CHAPTER XII
The Pneumonias
Section I. Primary Atypical Pneumonia
Norman L. Cressy, M. D.
The occurrence of respiratory illness among troops during periods of mobilization has always been a matter of great importance, and pneumonia as either a primary or secondary disease has usually been a major cause of death. During the winter of 1812 and 1813, there was a high incidence of acute respiratory disease among troops stationed on the northern frontier.1 Measles complicated by pneumonia was epidemic from September to December 1812. During the following winter, although the morbidity and mortality were lower for the Army as a whole, new troops joining the service were as severely affected as the men who were mobilized during the preceding year. In the War Between the States, acute respiratory disease was again an important cause of morbidity and mortality.2During the winter of 1862, there was excessive seasonal variation of respiratory disease rates with a curve for catarrh which was similar to the influenza epidemic of 1918, but there was no epidemic such as the one which occurred in the fall of 1918. In the Mexican-border mobilization of 1916, there was an epidemic of pneumonia with about; 400 cases occurring among 40,000 troops and a 20-percent case mortality.3 During World War I, the great pandemic of influenza swept through troops and civilian populations alike with large numbers of deaths caused in the main by secondary pneumonia. At the same time, measles was widespread, and this disease was also complicated by secondary pneumonia. 4
Knowledge regarding the recognition, epidemiology, and treatment, of pneumonia was more definite at the outbreak of World War II than it had been at the time of any previous mobilization. Primary atypical pneumonia had been recognized for several years. It was first recorded by the Army, in a separate diagnostic category on the individual medical records during 1941 and on the weekly statistical health report in March 1942. Whether this disease or group of diseases was present before or during World War I will
1 Mann. James: Medical Sketches of the Campaigns of 1812, 13, 14. Dedham: H. Mann & Co., 1816, p. 306.
2 TheMedical and Surgical History of the Warof the Rebellion. Medical History. Washington: GovernmentPrinting Office, 1888, vol. 1, pt. 111, p. 719.
3 Nichols,H. J.: The Lobar Pneumonia. Problemin the Army From the Viewpoint of the Recent Differentiation ofTypes of Pneumococci. Mil. Surgeon 41: 149-161, August 1917.
4 TheMedical Department of the United StatesArmy in the World War.Pathology of the Acute RespiratoryDiseases, and of Gas Gangrene Following War Wounds. Washington: U.S.,Government Printing Office, 1929, vol.X11, p. 7.
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probably never be known, but there is evidence to suggest that it was not a new disease. The following quotation is taken from the history of the Medical Department of the United States Army in World War I: 5
* * * the usual type of pneumoniaoccurring among young male adults in civil life is of course primarylobarpneumonia * * *. That such cases occurred among the troops is beyondquestion * * *. However, it was earlyrecognized clinically that in the larger number of cases observed inthe camps the pneumonia was of an atypicalnature. The onset tended to be slower than that of the lobar pneumoniaof civil life; the course more prolonged.Crisis was relatively rare; physical signs were slow of development andof patchy distribution and scattered inseveral lobes. These facts led careful observers to consider a largeproportion of the cases as bronchopneumoniarather than as the usual lobar type. The results of post-mortem studyof fatal cases lent confirmation to thisdistinction: The typical croupons consolidation of lobar pneumonia wasrelatively rare, patchy consolidation of asuppurative character more frequent. Even when the consolidationinvolved nearly or quite an entire lobe, carefulstudy often showed evidence of the formation of such lobarconsolidation by the confluence of smaller areas, lobularin origin.
The similarity of this description of pneumonia to the picture seen in primary atypical pneumonia during World War II will be obvious to all those familiar with the disease. It would seem quite likely that atypical pneumonia was indeed present in World War I and was classified largely as bronchopneumonia.
The first of the really efficient chemotherapeutic agents, the sulfonamides, had been in use for several years prior to World War II mobilization. These drugs, and later penicillin, proved to be so efficient in the treatment of pneumococcus infections among service personnel that in May 1944 it was recommended that antipneumococcus serum be dropped from the Medical Department supply table. This situation was in sharp contrast to that which existed in World War I when the only specific pneumonia therapy was an antipneumococcus type I serum. The total effect of the use of the sulfonamides and penicillin will probably remain immeasurable. One might expect that, in addition to lowering the mortality case rate of primary bacterial pneumonia and other bacterial infections, it must also have lowered the number of cases occurring as a complication of other diseases.
RECOGNITION OF THE DISEASE
It was during the late 1930's that primary atypical pneumonia was first recognized as a disease distinct from the bacterial pneumonias. In 1938, Reimann6 published an account of a respiratory illness which he called atypical pneumonia and suggested its probable viral nature. Others had previously described a similar disease which in retrospect might well have been the same thing. Bowen 7 published a radiologic description of an epidemic among
5 The Medical Department of the United States Army in the World War. Communicable and Other Diseases. Washington: U. S. Government Printing Office, 1928, vol. IX, p. 61.
6 Reimann,H. A.: An Acute Infection of the Respiratory Tract WithAtypical Pneumonia. A Disease EntityProbably Caused by a Filtrable Virus. J. A. M. A. 111: 2377-2384,December 1938.
7 Bowen,A.: Acute Influenza Pneumonitis. Am. J.Roentgenol. 34: 168-174, August 1935.
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troops in Hawaii which he called acute influenza pneumonitis. Gallagher8 described bronchialpneumonia and acute pneumonitis in adolescents. In 1916, Clough andRichter 9 published anaccount of a patient with a respiratory illness in whomautohemagglutinins were demonstrated.The failure of some cases of pneumonia to respond promptly to thesulfonamides undoubtedlyinfluenced the thinking of investigators and helped to bring about theconcept of this disease as aseparate entity of virus etiology.
Since many of the, early reports dealt with epidemics in young adults in camps and boarding schools, it, came as no great surprise when cases began to be recognized in the Armed Forces.
EPIDEMIOLOGIC ASPECTS
Statistics for pneumonia in the Armed Forces inWorld War II are neither accurate nor complete.Reasons for this vary all the way from the intrinsic difficulties ofgathering statistics in wartimeto the ability of the medical personnel to make accurate differentialdiagnoses. The diseasebecame officially reportable on the weekly statistical health report asPrimary AtypicalPneumonia, Etiology Unknown, by direction of Circular Letter No. 19,Office of the SurgeonGeneral, United States Army, 2 March 1942. It was probably somemonths following this beforeall medical personnel became sufficiently familiar with this newclassification to make thedifferential diagnosis regularly. Officers concerned almost exclusivelywith the respiratorydisease problem often had trouble ill making accurate distinctionbetween the various types ofpneumonia even while working under the best conditions. It would bereasonable to expect thatofficers responsible for all the medical problems of entire unitsworking under less favorable andoften hazardous conditions would have even greater difficulty. The factthat there was somedifficulty ill making accurate differential diagnoses was emphasized ina report from ETOUSA(European Theater of Operations, United States Army) for April 1944 byMaj. Charles D. May,MC.10 He stated
It was possible to substantiate the diagnosis of atypical pneumonia in 72% of the patients so diagnosed. But in only 35% of the patients diagnosed by the hospital as primary [i. e., bacterial or lobar] pneumonia was the evidence considered adequate to justify the diagnosis.
One hypothesis to account for the apparent increase in the incidence of both primary and atypical pneumonia without a corresponding rise in the incidence of common respiratory disease is that there was an actual increase in atypical pneumonia with a confusion in diagnosis leading to many of the cases being reported as primary pneumonia.
Available data show that primary atypical pneumonia was present in all theaters and that its clinical characteristics with but very few exceptions were similar wherever it was reported.
8Gallagher, J. R.: Bronchopneumonia in Adolescence. Yale J. Biol. & Med. 7: 23-40, October 1934.
9Clough, M.C., and Richter, I. M.: A Study of an Autoagglutinin Occurring in aHumanSerum. Bull. Johns Hopkins Hosp. 29: 86-93, April 1918.
10Memorandum, Maj. C. D.May, MC, for Lt. Col. J. E. Gordon, MC, 2 May 1944, subject:Pneumonia Study, ETOUSA, 1944--Considerations for Further Study.
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During the summer of 1941, an unexpectedly highincidence of pneumonia was observed in thesoldiers at Camp Claiborne, La. The unusual character of this diseasewas noted by thecommanding officer and by the chief of the medical service at thestation hospital whorecognized its similarity to the clinical syndrome of atypicalpneumonia which had recently beendescribed. The outbreak was reported to The Surgeon General and to theSurgeon, Fourth CorpsArea, which resulted in the institution of preliminary surveys at CampClaiborne by Drs. A. R.Dochez, Yale Kneeland, Colin M. MacLeod, and Kenneth Goodner. Theseworkers felt thatfurther investigation was warranted, and, accordingly in December 1941,Drs. John H. Dingleand W. Barry Wood took up residence at Camp Claiborne and remaineduntil 1 May 1942 todirect a group study of the problem. The results of the work led to theestablishment of alaboratory for the Commission on Acute Respiratory Diseases at FortBragg, N. C., on 19October 1942.
It is probable that the figures of morbidity and mortality obtained at Camp Claiborne during 1941 and 1942 and at Fort Bragg during the remainder of the war are fairly accurate because of the special studies which were conducted at these two stations. The early work at Camp Claiborne showed that the disease represented a real problem to the Army with an average attack rate of 28 per 100,000 per week and a recorded peak incidence of 88 per 100,000 per week during an epidemic. It was shown further that the average hospitalization period for patients with atypical pneumonia was 32 days.11 This clearly presented a threat to the well-being of troops in training and potentially to those in combat.
Available figures suggest that, excluding thecommon respiratory diseases, atypical pneumoniarepresented the major respiratory disease problem for the Army as awhole. In the 4-year periodfrom 1942-45, total Army admissions for atypical pneumonia were 160,940with an annualadmission rate of 6.32 per 1,000 (table 34). Comparable figures for allother pneumonias were109,882 and 4.31 (table 35). This general relationship was true both inthe United States and inoverseas areas taken as a whole. It is of interest that in 1942, theyear in which atypicalpneumonia was first accepted as an official diagnosis for thestatistical health reports, theincidence of reported atypical pneumonia in all areas except theCentral and South Pacific wasless than that for all other pneumonias. In 1943, the relationship ofthe two groups, for the totalArmy and for the United States, was reversed, in that atypicalpneumonia admissions exceededadmissions for other pneumonias; for total overseas admissions,however, other pneumonia stillexceeded atypical pneumonia, although not as markedly as in 1942. In1944 and 1945, so far asthe figures are available, the diagnosis of atypical pneumonia farexceeded the total for all otherpneumonias. This was true in all areas except in 1944 inChina-Burma-India, the Middle Fast,and North America, exclusive of the United States. Whether thisrepresented in part a growingawareness among medical personnel of the
11 Dingle, J. H., Abernethy, T. J.,Badger, G. F., Buddingh, G. J., Feller, A. E., Langmuir, A. D.,Ruegsegger, J.M., and Wood, W. B.: Primary Atypical Pneumonia, Etiology Unknown.WarMed. 3:223-248, March 1943.
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TABLE 34.-Admissionsfor primary atypical pneumoniain the U. S.Army, by area and year, 1942-45
presence of atypical pneumonia or whether it represented a true,increase in the incidence of thisdisease cannot be determined.
The peak incidence of atypical pneumonia for the entire Army was reached in 1943, when the rate per 1,000 per year reached 7.45 (table 34). This was largely a reflection of the rate for troops in the United States where the rate reached 8.95 in that year. The peak incidence in Europe, however, occurred in 1942, when it reached 9.23 per 1,000 per annum. Thereafter it declined to a low of 4.80 in 1944 but rose slightly to 5.35 in 1945. The Middle East had its greatest incidence in 1942. All other areas had a peak rate in 1945, when the incidence in the Mediterranean (North African) theater reached 14.13 per 1,000 per annum, the highest rate recorded anywhere for an entire area.
Generally, there seems to have been a somewhathigher incidence of atypical pneumonia duringcolder months when all respiratory disease was more prevalent, but itis obvious that sharpoutbreaks did occur during the warmer months as well. From the date onwhich the disease firstbecame reportable, it was present in all areas almost constantly.Comparative figures for allother pneumonias indicate that atypical pneumonia was the majorrespiratory illness.
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In spite of the widespread morbidity due toatypical pneumonia, the mortality was fortunatelylow in all areas. There were 170 deaths attributed to atypicalpneumonia in the entire Armyfrom 1942 through 1945. This is in contrast to 1,041 deaths caused byother pneumonias duringthe same period. It is of interest that the case fatality rates werehigher overseas than in theUnited States for all types of the disease; however, the death rate(number of deaths due topneumonia per 100,000 average, strength per year) was higher for bothatypical and otherpneumonias among those troops stationed in the United States than itwas for those stationedoverseas. The over-all case fatality rate (number of deaths per 100admissions for pneumonia)for atypical pneumonia was 0.12 per 100 admissions for the 4 -yearperiod 1942 through 1945 ascompared with a rate of 0.88 per 100 admissions for all otherpneumonias.
What conclusions can be drawn from the foregoing discussion? As stated previously, the figures are incomplete and are based on sample tabulations. It can be said, nevertheless, that, apart from the common respiratory diseases, atypical pneumonia was the major respiratory disease problem during World War II. Atypical pneumonia was present in all areas in significant
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numbers and accounted for a large share of the total morbidity fromrespiratory disease.
Since atypical pneumonia was not recognized as an entity in 1918, no direct comparison of figures for the two World Wars for this disease can be made. Study of the figures for all pneumonia for the two periods is very interesting. The admission rate for all pneumonia per 1,000 average strength per year for the total Army from April 1917 to December 1919 was 18.98, and the approximate case fatality rate per 100 admissions was 24.46. The admission rate for all pneumonia in the entire Army from 1942 to 1945 was 10.63 per 1,000 average strength per year, and the average case mortality rate (deaths per 100 admissions) for the same period was approximately 0.42. This great reduction of morbidity and mortality figures could have been caused by many factors, ranging from the type of warfare carried on to the many aspects of personal hygiene. Undoubtedly, the sulfonamides and penicillin were a great influence and may well have been the most important. The absence of pandemic influenza played an undetermined but probably important role.
SPECIAL STUDIES
The results of the early investigations at CampClaiborne, in 1941 and 1942, showed the need forcontinued study of the problem of atypical pneumonia. To this end, theCommission on AcuteRespiratory Diseases was founded, and a laboratory was later equippedat Fort Bragg. ThisCommission functioned as an active investigating unit from 1 August1942 throughout theduration of the war. The scope of its activities included not onlyprimary atypical pneumonia butalso influenza and other respiratory diseases. The complete work isfully reported in numerousarticles under the authorship of the Commission on Acute RespiratoryDiseases which werepublished from 1943 through 1946. Only the most important aspects ofthe work will be set forthhere. The most significant work of the Commission concerned the studyof atypical pneumoniain human volunteer subjects who were drawn from the ranks ofconscientious objectors.12 Thesestudies were carried out over a period of 3 years. The disease wassuccessfully transmitted tohumans by inoculation with bacteria-free filtrates of respiratorysecretions which had beencollected from patients with atypical pneumonia. This accomplishmentalone lends strongsupport to the widely held theory that atypical pneumonia is a virusdisease. These carefullycontrolled cases furnished a unique opportunity to study the clinical,roentgenographic, andlaboratory characteristics of atypical pneumonia.
Clinical Aspects
Onset.-The Commission's studies of these cases confirmed andextended previous descriptionsof the clinical picture of atypical pneumonia. The exact
_12 Commission on Acute RespiratoryDiseases: The Transmission of Primary Atypical Pneumonia to HumanVolunteers. Bull. Johns Hopkins Hosp. 79: 97-167, August 1946.
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time of onset proved to be almost as difficult to determine in thesecases as in the naturallyoccurring disease. Often the earliest symptoms were mild and inconstantwith no objectiveevidence of illness. This was quite in keeping with the previousobservations of the disease. Theincubation period varied from 7 to 14 days and was in general shorterfor those who receiveduntreated inoculation and longer for those who received filteredmaterial. The reason for thisvariation is not clear but could represent a difference in the amountof infectious material presentsince presumably some of the agent was adsorbed by the filter inprocessing.
The character of onset varied considerably among the 16 patients studied. In five, the simultaneous occurrence of fever and constitutional and local symptoms marked a rather sudden onset of illness. In the remaining 11, the onset was gradual and marked by varying local and constitutional symptoms. The latter type of onset was in accord with that described by numerous authors in the naturally occurring disease. Early symptoms included dry or sore throat, nasal stuffiness, and headache. Feverishness and headache developed early, and chilliness was common and most prevalent on the second day following the onset. Malaise occurred in more than half the patients and was also an early symptom. Anorexia was present at some time in all patients. Local symptoms included nasal stuffiness, mild sore throat, and hoarseness. Cough was a conspicuous feature and was usually dry at first but later became paroxysmal and productive. All patients developed coughs between the first and fourth day. Sputum was mucoid at first, later becoming purulent. No patient developed grossly bloody or rusty sputum, but two of the most severely ill produced a slight blood streaking. Fourteen of the sixteen patients with pneumonia experienced chest discomfort, usually described as a sense of pressure or substernal soreness. Only one developed sharp pleuritic pain.
Physical findings.-Fineand coarse rales were present in 15 of the 16 patients. Only one had norales at any time. Rales first appeared from the first to the ninth dayafter onset. They developedon the third and fourth day in the greatest number of patients. Slightdullness to percussion waspresent in 10 patients, changes in tactile and vocal fremitus in 5, andalterations of the breathsounds in 7. Only one patient developed pleural fluid. Two patientsshowed signs of centralnervous system disturbance. One developed partial loss of bladder andrectal function withmotor impairment of the lower limbs. In the other, there was transientareflexia of the lowerlimbs. Both eventually recovered completely.
Roentgenographic findings.-Roentgenographic findings conformed generally to those seen in the naturally occurring cases. The earliest findings were peribronchial infiltration, most commonly seen at the lung bases.The appearance was usually that of soft patchy densities of irregular size and shape. In some cases, the densities were small, discrete, and nodular, tending to become larger and confluent as the disease process continued. There was much variation in the development of these lesions. In four patients, it was limited to one or both lower lobes. In six patients, it spread toward the hilar region.
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The distribution involved the lower lobes solelyin 75 percent of the patients. In the others, thelower lobes were involved with concomitant lesions in other lobes.Average duration ofroentgen-ray lesions was about 10 days with a few being present foronly 1 to 3 days. It was notuncommon to find roentgenographic evidence of pneumonia before physicalsigns developed.
Fever.-All of the patients had fever. It began as early as the first day of illness in some and reached its peak incidence of onset between the second and fifth days. The maximum temperature observed was 104.8o F., and the average maximum was 102.8° F. By the ninth day following onset, most temperatures had returned to normal. The pulse and respiratory rates were not strikingly elevated except in a few patients who were severely ill with extreme pneumonic infiltration. The cases varied considerably in severity from very mild with minimal infiltration and fever for only 3 days to rather severe with extensive involvement of all lobes and fever for 15 days.
Complications.-Complicationswere observed in only four patients. One had maxillary sinusitisduring the recovery period; one had a toxic psychosis associated withfever. Pleural effusion andencephalomyelitis each occurred in one patient.
Minor respiratory illness. It is of interest that many of the subjects who were inoculated but did not develop atypical pneumonia did, however, develop evidence of a minor respiratory illness. Whether these represented mild infections with atypical pneumonia or infection with other agents present in the inoculum could not be determined.
Laboratory studies.-Total and differential leukocyte counts were in general within normal limits. Slight elevations were observed in a few of the more severely ill patients. Sedimentation rates showed no constant variation and, although they rose above normal in some individuals, the average for the group showed no striking increase.
Bacterial studies indicated that none of the common organisms found in the respiratory tract seemed to play any role in the infection. There were no concentrations of any one organism that suggested bacterial influence. Special efforts were made to recover the streptococcus MG described by Mirick and others.13 The Commission's studies failed to relate these organisms causally to atypical pneumonia. Cold autohemagglutinins were found in 13 of the 16 cases of pneumonia in significant titers. The significance of this test in its relationship to the etiology of atypical pneumonia is not known. It is apparently of some diagnostic value in those cases in which it is present.
Etiologic Studies
From the beginning of the first work of theCommission group at Camp Claiborne until the endof the war, research was in progress to uncover the
13 Mirick, Cx. S., Thomas,L., Curnen, E. C., and Horsfall, F. L., Jr.: Studies on a Non-HemolyticStreptococcus Isolated From the Respiratory Tract of Human Beings. J.Exper. Med.80: 391-440, November 1944.
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agent of atypical pneumonia. Commission studies involved the use ofchick embryos, mice, rats,cotton rats, hamsters, guinea pigs, cats, and monkeys. A few members ofthe Commission weresent to Puerto Rico to work with mongooses. In no instance was itpossible to reproduce thedisease until human volunteers were used. The electronic microscope andultracentrifuge atDuke University, Durham, N. C., were used in an attempt to find virusparticles but withoutsuccess. Acute and convalescent sera from patients with atypicalpneumonia failed to showantibodies against any of the known viruses or rickettsiae. Much ofthis work was done in thelaboratory of Dr. Thomas Francis, Jr., at the University of Michigan atAnn Arbor. Extensivebacterial studies over a period of 5 years failed to reveal anybacterial agent responsible for thedisease.
Epidemiologic Studies
The early work of the investigators at CampClaiborne showed that a moderately severeepidemic of atypical pneumonia occurred during the summer of 1941. Thepeak epidemic ratewas about three times as high as the average endemic rate prevalent atthat camp. Studies failedto reveal any possibility of contamination of water, milk, or foodsupplies as a transmittingagent. At the same time, the disease was too widely spread to be easilycharged to direct person-to-person contact of overt cases except for asmall number which occurred among medicalpersonnel. It was noted that many cases were mild and indistinguishablefrom commonrespiratory disease infections except by roentgenogram. It wasconcluded that these casesprobably formed an inapparent reservoir which spread the disease fromperson to person. Thiswas substantiated by subsequent work. It will be recalled that many ofthe inoculated humanvolunteers described earlier developed minor respiratory illnesswithout evidence of pneumonia.In addition, previously unknown cases of atypical pneumonia, withoutsymptoms, were foundduring roentgenographic surveys of entire units.
Later studies at Fort Bragg showed that new recruits experienced high rates of respiratory illness during the first 4 weeks after their arrival at camp.14 The peak incidence of atypical pneumonia was likewise greatest during this period. The attack rate at Fort Bragg for respiratory diseases, in general, and for atypical pneumonia, in particular, followed a more or less constant ratio of 10:1. This led to some speculation as to the possibility of a common etiology. However, this possibility was not supported by results from subsequent studies in human volunteers who failed to develop pneumonia following inoculation with material recovered from patients with common respiratory disease. Reports from England specifically note the increased incidence of atypical pneumonia in the presence of normal figures for common respiratory
14Commission on Acute Respiratory Diseases: Acute Respiratory DiseaseAmong New Recruits. Am. J. Pub.Health 36: 439-450, May 1946.
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diseases.15 A report from India takesnote of the sharp increase in all respiratory diseases,including atypical pneumonia, during the hottest months of the year.16A similar experience wasreported from Camp Claiborne during the summer of 1941, at which timethe incidence ofcommon respiratory diseases was at its usual seasonal level.17
The evidence indicates that atypical pneumonia is an infectious disease of virus etiology. It is generally, but not invariably, more prevalent at the time of greatest incidence of other respiratory diseases. It can be spread from person to person by infected respiratory secretions, and this is probably its natural mode of spread. The frequent finding of inapparent cases suggests the probability that such cases form a reservoir of infection from which clinical cases may arise.
SUMMARY
Atypical pneumonia, which first became recognizedas a clinical entity in the late 1930's, madeits appearance in the Army soon after large-scale mobilization began.It became clear afterpreliminary studies at Camp Claiborne that the disease was of majorimportance to the Army,and it eventually became an outstanding respiratory problem. Itappeared in significant numbersin all theaters.
Special research in this field was carried on by the Army throughout the war. These studies showed that atypical pneumonia is an infectious disease which can be transmitted to human volunteers by the inhalation of infected bacteria-free filtrates. The specific etiologic agent was not determined, and extensive serologic studies failed to suggest a relationship to any known virus or rickettsia.
Morbidity and mortality rates for all pneumonia taken as a group were much lower in World War II than in World War I. There are probably many reasons for these differences, but unquestionably the use of chemothera peutic agents and the absence of pandemic influenza were important factors. Extensive clinical, laboratory, and epidemiologic investigations were pursued which confirmed and extended the findings of previous workers. Available evidence suggests that the natural mode of spread is by person-to-person contact. Inapparent cases are known to exist which probably furnish a reservoir of infection. In general, atypical pneumonia was most prevalent during the colder months when there was an increase in all respiratory diseases. There were, however, some notable exceptions to this rule, and several epidemics were reported during the warm months.
15Gordon, J. E.: A History of Preventive Medicine in the European Theaterof Operations, United States Army.1941-194.5. Pt. 111, Epidemiology, sec. 3, Acute RespiratoryInfections, No. 3, The Pneumonias, pp. 1-14. [Officialrecord.]
16Blumgart, H. L., and Pike, G. M.: History of Internal Medicine inIndia-Burma Theater. Pt. II, Internal Medicinein the India-Burma Theater. Respiratory Diseases, pp. 116-123.[Inpreparation.]
17 See footnote 11,p. 214.
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Section II. Bacterial Pneumonia
Richard G. Hodges, M. D.
In great contrast to World War I and probably toall previous wartime mobilizations, bacterialpneumonia during World War II did not present a major problem. Thereasons for this wereseveral. Although influenza, both A and B, involved the militarypopulation, nothing resemblingthe pandemic of 1918-19 occurred with its wake of pneumococcal,streptococcal, and influenzalpneumonia. Furthermore, there were no epidemics of measles to introducepneumonia as acomplication. This may be due to the automobile and the motion picture,both of which broughtabout an earlier and more general exposure of the rural population tomeasles. Finally, thewidespread use of the sulfonamide drugs in the early treatment offebrile respiratory infectionsprobably resulted in the prevention or abortion of many cases andcertainly reduced the mortalityto an extremely low level.
No meaningful figures can be given as to the incidence of bacterial pneumonia during the war years. The general decline of accurate bacteriologic diagnosis made it impossible to distinguish between bacterial and primary atypical pneumonia. During the early years of the war, it is probable that many cases of nonbacterial pneumonia were diagnosed as bacterial; when the diagnosis of primary atypical pneumonia had become popularized, it is probable that the error was in the opposite direction. The best available data on the comparative incidence of the two conditions is given in the preceding section dealing with primary atypical pneumonia.
Historically, the most important aspect ofbacterial pneumonia was the information gatheredabout the spread and particularly the prevention of pneumococcalpneumonia.18 The studieswere carried out at a single installation, the Army Air Force TechnicalSchool at Sioux Falls, S.Dak. This was the only large military establishment that sufferedseverely from pneumococcalpneumonia. The investigation represented a joint project of theCommission on Pneumonia,Army Epidemiological Board, Office of the Surgeon General, and the ArmyAir ForceRheumatic Fever Control Program, Office of the Air Surgeon.
EPIDEMIOLOGY
Studies on the epidemiology of pneumococcal pneumonia covered a 3-year period at the Army Air Force Technical School at Sioux Falls, S. Dak. During this period of observation, more than 1,600 cases of pneumonia occurred. On several occasions, the attack rate exceeded 150 cases per annum per 1,000 ,average strength. The experience of the first year was studied in retrospect from hospital records; the data for the second year were gathered directly by an epidemiologist; during the third year, extensive bacteriologic and statistical
18 Hodges, R. G., andMacLeod, C. M.: Epidemic Pneumococcal Pneumonia, pts. I-V. Am. J. Hyg.44: 183-243,September 1946.
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facilities were available. From this large experience, certainfactors which contributed to the highpneumonia rates could be detected.
Influence of Population Characteristics and Environment
The two important population characteristicswhich influenced the pneumonia attack ratesappeared to be length of service and duration of stay on the post.During the first months afterthe establishment of the post, it was impossible to distinguish betweenthese two factors sincemen were brought to the school direct from basic training. Later, whenthe population was amixture of new recruits and of seasoned troops, it was possible so todistinguish. There was asmall but definite excess incidence in men newly introduced intomilitary service. Regardless oflength of service, the majority of pneumonia cases occurred in menspending their first 8 weeksat the post. Thus, it appeared that the troops became twice seasoned,first to military life ingeneral and secondly to the particular environment of this particulartechnical school.Of thesefactors, the latter was by far the more important.
No way was devised of subjecting the environmental factors to controlled study. However, there was much to indicate that environment was important. In many ways, the operations of the technical school were admirably devised to promote the spread of respiratory disease. The barracks were of the theater of operations type, ill-suited to the climate of South Dakota. No efforts were made to promote ventilation or to control dust. The school buildings were no better than the barracks in these respects. The exact role of dust could not be determined, but pathogenic pneumococci were cultured from 29 percent of 147 dust samples. Moreover, there was a thorough mixing of the school population. Each class was composed of men from several different squadrons and from many different barracks. These arrangements facilitated cross-infection. It was shown that common respiratory diseases, pneumonia, streptococcal sore throat, epidemic influenza, and even specific serologic types of pneumococci spread rapidly and evenly throughout the school population.
No evidence was obtained that implicated previousgeographic environment, age, chilling, orfatigue as being important factors in the production of pneumococcalpneumonia in thepopulation as a whole.
Influence of Pneumococcal CarrierState
During the third year of the study, extensivecarrier surveys were made in an attempt to relate thebehavior of the causative organism to the incidence of pneumococcalpneumonia. Serologictyping was carried out with great care. Three methods of survey wereused. A single squadronwas sampled three times a week throughout the year. Cultures were madefrom all men admittedto hospital for respiratory diseases. Cultures were also taken from theoccupants of a singlebarracks three times a week for 9 consecutive weeks. The carrier ratesfor the single squadronand for the hospital admissions, which
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came from all squadrons, were identical and were combined torepresent the population as awhole.
The total carrier rate was affected by season. Starting with a rate of approximately 40 percent in September, there was a sharp rise to 60 percent in November, and this high level was maintained throughout the winter season. Within the total carrier rate, the individual serologic types behaved rattier independently, each attaining its own peak of incidence. Surprisingly, neither the total nor the specific carrier rates appeared to be affected by the incidence of common respiratory diseases.
Men newly arrived at the post were relatively free of pneumococci and were almost entirely free of the types which were known to produce pneumonia frequently. However, the new arrivals rapidly acquired pneumococci. After 4 weeks in the environment, their carrier rate was equal to that of the total population. Moreover, the new men became rapidly infected with the pathogenic types. This was demonstrated in the single barracks study. Only 7 percent of new men carried either type IV or XII, the types that were currently the leading cause of pneumonia. After 7 weeks in the barracks, 40 percent of the new men had become carriers of one or both of these types.
The single barracks study also demonstrated that the carrier state was dynamic in character. Men rapidly acquired and lost several different serologic types of pneumococci during the period of observation.
The incidence of pneumonia did not correspond tothe total carrier rate nor did it correlateclosely with the carrier rates for the highly infective types ofpneumococci. At the times whenthe pneumonia rate was high, it was usual for the carrier rate to behigh also, but there wereseveral periods when the carrier rate for infective types was high andthe pneumonia rate low.This indicated that some other factor besides the presence of theinfective agent was necessary toproduce high pneumonia rates.
Influence of Nonbacterial Respiratory Disease
During the entire 3 years of observation, there wasa close relationship between the incidence ofnonbacterial respiratory disease and that of pneumococcal pneumonia. Onthe average, 1 case ofpneumonia was admitted to the hospital for every 10 patients admittedwith nonbacterialrespiratory disease. The seasonal occurrences of the two conditionsparalleled each other closely,there being only two periods when the 1:10 ratio was not closelyapproximated. The first of thesewas in the 4 months after the. post was opened. At that time, theincidence of nonbacterialrespiratory disease was high but that for pneumococcal pneumonia low.Presumably, this wasbefore the population had become thoroughly seeded with pneumococci.The other period wasduring the second winter of the study when, for a time, the ratio wasmore nearly 1:5 than 1:10.This corresponded to a period when the incidence of type II pneumoniawas very high,approximately 60 percent of the cases of pneumonia. Later, it waspossible to show that therewere considerable differ-
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ences in the "infectivity" of the various types of pneumococci.Infectivity was expressed as thenumber of men admitted with pneumonia due to type X divided by thenumber of respiratoryadmissions carrying type X. The value for type II was 0.52; whereas fortype IV, it was 0.17; fortype XII, 0.26; for type III, 0.10; and for type VIII, 0.09. Thus, whentype II was prevalent, morecases of pneumonia per case of nonbacterial respiratory disease wouldbe expected to occur.
Two epidemics, one of influenza A and one of influenza B, were identified. Both resulted in a sharp rise in the pneumococcal pneumonia rates, but during both the usual 1:10 ratio held good.
It was concluded that the incidence of pneumoniawas governed by the prevalence ofpneumococci, by the infectivity of the serologic types which werepresent, and by the incidenceof nonbacterial respiratory, disease.
PREVENTION OF THE DISEASE
The circumstances in the Army Air Force TechnicalSchool, Sioux Falls, S. Dak., appeared to beideal to test the efficacy of immunization against pneumococcalpneumonia. Of the recordedattempts to conduct such im munization,19each had been handicapped by one or more of thefollowing difficulties: (1) Differences in the composition of theimmunized and control groups,(2) uncertainty as to whether the specific pneumococcal types includedin the immunizingpreparation were the same as those currently causing pneumonia, (3)failure to determinewhether the observed decline in cases in the immunized group was due toa decrease in casescaused by the pneumococcal types in the vaccine, and (4) inadequatecontrol of the antigenicityof the preparation used.
In the investigation conducted at Sioux Falls, the situation was such that each of these obstacles could be eliminated.20 In the first place in the 2 preceding years, the population had been subjected to a thorough epidemiologic study of respiratory disease. It was known that the population was very uniform in respect to such epidemiologic characteristics as age, length of service, and duration of stay on the post, and that the environment of the troops was admirably devised to facilitate a rapid and uniform dissemination of respiratory disease throughout the entire population. This had been proven for streptococcal sore throat, pneumonia, influenza A, and the common respiratory diseases. Second, for the 2 preceding years, the pneumococcal pneumonia rates had been extremely high, and, equally important, the distribution of pneumococcus types causing pneumonia appeared to be uniform. For each of the 2 preceding years, the approximate distribution was: Type II, 34 percent; types I, V, and VII, 9 percent each; types XII and IV, 7 and 5 percent, respectively. Third, statistical machinery was established whereby the
19 Heffron, R.: PneumoniaWith Special Reference to Pneumococcus Lobar Pneumonia.NewYork: The Commonwealth Fund, 1939, pp. 446-483.
20MacLeod, C. M.,IIodges, It. G., Heidelberger, AT., and Bernhard, W. G.: Prevention ofPneumococcal Pneumonia by Immunization With Specific CapsularPolysaccharides. J. Exper. Med. 82: 445-465, December 1945.
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population could be carefully followed, and a laboratory capable ofdoing extensivepneumococcal typing was organized. Finally, through the efforts of Dr.Michael Heidelberger,highly purified capsular polysaccharides of known antigenicity wereavailable.
Accordingly, in September 1944, the entire personnel of the technical school was subjected to this test. A barracks was roped off longitudinally, and as the men were marched through they were given a random choice of which side of the rope they preferred. Those passing down one side received 1.0 ml. of saline containing 0.03 to 0.06 mg. of types I, II, V, and VII type-specific polysaccharide; those choosing the opposite side were injected with 1.0 ml. of saline containing 0.5 percent phenol. Subsequently, when a new troop shipment arrived at the post, alternate men received the polysaccharide solution or the saline, respectively. In all, 8,586 men were injected with the polysaccharide solution and 8,449 with saline. In terms of man-days exposure, the experience was 745,997 days for the immunized and 772,898 days for the nonimmunized. Many samplings of the population were taken to test for random distribution, and in each instance immunized and nommmunized men were found to be present in equal numbers.
The effect of the immunization on the developmentof clinical pneumonia is shown in table 36.Pneumonia due to the types against which immunization was not practicedwas equally dividedbetween the treated and control groups. Pneumonia due to types I, II,V, and VII occurred 4times in the treated group and 26 times in the control group. Moreover,each of the four cases inthe immunized group occurred within 2 weeks after the individual wasinjected, whereas thecases in the control group were distributed at random over the periodof observation (table 37).The number of type II cases was large enough to afford sound evidenceof the protective value ofthe type-specific polysaccharide. There was no reason to believe thatthe specific protectionagainst the other types was not equally good.
TABLE 36.-Incidenceof pneumonia inimmunized andnonimmunized groups
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The incidence for pneumonia due to types IV andXII, against which immunization was notpracticed, was approximately that expected from the experience of thepreceding 2 years.Fortypes I, II, V, and VII, even in the nonimmunized group, the incidenceof pneumonia was farbelow that expected. This strongly suggested that immunization ofone-half of the populationconferred a real protection on the nonimmunized subjects. There wereplausible explanations forthis. Reduction of the number of cases would comparably reduce thenumber of case contactsand might thus inhibit the spread of the organism. A more potent reasonstemmed from theresults of the carrier study which was being carried out simultaneously(table 38).The carrierrates for the types against which immunization was not practiced werealmost equal in theimmunized and nonimmunized groups. However, the rates for types I, II,V, and VII weresignificantly lower in the immunized group as compared with thecontrol. Thus, theimmunization of a given individual appeared to render him relativelyresistant to becoming acarrier of the specific types contained in the vaccine. Consequently,in a population consisting ofintimately mixed immunes and nonimmunes, every second transfer of apneumococcus wouldresult in the organisms falling on relatively infertile ground. Theconsistent behavior of types IVand XII in each of the 3 years of observation provided a means ofcalculating the amount ofreduction in the incidence of type I, II, V, and VII pneumonia amongthe nonimmunes whichwas achieved by immunizing one-half the population. Only 17.6 percentof the expected caseswere observed.
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CONCLUSIONS
Bacterial pneumonia was not a major problem inWorld War II. However, studies conductedunder the auspices of the Armed Forces did demonstrate the steps thatshould be taken to controlpneumococcal pneumonia during future periods of mobilization. A highcarrier rate forpneumococci and a high incidence of nonbacterial respiratory diseasewere shown to stimulatethe occurrence of pneumonia. Although neither of these factors could beattacked directly, theimplication was clear that more care in choosing the geographiclocation of military schools andmore attention to the sanitation of installations in unfavorableclimates would serve to lessen thespread of both bacterial and of nonbacterial respiratory disease.
Finally, it was possible to prove that a high degree of protection against pneumococcal pneumonia can be given by immunization with type-specific capsular polysaccharides.
