during the influenza pandemic of the fall of 1918. The measles cases of the fall of 1917 were accompanied by a high incidence of secondary pneumonia, with a high case fatality rate for pneumonia.
ii Source of information, except as otherwise indicated: Medical reports to the Surgeon General, 1917,1918, and 1919.
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CHART XII - The incidence and fatality of the acute respiratory diseases at Camp Pike
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Observations were made on 1,100 cases of pneumonia during the period from September, 1917, to April 27, 1918. kk
From the opening of the base hospital at Camp Pike, Ark., in September, 1917, to April 27, 1918, there were admitted to the medical wards 1,285 pneumonia patients; 857 of these had lobar pneumonia and 428 had bronchopneumonia.
The majority of the cases in September and October, 69 in number, were of the lobar pneumonia type, commonly seen in civil practice. During the month of September there were no deaths from either bronchopneumonia or lobar pneumonia, and during the month of October also there were no deaths from bronchopnuemonia; but there were 6 deaths, with a 10 percent mortality, from lobar pneumonia. The cases observed in September and October were typical of the lobar pneumonia described in textbooks. There were the sudden onset with chill, high temperature, rusty sputum, and well marked areas of consolidation. The cases of bronchopneumonia did not differ in any marked way and were essentially the same as those seen in civil practice.
In November there were 170 cases of lobar pneumonia and 75 of bronchopneumonia; in December there were 225 of lobar pneumonia and 139 of bronchopneumonia. The mortality of these two months of the lobar pneumonia cases was, respectively, 32 and 29 percent, and of bronchopneumonia, 4 and 29 percent. In January the mortality of lobar pneumonia was 29 percent and of bronchopneumonia 53 percent. The percentages of deaths gradually declined, and up to April 27, 1918, the total percentage of deaths in lobar pneumonia was 28. The total percentage of mortality in bronchopneumonia was 26, and from both bronchopneumonia and lobar pneumonia up to April 27, 1918, it was 26.07 percent.
The difference in the mortality in the later months compared with that of the first two months was possibly due to several factors: First, the large number of cases of bronchopneumonia that followed measles. Up to March 22, 1918, 33 percent of all pneumonias were those that followed measles. There were in the hospital up to the middle of April, 1918, 3,100 cases of measles. Second, in the wards in which there were many patients with respiratory diseases, the streptococci undoubtedly gained in virulence by their passage through the human host. Third, because of the large number of patients in a ward who were infected with streptocci, it must undoubtedly follow that the patients in that ward received a larger number of organisms than they otherwise would.
Many of the cases of bronchopneumuonia began with the most trivial subjective symptoms and with practically no objective signs. These men were sent to the hospital because they had been coughing for a few days and had had a rise of temperature, with a rather severe headache in the majority of cases. Many of these patients, on their entrance to the hospital, said they were not feeling ill and should not have been taken from their duty.
The physical signs were trivial and slight. In the majority of cases a few fine, moist rȃles were heard, usually at the back and near the angle of the scapula,
kk The following statements of fact are based, in the main, on: Pneumonia at a Base Hospital, by Arthur A. Small. Journal of the American Medical Association, Chicago, 1918, lxxi, No. 9, 700-702.
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on one or both sides. On percussion this area showed a slight amount of dulness. These were often the only physical signs present, and there were no subjective complaints of any kind, except a slight cough that was nonproductive. Examination made of the same patient from 12 to 24 hours afterward often showed a disappearance of these objective signs. The same patient examined in another 12 to 24 hours showed in the same area well-marked consolidation, with an increased number of moist rȃles and often bronchovesicular or tubular breathing. The fever usually was not high, rarely going above 103 º F. The pulse was not very rapid and did not become so during the course of the disease.
The large majority of these patients presented no respiratory distress of any kind. There was practically no dyspnea until dissolution approached.
Cyanosis was very rare, and was seen in only about 2 percent of the fatal cases.
At first there was no expectoration; it gradually became more free, but alwavs was moderate in amount. In practically all cases, the sputum was mucopurulent, though at times it was streaked with blood. At times the amount of blood in the sputum was so extensive that it might easily have been mistaken for hemoptysis due to tuberculosis of the lung, but on post-mortem examination, tuberculosis was proved not to exist. In none of the bronchopneumonia cases was the sputum rusty in color, nor did it have the gummy consistency seen in lobar pneumonia.
In contradistinction to this mild type of bronchopneumonia, there was seen a most malignant and fulminating type, which is illustrated by the following case:
Pvt. M., who was drilling in the afternoon, complained of feeling slightly ill. He entered the hospital at 7 o'clock that evening and died next morning at 6. On examination, he presented practically no signs of pneumonia, except a few moist rales which were distributed over both lungs and not confined or isolated to any particular part of the lung. He did, however, show the following signs of meningitis: Headache, depression, hyperesthesia and stiff neck. There was no rash, no Kernig sign, no Babinski reflex, no Oppenheim sign and no Gordon reflex. The diagnosis of bronchopneumonia was not made before death on account of the trivial findings. The post-mortem examination disclosed a small number of bronchopneumonia patches in the left lung and in the lower lobe of the right lung. There were no signs of meningitis. There was an acute and well-marked lymphadenitis of the bronchial lymph nodes. There was a cloudy swelling of the liver and kidney and an acute splenitis.
There were many cases in which there were signs of bronchopneumonia only in one lung, and some cases in which there was a bronchopneumonia in one lung and a lobar pneumonia in the other lung.
Empyema occurred in 9 percent of the total number of pneumonia cases. It was a most difficult matter to detect the presence of fluid, and because of this difficulty, exploratory puncture was made in every case in which the physical or constitutional signs indicated fluid or pus. There was a standing order in the pneumonia wards that roentgenoscopy be performed in all cases of pneumonia in which there was the slightest suspicion of fluid, and in every case of pneumonia at the expiration of 14 days.
In some cases it was impossible to detect the formation of pus. This was especially true when an isolated abscess cavity was formed by adhesions between the pericardium and the visceral and parietal layers of the pleura near the median
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line. In other cases the pus was contained in a fibrinous exudate, which acted not unlike a sponge, and confined the pus and limited its border as definitely as if it were surrounded by a cofferdam.
At times, the formation of pus was so slow that its presence was almost impossible to discover, for in many of these cases it simply plastered itself over the surface of the lung in a layer that was about one-half inch thick, so that the signs of the consolidated lung beneath it were transmitted through this layer, and there were no signs of the presence of fluid. In one case fluid had developed in a unique position. It developed and entirely covered the top of the right lung, fitting over it and displacing it down to the third rib in front and the fourth rib behind, capping it as an extinguisher does a candle. The upper lobe was pushed downward, forward, and inward and accounted for the increased tympany, which was found on percussion over and to the right of the sternum. The fluid was held in this peculiar and elevated position because of the dense adhesions, which existed in the whole of the pleural cavity below it. The formation of this fluid was extremely rapid, for over the area occupied by the fluid and 24 hours before death, there were all the signs of a consolidated lung with well defined tubular breathing. The breath sounds gradually became fainter and a tympany developed near the right margin of the sternum from the third rib downward. These were the only signs that were found, and their significance was misinterpreted. On the other hand, there were cases in which empyema developed with a tremendous rapidity.
In 48 percent of the cases in which the sputum examinations were made, pneumonia was due to the pneumococcus, of which 21 percent were Type I, 34 percent Type II, and 45 percent Group IV. Streptococci were found in 46 percent of the total number of cases. Of these, 46 percent were nonhemolytic and 54 percent were hemolytic.
In ward 1, 23 blood cultures were taken from patients in whom the clinical diagnosis was pneumonia. The blood cultures were taken as soon after admission as possible. The time of cultures relative to that of the prodromal symptoms ranged from three to seven days. Of the 23 cases examined, 6 gave blood cultures showing the Streptococcus hemolyticus. In none of these positive cases was the diagnosis of empyema made at the time or prior to the taking of the blood culture. In one case a blood culture was reported positive; but neither clinical examination, the exploratory needle nor the roentgen ray revealed the presence of fluid in the pleural cavity. A few days later, however, the exploratory needle revealed fluid which contained the same streptococcus as was secured from the blood. Three patients with positive streptococcus findings in the blood developed empyema. Two of the cases developed in the pleural cavity, the fluid containing the Streptococcus hemolyticus. In all of these cases the blood culture was taken not later than seven days after the onset of the disease, and in none of them was the patient in a serious or moribund condition when the culture was taken.
Jaundice was not infrequent and, in the Negroes suffering from pneumonia, it occurred in 10 percent of the cases. About 5 percent of all pneumonia patients had fibrinous pericarditis. There were three cases of purulent pericarditis.
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Pneumothorax occurred five times, on one occasion accompanied by pus in the pleural cavity, but this was complicated with chronic tuberculosis.
Otitis media occurred frequently, and in many cases was followed or acccompanied by mastoiditis. Strange as it may seem, mastoiditis occurred and was found, post mortem, without having given any objective or subjective signs during life.
This study indicates a very high incidence of pneumonia with a considerable number of the more severe varieties and with a rather high case fatality rate. Streptococcus hemolyticus was an important factor during this period.
A study of the bacteriology of patients admitted during February and March, 1918, gives further information on the bacteriology of this period which, as indicated in Chart XII, did not have an excessive case fatality rate.ll
Pneumococcus pneumonia presented but little out of the ordinary. Of the Type II cases several were complicated by severe jaundice. All were in colored persons, some of whom were known to have syphilis and one multiple gummas of the liver. The pneumococcus cases formed 48 percent of the 60 cases studied. Of these, 21 percent were Type I, 34 percent Type II, and 45 percent Group IV. Only one Type III case was seen in the hospital.
In 46 percent of the cases, streptococci were the predominating organisms; of these, 46 percent were nonhemolytic. These organisms formed colonies similar to the hemolytic streptococci, but had no effect on blood, neither hemolysis nor green formation being observed. The organisms were like the hemolytic streptococci as to morphology, but had more tendency to diplococcus formation, and the chains formed were short. Growth in both was flocculent and collected in the bottom of the broth. In the cases coming to necropsy the pneumonia in which this type of organisms was found resembled the ordinary pneumococcus lobar pneumonia. This type of streptococcus was found in the sputum in two cases diagnosed as influenza, and in the pus from a gangrenous appendix, in greatly predominating numbers.
Fifty-four percent of the streptococci found were hemolytic. The lesions found at necropsy in these cases were of two kinds: 1. A pneumonia similar to lobar pneumonia due to pneumoccoci, but with a tendency to pus formation. In many cases this was not more marked than that sometimes observed in the pneumococcus cases in others. Abscesses with areas of necrosis varied in extent, sometimes amounting to gangrene of large portions of the lung. 2. Bronchopneumonia in which the lungs were studded with bard, shotlike nodules, which were extremely hard to the palpating fingers. Cut sections of such lung showed areas up to 1 cm. in diameter which were dark red and completely consolidated. This form was most commonly observed following measles. The areas in some instances coalesced to form areas, in cases amounting to a lobe. In 25 of a series of 30 cases of mastoiditis, streptococci indistinguishable from these were isolated. The remaining five were Group IV pneumococcus infections.
ll The following statements of fact, except as otherwise indicated, are based on: A Bacteriologic Study of the Pneumonia Occurring at Camp Pike, Ark., by George F. Dick. Journal of the American Medical Association, Chicago, 1918, lxx, No. 21, 1529-30.
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Both the types of streptococci were more frequently complicated by empyema than were the pneumococcus cases. In the hemolytic cases in two instances there was peritonitis.
Leptothrix organisms predominated on the plates in 6 percent of the cases. These were very minute colonies, barely visible to the naked eye, but extremely numerous. There was no effect on blood. The organisms were Gram-negative, and varied in length from organisms resembling influenza bacilli to long, slightly wavy organisms extending half way across the field. It was not possible to cultivate these organisms beyond one or two subcultures, and their importance was undetermined.
The series is interesting on account of the high percentage of streptococcus infections, particularly those due to nonhemolytic organisms, which were found also associated with cases diagnosed as influenza and in the pus from appendicitis.
A board of medical officers, detailed for the investigation of respiratory diseases, centered their activities at Camp Pike during the pandemic, concerning which they made extensive studies.mm
The existence of an epidemic of influenza at Camp Pike was recognized when 214 cases of influenza were admitted to the base hospital, September 23, 1918. The epidemic was foreshadowed by a steady increase in the number of admissions to the base hospital diagnosed as acute bronchitis. This increase began about September 1, and on September 18 there were 50 admissions with this diagnosis.
Beginning September 23, the number of cases showed a sudden and alarming increase. September 27, there were 1,037 new cases, and the number continued in the neighborhood of 1,000 a day until October 3, when the final decline began. During the period from September 20 to October 19, there were 11,899 cases of influenza.
During the two months, September and October, there occurred 12,393 cases of influenza and 1,499 cases of pneumonia. Only two patients died with a diagnosis of uncomplicated influenza (not confirmed by necropsy), while of the patients with pneumonia, 466 died. Of the patients with influenza, therefore, 12.1 percent developed pneumonia, and the mortality for the epidemic as a whole was 3.8 percent of those attacked by influenza.
Between September 30 and October 14 there were 972 cases of influenza in the camp, with 107 cases of pneumonia.
The incidence of pneumonia in cases of influenza was much higher among the Negroes than among the whites. Of 10,296 white patients with influenza, 12.7 percent developed pneumonia, while among 1,429 Negroes with influenza, 283, or 19.8 percent, developed pneumonia. The rate of fatality from pneumonia was slightly higher in white men than in Negroes. Of 1,216 white pneumonia patients, 386, or 31.7 percent, died, while of 283 Negro pneumonia patients, 80, or 28.2 percent, died.
mm The following statements of fact are based, in the main, on: Pneumonia Following Influenza (at Camp Pike, Ark.), by Eugene L. Opie, Allen W. Freeman, Francis G. Blake, James C. Small, and Thomas M. Rivers. Journal of theAmerican Medical Association, Chicago, 1919, lxxii, No. 8, 556-565.
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The influenza was characterized by sudden onset with chilliness and sharp elevation of temperature, often from 103º to 105º F. There was extreme prostration, severe backache, suffusion of the face, and injection of the conjunctiva. Coryza, pharyngitis and tracheitis with a harrassing cough were almost invariable; epistaxis and slight hemoptysis, were frequent. In the majority of cases the temperature subsided after from two to five days, usually rather abruptly. About one-third of the patients developed purulent bronchitis.
Search was made for Bacillus influenzae in a group of 23 patients from 1 to 6 days after the onset of the disease. From each patient a culture on blood agar (5 percent horse's blood in meat, infusion agar) was made (a) from the nose, (b) from the throat, and (c) from sputum; and (d) sputum was injected into the peritoneal cavity of a white mouse.
Multiple cultures demonstrated in some instances in almost pure culture the presence of B. influenzae in all of the cases of early influenza. Passage of sputum through the white mouse proved the most effective means of demonstrating the organism; cultures from the sputum or throat were nearly as effective. There was some difficulty in demonstrating the organism in consequence of the minute size of colonies, which might be wholly overlooked by those not familiar with its cultural characters, in the presence of other organisms; for example, in the zone of hemolysis of the hemolytic streptococci the colonies became conspicuous.
In the 23 cases B. influenzae was found in the nose 5 times, in the throat 13 times, in the sputum culture 14 times, and in the sputum passed through the mouse, 18 times.
A considerable number of those attacked by influenza developed bronchitis. Of 103 influenza patients kept under observation, 36 had purulent bronchitis. The sputum was profusely mucopurulent and sometimes streaked with blood. The sputum on direct smear or on culture almost invariably showed B. influenzae, often in great numbers.
In attempting to establish the relation of B. influenzae to influenza and its complications, it was borne in mind that at Camp Funston, B. influenzae was found in the mouths of 35.1 percent of all healthy men examined and was present, in the absence of an epidemic of influenza, in the sputum of a very large proportion of those suffering with bronchitis. Observations at Camp Pike showed that the organism was invariably present in the upper respiratory passages of patients with influenza.
Pneumonia occurred in 12.1 percent of all influenza patients in this camp, and all pneumonia patients were treated in the base hospital. Among 103 influenza patients selected for observation from the onset of influenza, 4 developed clinical evidence of bronchopneumonia and 3 of lobar pneumonia.
Description of the clinical features of pneumonia following influenza is facilitated by division of the cases into three groups. 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. These groups are: (1) Bronchopneumonia, (2) lobar pneumonia, and (3) lobar pneumonia with purulent bronchitis.
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In the first group, bronchopneumonia usually developed gradually as a sequence to influenza in which purulent bronchitis occurred, one condition passing into the next without sharp demarcation. In the second group apparent recovery from influenza occurred, as evidenced by fall of temperature to normal. After from one to three days of normal temperature, typical lobar pneumonia with characteristic rusty sputum developed suddenly. In the third group, lobar pneumonia developed in cases of influenza that were complicated by purulent bronchitis. Such cases occasionally presented the picture of both lobar pneumonia and bronchopneumonia in the same individual.
Bacteriologic study disclosed that all these types of pneumonia were of pneumococcus origin in most instances. As described in greater detail below, some were further complicated by a superimposed Streptococcus hemolyticus infection.
The bacteriology of the sputum early in the disease was studied by inoculation of white mice and by direct cultures. The occurrence of pneumococci, B. influenzae and Streptococcus hemolyticus in 69 cases of lobar pneumonia was as follows: Pneumococcus Type I, 9 times (once with Group IV), or 13.1 percent; Type II, 3 times, or 4.3 percent; Type II atypical, 15 times, or 21.7 percent; Type III, 5 times (once with Group IV), or 7.3 percent; Group IV (alone), 37 times, or 53.6 percent.
Streptococcus hemolyticus was found three times, or 4.3 percent, in all three instances associated with pneumococcus Group IV. B. influenzae was found 43 times, or 62.2 percent, always associated with pneumococcus (Type I, 6 times; Type II, once; Type II atypical, 10 times; Type III, twice, and Group IV, 24 times).
Pneumococcus Types I and II, which have a predominant part in the production of the pneumonia of civil life, were present in a relatively small proportion of cases, whereas Type II atypical and Type III and Group IV were found with 82.6 percent of cases.
The bacteriology of the sputum in 43 cases of bronchopneumonia was as follows: Pneumococcus Type I, none; Type II, once, or 2.3 percent; Type II atypical, 3 times, or 7 percent; Type III, 3 times, or 7 percent; Group IV, 30 times, or 69.8 percent.
Streptococcus hemolyticus was found 6 times, or 14 percent; twice with pneumococcus Group IV and 4 times with no pneumococci.
B. influenzae was found 38 times, or 88.4 percent, associated with pneumococci 33 times (Type II, once; Type II atypical, 3 times; Type III, 3 times; Group IV, 26 times); with Streptococcus hemolyticus 3 times, and alone twice.
Here again pneumococcus Group IV was found predominant, being present in more than two-thirds of the cases. Streptococcus hemolyticus unassociated with pneumococci was found in 9.3 percent of these cases. B. influenzae unaccompanied by pneumococci or hemolytic streptococci was present in two cases; but in view of observations made at necropsy, it is doubtful if this organism alone was responsible for pneumonic consolidation of the lungs.
The characters of the group of pneumonias that occurred in association with the present outbreak of influenza may be defined by the pulmonary lesions found at necropsy, described in relation to the associated bacteria.
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Two hundred necropsies were performed during the outbreak of pneumonia, of which there are here analyzed 79 cases which, occurring with few exceptions in sequence at the height of the outbreak, were subjected to careful bacteriologic study. Cultures were made from the heart's blood, from the lung and from a bronchus. When the hemolytic streptococcus was found in the lung it was usually demonstrable in the blood. The number of instances in which B. influenzae was obtained in cultures would have been diminished more than half if cultures from the mucosa of the bronchi had not been made.
Necropsies showed the presence of purulent bronchitis in a large proportion of those who died with pneumonia during the course of this epidemic of influenza. When edema of the lungs was present, the content of the small bronchi was not usually purulent, though the mucosa might be intensely injected. B. influenzae could be grown with few exceptions from the mucopurulent material scraped with a platinum loop from the main branches. In 27 of 30 instances of purulent bronchitis from which cultures were made at necropsy, B. influenzae was found.
When purulent bronchitis was found, the lungs were very voluminous and preserved the shape and size of the thoracic cavity after removal; they showed little tendency to collapse, even when shut. Most of the affected lungs, being from men who came from rural districts, were pale pink and almost wholly free from coal pigment. After section a small droplet of mucopurulent fluid marked the site of each bronchus or bronchiole and doubtless explained the failure of the lung to collapse. The cyanosis of the patients with the disease was doubtless referable in part at least to the same change. The mucosa of the bronchi was intensely injected. Further evidence of severe injury to the bronchi was the frequent occurrence of a zone of hemorrhage about the smaller bronchi, particularly in the lower lobes. At times this zone of hemorrhage gave place to an encircling zone of pneumonia consolidation. Further evidence of profound injury to the bronchial wall was the dilatation of the small bronchi. Bronchiectasis was most conspicuous in the basal part of the lower lobes, and was usually more advanced on the left side than on the right. Small bronchi with no cartilage in their wall may reach a diameter of 0.5 cm. More advanced bronchiectasis was found in several necropsies performed late in the outbreak.
Among 79 necropsies, selected from the 200 performed, because they were in sequence and accompanied by careful bacteriologic study, there were 36 instances of lobar pneumonia, 19 instances of bronchopneumonia, 1 instance of associated lobar pneumonia and bronchopneumonia, and 23 instances of pneumonia with suppuration of lung tissue.
A group of 36 cases of lobar pneumonia, taken at necropsy in sequence and studied bacteriologically, gave further knowledge of the bacteriology of the disease as it occurred here. The results of this study were as follows: Pneumococcus Type I, 3 times; Type II, none; Type II atypical, 5 times; Type III, 6 times; Group IV, 19 times; total, 33, or 91.7 percent. Streptococcus hemolyticus with pneumococci, 10 times; with no pneumococci, 3 times; total, 13, or 36.1 percent. B. influenzae 31 times, or 86.1 percent.
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B. influenzae was present with few exceptions. Of pneumococci, which are frequently found in the mouths of healthy men, Type II atypical and Type III and Group IV were predominant, Group IV occurring in more than half of all cases, whereas Type I was found only three times in the present series, and Type II in no typical instance of lobar pneumonia. Hemolytic streptococci were found in approximately one-third of the cases of lobar pneumonia that were unassociated with gross evidence of suppuration. When the hemolytic streptococcus was unassociated with the pneumococcus it is probable that the latter had disappeared from that part of the lung from which the culture was taken.
The following two varieties of bronchopneumonia were observed repeatedly; however, they did not include all of the instances of bronchopneumonia that occurred: (a) Confluent consolidation of large parts of lobes; patches of consolidation, accurately limited to the secondary lobules of the lungs. The larger patches of consolidation were sharply limited by lobule boundaries so that the consolidated tissue on the cut section projected conspicuously above the air-containing lung substance. Even within the large consolidated areas, which were blackish red, red or grayish red and finely granular, the lobules were well defined; but there was no thickening of the interstitial tissue. Two instances of pneumonia due to pneumococcus Type II were of this character. In three other cases the lesion was caused by pneumococcus Group IV. (b) This confluent lobular consolidation was not the predominant variety, and disseminated nodules or patches of reddish, gray or yellow consolidation were more commonly seen.
The bacteriology of 19 cases of bronchopneumonia was as follows: Pneumococcus Type I, none; Type II, twice; Type II atypical, none; Type III, none: Group IV, 10 times; total, 12, or 70.6 percent. Streptococcus hemolyticus with pneumococci, 7 times; with no pneumococci, 5 times; total, 12, or 70.6 percent. B. influenzae, 17 times, or 89.4 percent.
Pneumococci doubtless had a predominant part in the production of the disease, and hemolytic streptococci acted as secondary invaders. Nevertheless it is possible that hemolytic streptococci in the presence of influenza may independently invade the lung and produce bronchopneumonia without suppuration.
Suppuration had occurred in more than one-fourth of the cases examined post mortem. Three varieties of suppurative lesion were found:
(a) Localized abscess formation within a patch of pneumonic consolidation. A patch of consolidation about one abscess was occasionally the only evidence of pneumonia, but more frequently there were multiple patches of bronchopneumonia. The abscess or abscesses were usually situated immediately below the pleura, often separated from the cavity by remains of the membrane no thicker than tissue paper, and the cavity was the site of purulent pleurisy with effusion varying from several hundred up to 1,700 c.c. In all but 1 of 11 cases of abscess with bronchopneumonia, hemolytic streptococci were found both in the blood of the heart and in the affected lung. In the one exceptional case, pneumococcus Type IV was obtained from the blood; no growth was obtained on the plate inoculated from the lung, and hemolytic streptococci with B.
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influenzae were found in the bronchus. B. influenzae was found in the bronchi (6) or in the lung (2) in all but 3 cases of these 11 cases. There can be no doubt that the suppurative process due to hemolytic streptococci was in some instances superimposed on pneumonia caused by pneumococci. In one instance, associated pneumococcus Type II was present in blood, lungs and bronchus; in one instance, pneumococcus Group IV was present in blood and bronchus. Of less significance was the demonstration of associated pneumococci, Type II atypical or Group IV, in the bronchi or lungs (three instances).
(b) Pneumonia with suppuration of the interstitial tissue. In association with bronchopneunionia (three times), with typical lobar pneumonia (twice) or with all defined patches of consolidation (three times), probably best classified as bronchopneumonia, suppuration of the interstitial tissue of the lung occurred eight times among the cases with completed bacteriologic examination. The interstitial septums appeared as conspicuous yellow lines from which purulent fluid might be scraped. The septums usually were swollen to a thickness of about 1 or 2 mm., but wide lines of suppuration 0.5 cm., across were seen. Edematous swelling of the septums outside of the consolidated tissue not infrequently was found. These suppurating septums extended up to the pleura, and the overlying lymphatics were often widely distended with fluid. Purulent pleurisy, usually with copious effusion up to 1,900 c.c., was found. In seven of these eight cases, hemolytic streptococci were found both in the heart's blood and in the affected lung. In one instance of lobar pneumonia with interstitial suppuration, pneumococcus Group IV with no hemolytic streptococci was found in the heart's blood and lungs. By unfortunate error, no culture from the affected lung was recorded. The relation of the lesion to associated infection with pneumococci is important. Pneumococcus Type II was found in one instance associated with hemolytic streptococci in the heart's blood, lung and bronchus. In one instance, pneumococcus Type II atypical with B. influenzae was found in the sputum during life unassociated with hemolytic streptococci whereas three days later pneumococci were not demonstrable in the lungs or bronchi, and hemolytic streptococci were found in blood, lungs and bronchus. In another case, pneumococcus Group IV and hemolytic streptococci were found in the sputum during life, whereas after death five days later pneumococci had apparently disappeared and hemolytic streptococci were found in the blood and the bronchus, with B. influenzae in the latter situation.
(c) Multiple abscesses clustered about bronchi. In four instances in the group of cases under consideration, suppuration occurred within bronchopneumonia patches clustered about a medium sized bronchus. These abscess cavities in communication with the bronchus were several millimeters up to 0.5 cm., in. diameter, and were surrounded by gray, consolidated tissue. The patch of consolidation studded with abscesses might be scarcely more than 5 cm. across, but a much larger area might be involved. There was no empyema or pleural effusion in these cases.
The bacteriology of the four cases cited was as follows:
Necropsy 280.- Hemolytic streptococci were found in the heart's blood, in consolidated lung tissue and in the bronchus. In the bronchus were found B. influenzae and a few staphylococci. Culture from the abscess was contaminated.
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Necropsy 322.- The blood was sterile. Staphylococcus aureus was obtained from consolidated lung; Staphylococcus aureus and pneumococcus Type III were obtained from the abscess .
Necropsy 329.-The blood was sterile. Staphylococcus aureus and pneumococcus Group IV were obtained from the abscess; B. influenzae, Staphylococcus aureus and pneumococcus Group IV from the bronchus.
Necropsy 333.- The blood contained pneumococcus Type II atypical; Staphylococcus aureus and pneumococcus Type II atypical were obtained from the lung on the opposite side; Staphylococcus aureus, B. influenzae and a few hemolytic streptccocci from the bronchus.
The foregoing observations indicate that Staphylococcus aureus may be engrafted on a pneumococcus pneumonia and cause suppuration in clustered foci, unaccompanied by empyema.
Hemolytic streptococci introduced into ward 1 containing patients suffering with pneumonia due, as experience showed, to pneumococci, produced an epidemic of secondary infection with streptococci. Routine necropsies with bacteriologic examination of the blood and lungs of every patient that died with pneumonia furnished a certain means of recognizing the occurrence of ward infection with hemolytic streptococci. These necropsies, with the accompanying bacteriologic studies, gave the first conclusive evidence that the pneumonia in this hospital following influenza was subject to secondary invasion with hemolytic streptococci.
Infection with pneumococcus Type II occurred in two patients apparently recovering from other types of infection, in one instance caused by pneumococcus Type II atypical, and in another by Group IV. In both instances pneumococcus Type II apparently was acquired from a third patient occupying an adjacent bed.
There were two instances in which, after one type of organism, namely pneumococcus Group IV, was found in the sputum by inoculation of white mice and subsequent identification of the pneumococcus, a different type was demonstrated in the blood or lung at necropsy.
Pneumonia of one type does not establish any trustworthy immunity from other types of pneumococci. Patients with one type of pneumococci, notably in the examples cited of Type II, may infect with fatal result patients suffering with or recovering from other types of pneumonic infection. In the absence of streptococcus pneumonia it is essential to maintain in a pneumonia ward precautions that will prevent transmission of infection from one patient to another.
The studies at Camp Pike show that the primary lesion of the respiratory tract in this epidemic was descending bronchitis and bronchiolitis, which, according to the cultural results, was considered due to Bacillus influenzae. Lesions in addition to that pathology were produced by pneumococci and streptococci or both, and consisted of all the varieties of bronchopneuimonia described, with a smaller proportion of the typical croupous lobar pneumonia. Among other things of pathological importance, the study shows that the deaths which occurred in the early days of the disease from an interstitial type of reaction of acute nature, usually accompanied by areas of hemorrhage, were due apparently to the Streptococcus hemolyticus. The Streptococcus hemolyticus is a relatively common secondary invader in any type of pneumonic condition,
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and is to be suspected in any lung where abscesses are found and where empyema results. Any one of the following organisms--pneumococcus, streptococcus, and Friedlander bacillus--may invade a lung already the site of an infection by any of the others. Increase of virulence as well as invasiveness of the streptococcus, is clearly shown in the studies made at Camp Pike.
CAMP SHERMAN, OHIO nn
The curve for respiratory diseases rates at this camp, as shown in Chart XIII, rises gradually. The case fatality rate for all respiratory diseases reached a high point in January, 1918, at 1.1 percent, dropping during February to 0.5 percent and increasing sharply in the month of March, 1918, to 1.16 percent. At this time the pneumonias appeared to be somewhat more severe and streptococci were found in a greater number in cultures. From then on relatively low rates prevailed until August, when the case fatality rate rose from 1 percent in July to 2 percent in August. In September the influenza pandemic struck the camp and the case fatality rate rose sharply to. 11.25 percent and was maintained at about this figure (11.05 percent) in October. These high case fatality rates at this camp, which was visited by approximately the same varieties of pneumonia as seen in other camps, can be explained by the fact that considerable numbers of patients were treated at the regimental infirmaries and did not reach the hospital, therefore these cases did not appear on the permanent sick and wounded records. Over 3,000 cases were treated in the regimental infirmaries during the month of October. If these were included, the case fatality rate was only about 7.75 percent, a rate quite close to that seen in many other camps throughout the United States.
There are no data concerning the pneumonias preceding the pandemic of influenza, with the exception of the sick and wounded report made to the Surgeon General.
The respiratory lesions of the pandemic of influenza were carefully studied by members of the base hospital staff. oo
The camp medical personnel realized that cases of coryza and bronchitis were increasing during the early part of September but did not consider the clinical picture sufficiently definite to justify a diagnosis of influenza. This uncertainty was definitely terminated by the sudden occurrence, about September 24, of large numbers of cases exhibiting the characteristics of clinical influenza.
At this time the population of the camp was 33,044. Of this number, 24,513 were white, and 8,531 were colored. Two-thirds of these cases occurred in a group of 15,493 recent arrivals, comprising less than one-half of the camp's population.
In addition to the cases admitted to the base hospital, other cases of influenza to the extent of 3,361 were reported from the various camp organizations. The addition of this number to those admitted to the base hospital afforded a total of 10,979 as the number of individuals affected in this epidemic.
nn Source of information, except as otherwise indicated: Medical reports to the Surgeon General, 1917, 1918, and 1919.
oo The following statements of fact are based, in the main, on: The Epidemic of Influenza at Camp Sherman, Ohio, by Alfred Friedlander, Carey P. McCord, Frank J. Sladen, and George W. Wheeler. Journal of the American MedicalAssociation, 1918, lxxi, No. 20, 1653-56.
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CHART XIII.- The incidence and fatality of the acute respiratory diseases at Camp Sherman
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The following accrued statistics are of significance in relation to the extent of the epidemic: Of the camp's population (33,044), 33.22 percent were affected, and 23.05 percent were admitted to the hospital; 18.22 percent of those affected developed pulmonary edema or pneumonia, and the total mortality or case fatality of the total nember affected was 7.66 percent, while the mortality among those developing pulmonary edema or pneumonia was 42 percent. The mortality of the total population of the camp was 2.55 percent.
During all stages of the epidemic, examinations were made to establish the identity of the responsible organism. This organism was sought in materials obtained from: (1) Smears and cultures from sputum of influenza patients; (2) cultures from swabbings of throat and nasopharynx of influenza patients and immediate contacts; (3) cultures from sputum of patients after development of pneumonia; (4) blood cultures from patients after development of pneumonia; (5) post-mortem cultures from heart's blood, lung exudate, pleural fluid, pericardial fluid, spleen and kidneys.
Smears and cultures of sputum of influenza patients uniformly exhibited the pneumococcus as the predominating organism. On typing, these pneumococci conformed to the following groups: Group IV, 80 percent; Type III, 18 percent; Type II a, 2 percent. One culture containing the pneumococcus as the predominating organism presented two colonies of Pfeiffer's organism. Certain immediate contacts with influenza patients were examined bacteriologically at a time when free from any manifestations of disease. Seventy-six percent exhibited pneumococci. Such of these as were typed were uniformly Group IV.
Cultures from swabbings of the throat and nasopharynx of influenza patients exhibited pneumococci in 54 percent and hemolytic streptococci in 4 percent of all examined. In none of these cases were influenza bacilli demonstrated.
On the detection of a complicating pneumonia, cultures were again made of the sputum. Regularly the pneumococcus was demonstrated with 80 percent characteristic of Group IV. Cultural conditions were suitable for the propagation of Bacillus influenzae, but in no instance was it detected.
Blood cultures were obtained from 100 patients after the recognition of a complicating pneumonia. In 6 percent of these cultures, growths were obtained. All were identified as pneumococcus Group IV. No other organisms have been detected in blood cultures, the remaining 94 percent being sterile.
Cultures obtained at necropsy from various thoracic and abdominal tissues and fluids indicated the presence of the pneumococcus as the dominating organism in 53.3 percent of the bodies examined post-mortem, while in 46.7 percent Streptococcus hemolyticus was the outstanding organism. The pneumococcus on being typed was classified as 75 percent Group IV and 25 percent Type III. In only one instance were both pneumococci and hemolytic streptococci encountered in large numbers in the same case. In this instance Group IV pneumococci and hemolytic streptococci were demonstrated in all cultures taken, heart's blood, lung exudate, pleural fluid, pericardial fluid, spleen and kidney. In conjunction with the Group IV pneumococcus isolated from the lung exudate
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of one body, numerous colonies of the Bacillus influenzae (Pfeiffer) were detected.
The persistent absence of influenza bacilli in the diverse materials examined militated against attributing this epidemic to the Pfeiffer organism. Cultural conditions favorable to the growth of influenza bacilli were maintained. However, within the period covered by this study, this organism was exhibited in only two individuals. More consistently did the cultures yield growths of the pneumococcus, to the end that significance is to be attached to the pneumococcus-streptococcus group of organisms as a dynamic factor in this epidemic. It was not maintained that the pneumococcus was the specific agent causing the epidemic, as prior to the epidemic a high percentage of this camp's population harbored Group IV pneumococci. The nature of the clinical manifestations and the process evidenced at necropsy strongly bore out the contention that some member of the pneumococcus group had rapidly been distributed among the individuals of the camp, with activities of a character and severity not previously observed in this camp.
The clinical manifestations observed necessitated a grouping into two form types. As already intimated, this epidemic was introduced by an atypical clinical picture characterized by mildness (Type I). The rapid spread gave a serious aspect to this simple catarrhal infection of the respiratory tract. The clinical features were fever, coryza, conjunctivitis, dry hacking cough, little or no leucocytosis, and no noteworthy chest findings.
This type of infection was noted first among patients already in the hospital. It probably occurred also in the camp, as within a few days increasing numbers of such admissions required special provisions for their separate care.
The absence of prostration and aches and pains led some to regard the diagnosis of influenza as unwarranted. Gradually, however, the type changed, and within five days there was a full realization that an epidemic of influenza was in force. The transition seemed rapid, once it started, and the momentum the epidemic acquired was appalling. This second type (Type II), recognized as true influenza, was characterized by sharper onset, chills, and quicker and higher rise of temperature, frequent epistaxis, distressing aches and pains, increasing prostration, red, glazed pharynx without tonsillitis, and an increase in the subjective manifestations of bronchitis, but still without noteworthy physical findings in the chest. Some cases of gastroenteritis and a few of the so-called nervous form of influenza were observed.
At once two types of more seriously ill patients demanded attention. In the one (Type III), respiratory distress was marked, with meager signs in the lungs. At the most, suppressed breath sounds with fine rales in the lower axillary spaces were found. There was no local change in expansion, vocal fremitus, percussion, or transmission of whispered or spoken voice sounds. Such signs did not necessarily progress to pneumonic consolidation. The other severely ill type, at this stage (Type IV), was the outstanding clinical feature of the epidemic. This formed a distinct clinical picture not emphasized in any published reports. During the height of the epidemic, many patients exhibited on admission a strikingly intense cyanosis, especially noticeable in the lips. This was not the dusky pallid blueness to which one is accustomed in a failing pneu-
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monia, but rather the deep blueness characteristic of methemoglobinemia. These patients had high fever, intense air hunger, complete exhaustion, and prostration. They were semicomatose or in a low, muttering delirium. The lungs contained diffuse bubbling râles, increasing rapidly in number and extent, in addition to subcrepitant râles. The course was rapid to death in 24 or 48 hours. The patient was practically a drowning man. The picture resembled an acutely progressive pulmonary edema. With the increasing moisture in the lungs, hox, ever, there was no sign of myocardial insufficiency or dilatation. The pulse was fair in volume and tension. Cardiac outlines were unchanged. There were neither enlargement of the liver, nor serous effusions or edema in other portions of the body.
These clinical observations were supported by the necropsy findings in these cases.
At necropsy, those dead of the condition designated clinically as an acute inflammatory pulmonary edema presented lungs having one or more lobes dark red or bluish gray, firm and rounded, with no tendency to collapse. The pleural surface was smooth and glistening, not thickened, without exudate. The lung tissue pitted deeply on pressure. The process was essentially massive and confluent. There was no evidence of a lobular distribution. Section through an involved lobe revealed an extreme grade of congestion and edema. Immediately on section there was a free outflow of thin, dark red fluid from the cut surface. From 150 to 200 c.c. of this fluid were measured from a single section across the lung in the different cases. The cut surface was somewhat rough but not granular; there was no evidence of fibrinous exudation. Stained films of this thin fluid showed large numbers of red cells, very few leucocytes and epithelial cells, and many Gram-positive cocci in pairs and short chains. The appearance of the bronchi was the same as that described below. The pericardium was normal throughout. The pericardial cavity contained from 25 to 30 c.c. of clear, straw-colored fluid. No portion of the heart evidenced any enlargement. The myocardium presented normal color and consistency.
These cases occurred frequently during the first three days and persisted to a less degree throughout. They diminished as bronchopneumonia increased.
The condition was suggestive of that occurring after exposure to chlorine gas. In many, the serous fluid almost poured from mouth and nostrils on change of position, or bubbled out in the distressing efforts to breathe. The man struggled against asphyxia with all the accessory muscles of respiration. Some of the patients retained consciousness for a remarkable period, suffering intensely. In a word, it was as if the irritation in the respiratory tract was so caustic as to produce an immediate reaction, serous in character. It was essentially an acute inflammatory pulmonary edema.
The complication naturally to be anticipated in an epidemic of the respiratory type of influenza was pneumonia. By October 2, the cases of pneumonia were so numerous as to occupy the entire bed capacity of the hospital. Arrangements were then in force to admit influenza patients to an improvised annex and only pneumonia patients to the hospital. Shortly thereafter the available hospital beds were filled, and it was necessary to place 383 pneumonia patients
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in a special section of the annex. Secondarily, the epidemic resolved itself into a pneumonia rather than an influenza problem.
A careful estimation of the circumstances would lead one to expect a secondary bronchopneumonia of virulent character, in an already acutely prostrated individual. This was the picture: The early cases in particular showed leucocyte counts, low fever, and rapid pulse and respirations. The asthenia incident to influenza was so profound as to greatly diminish the resistance to the pneumonia.
A striking feature at this stage was the absence of physical signs to localize the particular area of involvement. A peculiar tympany with crepitant rales and distant bronchovesicular breath sounds was frequently all that was found. This was explained at necropsy by finding the pneumonia exudate in lobular distribution mainly about the hilum of the lung and progressively diminishing toward apex and base.
In the cases enduring longer than the average, as well as later in the epidemic, impairment of percussion was found more frequently, in varying superficial areas. With this were bronchial breathing and the other signs indicative of outspoken superficial consolidation. In many of these cases the consolidation was lobar in distribution, often distinguishable with difficulty from acute lobar pneumonia. In some a clearing by crisis occurred. However, as noted below, the pathology of the fatal cases of this type was distinctly different from that of acute lobar pneumonia.
Many of these patients lay in muttering delirium which persisted after the temperature was normal. This could be explained by the asthenia, although there were several instances of serous meningitis. Only once did secondary pneumococcal meningitis complicate the picture. Acute hemorrhagic nephritis was a frequent clinical observation.
Five cases developed subcutaneous emphysema without demonstrable pneumothorax. This was distributed over chest wall, neck, and face, although in one case it involved the abdominal wall, scrotum, and lower extremities.
Acute fibrinous pleurisy, even pleural pain, was not observed, except in a few instances in the latter days of the epidemic. One case of empyema appeared.
The more hopeful cases frequently were characterized by small patches of consolidation which completely cleared, often in from 10 to 12 hours. This was one of the striking features of the epidemic.
Other than pneumonia, complications of influenza were slight. Profuse epistaxis without nasal ulceration was very frequent at onset, and later acute catarrhal otitis media was common, but fortunately always cleared without perforation of the drum. Hemorrhages into the middle ear and a few instances of acute sinusitis occurred.
In the necropsies of patients who died of pneumonia the lesions noted in the lungs were those of a confluent bronchopneumonia involving one or more lobes. In the average case more than 50 percent of the lung tissue was involved and frequently as much as 90 percent. The order of frequency of lobe involvement in this confluent pneumonia was right lower, left lower, right upper, left upper, right middle. In addition to this massive confluent
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process, there were patches affecting only a few lobules scattered throughout the remainder of the lungs, which resembled the ordinary type of bronchopneumonia.
The lobe affected with the confluent pneumonia was rounded, tense, and firm, with no tendency to collapse; it pitted on pressure and did not crepitate. The affected lobe, when placed in water, invariably sank. The pleura was smooth and glistening; a few presented a beginning fibrinous exduate. The color of the involved lung in some was a deep red, in others a deep bluish-gray, giving the lung a cyanotic appearance. Lobular outlines were indistinct or wholly obliterated. At rare intervals in a confluent involvement isolated lobules were unaffected.
On sectioning the lung there occurred an immediate exudation of dark bloody fluid. In patients characterized clinically as having pulmonary edema, this exudation was profuse to the extent of the spontaneous outflow of from 150 to 200 c.c. of this thin, dark red fluid. The consistency of the lung tissue was that of soft muscle and not friable. On scraping the surface with a knife only a thin bloody exudate was expressed; no air bubbles or fibrinous plugs. The scraped surface was dull and somewhat rough, but not granular. The color was a deep red, showing in places small areas from 4 to 5 mm. in diameter which were firm in consistency, almost black, and slightly raised above the surrounding tissue. These were noted more frequently adjacent to the smaller bronchi. The blood vessels of the affected lobe were dilated and contained dark fluid blood.
In the discrete lobular type of involvement, the affected lobules were distinctly raised above the surrounding lung tissue and were rather firm and resistant to the touch. The color, consistency, and appearance on cut section were similar to those of the confluent lesion described above, excepting that the amount of fluid exudate was much less. These discrete areas were more numerous near the hilum of the lung and diminished in number and size toward the apex and base.
The portions of the lungs not affected by the pneumonic process showed varying degrees of congestion and edema. At times the amount of congestion was surprisingly small, even in portions of the lung that were contiguous to the involved areas.
The bronchi contained thin, frothy, blood-tinged fluid, no mucus, no purulent material. The mucous membrane of the trachea and larger bronchi was swollen, causing distinct narrowing of the lumen. The color was pink, deep red, or purplish, the small blood vessels showing intense injection. The smaller bronchi were dilated, the walls thin, and the swelling and infection of vessels not so prominent as in the larger tubes.
Most cases showed a complete absence of pleural involvement, no excess of fluid, and no adhesions. In one case the right pleural cavity was filled with thin pus, from which a pure culture of pneumococcus was obtained.
The pericardium presented no indication of involvement. The pericardial cavity contained from 16 to 60 c.c. of clear straw-colored fluid at times slightly greenish. The heart usually presented trivial enlargement on the right side; the right auricle was distended with blood; the right ventricle presented moder-
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ate dilatation; the myocardium was red or brownish-red, bled easily and was usually of firm consistency. On occasion the right ventricular wall was moderately thin and flabby. The valves and cavities of the heart presented no characteristic findings.
The liver and spleen presented varying degrees of congestion, but were without other significant findings. The kidneys in a number of necropsies exhibited a beginning acute hemorrhagic nephritis.
There are 144 protocols of necropsies performed on cases dying of acute respiratory disease at Camp Sherman. Twenty-five of these are illustrated by specimens of lungs as well as other tissue. A great deal of the material has excellent fixation, autopsies being done relatively shortly after demise. In several of the cases especially studied, which showed relatively early lesions, minute Gram-negative bacteria were found along the smaller air passages. While it is realized that this morphological and tinctorial resemblance to Pfeiffer's organism does not constitute an absolute diagnosis, it is strongly suggestive that all the bacteria which were present in this epidemic were not discovered as a result of the cultural methods used. It was demonstrated in other camps as the result of particularly careful methods that cultures must be made from the bronchial tree soon after death if one is to show the total incidence of B. influenzae in the lungs. The fact that media are satisfactory to the growth of the organisms does not make certain that the material planted on the media contains it as it may have had a prominent part in the production of the pathological lesions without being present in the particular area cultured.
CAMP TAYLOR, KY. pp
Measles occurred in epidemic form immediately on the mobilization at this camp in September, 1917. It was accompanied by bronchial pneumonia in a considerable number of cases. Influenza, which was present with the measles, increased in December, and this increase was accompanied by an increase in the case fatality rate, ascribed in the records to primary pneumonia but actually due to pneumonia secondary to influenza, and other respiratory diseases. The sharp rise in acute respiratory diseases in March and April, 1918, was due to influenza and measles, over 50 percent of the deaths being due to pneumonia following measles. The pandemic of influenza occurred over the months of September, October, and November, 1918, the peak being in October. The case fatality rate for the pandemic was 6.04 percent in September, and 6.12 percent in October, dropping sharply to 1.26 percent in November. This drop is of considerable interest, for in many of the camps a rise in case fatality rate took place during the latter part of the pandemic period. The sharp rise in the case fatality rate in the month of December, 1918, to 3.07 appears to have been due to the streptococcus and the staphylococcus acting as secondary invaders during a wave of influenza.
A careful study was made of pneumonia and empyema as they occurred in the winter of 1917-18. qq
pp Source of information, except as otherwise indicated: Medical reports to the Surgeon General, 1917, 1918, and 1919.
qq The following statements of fact are based, in the main, on: Pneumonia and Empyema at Camp Zachary Taylor, Ky., by Walter W. Hamburger and Lawrence I. Mayers. Journal of the American Medical Association, Chicago, 1918, 1xx, No. 13, 915-918.
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CHART XIV.- The incidence and fatality of the acute respiratory diseases at Camp Taylor
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There were admitted to the medical service 374 pneumonia patients, 176 with the lobar and 98 with the bronchopneumonia type.
The early cases, in September and October, about 30 in number, apparently conformed to the usual picture of lobar pneumonia, with sudden onset, chill, temperature, rusty sputum, localized areas of consolidation, etc. Although type determinations of sputum could not be made, because of inadequate laboratory facilities in the early days of the hospital, these pneumonias undoubtedly belonged to the more benign type of organisms (Group IV), as only one death occurred in the series. This patient, who apparently had a mild case, developed a severe pneumococcic meningitis three days after a typical crisis, and died within 24 hours. The first case definitely diagnosed bronchopneumonia occurred, October 22, 10 days after the first measles admission. From then on the number of cases of pneumonia following measles increased rapidly, paralleling closely the measles admissions, latterly decreasing pari passu. In contrast to the early benign lobar pneumonias, these bronchopneumonias following measles were most severe and fulminant. Developing usually during the third or fourth day of the rash, the pneumonic process was ushered in by an increase in temperature, respiratory rate, patchy areas of dullness, roughened bronchovesicular breathing, moist bubbling rAles and, of particular interest, marked dyspnea and dusky cyanosis of the face. The latter two symptoms, interpreted as evidences of air hunger, increasing in severity with the progress of the pneumonitis, were most distressing and difficult to relieve. With fair degree of accuracy, one often could pick out the incipient pneumonias by noting the degree of cyanosis and blueness of the face, and by the same token could estimate the patient's chances of recovery.
Of a total of 102 cases of pneumonia following measles developing up to January 17, 1918, 87 developed during the soldiers' stay in the hospital, while only 15 were readmitted after discharge to quarters. In other words, the majority developed while in the hospital wards as close sequelae to the primary disease.
At necropsy, the lungs of these patients contained scattered, small or large areas of bronchopneumonic consolidation, with often multiple peribronchial abscesses from which thick greenish-gray pus could be expressed. Hemorrhagic and purulent tracheitis, bronchitis, bronchiolitis and bronchiectasis were usually present, while a markedly dilated right auricle served as evidence of ante-mortem cardiac failure.
About December 1, 1918, the fulminant atypical lobar pneumonias, later proved to be streptococcal in origin, began to appear and continued well past the middle of January. From the standpoint of the prodromes, these cases divided themselves into two classes: First, those starting insidiously with "sore throat," "cough," "grip," for a few days, progressing gradually until frank signs of consolidation could be elicited, and second, cases starting abruptly, severely, with sudden overwhelming prostration and collapse, profoundly toxic, progressing rapidly to death within three or four days, with symptoms so profound and acute as to suggest a general sepsis. These cases were most distressing. Because of the speed of development of the disease, and the evident urgency of the soldier's distress, little could be done to stay the progress of the disease.
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In both of these groups of cases, empyema developed in an extremely high percentage, 86 cases in 274 pneumonias, an incidence of 31.4 percent. In the four-week period from December 17,1917, to January, 1918, the empyema"epidemic" reached its height. Of 109 pneumonias, 52 developed pus in the pleural cavity, an incidence of almost 50 percent. This rise in the empyeina cases, reaching its height Christmas week (15 out of 18 lobar pneumonias developing empyemas), was in marked contrast to the week of January 15 (of 26 pneumonias,only 4 empyemas). These variations in the ernpyema curve were quite separate and distinct from the pneumonic curve per se, and were probably due to the virulence (selective action?) of the invading organisms (hemolytic streptococci).
This series of 86 empyemas differed in several striking respects from the metapneumonic and parapneumonic empyemas usually seen. Many patients came into the receiving ward from the regiments with chests full of pus. In other cases, within an hour or two of admission to the wards, quantities of pus could readily be demonstrated. In both, a history of illness not to exceed 24 hours often was obtained. The extremely rapid development of the empyemas, often well within 24 hours, was demonstrated repeatedly by fluoroscopic and roentgenographic examination.
Clinically, the severe prostration, with flushed cheeks, hollow bright eyes, short grunting dyspnea, deep boring chest pain, and asymmetric chest excursion were most prominent. Later this severe pleural pain was relieved somewhat, owing probably to the separation of the inflamed surfaces by the developing exudate.
Many cases, diagnosed clinically massive lobar pneumonia, showed at necropsy widespread atelectasis, with the lung compressed to half its normal size, but with little or no evidence of pneumonic consolidation. In these cases, purulent pericarditis frequently was associated, the pericardium containing a pint or more of thick, creamy pus.
Hemolytic streptococci were found in pure culture in a majority of the empyema fluids, 52 out of 93 examined, the remaining containing pneumococci or mixed organisms, or remaining sterile. The preponderance of streptococci was emphasized further by their presence in blood culture, pericardial pus, lung smears, and the heart's blood in these cases. Similar organisms were found widely distributed in various types of disease coming into the hospital at this time-almost universally in tonsil and throat smears, mastoid, middle ear and antrum pus, joints, abscesses, etc. The laboratory findings, together with complete absence of lung involvement in many instances, and the sudden overwhelming prostration and profound toxemia, with death in a few days, suggest that these so-called pneumonias were, in fact, true cases of streptococcic sepsis, with early localization in pleura and pericardium.
Another study was reported of a series of 233 cases occurring from January 3 to April 20, 1918, including infections of the lung and pleura only.rr In the group were 98 cases of lobar pneumonia, 59 of pneumonia complicated with
rr The following statements of fact are based, in the main, on: Report on a Series of Cases with Acute Infection of Lung and Pleura at Camp Taylor, by P. J. McDonnell. Interstate Medical Journal, St. Louis, 1918, xxv, 837-849.
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empyema, 27 of pleuritis with empyema, 24 of bronchopneumonia, and 25 of pleurisy, none of which was of the measles-pneumonia group.
Previous to December, 1917, the cases were nearly all straight pneumonias. In December, a peculiar empyema began to complicate the usual type. At the time when the study of this series of cases was started one had to deal with the lobar type, with its complicating empyema, and a few cases of pleuritis with empyema. In addition to this, the medical service of the base hospital was burdened with measles-pneumonia and empyema group. At the middle of March and continuing through April the type of pleuritis with empyema predominated. These were called "primary empyema" cases because no consolidation was found in the lung at autopsy or by physical signs. The onset was an intense pleuritis, which rapidly threw out a serous exudate. The effusion was nearly always massive and required frequent aspirations. In every instance the isolated organism was the hemolytic streptococcus.
There were periods when the streptococcus infections seemed far more virulent than at others. There were two large epidemics of measles-pneumonia, and at the end of both the patients were not so ill and the mortality was not so great as the beginning. After the early part of May this was noticeable also in the other types of pneumonia and empyema, as there were very few deaths.
The following figures show the distribution of lesions, empyema, and pleurisy in the 233 cases: Lobar pneumonia, 98 cases, with 10 deaths; lobar pneumonia with empyema, 59 cases, with 16 deaths; primary empyema, 27 cases, with 8 deaths; bronchopneumonia, 24 cases, with 2 deaths; pleurisy, 25 cases with no deaths; a total mortality rate of 15.4 percent.
In this group of 233 cases there were 98 cases of lobar pneumonia uncomplicated by empyema. Of this number 10 died, giving a mortality of slightly over 10 percent. Many of the cases had mixed infection, as both the pneumococcus were obtained from the sputum. Furthermore, a streptococcus empyema often developed upon a typed lobar pneumonia. In a large number streptococcus alone was isolated from the sputum.
The onset and course in the lobar group was very atypical. Instead of sudden pain in the side and chill, the patient would give a history of a slow onset with a cold or grippe infection. Usually he performed his duties until his strength gave away. With most of them the temperature dropped by lysis and the rusty sputum was absent. No doubt many of these cases had a pseudo-lobar consolidation with a large area of infiltration. To separate this form from the true lobar type was difficult in all cases and impossible in the many that developed fluid early.
Of the 157 cases, from only 19 was the Type I pneumococcus obtained. These, as a rule, were very sick and the serum was used in all but a very few instances. Among the 19 there were 4 deaths, giving a mortality of 21 percent. Every one of the four, however, had a severe complication and three had apparently recovered from the pneumococcus infection.
The total number of cases of lobar pneumonia in the group was 157. Of these 59, or 39.5 percent, developed empyema, a higher percentage than found in the measles-pneumonia cases. Of the 59 cases of empyema 16, or
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27 percent, died. The mortality of the entire pneumonia group, including all complications, was 16.6 percent.
In the series of 59 cases of empyema complicating pneumonia, 50 were of the hemolytic streptococcus type, 7 of the pneumococcus type, and in 2 the organism was undetermined. All the deaths took place among the streptococcus infections. In the pneumococcus group not a single death occurred, although every case showed a severe toxemia. From the streptococcus cases these seven differed remarkably in one respect, namely, in the amount of fluid that formed. This was greatly decreased. The fluid formed slowly and seldom was it necessary to aspirate oftener than once a week. No case totaled over 500 c.c. in all its aspirations, an ordinary amount for one tapping in a streptococcus case.
In this series there were 27 cases of pleuritis with empyema, of which 8 died. All were completely prostrated and many recovered that seemingly had no chance. All had a most intense pleuritis, of which they continually complained. They presented a typical picture, with flushed face, rapid and shallow breathing, and signs of great suffering. Nearly all were what was termed "rapid fillers," and required almost daily aspirations at the beginning. Several entered with a chest full of fluid and giving a history of only a few days' illness. In this respect they differed markedly from the lobar cases, where a history of preceding infection was usually obtained. Nearly all of the 27 cases came in at the end of March and the first three weeks of April. Many had pericarditis and two a purulent peritonitis, thus showing the severity with which the patient was attacked. In every instance the hemolytic streptococcus was obtained from the pleuritic effusion.
This type of case was called primary empyema, because no signs of lung consolidations were found previous to the pleuritis and effusion. Inside of a day or two the loud leathery friction rub would be replaced by the signs of fluid. In none of these cases were there present the typical tubular breathing and increased fremitus as with consolidation. Any that showed the slightest pneumonic signs were not placed in this group. Quite a number started off with a pleurisy, then showed signs of consolidation, and later fluid. These undoubtedly developed the empyema from the beginning pleurisy and not primarily from the lung infection. These, however, were not placed in this group. During this period there were numerous cases of plain pleurisy. They usually went to normal in a few days, while the infected ones went on to pus formation. It was impossible to predict which would develop pus. A few had large serous effusions in which no organism was found, and these cleared up nicely.
The autopsies performed on these cases showed no consolidation. Usually small patches of bronchopneumonia were present, but this condition was in all likelihood secondary to the pleurisy. The mortality in the 27 cases was 30 percent.
Of straight pleurisy, uncomplicated, there were 25 cases, without a death. The group was interesting in two respects. In the first instance nearly all occurred at the same period when the primary empyema cases developed in such numbers. And secondly in the first few days of the illness it was most
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difficult to differentiate the two types. It was impossible to forecast which would develop pus or which would clear up with the ordinary symptoms of pleurisy. Seemingly it was a matter of degree of infection or ability to combat it. After a few days all symptoms would disappear wherever fluid did not form. In some, however, the physical signs would remain much longer. Many of these could easily be mistaken for a pneumonia with a small patch of consolidation, as with impairment present the breath sounds were markedly accentuated over a certain area. Typical tubular breathing would persist in some cases for a week with the patient feeling perfectly well. This was a most disconcerting physical sign and one apt to be given the wrong interpretation. Apparently it occurred only when there was present a very thin layer of serum. The X ray would demonstrate a light shadow and usually a few cubic centimeters could be aspirated with a small needle. All had to be carefully observed as in several instances a flare-up occurred and empyema developed. Three of the cases had large serous effusions, which cleared up after aspirating. This group, occurring in large numbers at one certain period, with many developing a purulent effusion, offered a most interesting study from a diagnostic and prognostic standpoint.
The average high leucocyte count was: Simple pleurisy, 13,100: bronchopneumonia, 16,200; lobar pneumonia, 20,400; primary empyema, 27,000; pneumonia empyema, 27,500.
The leucocyte count in the entire series of 233 cases ran about as might be expected, being highest in the most toxic group. The lowest count was in the pleurisy group, and the highest in the empyema group. Nothing new was learned. Where daily counts were made, the change in the condition of the patient usually was reflected by the leucocytosis.
Of the 157 cases of pneumonia, in 90 the right lung was affected, in 56 the left, and in 11 both lungs. Of this number 59, or 37.5 percent, developed empyema, 29 in the right pleura and 29 in the left. This shows a marked proportionate preponderance of the infection for the left pleural cavity. This same tendency was apparent in the cases of pleuritis with empyema, where 17 of a total of 29 occurred in the left pleura. This is probably a coincidence, and doubtless no significance can be attached to it.
Pericarditis occurred in about 8 percent. In only three cases was there a well-developed effusion and one of these died following a thoracotomy. In the other two the fluid disappeared without leaving any bad effects. This complication was always a serious sign because the cases were the very sickest. Delirium was constantly present at the start. In nearly all the rub disappeared as soon as the acute symptoms subsided, and in none of this series was pus demonstrated in the pericardium. The rub in most of the patients was heard at the start, but with several it was not noticed until the pleuritic effusion began. With the primary empyema cases pericardial pain was often the first symptom, and in auscultation both pericardial and friction rubs were heard. The complication was far more frequent in left than in right side empyema.
Otitis media was the most frequent complication, occurring in about 10 percent. It was not usually of serious omen, but often produced a sudden rise in the temperature. It was present at all stages of the disease. Only two developed mastoiditis, one being double.
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Deep jaundice was present in five cases. These comprised a most toxic group, as the severity of the infection was manifested by three deaths.
Three developed a purulent peritonitis, all of whom died. At the same time all had a hemolytic streptococcus empyema.
One patient developed an ileus overnight. He had a very painful pleuritis and pericarditis, and had just been transferred from the cardiac ward. Inside of six hours there was a complete obstruction which could not be relieved by the usual measures. He was then transferred to surgery and the abdomen was explored. No pus was found. He died three hours after laparotomy. The sudden onset overnight and the complete paralysis of the bowel were striking features.
Abscess of the lung occurred in two patients. One, who had also a streptococcus empyema, died. Several cases developed body abscesses, usually on the back. Most of these occurred in the empyema group, and were largely due to the infection being carried back by the aspirating needle.
Four of the patients had a well-marked meningeal irritability, but in all of them the spinal fluid was negative. The meningismus usually cleared in about three days.
There were two cases of slow resolution. Both presented marked inpairment, with distant tubular breathing and rales. The X ray showed shadows to correspond.
Pyopneumothorax complicated two cases. In the group of 86 empyemas no case had pus in both pleural sacs.
During the winter 1917-18, necropsies were performed in 62 cases at Camp Zachary Taylor, Ky.ss The patients were soldiers, with one exception white, native born, physically and mentally sound, in the third decade of life, most of them country bred and from the Central States. This uniformity of type permitted comparative study.
In the fall of 1917, the etiologic agent was the pneumococcus with its customary results. Measles appeared late in October, causing the first death, November 7, from what is considered a typical measles pneumonia, with a catarrhal or purulent bronchitis. On the advent of the streptococcus infection, causing the first death, December 13, the pathologic picture changed, the bronchitis being now hemorrhagic, the pneumonia patchy and hemorrhagic, while the causative organism began to show a predilection for serous surfaces.
Causes of death as determined by necropsy in this series were: Bronchopneumonia, 27; lobar pneumonia, 8; empyema, primary, 6; pericarditis, primary, 1; the rest being meningitis and noninfectious diseases.
Bronchopneumonia was the lesion most frequently found, 35 of the 52 cases presenting this change; in 27 it was looked on as a primary cause of death.
To study more closely the effect of the various etiologic agents on the disease picture, all cases of bronchopneumonia were grouped into four classes: (A) Following measles; the Streptococcus hemolyticus isolated; 3 cases. (B)
ss The following statements of fact are based, in the main, on: Post-mortem Findings in Measles, Bronchopneumonia, and Other Acute Infections, by Baldwin Lucke. Journal ofthe American Medical Association, Chicago, 1918, lxx, No. 26, 2006-2011.
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Following measles; the Streptococcus hemolyticus not isolated; 13 cases. (C) Not following measles; the Streptococcus hemolyticus isolated; 10 cases. (D) Not following measles; the Streptococcus hemolyticus not isolated; 9 cases.
The bronchopneumonia, then, was preceded by measles in 16 instances, and not preceded by measles in 19 cases. The streptococcus was isolated in 13 cases, and not isolated in 22 cases. In the latter group the pneumococcus was frequently found. In a small number of cases, no bacteriologic studies were made.
Four anatomic types of bronchopneumonia were observed. These were found with such regularity that they were classified as Types Ia, Ib, II, and III. The first two types were found mainly in bronchopneumonia following measles; the last two in hemolytic streptococcic infection.
In Type Ia the lungs were large, expanded, and very heavy. The weight of each lung ranged from 600 to 1,100 gm., the combined weight often approaching 1,500 gm. The pleural surface might be smooth and glistening, but more often was dulled and overlaid with fibrin exudate. The general surface of the lung was mottled, dusky gray-red with a distinct bluish tint. Small, ill-defined areas of elevation and depression often were seen. On palpation, innumerable small, firm areas were felt throughout all the lobes. The lungs may be said to have had a "shotlike" feel. The intervening lung tissue was boggy. The cut surface was pale bloody-red; light pressure caused the outpouring of a large amount of moderately blood-stained, frothy serum. Scattered over the entire cut surface were numberless rounded, light gray-red, definitely raised, firm areas, appearing very much like large, gray miliary tubercles. They usually distinctly surrounded a small bronchial branch, and measured from 3 to 5 mm. in diameter. About one-half to one-third of the entire tissue was taken up by these consolidations.
The bronchial branches stood out distinctly; from many, a thick, yellow purulent fluid exuded. The bronchial mucosa was swollen and somewhat reddened. In some instances the bronchial tubules were dilated, forming small and rather smooth-walled cylindric or globular bronchiectases. The peribronchial lymph nodes were swollen, juicy, and dark grayish red. Their cut surface was very moist and had a mottled appearance.
Type Ib was a later stage of the preceding process. All the various anatomic changes were more accentuated. The pleura generally was covered with soft yellow exudate. The organ was markedly distended and the combined weight of the lungs approximated 2 kg. The surface of the lung lacked definite rounded contour, showing many smaller and larger elevations, blue, reddish brown or purplish in appearance, fading gradually. Subpleural punctate hemorrhages occasionally were encountered. The nodules palpated were larger than in the preceding type, but were of approximately uniform size. No large consolidated patches were felt. The anterior edges of the lung and the upper lobes might be inflated. The cut surface was moderately bloody. The general color was grayish red; innumerable well outlined, slightly but definitely raised areas of a vellowish, grayish red or dark reddish brown surrounded the bronchial tubes. These consolidations varied from about 5 mm. to 1 cm. in diameter. The grayish areas were quite firm, while the yellowish patches were
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more or less softened. The bronchi showed the same general changes as in the preceding type.
The principal features of Types Ia and Ib, then, were marked edema, the discrete character of the consolidations, their distinct peribronchial situation and their occurrence in all lobes. They varied in color, size, and consistency, being small, firm, and light gray in the earliest stages and then becoming larger, grayish red, dark red, and finally yellow and softer in appearance and consistency. The aggregate total of these areas would equal from one-third to two-thirds of the entire pulmonary substance, depending on the stage. A purulent bronchitis accompanied the lesions. The marked edema and the very small size of the consolidations often obscured the clinical picture of broncho-pneumonia.
In Type II the pleura usually showed inflammation; empyema was often present and the lung was slightly or not at all enlarged. On palpation, various sized areas of resistance were noted. On section, the lung tissue was not nearly so moist as in Types Ia and lb. The areas of consolidation were several centimeters in diameter, of irregular contour, slightly or indefinitely raised and not visibly peribronchial. They varied in color from dark red to grayish yellow and often showed a surrounding hemorrhagic zone. Usually the lesions were confined to one or two lobes. The bronchial branches were not unduly distinct and almost always showed a deep red hemorrhagic mucosa and exuded a sanguineous or sanguinopurulent fluid. The peribronchial lymph nodes were large and more reddish than in Types Ia and Ib. This type of bronchopneumonia resembled the ordinary kind seen in the necropsy room excepting the great frequency with which empyema occurred and the hemorrhagic character of the bronchitis.
Type III was confluent bronchopneumonia or pseudolobar lobular pneumonia. A large part of a lobe was consolidated. The cut surface was moist and finely granular; the granularity being less distinct than that of lobar pneumonia. The lobes showed several distinctly different processes. While the general color was brownish red, there were areas more yellowish and others more grayish or reddish; but all faded into one another, so that the end picture appeared at first glance more homogeneous than heterogeneous. The pseudolobar pneumonia, therefore, was made up of a number of units placed so closely together that they gave the appearance of a single large consolidated patch.
Nine of the 16 cases of bronchopneumonia following measles were of Type Ia or lb. The spleen was slightly enlarged, being about one and one-half to twice its normal size and averaging 225 gm. in weight. The capsule was smooth and transparent, the outside cover being bluish red. The organ was somewhat less firm than normal, the cut surface dull red, the trabecule of usual size, the splenic follicles were prominent, a light yellowish gray, and about twice their normal size. The splenic pulp showed no gross changes. The splenic picture, therefore, was one usually termed "acute follicular splenitis."
In five cases not showing Type I bronchopneumonia, complications were present which may have influenced the character of the lung lesions. In two instances a streptococcic infection was superimposed. In others epidemic
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meningitis, lobar pneumonia, and erysipelas coexisted. As to the development of the bronchopneumonia after the onset of measles and as to its duration no uniformity existed. The kidneys, in a majority of cases, showed various grades of acute parenchymatous nephritis.
One of the dominant symptoms of measles is bronchitis appearing early and often persisting. The cause of this bronchitis is not known, but it is reasonable to suppose that it is due to the virus of measles. In the epidemic under consideration, hemolytic streptococci appeared in the throat in a large percentage of the cases of measles, general medical cases as well as apparently normal cases. The great invasive power and virulence of the streptococcus found in this epidemic was demonstrated at necropsy by the extensive involvement of all the principal organs. It was most likely that they would thrive readily in an already pathologic field, that is, the inflamed bronchial tubes of measles. In the early postmortems, before the epidemic of streptococcus had appeared, a definite type of measles-bronchopneumonia was found, here termed Type Ia and Type Ib. From a study of the necropsies, it was believed that these were true measles-bronchopneumonia, caused by the virus of measles. Since, however, a number of organisms, as pneumococci and streptococci, occurred almost constantly in the throat, secondary invasion would take place in the bronchial system and one or another organism would be found in the bronchial branches and pulmonary lesions. If these organisms possessed marked virulence and invasive powers, and if they intruded early in the disease, the anatomic picture would be determined by the invading bacteria, and the possible influence of the measles virus might be obscured. In fact, the lesions established would be a true streptococcic or pneumococcic bronchopneumonia. If, on the other hand, the invading organisms entered the system late in the disease, were few in number, or did not possess marked virulence and invasive powers, they would influence the pathologic process slightly or not at all, and a true measles-bronchopneumonia would be produced. This explanation readily fitted the anatomic findings. Because of certain technical accidents, the microscopic sections were largely unfit for study; for this reason, only the gross anatomic picture is given.
The majority of cases of streptococcic bronchopneumonia were of Type II. The bronchi showed hemorrhagic inflammation. Empyema occurred frequently. The spleen presented the picture of an acute splenitis often with hemorrhages, or a distinct hemorrhagic condition; it was slightly enlarged, having a smooth capsule of a slaty color or dark red. The consistency was flaccid, the cut surface pale grayish brown and often containing irregular dark red hemorrhagic areas; the follicles and trabeculw were indistinct.
Otitis media, mastoiditis, and other complications were frequently present. The mastoiditis was characterized by reddish-black discolorization of the bone, which was so necrotic that it could be easily cut with a knife. Subserous hemorrhages, usually small and of pin-point size, were frequently encountered on the pleural, pericardial, renal, cerebral, and hepatic surfaces. Similar hemorrhages were found in the mucosa of the renal pelvis, the stomach, and the intestine. In a general way, organic changes were more widespread and of greater severity in the streptococcic infections.
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Cases of bronchopneumonia not following measles and not streptococcic occurred usually as a complication of some other disease. The lung picture was classified as Type II, but the bronchial and visceral changes were less pronounced.
The eight cases of lobar pneumonia resembled, in every way, those usually encountered. In three, coexisting bronchopneumonia was found, in all of which the pneumococcus was isolated. One pneumonic lung presented an interesting picture. The entire right lung was consolidated; the upper and middle lobe had a grayish-red cut surface, granular in appearance, from which pneumococcus cultures were made. The lower lobe possessed a distinctly more reddish appearance, and from this part hemolytic streptococci were isolated. It may be that the streptoccocic and pneumococcic inflammation coexisted, or, what is more likely, the streptococcus process was superadded to the pneumococcic involvement.
The necropsies during the winter of 1917-18 showed an unusually high percentage of empyema, this condition being present in 21 of 52 cases. (The term "empyema" is here used to include serofibrinous pleurisy).
Clinically, a "cold " or "sore throat" frequently preceded the empyema by a few days; then, after exertion, or without discoverable cause, the following syndrome was noted: A chill, which was described as severe and sometimes lasting for an hour, followed by a cough, pain in the side, fever and dyspnea. This clinical history, with the finding of dullness in the side often led to the diagnosis of lobar pneumonia. The roentgen ray and clinical studies showed that the empyema was of unusually rapid occurrence, often developing overnight
Only five cases of measles were complicated by empyema; in 10 instances "sore throat" or a "cold" preceded the disease. The organisms found were: Hemolytic streptococcus, 14; pneumococcus, 5; no growth, and undetermined, one each. In all cases the fluid obtained at necropsy was distinctly turbid, in most cases frankly purulent. It usually was a thick, yellow, and creamy liquid, in which large clumps of fibrin floated. Occasionally a greenish tint was found, and, in the streptococcic cases, a brownish, light coffee color. The quantity varied from 100 to 2,500 c.c.; this variation was due, in part, to previous aspiration or operation. In 9 instances the right, in 8 the left, in 4 both pleural cavities were affected. In the latter, various developmental stages could be observed; the empyema was walled off or pocketed by a tough, fibrinous adhe- sion between the lung and the lateral chest wall. Interlobar empyema was found only once. Sometimes only one, sometimes several pus pockets were present; a certain amount of free basal empyema usually existed. These cases were of considerable clinical interest since drainage proved difficult and occasionally a large pocket was not reached, while another was perfectly emptied. In all cases of empyema, the pleural surface was almost completely enveloped by a thick coat of yellow, soft exudate averaging from 3 to 10 mm. in thickness, and binding the lung lightly to the chest wall here and there. If the exudative process had existed for some time, organization occurred. The pleural surface then was grayish, and had a somewhat scaly, dry appearance. The exudate was much tougher and adhesion firmer; in the latter cases empyema pockets
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were found. This would seem to indicate that, other conditions permitting, early operations offered the best chance for complete drainage. The changes in the lung were usually those of bronchopneumonia; lobar pneumonia was found in only one case. The lung on the infected side showed compression varying in degree with the quantity of fluid present. In several instances the lung was no larger than a fist, having then a dry fleshy appearance and a tough meat feel. The cut surface was dark red, airless and dry, the bronchial branches standing out prominently because of the loss of separating tissues. More often than atelectasis of the entire lung, compression of only one lobe was found; this had the same appearance as described above. The uninvolved side showed compensatory inflation, the organ being widely distended and hypercrepitant.
In six cases no inflammatory changes were present in the lungs, and the empyema had to be looked on as primary. The lung tissue was carefully examined in these cases; and while it is conceivable that the existing atelectasis obscured the inflammatory changes, careful study failed to reveal any. Five of these primary empyemas were streptococcic in origin. In the other, no organism was isolated.
Ten instances of acute pericarditis were discovered, with one exception, in the serofibrinous or purulent stage. One case was preceded by measles, another by "rheumatism." The hemolytic streptococcus was isolated six, the pneumococcus four times (twice Type II, once Type I, once type not determined). Lobar pneumonia existed in one of the cases, bronchopneumonia in six, and in three instances the lung did not show any inflammatory processes. In all but one patient the pericardial inflammation was associated with empyema. In one case the pericarditis was looked on as primary, since no inflammatory processes in other organs were found present. In this case hydrothorax and ascites of undetermined origin were found.
The heart, in the majority of cases of bronchopneumonia and lobar pneumonia, showed right-sided dilatation and cloudy swelling. The aorta, in an unusual percentage of instances, presented atheroma. In 42 cases detailed notes concerning the state of the aorta were made. In 30 of these aortic atheroma was present in the form of elevated yellow patches or streaks. They were situated mostly in the ascending arch, and to a less extent in the abdominal aorta and other portions of the arch. The thoracic aorta was almost always normal. The atheromatous lesions numbered from a very few to several dozen. They were subintimally located, and varied in consistency from hyaline firmness to definite softening. The coronaries showed distinct involvement in a considerable number of cases. Since the common causes of aortic disease, syphilis and other chronic infections, were not to be elicited in the history or necropsy findings, one was forced to consider the possibility that this infection was the cause of the intimal changes, which speculation pointed out that close observation should be made of aortas in these young men coming to necropsy from acute infections. Since the patients were only in the third decade of life, the presence of aortic change is of interest.
The liver usually showed cloudy swelling. The gastrointestinal tract presented no noteworthy changes.
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Pneumococcic meningitis occurred in one instance and was associated with bronchopneumonia. The anatomic picture was similar to that of meningococcic meningitis.
In three cases of streptococcic meningitis, purulent otitis and mastoiditis was the atrium of the infection. Parts of the mastoid and petrous bone were bluish black and necrotic. The mastoid cells and internal ear contained greenish pus. The pia-arachnoidal vessels showed greater infection than in meningococcic meningitis. The exudate had a greenish tint, and was more abundant. Punctate subpial hemorrhages were present. Thrombosis of the right lateral sinus was seen once. The ventricles were overdistended in one instance, and in all cases contained semipurulent fluid. The ependyma was moderately reddened. The visceral changes were more pronounced than those of meningococcic meningitis. Parenchymatous nephritis was the principal lesion noted.
One case of bronchopneumonia was complicated with a marked hemorrhagic encephalitis. Clinically the patient developed delirium two days after the onset of the bronchopneumonia, and the neck became stiff. Lumbar puncture yielded clear spinal fluid containing a considerable number of polymorphonuclear cells.
The brain showed extensive subpial hemorrhagic extravasations, particularly over the frontal and superior parietal areas. The large veins were greatly congested. In the cut surfaces an unusual number of bleeding points were present. The cortex of the superior portion of the right frontal lobe contained an area of punctate hemorrhages about 2.5 cm. in diameter. In the cortex of the left parietal region a similar hemorrhagic area was found. The ventricles were normal in size and contained a slightly blood-tinged fluid. The ependyma was normal in size. The internal ear and mastoid cells showed no evidences of inflammation. In microscopic sections, extensive subpial hemorrhages were seen. The vessels in the cortex were greatly distended, and in many instances packed with polymorphonuclear leucocytes; at many points hemorrhagic extravasations were present in the cortex.
The pathologic anatomy and bacteriology of influenza during the epidemic of the fall of 1918 at Camp Zachary Taylor and Camp Knox, Ky., were reported from the cantonment laboratory, base hospital, Camp Taylor.tt
Necropsies, with routine bacteriologic cultures, were performed throughout the entire epidemic, so that a fairly definite picture of its various stages could be formed. The investigation was limited to 126 definitely proven fatal cases of influenza. These were selected from a considerably larger number by ruling out all patients who clinically gave evidence of preexisting disease, such as tuberculosis, measles, etc., or where such evidence was found at the necropsies. Thus the morbid changes encountered may be looked on as primarily representing the end results of the virus of influenza and its commensals.
The pandemic manifested itself here (Camp Taylor) first September 22, 1918, reaching an apex comparable to the first on October 5, and terminated about November 15, after which time only a small number of cases occurred.
tt The following statements of fact are based, in the main, on: Pathologic Anatomy and Bacteriology of Influenza, by Baldwin Lucke, Toynbee Wight, and Edwin Kime. Archives of Internal Medicine, Chicago, 1919, xxiv, 154-237.
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The first death due to influenza occurred September 28. The death curve gradually rose, reaching its highest point (70 cases) October 5, and then gradually declined.
The average aggregate population of this camp and of Camp Knox (30 miles distant) during the influenza epidemic was 58,000. Of these, 5,500 were Negroes. A considerable discrepancy in the morbidity and mortality rate was observed between the two races. The number of cases of influenza per 1,000 population was 231 for the whites and 70 for the Negroes. The number of deaths per 1,000 population was 16 for the whites and 7 for the Negroes, but the number of deaths per 100 cases of influenza was 6.8 for the whites and 10.2 for the Negroes. It showed, then, that while the incidence of influenza was considerably less among the colored soldiers, the mortality among those that contracted the disease was considerably higher.
There are three possible explanations for this discrepancy: Exposure to infection, immunity, and anatomic differences. Exposure may be dismissed since practically all men were exposed equally. Immunity does not seem to have played any part here, since once the disease was contracted the mortality among the colored race was higher. It was observed in Camp Taylor throughout the years 1917 and 1918 that various acute respiratory infections, such as catarrh of the nasal sinuses, were relatively uncommon among the colored soldiers, and the explanation seemed to be that the rarely obstructed air passages of the Negro afforded a good defense against lodgment of microorganisms. This would hold true, of course, only for the individuals with more pronounced African features, disappearing with increased admixture of white blood.
The duration of diseases was as follows: 8 patients, or 6.7 percent, died within the first 5 days; average duration, 4.3 days; 49 patients, or 40.8 percent, died within 6 to 10 days; average duration, 8.2 days; 31 patients, or 25.8 percent, died between 11 and 15 days; average duration, 12.8 days; 13 patients, or 10.8 percent, died between 16 and 20 days; average duration, 17.5 days; 19 patients, or 15.8 percent, died after 20 days; average duration 25.3 days. In one case the duration of the disease was not obtainable. The average duration for the entire series was 14 days. In 5 cases the disease exceeded 40 days in duration. These, however, were typical influenza patients and may be looked on as having suffered from the chronic form of this disease.
ACUTE INFLUENZA
The following statements, apply to the 121 cases of acute influenza.
The relation of the duration of the disease to the period of epidemic was estimated. For this purpose the entire epidemic was divided into five periods, generally of 10 days each, except the last, which comprised the more scattered forms occurring in November and December. Of the 42 cases necropsied during the first 10 days after the first death of influenza had occurred, the average duration of the disease was 10 days. In the second period, it rose to 13.6 days, in the third to 16.6, in the fourth to 16.7 days. In the fifth period it dropped to 13.1 days. This last period, as stated, comprises the time when the disease had lost more or less of its epidemic character. The difference in the duration of disease as the epidemic progressed is doubtless due to the fact that the most
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susceptible patients succumbed first, and that the least susceptible resisted a longer period. The duration of disease during the fifth period is more difficult to explain, but it may have been due to the incoming of nonexposed troops, or to fewer precautions taken by individuals because of the belief that the epidemic was over. Later it will be shown that the bacterial findings of this period approximated those of the earlier stages of the epidemic. It should also be remarked that at this time there occurred a particularly severe outbreak of the disease in the neighboring town of Louisville.
PATHOLOGIC ANATOMY
The necropsies were performed under ideal conditions, usually within a few hours, only rarely later than 12 hours after death. The tissues were preserved in Zenker's fluid, occasionally in liquor formaldehyde. Fresh material sometimes was used for the study of cloudy swelling. Tissues sectioned were heart, lungs, peribronchial lymph nodes, suprarenal, kidney, liver, and brain. As occasion demanded, sections were taken from skin, subcutaneous tissues, muscles, aorta, and vessels in general, thoracic duct, extra-pulmonary bronchi, semilunar ganglia, ureter, prostate, bladder, testes, tongue, tonsils, intestines, pancreas, mesenteric lymph nodes, pituitary gland, and spinal cord.
The description of the structures will be given in the order in which they usually were examined here at the necropsy (modified Zenker-Letulle method).
External appearance. - The average age was 25. 21 years; the average weight 76 kg., the average height 174 cm. No great variations from these figures occurred. Emaciation was observed only in the more protracted cases. The post-mortem lividity was generally most extensive. The face as well as almost the entire body was of a dusky color, sometimes even purplish black. In about two-thirds of the cases a bloody, sometimes frothy discharge exuded from the nostrils and from the mouth. There was no marked variation from the standard of cadaveric rigidity, but there seemed to be a tendency for it to be somewhat delayed. The superficial glands were never found palpably enlarged. Edema, although always looked for, was never present, and this should be emphasized in view of considerable kidney changes to be described below. The joints never were enlarged, nor was any arthritic condition demonstrated at necropsy, although it sometimes was seen clinically.
The chest was frequently considerably expanded, often unequally. This was due, no doubt, to the marked compensatory inflation of the lung and the pleuritic effusions. Scaphoid abdomen, which was probably coincidental, did not occur here, excepting in isolated cases.
Skin.- Miliaria was very frequent and due to the profuse sweating (grippe sudorale). In this series two cutaneous lesions occurred in a large number of cases. In about 29 per cent of the patients there were multiple petechial hemorrhages in the form of minute, dusky, blue-black areas, varying in diameter from 1 to 3 mm., and being most frequently met with in the axilla and over the scapula, although occasionally seen elsewhere. Because of the intense post-mortem lividity they were recognized with difficulty. Microscopically, small hemorrhages (up to the size of a low power microscopic field), were seen in the papillary layer of the skin, a papillary projection being often entirely flooded with
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red cells and only occasionally were these hemorrhages seen in the deeper layers. These extremely superficial hemorrhages may be looked on as resembling the purpura hemorrhagica of influenza.
The other skin lesions occurred in the form of small, discrete, slightly raised, red papules or vesicles with slightly turbid but rarely frankly purulent contents, in about 60 percent of this series. This condition was almost entirely confined to the sternal region. Microscopically, the sebaceous glands were hugely dilated and heavily infiltrated with polymorphonuclear cells; frequently they were destroyed entirely and replaced by a necrotic mass of a small abscess. Besides the polymorphonuclear cells, small, round cells, with occasional plasma cells, could be seen. The sweat glands seldom were involved. This condition did not seem to resemble acne nor the several forms of erythema multiforme described in relation to influenza. It was regarded as a toxic necrosis of the sebaceous gland, produced, perhaps by endothelial proliferation of its vessels, and analogous to the toxic acnitis of tuberculosis. Its characteristic site, over the sternal region, rendered it unlikely that it was a simple acne.
In about 19 percent of our series jaundice was present. This was never very marked, and amounted to little more than a tingeing of the sclera and skin. In the majority of cases it appeared late in the epidemic.
Subcutaneous tissues.- In most of the cases the tissue was grossly somewhat more moist and congested than normal. Microscopically, nothing further was noted. In three necropsies, and in another not included here, a generalized subcutaneous emphysema was present. In Camp Taylor, including all the clinical cases, it occurred nine times, the incidence, therefore, being 0.07 percent. It was always most pronounced over the upper anterior chest, the neck, and the lower part of the face, but in several cases it was distributed over the entire body; in one instance the left side of the scrotum was hugely ballooned. The subcutaneous tissue appeared as if innumerable air bubbles were scattered throughout. There were found neither gross nor microscopic changes in the various organs which differed in any way from those of the rest of this series, with the exception that acute ulcerative bronchiectasis was noted more frequently here. It was believed that the air escaping through the eroded bronchial wall was forced into the loose peribronchial areolar tissue, and thence by line of least resistance gained the mediastinum and the subcutaneous tissue.
Muscles.- In three instances considerable portions of the recti were of smooth, light reddish-brown color, and had a peculiar, translucent appearance; in several more cases, about 10 similar but smaller areas could be seen. This condition was confined to the abdominal muscles. Microscopically, typical Zenker's coagulation necrosis was met with. This sometimes was present in only isolated fibers, but, in the three cases mentioned, extended over large areas. In one instance a marked acute myositis, with areas of necrosis and peripheral regeneration, was seen. Here dense masses of fibrin penetrated between the muscle fibers and into the structureless necrotic mass. Large numbers of round cells, polymorphonuclear cells and aggregations of muscle nuclei, in bundles and rows, were seen, especially at the periphery of the necrosed area. Abscesses occurred in only one of this series, and in another instance among the cases of chronic influenza, although in the surgical wards, six abscesses of the rectus
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muscle were treated as complications of influenza. Rupture of the rectus muscle and hemorrhagic exudations did not occur in this series, although it was found in noninfluenzal infections. The two most pronounced instances of coagulation necrosis were present in conjunction with subcutaneous emphysema; this, however, is probably coincidental.
General internal inspection.- Usually the liver and the lower pole of the spleen extended well beyond the costal margins, due not only to a general increase in the size of these organs, but also to accumulations of pleural fluid, pressing them downward.
Peritoneum.- Peritonitis occurred in none of the acute, and three times in the chronic cases, associated, in every instance, with pleuritis, and undoubtedly secondary to the pleural complication. The rarity of this condition was in striking contrast to the frequency with which it occurred during the measles-streptococcic epidemic of 1917.
The blood vascular system.- Grossly, there was an extreme congestion of practically all the structure of the body, the cut surface generally being excessively bloody. This was especially noticeable in the heart, kidneys, liver, and brain. Microscopically, congestion and hemorrhages constituted ever recurrent findings. The capillary endothelium was frequently considerably proliferated, and the lumen of even good sized arterioles and venules was occluded with smooth, homogeneous, hyaline thrombi, or densely packed conglutination thrombi, consisting of degenerating red cells. The occlusion of the capillaries occasioned hyperemia of the neighboring parts, inflammations and exudations, and the deposition of pathogenic organisms which found in the thrombotic tissue a favorable medium.
Throughout the tissues one frequently saw shadow erythrocytes, denoting considerable blood destruction. The relative scarcity of polymorphonuclear leucocytes in the various tissues showing pathologic changes was striking, and gave the impression that a myeloid intoxication existed here. Leucopenia occurred practically in all clinical cases, and was looked on as one of the most important diagnostic aids. Generally the leucopenia persisted throughout the disease, but sometime a slight leucocytosis occurred toward the end. In the case where leucocytosis was present throughout, the pneumonic complications were of the croupous lobar type, or an associated purulent meningitis existed.
Aorta, thoracic duct and vena cava.- Definite subintimal changes, commonly looked on as the earliest manifestation of arteriosclerosis, were found in 98 of a total of 120 cases in which a note was made on the condition of the aorta. The changes appeared as opaque, pale yellowish, or light orange yellow, narrow firm streaks and corrugated ridges, generally occurring longitudinally on the posterior wall. The term "willow-tree branches," which has been applied to this condition, aptly describes it. Only exceptionally were hyaline plaques found. The elasticity was never impaired, as tested in instances by a stretching apparatus. Generally, the entire length of the vessels presented these changes, but sometimes they seemed more marked in the ascending arch than in the abdominal aorta. Microscopically, the endothelium was not affected. The more superficial layers of the intima were generally somewhat loosely arranged. The deepest layer was fibrous and swollen. At what appeared to be a later stage the swell-
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ing was more pronounced. Very large cells with a ragged, granular, vacuolated, distintegrating autoplasm were seen. Their nuclei were variable in their staining affinities and were often entirely absent.
Small, ragged-walled cavities, bounded by the muscular wall and the most superficial layer of the intima were met with commonly. These, no doubt, were sometimes due to the dropping out of the degenerated cells during the process of sectioning, but were likewise the product of fatty and granular degeneration. A few scattered, small round cells were found, but no definite infiltration.
The only other condition worthy of note was a diffuse hemoglobin tinting of the aorta and other great vessels. This occurred in many instances, even at necropsies performed within a few hours after death, and was probably a manifestation of rapid blood destruction. The vena cava and the other large vessels presented no gross alterations.
The thoracic duct, in every instance, was of normal diameter, thin walled, with a slightly pink mucosa. Neither gross nor microscopic changes were noted.
Pericardium.- Pericarditis was met with seven times; twice serofibrinous, on three occasions fibrinous, once fibrinopurulent, and once frankly purulent. Microscopically, the usual fibrinopolynuclear exudate was found. In each instance an associated pleuritis was probably the startingpoint of theinflammation. In approximately 20 percent of the series the pericardial fluid amounted to 50 or 60 c.c.; this, however, was most likely mechanical in origin, due to the pressure on the great veins by pleural exudate. Punctate, hemorrhagic extravasations were often seen over both the visceral and parietal pericardium, and in a majority of cases definite hyperemia was present.
Heart.- The weight of the heart was estimated in detail in 66 cases. In 30 percent of these it was below 300 gms., and in 10 percent it weighed 400 gm. with an average of 429 gms. On the whole, the heart weight appeared increased, due probably more to congestion and edema than to actual hypertrophy. In 115 cases of the series the right heart presented more or less dilatation, and in a number of instances the left side was likewise relaxed. In 89 cases an associated cloudy swelling was diagnosed grossly. In the majority of instances, then, parenchymatous changes were encountered, analogous to those seen in other acute infections.
The heart muscle was usually flaccid, sometimes excessively so. The cut surface practically was always opaque, grayish red, with fine lines due to capillary congestion. The characteristic tigroid markings of fatty degeneration were never seen. Microscopic examinations were conducted on both fresh and fixed preparations. As a rule, a granularity obscuring striations and clearing on the addition of acetic acid was found. In the stained preparation these changes were less clear, but here also one would frequently see haziness or disappearance of the cross striations, and very frequently, small vacuolization. Here and there the nuclei were pale and irregularly stained; many being swollen, oval, granular, and fragmented. All these changes are similar to those seen in diphtheria and typhoid fever. In the interstitial tissue, occasionally, a few wandering cells, or a granular debris, were found. The intermuscular spaces were sometimes broad and contained a precipitated, granular mass, probably edematous in origin. The capillaries were often distended to an extreme degree;
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but very rarely small hemorrhages were seen. Conglutination and hyaline thrombi, spoken of above, were often seen, but not with the same frequency as in some of the other organs.
The endocardium, in a few instances, presented subendothelial, petechial hemorrhages of slight extent. The valve leaflets were involved only once, where acute vegetations were seen on the mitral valve.
Respiratory system.- The mucosa of the nares, especially in the cases early in the epidemic, was somewhat swollen, deep red and frequently exuded blood. No microscopic sections were made.
Accessory nasal sinuses.- In 65 cases the accessory nasal sinuses were examined. In eight of them no gross alterations were present. Generally, the mucosa was reddened, thickened, loose, and the cavity contained a purulent or seropurulent material. Frequently this was heavily blood-stained, varying in consistency from a thin, watery, sanguineous exudate to a heavy creamy, yellow, thick pus. The sphenoid sinus was involved 51 times, the ethmoid sinus 43 times, the frontal sinus 17 times, and the mastoid cells, on one or both sides, 14 times. Necrosis of the bone was never present, in marked contradistinction to the frequent and pronounced bone necrosis seen here during the measles outbreak of 1917-1918, even though at that time the accessory nasal sinuses were on the whole not so frequently affected as during the present pandemic.
Peribronchial lymph nodes.- In 115 cases congestion and edema of the peribronchial lymph nodes were grossly noted. In 11 cases no microscopic changes were demonstrable. The glands often attained remarkable proportions, and it was not uncommon to see a mass the size of a walnut. Such excessive enlargement was present in 32 instances. The external appearance was generally a light reddish gray, occasionally a dark pinkish red. The consistency varied from mushy softness to flaccidity. The cut surface was practically always very moist, dripping blood-stained fluid. The degree of congestion varied, but the majority of cases were definitely congested, and, in some, tiny hemorrhages visible to the naked eye occurred. Microscopically, the lymph sinuses were widely distended and often packed with very large mononuclear, pale staining, phagocytic cells, containing bacteria and cell remnants. Other sinuses showed a granular debris with delicate threads of fibrin, and, in some, dense accumulations of red cells were intermingled with the other constituents. Many cells resembled the phagocytic epithelial cells of the lung exudate. A number of camera lucida drawings of these cells made from both sources were compared and it seemed very probable that they belonged to the same group of elements. The lymphoid tissue was generally loosely arranged, sometimes intermingled with a fine precipitate and occasionally fibrin. An active proliferation, as indicated by great numbers of large cells of the lymphoid type, appeared to be going on. Plasma cells occurred in considerable numbers in cases where the disease had persisted for some time.
The vessels throughout the glands were enormously congested, and now and then hemorrhagic foci were encountered. Almost in every instance some of the vessels contained smooth hyaline or conglutination, and in a few cases,
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fibrin thrombi. The vascular endothelium was considerably swollen, the nuclei being often very large and the cytoplasm protruding into the lumen of the vessel. On the whole, bacterial phagocytosis in the lymph node was rare. The perivascular spaces were packed with cells similar to those described, the relative absence of polynuclear elements being striking. In fact, these latter occurred only when the adjacent lung surface was covered with fibrinocellular exudate. Now and then eosinophiles, in inconspicuous numbers, were encountered. Occasionally the reticular fibrous tissue was actively proliferating, and large numbers of loosely arranged young connective tissue cells could be seen throughout the section. This subacute productive lymphadenitis occurred mainly in cases of some duration and appears to indicate the end-result of the process.
Larynx.- The mucosa of the larynx was definitely reddened and somewhat swollen in only about one-third of the cases. Occasionally the glottis and surrounding structures were edematous, but ulcerations were never encountered. In a general way, the laryngeal mucosa was never as much involved as that of the lower trachea or of the bronchi.
Trachea and bronchi.- The mucosa of the trachea and principal bronchi was generally markedly reddened, cloudy and swollen, at other times it was of a paler red color and overlaid with mucopuruient or purulent secretions. The changes may be summarized as follows: The tracheitis and bronchitis were hemorrhagic in character 63 times, catarrhal 31 times, purulent 23 times, while in 9 cases no gross alterations were noted. Hemorrhagic types were chiefly met in the more acute cases, the catarrhal and purulent forms occurring usually at later stages. Fibrinous exudates now and then covered a part of the tracheal or bronchial walls, but there were no distinct macroscopic ulcerations. The contents of the tubes consisted usually of large amounts of frothy, blood-stained material in the hemorrhagic types, while in the catarrhal and purulent forms great quantities of mucopus, or thick yellow, purulent fluid were found.
The alterations, with respect to distribution of bronchial inflammation, were usually not uniform. Thus, the bronchi leading to diseased parts were usually more affected than those supplying healthy lung tissue. On the other hand, occasionally there were seen bronchial tubes intensely inflamed, while no marked changes in the surrounding lung tissue existed. The small bronchial branches presented generally the same changes as the larger tubes. Microscopically, most pronounced alterations were observed. Of these, desquamative bronchiolitis was the most frequent, the mucosa here being almost entirely destroyed. Ulcerative bronchiolitis was also very common. Sometimes the the entire bronchial wall was eroded and replaced by a densely necrotic mass containing strands of fibrin and polymorphonuclear cells in various stages of degeneration. In the less affected bronchioles, and in the larger bronchial branches, extreme congestion and submucous hemorrhages were very general. Thrombi of various natures, but usually hyaline, were common. The endothelium was often actively proliferated. Infiltration of the bronchial walls with polynuclear cells was frequent. The mucous glands usually presented mucoid degeneration. Bronchiectasis was relatively uncommon. Large ulcerations occurred in four instances only. This was referred to above in connection with subcutaneous emphysema.
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Pleurae.- Early cases presented far less pleural involvement than those occurring later in the epidemic. In each instance an associated pneumonitis was present. Primary pleuritis was never observed.
The pleura was involved on one or both sides in 90 cases. The exudate was sanguineous in 12, fibrinous in 27, serofibrinous in 19, serofibinopurulent in 23, and frankly purulent in 9 instances. The left pleura was somewhat more frequently involved than the right. The exudate was generally thin and apparently low in fibrin content. In the early part of the epidemic the sero-sanguineous types occurred most frequently, the fluid being definitely blood-tinged. Under fibrinous pleuritis are included all degrees of fibrinous exudation. Generally, only a small, fine, grayish, patchy deposit, often not more than a roughening of the pleura, was present. In the serofibrinous exudates small clumps of fibrin were floating in a relatively clear or only slightly turbid fluid. By serofibrinopurulent exudates are understood those fluids which were most definitely turbid. The purulent exudates were of the usual type. Analysis as to the amount of fluid could be made in 71 instances. The figures given apply to the fluid in either cavity. Thus, if both the right and left cavities contained a varying amount they were considered separately. Fluid was less than 100 c.c. in 10, between 100 and 500 c.c. in 38, between 500 and 1,000 c.c. in 15, between 1,000 and 2,000 c.c. in 7, and over 2,000 c.c. in 1 instance; the greatest number, therefore, containing less than 500 c.c.
Analysis in reference to the duration of the disease and period of the epidemic reveals the fact that the purulent and more pronouncedly fibrinous fluids occurred at a later stage of the disease or epidemic. Petechial hemorrhages were observed frequently, varying in extent, sometimes involving considerable areas and being in 50 percent associated with a pleuritis. Cytologically, the pleural exudate consisted chiefly of large mononuclear cells, with considerable numbers of polynuclear elements. Phagocytosis of bacteria was common. Microscopically, the pleura presented the usual changes encountered in exudative inflammations. The subserous vessels were generally hyperemic and frequently contained hyaline or conglutination thrombi.
Lungs.- The anatomic alterations of the lungs were usually the most pronounced and most striking.
The duration of the pneumonitis was estimated from the day that lung involvement was first observed to day of death. Such an estimation is only accurate in a relative way, but certain interesting features were brought out thereby. Eight of the 109 cases developed pneumonia within the first 5 days of the disease, and 43 more within the first 10 days, so that about half of the entire series presented lung involvement relatively early in the attack. The other half showed definite pneumonitis considerably later, 15 cases developing it after the disease had persisted for 20 days. Once the pneumonitis was established it proved fatal within a relatively short time. Thus, in 45 instances, the duration was 3.68 days, in 37 it was 8.02 days, while in only 3 cases did the pneumonic process persist over 20 days, giving an average of 26 days. Pneumonitis occurred in 124 instances, in 2 cases none was present. In both of these a rapidly fatal epidemic meningitis occurred.
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Usually the involvement was extensive, in 98 cases 3 or more lobes presented areas of consolidation. Both lungs were involved in 116 cases, the right lung alone in 3, the left alone in 5 instances.
The weights of the lungs were estimated in 65 instances. In only a small percent relatively was the weight of either lung below 500 gm. In 67 percent of the cases the left lung averaged 717 gm.; in 55 percent the right lung averaged 761 gm., in 17 per cent the left lung averaged 1,328 gm., and in 36 percent the right lung averaged 1,343 gm. The lungs, therefore, were considerably heavier than in the average case of bronchopneumonia, especially that of the aged.
The cut surface of the lung was generally very moist and excessively bloody, especially in the cases dying after a relatively short duration of disease. From the inflated anterior edges large amounts of lightly and heavily blood-tinged, frothy serum could be expressed. In the posterior two-thirds larger and smaller areas of consolidation were present. These varied in color, size, and consistency, resulting in a number of distinct pictures, often within the same lobe. Generally, the consolidated areas were indistinctly outlined and gradually faded into the surrounding hyperemic lung tissue. A marked tendency to become confluent was noted, and pseudolobar involvement occurred very commonly.
The texture was as diverse as the other features; smooth and velvety consolidations, bordering on coarsely and finely granular neighboring areas. These granular consolidations resembled in every way the cut surface of a croupous pneumonia, except for their lobular character. The consistency ranged from definite necrotic softening to total firmness, and the color varied through all shades of red and gray. Only exceptionally were the consolidated areas definitely peribronchial. Now and then the interlobar septa were thickened and indurated areas were present. Atelectasis, due to obstruction of bronchial branches, was common, sometimes involving considerable areas. In a general way, the consolidations according to their extent, might be classified as patchy and confluent or pseudolobar. There was but slight difference in the distribution of these two types in the various lobes of the lung; that the upper lobes were somewhat less confluent than the lower lobes, and that the middle lobes were the least affected.
Microscopically, as wide a variation was seen as in the gross appearance. The exudates had, however, sufficiently distinctive character to allow the division into three main groups. In the first, the exudate was chiefly catarrhal, consisting of large, desquamated, epithelial cells. In the second group the same features obtained, with the addition of a heavy fibrin network. In the third group, the exudate was mainly purulent, with the addition of fibrin. All three types often existed in the same lung. Commonly, even the same microscopic section presented all three of them, so the great variation of the exudate might be taken as one of the main characteristic features of influenzal pneumonitis. This is readily explained if it is remembered that one or more organisms invade these tissues, and that each class of bacteria may set up distinctive inflammatory processes in adjoining or closely placed together alveoli. In addition to the cellular character of the exudates, there was usually a heavy admixture of red blood cells with large amounts of precipitated serum. It is very difficult to estimate the incidence of the three groups of exudates, since
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they so commonly occurred together. By taking several sections from each lung and noting the predominant character of the exudate, the following group might be made: Catarrhal bronchopneumonia, 34 percent; fibrinocatarrhal bronchopneumonia, 39 percent; fibrinopurulent bronchopneumonia, 27 percent.
Such grouping, however, is only highly approximate and represents but the predominating character of the exudate in the majority of the sections examined. Fibrin, in varying amounts, could practically always be found in some sections, and in over two-thirds of the cases it was prominent. The exudate of the more catarrhal types generally presented pronounced swelling of the lining epithelium, and not infrequently groups of alveoli were lined with huge cuboidal cells, giving the appearance of tubules and resembling the condition of the fetal lung. Such changes, as is well known, are often seen after indurative bronchopneumonia processes, but only rarely is this extreme proliferation encountered in an acute pneumonitis. In some sections the condition was so uniform as to make one consider the possibility of a reversion to fetal types, an anaplasia produced by excessive stimulation of the lung epithelium. It is doubtful whether such anaplastic changes ever occur in acute inflammations, and the statement here is merely an analogy.
In sections where definite fibrosis was present-usually in cases where the pulmonary infection had persisted for a relatively considerable time--such proliferation of the lining membrane was likewise frequently encountered. Occasionally the alveolar membrane was intact, but more generally a part, at least, was desquamated, and these huge cells were lying free in the air sacs.
All stages of cellular degeneration could be observed, the most noteworthy being vacuolization with shrinkage of the nucleus. Phagocytosis was often seen; the phagocytized structures being most often red blood cells, polymorphonuclear leucocytes and cellular debris. Bacterial phagocytosis was relatively infrequent in the large cells, but quite common in polymorphonuclear leucocytes. Sometimes the epithelial cells were fused together, forming huge, syncytial masses, apparently consisting of from three to five fused cells and measuring up to 60 microns in diameter. These giant structures frequently contained inclusions of red cells and leucocytes, and were probably degenerative in character. Besides the lining cells the exudate consisted chiefly of precipitated serum and red corpuscles, polymorphonuclear elements being uncommon. Definite hemorrhages were frequent and often involved large areas. The alveolar capillaries were hugely distended and often contained hyaline conglutination thrombi. Generally, the walls were well preserved and cellular infiltration was rare. The perivascular and peribronchial spaces contained cells of the same type as those described.
This catarrhal type of pneumonitis predominated early in the epidemic and throughout the epidemic in patients dying after a relatively short illness, and it was believed that the changes enumerated were more directly due to the virus of influenza than to the associated bacteria; in fact, that the pronounced epithelial proliferation and the marked hyperemia constitute the essential early lesions of true influenza.
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The second type of pneumonitis was fibrinocatarrhal in character, and differed from the preceding not only in the addition of large amount of fibrin, but also in cellular reaction. Catarrhal cells were still present in relatively large numbers and presented the general characters mentioned above, excepting that more intense degenerative changes were seen. The fibrin occurred in the form of dense networks, consisting sometimes of fine, sometimes coarse, strands, and it was generally more pronounced at the periphery of the air cells. Polymorphonuclear cells were present in greater numbers than in the preceding forms. Red blood cells were abundant, but generally not so excessive as in the preceding type. The alveolar walls were frequently ruptured and infiltrated with mononuclear and polymorphonuclear leucocytes, and often showed a fibrin network. This type was looked on as an intermediate stage in the disease process.
The third group was fibrinopurulent or purulent in character, the exudate containing relatively few epithelial cells, while polymorphonuclear leucocytes were abundant. Fibrin was present in varying amounts. The alveolar contents were rarely hemorrhagic, though sometimes a few red cells were seen. Serum was seldom as pronounced as in the earlier stages. Typical plasma cells were frequently observed in considerable numbers in the exudate as well as in the lymphatics and alveolar walls. These last often showed widespread destruction, and large areas of necrosis were often seen.
Fibrosis was not infrequent. The bronchial walls were often entirely destroyed and abscesses were many times encountered. This was considered the end of influenzal pneumonitis. It occurred at a later period in the epidemic when the duration of the illness was considerably longer than in the earlier part of the epidemic, and when the pneumonic processes had persisted for some time. It is the second and third type of influenzal pneumonitis which is probably produced by the commensals of the virus of influenza.
An attempt was made to correlate the anatomic findings with the bacteriologic results, and to classify the types of pneumonitis encountered according to the bacteria present. As will be seen in the bacteriologic part of this discussion, the microorganisms which were most often isolated were: B. influenzae hemolytic and nonhemolytic streptococci, pneumococcus of various types, M. catarrhalis and staphylococcus. These were usually present in various combinations. Indeed, it was not uncommon to find most or all of them in cultures from the different lobes of the same lung. It was exceedingly difficult therefore to attribute this or that anatomic change to any special bacterial type. The fact that all of these bacteria must be looked on as commensals, or as secondary or tertiary invaders of the pathologic tissue prepared by the virus of influenza, make separation on an etiologic basis generally quite impossible.
It was the custom at Camp Taylor to take cultures from all lobes of the lungs, as well as from the principal organs. In only two instances were pure cultures of the influenza bacillus isolated; once the staphylococcus, once M. catarrhalis, five times the nonhemolytic streptococcus and somewhat more frequently the pneumococcus, and hemolytic streptococcus were found in an unmixed form in the lungs and elsewhere. If to this be added the difficulty
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in isolating this or that bacterium there is introduced an added source of error; nevertheless, in the patients where pure cultures of one type were obtained, a correlative study was undertaken.
It has been stated that it was not uncommon to find several distinct types of exudates within the same lung, and even within the same microscopic section, and it was not surprising, therefore, to obtain the same results when comparison of the anatomic and bacteriologic studies was undertaken. Thus, for instance, in the two cases where B. influenzae occurred in pure culture, the exudate was fibrinocatarrhal in the majority of sections of one case, and purulent, with relatively small amount of fibrin, in the other. The same condition was present in the staphylococcus and M. catarrhalis cases, while in the pneumococcus and hemolytic and nonhemolytic streptococcus cases the results were even more confusing. Thus, in 19 cases where the hemolytic streptococcus predominated, the lung exudate in the majority of the sections was catarrhal 8 times, fibrinocatarrhal 5 times, fibrinopurulent 4 times, purulent with areas of necrosis twice. The nonhemolytic streptococcus and the pneumococcus cases showed a similar discrepancy. It is not feasible, therefore, to divide the pneumonitis of influenza on bacteriologic basis excepting in a general way, and this can be done by considering the mixtures of bacteria that predominated at the various stages of the epidemic and in the different periods of the disease, remembering always that one deals with a definite morbid process, more or less modified by commensual or invading organisms.
Spleen.- In 10 of 68 cases the spleen weighed less than 150 gm., in 31 it weighed between 150 and 249 gm., with an average of 195 gm. In 25 it weighed between 250 gm. and 449 gm. with an average of 321 gm. In 2 cases it weighed more than 450 gm. with an average of 590 gm. It would seem, then, that in more than 80 percent of the cases the spleens were definitely enlarged, and in almost one-third of the total number they were considerably increased in size. Definite diminution never occurred, the spleen in no instance weighing less than 100 gm.
The capsule was generally tense, the external color reddish brown to purplish red, consistency slighty flaccid, occasionally much softened. The cut surface was usually uneven, moist, and often very bloody. The trabeculae could not rarely be recognized distinctly. The follicles were plainly visible or somewhat prominent in 57 instances and indistinct or entirely obscured in 69 instances. The pulp was usually softened, and in about 20 percent of the cases it was definitely mushy. The duration of the disease process, the period of the epidemic, the size of the spleen and its follicular or diffuse character did not appear to exhibit any constant relation. Microscopically, the commonest change consisted in the excessive blood contents; often large areas flooded with red cells, constituting undoubted hemorrhages, many of these cells being shadow rings. An endothelial hyperplasia of the vessels and sinuses was usually present and often pronounced. Oftentimes desquamated endothelial cells were found free in the venules and arterioles, occasionally obstructing their lumen; hyalin and conglutination thrombi were likewise present. Widespread necrosis of the reticulum commonly occurred, partly due, probably, to the hemorrhages and partly to toxic action. Now and then the arterial
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walls presented a smooth, homogeneous staining, evidencing toxic hyaline degeneration. Elsewhere definite hyperplasia was present, manifesting itself by greatly increased numbers of large mononuclear splenic cells. Polymorphonuclear cells were rarely met with, and then only in small numbers. The malpighian bodies were generally loosely arranged, with many large, pale, staining, germinal lymphocytes. Within the follicles one frequently encountered eosin staining, smooth, hyaline areas, occasionally of considerable size. On minute inspection these areas seemed to be composed of huge, partly fused, indefinite staining, degenerating cells.
Semilunar ganglia.- These structures in practically every instance were slightly swollen and occasionally of a faint pink color. There was no appreciable change in the consistency. The cut surface was usually moist, often decidedly pinkish, and a number of bleeding points were always seen. Microscopically, the ganglion cells were swollen, devoid of definite outline, with a granular cytoplasm which stained poorly and did not show Nissl granules. The nuclear changes varied from loss of nuclear outline to poor or excessive staining, granularity, and often total disappearance of the nucleus. The nucleoli, as a rule, remained, but occasionally they likewise disappeared. Extreme changes consisted in loss of the entire cell. The above-enumerated alterations usually affected only isolated cells or groups of cells, for in other parts of the section the structures were normal. The condition was comparable to the ganglionic changes in the cerebral cortex and seems to point to the widespread toxic effects of the virus. The vascular changes were similar to those described in other organs, such as definite hemorrhages, and practically always, marked congestions. Occasionally, the perivascular lymphatics were dilated and packed with large and small round cells. The interstitial substance was often loosely arranged.
Suprarenals.- In three instances frank hemorrhages were present in the suprarenal substance, enlarging the organ to about twice its normal size. In 20 cases the suprarenals showed no gross changes. In the remaining 103 cases there was slight increase in size and definite congestion. In these latter cases the outside color was pinkish-brown, and the cut surface decidedly bloody. The outer zone of the cortex was generally narrow and pale grayish-yellow, rarely presenting the deep orange yellow tint so frequently seen in the suprarenal cortex. The intermediate zone was a deep reddish brown and exuded blood, while the medulla varied from a reddish-gray to a deep red. Microscopically, extreme congestion and frequent small hemorrhages were found, involving the medulla and intermediate zone. The cells of the cortex appeared slightly swollen and usually devoid of their lipoid granules. This lipoid exhaustion was observed almost constantly. Other cells appeared in the state of acute cloudy swelling, with indefinite cell outlines and poorly staining nucleus. The interstitial substance was usually arranged loosely and was definitely edematous. Focal necrosis, with small round cell infiltrations, was occasionally observed. In a number of the gland cells, especially of the cortex, numerous deep blue staining, coarse granules were encountered. Very occasionally diffuse infiltration with polymorphonuclear cells, pointing to an acute inflammatory suprarenalitis, was seen.
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Kidneys.- The details of the weights and measurements were tabulated for 50 pairs of kidneys. In 10 percent both kidneys weighed less than 150 gm. each. In 86, or 88 percent, the weight of each organ averaged 202 and 207 gm., respectively. In 4, or 2 percent, respectively, each organ weighed 210 gm. Both kidneys were of the same weight in 7 percent, the left was heavier than the right in 54 percent, and the right kidney heavier than the left in 39 percent of the cases. The measurements corresponded to the size. This means that in 90 percent of the examinations the kidneys were somewhat increased in size or weight. In every instance parenchymatous changes, usually of mild degree, but often quite severe, were observed. It was not possible, grossly, and frequently impossible minutely, to decide whether the condition present should be looked on as an early parenchymatous nephritis, or as a transitory cloudy swelling. Definite nephritis was present in about 10 percent of the cases, but generally the organs were flaccid, with an easily stripping capsule, leaving a smooth, grayish red, often mottled, surface, on which the stellate veins often stood out prominently. The cut surface, as a rule, was moist and bloody. The cortex was usually moderately increased in width, the cut edges gaping slightly, and, in a number of cases, considerably. The glomerular markings were sometimes washed out, but at other times very definite, and, in a considerable number of instances, the glomeruli and cortical striations were prominent. The corticomedullary junction, as a rule, was very indefinite. The medullary junction was usually very indefinite. The medullary striations varied, but, as a rule, were distinct. The pelvic mucosa usually presented injection, and in about 30 percent of the cases submucous, petechial hemorrhages were encountered.
Microscopically, the kidney picture was quite uniform, varying only in degree. The interstitial substance was moderately edematous, the glomeruli were large, the capsule of Bowman was not thickened. The capsular epithelium was swollen and proliferated in about 20 percent of the cases. Multiple layers of capsular epithelium were met with in a few instances. The capsular space, in 50 percent of the cases, contained a granular, eosin staining precipitate. The tufts were large because of vascular congestion. The endothelium was swollen, with large nuclei, but there was no evident active multiplication. Frequently, hyaline and conglutination thrombi were seen. The tubular epithelium was generally swollen, the cell outlines poor, the cell borders ragged, and the lumen filled with granular debris. Often vacuolization was observed. The nuclear changes ranged from poor staining reactions to total absence. In one instance, a large part of the kidney appeared necrotic. Small microbic abscesses were present in only one instance. In every case the convoluted tubules were more affected than the straight tubules. The degeneration and necrosis of the epithelium was rarely uniformly distributed, sometimes entire tubules, or groups of tubules, were attacked, with apparently normal epithelium in close proximity.
The kidney changes observed here and elsewhere during the epidemic seem to be of the nature of a parenchymatous degeneration, with edema, rather than of a productive nephritis, although this too occurred several times.
Ureter and bladder.- The ureter, in its upper fourth, frequently showed submucous, hemorrhagic extravasations, similar to those observed in the renal
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pelvis. The rest of the mucosa was occasionally moderately injected. The urinary bladder was similarly affected, showing injection, and commonly submucous, petechial hemorrhages.
Prostate.- No gross or microscopic changes were observed, with the exception of slight congestion. The prostatic acini presented no noteworthy alterations.
Seminal vesicles, spermatic cords, and testicles.- The seminal vesicles were generally filled with a viscid, sometimes slightly turbid fluid. The spermatic cords presented no gross changes. The testicles very frequently possessed at moist, definitely bloody, cut surface and were of softened consistency. The cells, microscopically, were commonly swollen and ragged; cessation of spermatogenesis was frequently seen.
Tongue.- The tongue was often reddened, but no characteristic changes, as in typhoid fever or scarlet fever, were observed. The mucosa of the mouth and posterior pharynx was likewise often reddened. Microscopically, the lymphoid tissue was frequently very prominent. The youthful age of the patients made it unlikely that a pathologic change was being dealt with, although the lymph tissue generally in the body was proliferated above the normal state for the age of these patients.
Tonsils and thyroid.- An acute tonsillitis was occasionally ecnountered, but it is probably coincidental. The thyroid was now and then somewhat enlarged, but presented no noteworthy microscopic changes.
Pharynx, esophagus, and stomach.- The mucosa was frequently dusky. The lymph follicles, in the lower part of the esophagus, were usually prominent. In the stomach there was found almost constantly extensive submucous, petechial, hemorrhagic extravasations, not confined to the dependent parts, and probably not post-mortem in origin, since they were found in bodies necropsied within an hour or so after death. The condition is comparable to the hemorrhagic extravasation noted beneath mucous and serous surfaces and in the skin. The stomach contents, which were generally fluid, often had a light brown or reddish-brown tint, due, probably, to slight leaking of the extravasated areas. No other gross or microscopic changes occurred.
Liver.- The details of the weight and size of the liver were estimated in 61 instances. In 7 percent the liver weighed less than 1,500 gm.; in 47 percent the weight averaged 1,829 gm.; in 46 percent the weight averaged 2,254 gm. The consistency was generally flaccid, occasionally definitely soft. The lower edge was, as a rule, rounded, the capsule smooth and translucent and the subcapsular lobulation generally indefinite but sometimes prominent. The cut surface was generally slightly btut onsiderably bloody. The lobulation appeared washed out. The translucency of the tissue, in the majority of instances, was dull, gray and often parboiled. In about one-third of the cases the centers of the lobules were large and deeply congested. Frequently, especially near the periphery of the organ, pale, yellowish fatty areas were seen. In a number of cases lobulation appeared usually distinct, the centers being very large and dull brownish-red or yellowish-red, with a narrow, grayish-brown peripheral zone. Very exceptionally the surface possessed a fatty sheen; evidences of biliary pigmentation were never observed grossly.
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Microscopically, the principal change was albuminous degeneration, the cells being large, with cloudy cytoplasm, the nucleus presenting various degenerative changes. Inconspicuous biliary pigmentation was common but not prominent. A few areas of fatty infiltration were frequently seen, but this was never excessive. Fatty degeneration was rare, but hydropic degeneration was common. In fully 50 percent of the cases areas of focal necrosis were present. In 11 percent these were pronounced and large, and, in one instance, a marked acute yellow atrophy was present. The areas of focal necrosis, in the majority of instances, were relatively small, involving only groups of a few liver cells, but all degrees were present with an extreme condition in one case where practically no normal liver cells occurred. The necrotic tissue consisted of structureless, eosin staining cells, intermingled with free nuclei, lymphocytic elements and moderate numbers of plasma cells with relatively few polynuclear elements. In the cases of acute yellow atrophy all but the periphery of the lobules was destroyed, the peripheral cells being swollen and multivacuolated and presenting pronounced nuclear changes. The Kupfer cells throughout the liver, but especially in the necrotic areas, possessed swollen, oval nuclei and large amounts of cytoplasm. Red cells were present in moderate numbers. The gross appearance of the liver gave little evidence of the excessive microscopic changes. It was softened, of reddish-brown color, the cut surface presenting very large, reddish-brown lobular centers with a pale periphery.
Frequently, the liver cells contained fine, blue-staining granules. Searching with the oil immersion lens, one occasionally saw small groups of micrococci in the sinusoids, and it seems that these granules were similar to those described by Adami in his subinfection theory as being the final stages of bacterial destruction. The same doubtless holds true of the blue granules described above in connection with the suprarenals. Sometimes this condition could be studied exceptionally well, especially when only small numbers of microorganisms were present in the simisoids, for here all stages of bacterial lysis could be observed in the adjoining liver cells. The periportal connective tissue was rarely proliferated, but occasionally a lymphocytic or leucocytic infiltration of unimportant degree was observed. The number of biliary ducts was never increased, but in extensive necrosis there was a swelling, without multiplication of the component cells. The vascular changes were similar to those described elsewhere, and frequently consisted of intense congestion and hyaline or conglutination thrombosis.
Pancreas.- The gross changes were slight and consisted in flaccidity and dusky gray appearance, and the cut surface was often moderately bloody. Microscopically, the vascular changes were of the usual type. The cells of the acini were frequently swollen, with poor staining or faulty staining nuclei. The ductal cells presented similar changes, and occasionally were desquamated. The most important alterations were noted in the islands. These were indefinitely outlined; their cells had a washed out appearance, and were poorly differentiated from one another. They were increased in size, often fragmented, and usually presented pronounced nuclear changes or absence of nucleus. This is a similar toxic degeneration to that observed in the liver, spleen and elsewhere.
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Mesenteric lymph nodes.-The lymph nodes were moderately swollen, but never were larger than a bean. Their cut surface was slightly moist and had a grayish-pink appearance. Frequently, they were definitely reddened. Microscopically, there was a slight sinus catarrh, slight lymphoid proliferation, and a moderate edema, the changes being comparable to those in the peribronchial lymph nodes, although always of a much less degree.
Intestines.- Practically always, larger or smaller areas of the mucosa were definitely congested and frequently submucous hemorrhages were seen. The mucosa was commonly swollen, gray and turbid, and, in the duodenum, much bile stained. In the majority of instances, the lymphoid tissue was definitely hyperplastic, this condition being especially pronounced in the ileum. Of 97 cases, where notes as to the lymphoid status were made, the solitary follicles and Peyer's patches were markedly hyperplastic in 40, the hyperplasia being slight, or not present in the remaining 57 instances. In the pronounced cases the follicles were swollen to the size of two or three millimeters, and usually were surrounded by a definite hemorrhagic zone, giving the mucosa a coarsely granular appearance. The Peyer's patches were well raised above the surface and of a grayish-brown color. Occasional central liquefaction necrosis of the follicles was encountered, resulting in the formation of vesicular structures with turbid contents. Microscopically, congestion and submucous hemorrhages were the rule. The lymphoid tissue was actively hyperplastic, presenting many large lymphoid cells and some endothelial elements.
Nervous system.- The brain and its membranes were examined in 85 cases, and next to the diseases of the respiratory apparatus, the changes in the nervous system seem to be the most frequent and important complications in influenza.
Dura mater.- Congestion, generally of a mild degree, was found in 29 instances. In one case a marked internal hemorrhagic pachymeningitis occurred in conjunction with a purulent meningococcic meningitis. The entire inner surface of the dura was coated with a thick layer of firmly clotted blood, averaging from 2 to 5 mm., which adhered but slightly to the pia-arachnoid, but was firmly affixed to the dura.
Pia-arachnoid.- Fibrinopurulent leptomeningitis was found thirteen times, serolymphatic meningitis with congestion seventeen times, and in the remaining 55 cases edema and congestion of more or less pronounced degree. The origin of the purulent meningitis was meningococcic in seven cases, pneumococcic in four, and streptococcic in two instances. The constantly present congestion and edema doubtless created a focus of lessened resistance, explaining the frequency of meningeal complications. The frankly purulent inflammations generally occurred late in the disease, but some developed within a few days after the onset of the influenza. They differed anatomically in no way from the usual lesions of this type. The other meningeal infections which we have here termed serolymphatic appear to be the direct result of the virus of influenza. In all of these cases the membranes were soft, watery, and considerably congested.
The subarachnoid fluid, especially in the large cisterns, was definitely turbid. In the sulci and surrounding the larger vessels, there was a cloudy, turbid, grayish-yellow exudate. This was most frequently observed over the temporal and parietal regions, and was slight or absent over the base of the
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brain. Microscopically, two types were recognized. In the first the pia-arachnoid was loosely arranged and distended with fluids, the vessels were densely filled. Isolated red blood cells and small round lymphatic cells were scattered throughout the tissue with occasional large endothelial cells. In the second type the pia-arachnoid was densely infiltrated with small round, many large, deep-staining mononuclear, some pale-staining endothelial together with plasma cells. Polymorphonuclear leucocytes were rarely encountered, and then in small numbers; fibrin was absent, or at most present only in small traces. This type of meningitis was characterized, then, by the lymphocytic type of the cellular exudate and the scarcity or absence of polymorphonuclear cells and fibrin, together with pronounced hyperemia, edema, and occasional hemorrhages.
Brain.- The weight of the brain was tabulated for 46 cases. In 39 percent it averaged 1,300 gm., in 50 percent 1,452 gm.; in 11 percent 1,739 gm. The weight, therefore, was increased from 100 to 200 gm. in about half of the patients. Consistency was somewhat more flaccid. The ventricles were generally of normal size, or only slightly distended. Slight cloudiness of the ventricular fluid often was observed, even in the cases not associated with purulent meningitis. The ependyma presented no noteworthy alteration. The pineal gland was grossly normal, or at the most, somewhat softened. No microscopic studies of them are included in this series. The cut surface of the brain in practically every instance, presented an excessive number of bleeding points. They were most pronounced in the white matter of the hemispheres, but occasionally the corpus thalamus was especially involved. The cerebral cortex was less affected and the pons, cerebellum, medulla, and spinal cord presented these changes in considerably less degree. These bleeding, points appeared usually as closely placed, punctate, minute, hemorrhagic areas.
Microscopically, intense congestion of the vessels and numerous minute hemorrhagic foci were encountered. Their distribution corresponded to the grossly hyperemic areas. The hemorrhages never exceeded, in size, the diameter of a low-power microscopic field and were generally only of about half this size. The vascular endothelium was frequently swollen and hyaline and conglutination thrombi were often met. The perivascular spaces were frequently large and contained precipitated, edematous fluid. Occasionally only was a perivascular cellular infiltration noted. The ganglion cells presented most pronounced changes. Sometimes only isolated, sometimes large groups of cells, were affected. They were generally swollen and without definite cell outline. Commonly, a small, clear, edematous zone surrounded the cells. The cytoplasm was devoid of Nissl granules and the nuclei were frequently entirely absent or showed a loss of outline. In short, all stages of cell degeneration were present, ranging from acute cloudy swelling to chromatolysis and total disappearance. In no instance, however, was invasion and phagocytosis of ganglion cells observed. The glia matrix was generally arranged loosely. The cell degenerations enumerated did not appear to attack constantly any special part of the brain, and the sections of spinal cords examined were too few to formulate an opinion.
Pituitary gland.- This gland was examined only a few times. In each instance it was somewhat swollen, pinkish in color, the cut surface being moist.
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definitely bloody, and reddened. Microscopically, the tubular acini were markedly distended with a colloid material, the lining cells flattened; sometimes throughout the section coarse strands of fibrin were present. The vessels were much dilated and small hemorrhages frequently were seen. Unfortunately, the posterior lobe never was included in the sections. These unusual findings are explained readily by the great frequency of purulent nasal sinus involvement and by the frequent association of suppurative meningitis.
Ear.- Suppurative otitis media was present in only four instances. This stands in marked contrast to the frequency with which it occurred during a coexisting epidemic of measles where it was present in 9 of 25 necropsied patients.
Eye.- Hyperemia and inflammation of the conjunctiva very frequently were found and would probably indicate the generalized vascular engorgement rather than a localized condition. No microscopic sections of the eyes were made.
CHRONIC INFLUENZA
While influenza, as a rule, runs an acute course, it may become protracted over a considerable period. Any case of influenza which extends over a period of four weeks or more, generally with remittent or intermittent fever, and various lung symptoms, may be looked on as typical of the chronic form of this disease. Clinically such a condition often resembled typhoid fever, malaria, tuberculosis, or low-grade septicemia.
Five patients of the series of 126 presented this condition. The duration of the disease varied from 44 to 88 days, with an average of 60 days. Judging from the clinical records, each patient suffered with an initial typical attack of influenza, which was followed, sooner or later, by signs of pneumonic consolidation and accompanied throughout by a fluctuating fever curve. The pneumonitis seemed to persist, but shifted from place to place, constantly involving new areas, while the older pneumonic patches persisted or sometimes cleared up.
PATHOLOGICAL ANATOMY
All these cases came to necropsy during the last period of the epidemic, or rather after the bulk of the epidemic had subsided. They showed certain anatomic differences which justify their separate discussion.
There was emaciation in each instance, two showed slight icterus, none the intense cyanosis and lividity so commonly seen in the acute cases. The cut surface of the subcutaneous tissues and muscles was never so bloody and moist as in the acute disease. In one instance a large abscess in the rectus muscle was present. Acute purulent peritonitis occurred thrice, which is in marked contrast to its absence in the acute cases of the series. The changes in the aorta and other vessels were similar but more profound.
Pericardium and heart.- Purulent pericarditis, associated with a purulent inflammation of the other serous membranes, was present once. In the rest no noteworthy changes were found. There was particularly an absence of subserous, hemorrhagic extravasations and of hyperemia.
The heart varied in weight from 205 to 425 gin., with an average of 310 gm. The right heart was constantly dilated, and in one instance both chambers
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were markedly dilated. The muscle was always very flaccid, light grayish-red and turbid
Microscopically, there was shown marked swelling and vacuolization of hydropic character, and while the vessels were not congested, usually they contained hyaline thrombi, which were more pronounced in the chronic than in the acute cases. Endothelial hyperplasia varied in degree in the chronic form, and no definite comparative picture could be formed.
Respiratory tract.- The peribronchial lymph nodes were always greatly swollen, soft and edematous, but only slightly congested. Microscopic section presented edema, sinus catarrh, slight connective tissue proliferation, and, in two instances, an acute purulent adenitis, with the presence of large numbers of polymorphonuclear leucocytes and small areas of necrosis. The vessels showed no other changes than those mentioned above.
The trachea and bronchi possessed a relatively pale mucosa which was covered in every instance with mucopus; in the smaller branches a thick, creamy, yellow pus was present. Microscopically, well marked erosion of the wall, and the presence of enormous numbers of polymorphonuclear cells characterized the picture. Bronchiectasis never occurred, although commonly seen in chronic influenza.
The pleurae, in each instance, were adherent in places by relatively firm, fibrous bands and by more recent fibrinous exudate. This seemed to have persisted for some time, since it was generally rather tough. The pneumonic process, according to the records, varied in duration from 27 to 74 days with an average of 44.1 days. The lungs were never so voluminous as in the acute type, and in no instance exceeded the volume usually seen in a chronic bronchopneumonia, the left lung averaging 440, the right 480 gm. in weight. Slaty blue, sometimes depressed, firm areas could be felt, especially on the posterior border in either lung. The cut surface was only slightly bloody, and in every instance the interpulmonary septa were prominent and there were larger and smaller areas of fleshy appearance and consistency. Soft, grayish-brown foci, finely and coarsely granular, apparently recent consolidations, and smooth, velvety, firm areas could be seen, but in general the extent of pulmonary involvement was less than in the acute cases.
Microscopically, certain characteristic features were always present; namely, areas of atelectasis, sometimes of considerable extent; areas of young connective tissue overgrowth (carnification) and areas of necrosis and abscess formation. All stages of pneumonic involvement could be observed in the sections from these lungs. In every instance small, bronchopneumonic patches, with fibrinocatarrhal exudate of recent origin, were found. Generally, however, the exudate consisted of polymorphonuclear leueocytes, with little or no fibrin; the alveolar walls were infiltrated in places with such cells, and were frequently destroyed, resulting in abscesses which often reached considerable dimensions. The perivascular and peribronchial tissues were often definitely fibrous. In one instance a pronounced hyperplasis of epithelium, similar to that described in acute cases, was encountered.
Spleen.- The spleen varied in weight from 105 to 260 gm., with an average of 185 gm.; on the whole, the organ was therefore smaller than in the acute
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cases. The capsule was generally wrinkled; the color of the organ was a reddish-gray; the consistency was always flaccid, but never soft or mushy. The cut surface was only slightly bloody; trabeculae could generally be seen, but were not thickened. In one case the follicles were prominent, in the others indistinct.
Microscopically, there was a distinct hyperplasia of endothelial cells throughout the organ; in two instances large numbers of polymorphonuclear leucocytes were present. Fibrosis of the reticulum was noted twice. Definite toxic hyaline degeneration of the arterial walls was noted in another case. Areas of hemorrhage were seen twice.
Suprarenals and semilunar ganglia.- Slight congestion and edema were observed. In one instance there was infiltration of the adrenal with polynuclear leucocytes, otherwise the changes were similar to those previously described.
Comparative incidence of bacterial flora in one or more organs of 120 necropsies of influenza, and 101 other acute diseases occurring during the influenza epidemic
Kidneys.- Twice the kidneys were below average weight, and three times increased in size and weight, the average for the series being 193 gm. for the left and 190 gm. for the right kidney. In two cases the capsule was slightly adherent, tearing the parenchyma on stripping. The consistency in every instance was flaccid; the cut surface was pale, swollen, and reddish-gray, with poor differentiation of cortex and medulla. Cortical and medullary markings had a washed-out appearance. Hemorrhagic exudates in the renal pelvis were never observed.
Microscopically, there was a slight edema and congestion present in all, but no connective tissue overgrowth. The glomerular and tubular changes were similar to those described, differing only in greater degree of severity. In one instance polymorphonuelear leticocytes in large numbers were present in the glomerular capillaries; in another case the capsular epithelium was slightly proliferated. The tubular epithelium was considerably more degenerated than in the acute cases; many tubules were lined with entirely necrotic cells.
Liver.- Two cases were below the average in weight (1,330 gm.) the other three averaged 2,270 gm. The consistency was flaccid in each instance, the lower border well rounded. The color was generally grayish-brown. The cut
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surface was slightly bloody. Lobulation was indistinct, but sometimes the centers of the lobules were large and deep red.
Microscopically, the two small livers presented marked degeneration of cells, areas of focal necrosis and a diffuse infiltration of polymorphonuclear cells which latter was somewhat more marked in the periportal tissue. In the other organs varying degrees of cloudy swelling were observed.
Meninges and brain.- The dura mater presented no changes. The pia-arachnoid was twice slightly edematous, and in one case of the three examined the vessels were considerably congested. Much opacity was present in this case, and over the superior surface of the cerebellum there was a small amount of grayish-yellow exudate. This patient had shown symptoms of spinal meningitis for about one month, but repeated lumbar punctures failed to bring out the causative organism.
Microscopically, there was a round cell infiltration with few leucocytes and some fibrin. The brain weight in the 3 cases averaged 1,480 gm. Only once did the cut surface show the marked congestion and petechial hemorrhage described above, while in the other two no gross changes were noted. Microscopically, there were degenerative changes in the ganglion cells similar to those already described; hemorrhages never were found.
BACTERIOLOGY
From the inception of the epidemic at Camp Taylor it was the routine to take cultures from the principal tissues at each necropsy-heart's blood, pericardium, right and left pleura, right and left lungs (all lobes), spleen, bronchial exudate, nasal accessory sinuses, subarachnoid space and ventricles, and elsewhere as occasion demanded.
Besides cultures, routine smears were made to act as a check on cultural findings.
The reports, both pathologic and bacteriologic, of this pandemic, as shown in the literature, revealed such an appalling divergency in conclusions, such diversity in reading results and in the means employed to get those results, that the findings in the study at Camp Taylor were analyzed in comparison with those from cases not to be considered as due in any degree to the prevailing epidemic, in order to see if there were not some underlying principles governing what appeared to be a disordered melange in the organisms found.
In this series the bile solubility test was regarded as final; a diplococcus or diplostreptococcus, whether capsulated or not, whether lanceolate or not, if bile insoluble was regarded as streptococcus, either hemolytic or nonhemolytic according to a predetermined estimate of hemolysing ability. Frequently there were encountered pneumococci agglutinating with two or more of our type antisera; these were properly regarded as Group IV.
The gradations between hemolytic and nonhemolytic streptococci are so fine and indistinct that it was necessary to adopt a standard of differentiation and arbitrarily choose the ability of an 18 hours' broth culture to produce hemolysis with equal parts of a 5 percent sheep suspension in the water-bath at 37.5° C. for two hours. The amount of the hemolysis, whether complete
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or not, was not considered. Some strains would give complete hemolysis in half an hour or less, while others would not cause complete hemolysis in the two hours, but an evident hemolysis, however slight, at the end of the time period was sufficient to enable one to make a differentiation. All tests were run with two saline controls. The hemolytic streptococci were again subdivided in a number of instances by the Holman sugar standard (Manual of Medical Research, 1916, xxxiv, 377). By this means was determined the curious fact that S. pyogenes, which had so abounded at Camp Taylor in 1917-1918 (reported: Journal of Infectious Diseases, 1919, May 25; Journal of the American Medical Association, 1918, lxx, 775) was not represented among those found in the epidemic of autumn, 1918, its place being taken by hemolytic streptococcus No.2. Double tests with fresh sugars were taken and corroborated these findings. Fifty strains of streptococcus were examined with the following results:
Hemolyticus streptococcus: Percent Nonhemolytic streptococcus: Percent
No. 2......................................................70.3 Equinus.....................................................45.5
No. 1...................................................... 3.7 Ignavius.....................................................22.7
No. 3...................................................... 7.4 No.2.........................................................11.3
Equinus.................................................. 11.2 Mitior........................................................11.3
Infrequens............................................... .7.4 Salivarius ..................................................11.3
This hemolytic streptococcus No. 2 was very frequently Gram-negative, not taking the Gram stain after repeated cultivation. It was recovered at one time or another from practically every organ or tissue, and on two occasions from the spinal fluid.
By the B. influenzae is meant a minute organism, Gram-negative, pleomorphic, hemophilic, which would not grow at room temperature, or only very slightly, and was generally killed by ice-box temperature. As a medium, rabbits' blood glycerin agar was used for a time, the growth appearing as multitudinous dewdrop colonies in from 20 to 48 hours. With the Washington formula the colonies were much larger, ringed and diverse in size and contour, giving a false impression of contamination. More latterly Avery's oleate medium (Journal of the American Medical Association, 1918, lxxi, 2051) was used with very gratifying results. Agglutination experiments of cultures against serum from recovered cases were doubtful or unsuccessful, except in two instances where the following results were obtained after incubation at 55 º C. for 18 hours followed by 12 hours in the ice box:
1:2 1:10 1:20 1:40 1:80
+ + + + + + + + +/-
Under the head of Micrococcus catarrhalis were included all members of this group, hardly any attempt at sugar or other differentiation having been made in the time at our disposal. Latterly, though, a prevalent diplococcus was found, both in sputum and at necropsy, the colonies resembling the Micrococcus catarrhalis, but morphologically showing slight differences. Since it fermented dextrose, saccharose and lactose the possibility of its being Micrococcus crassus was considered.
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In the preceding table a comparison is made of the bacterial findings from 120 influenzal cases with those from 101 necropsies from other causes. These deaths all occurred during the period under consideration and should give a fair line, if such is to be obtained, on the leading bacterial factors in the epidemics seen at Camp Zachary Taylor. Four organisms especially predomi- nated in the influenza cases; these were B. influenzae, a nonhemolytic streptococcus, pneumococcus of the various types, and M. catarrhalis.
The presence of the Pfeiffer bacillus in the heart's blood of 3.9 percent of the noninfluenza cases is to be explained by the fact that there was a concurrent epidemic of measles, and these cases in a high percentage carried an organism indistinguishable from the B. inftuenzxe, judging from a series of nasopharyngeal swabbings. The hemolytic streptococcus was not found in so high a percentage as in the noninfluenzal cases, and it was only at the latter end of the epidemic, and in those cases which were protracted, that it was met with to any considerable extent; so that it was looked on as a tertiary invader, in view of the fact that it had been endemic in this camp for 18 months.
The outstanding prominence of the B. influenzae is very noteworthy, and when the difficulty of its isolation and the fact that in the long continued cases it seemed to have died out or been replaced by the secondary or tertiary invaders, it is evident that these figures represent only the minimum number of times it was present during some period of the disease. In only two of the series was there a pure infection with this organism, and these were very early in the epidemic. Early also were eight cases of mixed infection with B. influenzae and a nonhemolytic streptococcus, and three of B. influenzae and pneumococcus; eight cases scattered throughout the epidemic of pure nonhemolytic streptococcus. Midway was one of pure M. catarrhalis; 10 cases mostly at the very end of pure hemolytic streptococcus, and 8 cases in this last period of mixed hemolytic streptococcus and staphylococcus. Nonhemolytic streptococcus and pneumococcus were found about three times as often in the influenza as in the noninfluenza cases. M. catarrhalis was very prominent in the latter part of the middle of the epidemic.
One very interesting organism encountered was a small biflagellated protozoon, measuring from 5 to 8 microns, and without undulating membrane, tentatively assigned to the Prowazekia. This was discovered in three cases close together toward the middle of the epidemic. In one instance it was recovered from the heart's blood; in another from the sphenoid sinus, and in the third from the left lung.
The following table gives the incidence and distribution of the bacteria according to the period of the epidemic. This table points out forcibly (a) the gradual lowering in the incidence rate of B. influenzae, nonhemolytic streptococcus, and pneumococcus; (b) the sudden rise into prominence in the third period of the M. catarrhalis, and (c) the remarkable manner in which the hemolytic streptococcus and the staphylococcus came to the fore in the last period. The latter especially had been practically nonexistent, so far as the necropsy cultures showed during the first three periods. The sudden recurrence of B. influenzae in the fourth period will be discussed later.
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Incidence and distribution of bacteria, according to period of epidemic (in percent)
The following table shows the incidence of the bacteria in the various organs. In this table is given in brackets the actual number of times each organism was found, also the resulting percentage per number of examinations made. Here again it is seen that the trinity, B. influenzae, nonhemolytic, streptococcus and pneumococcus were the predominating findings in all the tissues examined. The high percentage of hemolytic streptococcus was due in most part to the very considerable frequency with which it appeared in the fourth period, as above pointed out. Group IV, as elsewhere, was the principal pneumococcus found, followed by considerably less than half that number of Types IIa and II,
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which were almost equal in point of frequency. In this table the figures for the heart's blood are based on the total number of cultures taken, and not excluding the hopelessly contaminated, 13 in number. If these last be taken into account, a slight increase in all the percentages would have to be recorded.
It is in line with the pathologic picture revealed at necropsy that the findings for the subarachnoid and brain ventricles were so frequently positive.
Incidence of bacteria in the various organs
The following table divides the findings according to a different method; that is, according to the time the disease lasted before a fatal termination. Detailed figures have already been given in showing the relation of duration of disease to period of epidemic. Naturally, those that endured the longest came to necropsy in the later periods; so that there must necessarily be some
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similarity between this and the preceding table. But this table shows most forcibly the gradual disappearance of the B. influenzae in the longest enduring cases and the encroachment of the hemolytic streptococcus in the same. The relative infrequency of the hemolytic streptococcus, in the bronchial exudate as compared with its appearance in the lungs may be due to the fact that so many more lung examinations were made, especially as toward the end of the epidemic examination of the bronchial exudate was discontinued, and at this time the hemolytic streptococcus flourished most vigorously.
Distribution and incidence of bacteria present according to duration of disease (in percent)
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Early in October, 1918, the sputum of 129 influenza patients was examined, as shown in the following table. It will be seen that in the early days the hemolytic streptococcus was not very prominent, showing in 5 percent, whereas the trinity of B. influenzae, nonhemolytic streptococcus and pneumococcus, and of those typed, Group IV constituted 76.9 percent, were very much the most prominent organisms. One hundred and fifty other sputums sent to the laboratory routinely during October and November showed B. influenzae in 9.4 percent, and hemolytic streptococcus in 33 percent, indicating how much oftener hemolytic streptococcus was generally found than in the actual influenza cases.
Sputum examination from influenza patients during October, 1918
In the very first 10 days of the epidemic (from September 21 to October 1) swabbings from the throats of 250 influenza cases were taken. (See following table.) It is remarkable how closely the findings simulate those of the sputum from the same class of patients taken during the ensuing 10 days or so. Here again the hemolytic streptococcus was found in only 5 percent, while nonhemolytic streptococcus, M. catarrhalis and B. influenzae together with pneumococcus and staphylococcus in lesser degree were the most prominent. In other words, the organisms which were considered most responsible were most evident even in the initial swabbings before the epidemic had broken in its full fury.
Incidence of organisms in throats of 250 cases of influenza
It is interesting to note from the records that in two months--January and February--following the epidemic, 178 sputum examinations were made with the following findings:
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CHART
These last are very interesting as showing the extraordinary predominance of hemolytic streptococcus to the exclusion of the main factors during the epidemic. As regards the overwhelming preponderance of Group IV pneumococcus in these more recent sputum examinations, it should be remembered first, the liability to salivary contamination, and second, in the wave of enthusiasm for type determination of pneumococcus one unconsciously subscribed to the premise that it alone, when present, was responsible for the pathologic condition, often overlooking entirely the more dangerous cohabitant. It is worthy of note, too, how the B. influenzae almost disappeared from both necropsy and sputum findings. These latter statistics contained a very few cases of undoubted influenza, so the presence of bacillus of Pfeiffer in small percentages was agreeably accounted for.
In every one of the five cases which lasted 40 days or more, hemolytic streptococcus was the offending organism. In four cases it was recovered from the heart's blood. In one it was associated with M. catarrhalis in the left lung. But with this exception they were all five pure hemolytic streptococcus infections. This bears out the contention that hemolytic streptococcus was a tertiary invader, and by its luxuriant growth supplanted the original organisms.
From the foregoing studies of acute respiratory diseases as they occurred at Camp Taylor it is seen that the streptococcus, which played so important a part prior to the pandemic, had little effect during the latter period until its close, when it presumably was a factor in the production of a secondary rise in case fatality in the month of December, 1918. Practically every variety of pneumonic lesion is described and is attributed, in so far as possible, to the type of organisms with which it was most frequently associated. Lesions of organs other than those of respiration, while possibly in part due to the virus or organism causing clinical influenza, were undoubtedly in large part the result of the secondary or tertiary infections. This has particular reference to such lesions as focal necroses in the spleen and lymph nodes, degeneration of parenchymatous organs and possibly the purpuric eruptions.
