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Chapter I

Contents

CHAPTER I

Respiratory Diseases

Yale Kneeland, Jr., M.D.

GENERAL CONSIDERATIONS

Diseases of the respiratory tract may be divided into two groups: The acute infections and the chronic diseases which may or may not be infectious. Most of these conditions will be dealt with in this chapter, although certain exceptions will be made. For example, in World War II, the interrelationship of tonsillitis, scarlet fever, rheumatic disease, and nephritis was intensively studied; the subject of streptococcal infections as a whole will be discussed elsewhere. Similarly, two chronic infections, tuberculosis and coccidioidomycosis, will be described by others. Lastly, chronic sinusitis, aero-otitis, and the like, are primarily the concern of the otologist and will not be considered here.

The acute respiratory diseases which immediately come to mind are the common cold, influenza, and pneumonia. These are communicated by droplets and droplet nuclei and are thus allied to certain virus infections, such as measles, which are also presumably transmitted in this way. Certain communicable diseases of childhood will also be included here. Cerebrospinal fever and diphtheria, however, although their portal of entry is the respiratory tract, will be discussed elsewhere in this volume. Clinical syndromes of unknown etiology, bizarre manifestations occurring only in localized outbreaks and not generally recognized as disease entities, are not included. This still leaves a large field for discussion.

Any general consideration of disease in World War II immediately invites comparison with the experience in World War I. Exact comparisons of morbidity and mortality of acute respiratory diseases in the two wars are not, however, possible for two reasons: First, more exact knowledge of the diseases led to a change in terminology; and second, certain new concepts, for example, that of atypical pneumonia, evolved. In spite of this, a rough and startling comparison may be made of the 46,640 deaths from influenza, lobar pneumonia, bronchopneumonia, bronchitis, and measles in the First World War,1 roughly 73 percent of total deaths from disease, and the 1,285 deaths from the same causes in the Second World War when an army well over twice the size of that of World War I was mobilized for a longer period.

Factors which played a role in this extraordinary change in importance of the disease just mentioned were the advent of sulfonamides and anti-

1The Medical Department of the United States Army in the World War. Washington: U.S. Government Printing Office, 1928, vol. IX.


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biotics, the absence of pandemic influenza of the 1918 type, an apparent change in the whole pattern of respiratory infection between the wars, and a greater degree of immunity to certain communicable diseases in the general population. The last was probably brought about by greatly increased communications which lessened isolation of rural areas. In addition, the almost universal roentgen examination of the chest at induction undoubtedly lowered the incidence of chronic pulmonary diseases found in troops during World War II.

In the following pages, the occurrence and course of each disease in question during World War II is discussed, with emphasis placed upon problems of diagnosis, treatment, and general management which were significant in a military sense. The chief military significance of many of the acute communicable diseases is epidemiological, and this aspect of the question has been exhaustively presented in other volumes in the history of the Medical Department in World War II.2 It is obvious that in many instances information will overlap. Some of the material will of necessity be repetitious.

Insofar as possible, proper names are avoided in the text, but where published material has been drawn upon, full acknowledgment is given. Other sources employed are as follows: Preliminary data from the Medical Statistics Division, Office of the Surgeon General; the writer's own notes while he served as consultant in an oversea theater; essential technical medical data sent in by various theater surgeons; reports submitted by medical consultants throughout the world; and other unpublished notes, manuscripts, and memorandums in the Professional Service Division, Office of the Surgeon General.

Part I. Acute Respiratory Diseases

COMMON UPPER RESPIRATORY INFECTION

Introduction

The term "common upper respiratory infection" includes a heterogeneous group of ill-defined conditions. In fact, it is a kind of scrapbasket which encompasses all the acute respiratory diseases after eliminating the pneumonias and influenza. In a general way, the group includes the common cold; nasopharyngitis which may or may not be due to the influenza virus; infection of the pharynx and tonsils produced by certain micro-organisms, such as the hemolytic streptococcus and Vincent's organisms; and bronchi-

2(1) Medical Department, United States Army. Preventive Medicine in World War II. Volume IV. Communicable Diseases Transmitted Chiefly Through Respiratory and Alimentary Tracts. Washington: U.S. Government Printing Office, 1958. (2) Medical Department, United States Army. Preventive Medicine in World War II. Volume V. Communicable Diseases Transmitted Through Contact or By Unknown Means. Washington: U.S. Government Printing Office, 1960. (3) Medical Department, United States Army. Preventive Medicine in World War II. Volume VI. Communicable Diseases: Malaria. [In press.] (4) Medical Department, United States Army. Preventive Medicine in World War II. Volume VII. Communicable Diseases: Arthropodborne Diseases Other Than Malaria. [In preparation.]


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tis. The latter is a loose term limited by some physicians to cases in which dry rales are audible; that is, the asthmatic type, while others may use it to describe an acute respiratory infection with substernal soreness and paroxysmal cough. It is probable that the viruses of common respiratory diseases, influenza, and atypical pneumonia can all produce this clinical picture, and it may also be the result of infection by such organisms as pneumococci or Hemophilus influenzae following a cold. In any cases, it is not an etiological entity.

The common cold had been shown before World War II to be primarily a virus disease.3 Experimental studies are handicapped by the fact that only man and the anthropoid ape are susceptible to the virus, and such questions as that of immunity and whether the virus is an entity or whether several distinct viruses exist were not settled. The Commission on Acute Respiratory Diseases of the Army Epidemiological Board (Board for the Investigation and Control of Influenza and Other Epidemic Diseases in the Army) during the war undertook, under the direction of Dr. John H. Dingle, to investigate the transmission of common respiratory diseases. Evidence was produced4 that there are at least two viruses: One, the coryzal type with a short incubation period, producing little if any active immunity; the other, with a longer incubation period, giving rise to more constitutional symptoms, often attended by fever, and conferring immunity against homologous reinoculation. The second type came to be known as "undifferentiated respiratory disease." As the number of transmission experiments was small, there is no information as to the relative frequency of infection with these two agents. Recent observations by Atlas5 suggest that more viruses of common respiratory infection may exist.

The presence of pathogenic bacteria in the upper respiratory tract adds to the complexity of the etiology of common respiratory diseases. Purulent complications, such as otitis and sinusitis, are due to bacterial infection, but there is no proof of the role played by identified pathogenic organisms in the production of subacute catarrhs, sphenoethmoiditis, and the like. The best opinion during the war, confirmed by the use of chemotherapeutic agents in adults,6 was that the average cold is a fairly pure virus disease, but that the relationship of virus to bacteria was often not clear.

Colds are, on the whole, more serious in infants than in adults. Infants usually develop a fever with a cold, and complications are more frequent.

3Dochez, A. R., Mills, K. C., and Kneeland, Y., Jr.: Studies on the Common Cold; Cultivation of Virus in Tissue Medium. J. Exper. Med. 63: 559-579, April 1936.
4Commission on Acute Respiratory Diseases: Experimental Transmission of Minor Respiratory Illness to Human Volunteers by Filter-Passing Agents. I. Demonstration of Two Types of Illness Characterized by Long and Short Incubation Periods and Different Clinical Features. II. Immunity in Reinoculation With Agents From the Two Types of Minor Respiratory Illness and From Primary Atypical Pneumonia. J. Clin. Investigation 26: 957-973; 974-982, September 1947.
5Atlas, L. T.: Minor Respiratory Diseases; Studies With Four Agents in Human Volunteers. Abstract in J. Clin. Investigation 32: 552-553, June 1953.
6Cecil, R. L., Plummer, N., and Smillie, W. G.: Sulfadiazine in the Treatment of the Common Cold. J.A.M.A. 124: 8-14, 1 Jan. 1944.


4

Various pathogenic bacteria are more conspicuous in cultures made from children,7 and this suggests that they may have some influence on the severity of colds even in the absence of definite purulent complications. Controlled studies made during the early war years of the use of sulfonamides in very highly susceptible children support this concept.8

It was the writer's impression that soldiers reacted to common respiratory diseases in a manner more suggestive of childhood than of adult life. They tended to develop fever of higher degree than that seen in general civilian life. Youth, exposure, and crowding probably contributed to this clinical pattern. Incidence of infection with the virus of undifferentiated respiratory disease may have been higher in the Army than in civilian life. Whatever the reasons, the acute phase of the common cold was apt to be more prostrating to soldiers than to office-working civilians. However, the soldier's convalescence was usually rapid.

Severe throat infections caused by the hemolytic streptococcus, scarlet fever, and rheumatic fever will be discussed elsewhere. However, a certain proportion of admissions to the respiratory service of an Army hospital were infections caused by this organism. Various complications to the usual sore throat or inflammation of the lymphatic tissue are recognized, but in the Army the most common was peritonsillar cellulitis.

The clinical picture of exudative pharyngitis is well recognized, and when an acute tonsillitis or pharyngitis is observed showing whitish exudate, most physicians assume it is caused by hemolytic streptococci. However, when endemic exudative pharyngitis was studied closely by the Commission on Acute Respiratory Diseases,9 in only about 50 percent of cases could the hemolytic streptococcus be recoverd on culture and in only half of these was there a rise in the titer of streptococcal antibody during convalescence to suggest that the organism was playing an important role in the disease. Since in only 25 percent of the cases of endemic exudative disease was the laboratory evidence for streptococcal infection complete, the Commission designated the other cases as nonstreptococcal exudative pharyngitis, and some speculation occurred as to the possible viral origin of this condition. Although, in the aggregate, cases of proved hemolytic streptococcal pharyngitis differ clinically from the nonstreptococcal variety, mild cases may be indistinguishable.

Vincent's organisms may also at times produce throat lesions which resemble streptococcal infections. The appearance of a typical case of so-called Vincent's organisms differed, however, from that of a streptococcal infection. The thick pseudomembrane and the tendency to ulceration were

7Kneeland, Y., Jr., and Dawes, C. F.: Studies on the Common Cold; The Relationship of Pathogenic Bacteria to Upper Respiratory Disease in Infants. J. Exper. Med. 55: 735-744, May 1932.
8Siegel, M.: Studies on Control of Acute Infections of the Respiratory Tract. II. Oral Administration of Sulfadiazine at the Onset of Acute Respiratory Illness. Am. J. Dis. Child. 66: 114-120, August 1943.
9Commission on Acute Respiratory Diseases: Endemic Exudative Pharyngitis and Tonsillitis; Etiology and Clinical Characteristics. J.A.M.A. 125: 1163-1169, 26 Aug. 1944.


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characteristic, but differential diagnosis was not always possible, and it was always necessary to rule out diphtheria. Vincent's stomatitis presented itself often as only a dental problem, but occasionally the throat was involved as well as the gums; likewise, Vincent's infection of the throat without involvement of the gums was also encountered. A comparison of the admission rates for the various designations of Vincent's infection in World Wars I and II is presented in table 1.

TABLE 1.-Admission rates for the various designations of Vincent's infection in the U.S. Army during World War I and World War II

[Rate expressed as number of cases per annum per 1,000 average strength]

Diagnostic terminology


Admission rate

World War I


World War II


1942-45

1942-43

1944-45

Trench mouth

0.02

0

1.94

0

Vincent's angina

11.56

0

0

0

Vincent's infection (not elsewhere classified)

0

0

2.30

0

Vincent's infection (all forms)

11.58

3.93

4.24

3.73


1Enlisted personnel only.

Experience in the Continental United States

Noneffectiveness

Common upper respiratory infection was the most prolific cause of noneffectiveness in the U.S. Army. A graphic representation of its incidence in the Army from 1925 to 1945, inclusive, would show a sharp rise around the beginning of each year. An unusual peak was reached around the beginning of 1941, when no major general epidemic was prevalent. This military peak was coincident with a rapid increase in mobilization, the opening of new camps, and the hurried assembly of large numbers of unseasoned civilians.

A careful statistical analysis presented by Dr. Philip E. Sartwell in another volume in the history of the Medical Department in World War II shows that the magnitude of incidence of common respiratory diseases in any area is related to the proportion of new recruits.10 It is conceivable that the unexpected increment of respiratory infection in recruits was due to infection with the virus of undifferentiated respiratory disease; that is, the one which leaves some active immunity in its wake. The seasoning of troops is of military importance insofar as common respiratory diseases are concerned as it governs the amount of noneffectiveness to be expected.

For the remainder of the war, the curve of incidence of common respiratory diseases in the United States was astonishingly symmetrical. At about

10See footnote 2 (1), p. 2.


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the same time during each war year, there was a recurring peak of almost the same dimension. Individual differences in type of disease and frequency at various stations were cancelled out by the large numbers and wide geographic distribution.

Streptococcal infections were particularly numerous in the eastern slopes of the Rocky Mountains and the Great Lakes area. Here, they were the subject of considerable study both in their less conspicuous form as part of the mosaic of common respiratory disease and when they became epidemic and were associated with scarlet fever and rheumatic fever. In cases associated with common respiratory disease, treatment varied in different stations. The types and amount of sulfonamides employed differed, although, when available, sulfadiazine was probably the most widely used. Controlled studies11 in large numbers of cases indicated that sulfadiazine had no more effect than the routine APC capsule on the duration of the febrile period or on the length of hospital stay. In more severe cases, however, the drug seemed to limit spread, to lessen cervical lymphadenitis, and to prevent the development of frank abscess.

A study of air disinfection directed by the Army Epidemiological Board demonstrated that certain glycols, when vaporized, killed micro-organisms12 and also influenza virus.13 These substances seemed wholly nontoxic in bactericidal concentration, but their efficacy was influenced by environmental factors, such as humidity.14 Under clinical conditions, they diminished airborne cross-infection.15 These reports represented progress in the control of infection, but practical limitations in the application of aerosols prevented their use in the field. Oiling floors and bedding, another method aimed at reduction of airborne infection, could not be shown to lower incidence of common respiratory infection at Fort Bragg, N.C.

In summary, common upper respiratory infection, while the commonest single cause of military noneffectiveness, did not seriously interfere with the training program. Prolonged disability as a sequel was almost entirely limited to the streptococcal infections. Mortality was insignificant.

Experience Overseas

Incidence-The "transport cold" was a well-known feature of crossing the Atlantic in wartime. Its widespread occurrence could be attributed to

11Rusk, H. A., and van Ravenswaay, A. C.: Sulfadiazine in Respiratory Tract Infections; Its Value in Treatment During the Winter of 1942-1943 at Jefferson Barracks, Missouri, J.A.M.A. 122: 495-496, 19 June 1943.
12Robertson, O. H., Bigg, E., Miller, B. F., and Baker, Z.: Sterilization of Air by Certain Glycols Employed as Aerosols. Science 93: 213-214. 28 Feb. 1941.
13Robertson, O. H., Bigg, E., Puck, T. T., and Miller, B. F.: Protection of Mice Against Infection With Air-Borne Influenza Virus by Means of Propylene Glycol Vapor. Science 94: 612-613, 26 Dec. 1941.
14Robertson, O. H.: Sterilization of Air With Glycol Vapors. Harvey Lect. (1942-1943) 38: 227-254, 1943.
15Harris, T. N., and Stokes, J., Jr.: Air-Borne Cross-Infection in the Case of the Common Cold. A Further Clinical Study of the Use of Glycol Vapors for Air Sterilization. Am. J.M. Sc. 206: 631-636, November 1943.


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the great crowding, poor ventilation, and the bringing together of troops from many different units, thus introducing new infective strains. It was commonplace for as high as 80 percent of U.S. troops to contract a cold in the course of the voyage to England.

In spite of the climate in England, colder and damper than that to which Americans had been accustomed, the noneffective rate due to respiratory diseases was considerably lower there than in the United States. The fact that U.S. troops were seasoned when they arrived undoubtedly contributed to the lower rate. In some Americans, the cold had a tendency to become chronic, particularly during the first year overseas, but usually thereafter the men had become acclimatized, and chronic catarrh and cough were much less marked. Individuals with a history of recurrent bronchitis were apt to have difficulty with the English climate; in particular, any tendency to asthma seemed accentuated. On the whole, however, the health of the Army was excellent, and there was no undue incidence of sinusitis.

The incidence of common upper respiratory disease and influenza in the European Theater of Operations, U.S. Army, pointed up the result of seasoning of troops. In November 1943, at the time of the epidemic of influenza A, the incidence was slightly higher than in January 1943 when influenza was not identified. After November 1943, there was a steady decline so that in June 1944 and thereafter throughout the winter of 1945 the noneffective rate was at a very low level.

Clinical features of common upper respiratory infection in the European theater were not remarkable. Throat cultures yielded moderate numbers of higher type pneumococci and H. influenzae. The number of hemolytic streptococcus carriers was not large, and only sporadic cases of streptococcal sore throat appeared during the winter months. The tendency to develop peritonsillar cellulitis has been mentioned. In 80 percent of such cases, the hemolytic streptococcus could be cultivated. The remaining 20 percent, clinically indistinguishable, may represent cases of nonstreptococcal exudative pharyngitis with an unusual degree of swelling of faucial pillars.

The incidence of common respiratory infection in the Mediterranean (formerly North African) Theater of Operations, U.S. Army, was considerably below the average for the European theater and for the United States in 1942 and 1943. In the summer of 1944, it was slightly higher, but at this time morbidity elsewhere was unusually low. Common respiratory disease presented one special problem in the Mediterranean theater-the likelihood of its being confused with certain conditions which were endemic in the area, particularly sandfly fever, malaria, and the preicteric stage of hepatitis. Complications of common respiratory infections were not conspicuous, and a total of but 10 deaths was recorded from such purulent infections as meningitis.

Incidence of streptococcal infections in the Mediterranean theater was low. According to Circular Letter No. 16, Headquarters, North African


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Theater of Operations, Office of the Surgeon, 22 March 1944, subject: Preparation of Medical Department Reports and Records, U.S. Army, the term "streptococcal sore throat" was applied only to acute pharyngitis and tonsillitis known or suspected to be caused by the beta hemolytic streptococcus, and foodborne and milkborne outbreaks of septic sore throat. During the 11-month period from 1 May 1944 to 31 March 1945, inclusive, when streptococcal sore throat was reported separately, only 803 cases were reported. Two small outbreaks were studied, one involving 112 men and the other, 38. In both instances, it was thought that the streptococcal infection was either foodborne or milkborne. Interestingly enough, not a single case of scarlet fever developed as a result of these outbreaks.16

An acute outbreak of membranous pharyngitis in Sicily, in October 1943, involved 96 men, 66 of whom were reported by the local civilian laboratories as having throat cultures positive for Corynebacterium diphtheriae. Subsequent investigation by the staff of the 15th Medical General Laboratory, Naples, Italy, threw doubt on the diagnosis of diphtheria in this outbreak, and the theater consultant in medicine later expressed the opinion that in all probability it was of streptococcic origin. The epidemic was explosive and had the character of a foodborne or milkborne infection.

Vincent's angina (as distinct from stomatitis or trench mouth) was reported only 990 times from the Mediterranean theater. Nevertheless, the estimated admissions for the various types of Vincent's infection numbered about 2,800.

The admission rate for common respiratory infection in U.S. Army Forces, China-Burma-India, was comparable with that observed in temperate climates, although the curve of incidence was relatively devoid of seasonal peaks. Clinical characteristics were stated to be astonishingly similar to those noted in the United States, and the complications as frequent.

The Pacific area is so vast that generalizations about disease therein would be dangerous. Conditions in parts of Australia are quite similar to those in temperate regions elsewhere, and common upper respiratory infection conformed to the familiar pattern. On small tropical islands, however, the incidence was stated to be much less under normal conditions, rising sharply with the arrival of large numbers of troops. Studies have been reported from such areas indicating that the bacterial flora was different from that noted in temperate climates. One study,17 for instance, included 272 throat and sputum cultures in which pneumococci were found only 7 times. It was stated in this report that pneumonia was very infrequent.

16Report [Final], Lt. Col. Daniel W. Myers, MC, and Maj. Edward deS. Matthews, MC, MTOUSA, to Office of the Surgeon General, subject: Respiratory Diseases in the Mediterranean Theater of Operations, 1945.
17Norris, R. F.: Symposium on Recent Advances in Medicine: Observations on the Epidemiology and Bacteriology of Acute Respiratory Tract Infections Among the Armed Forces of the Tropical South Pacific. M. Clin. North America 28: 1418-1427, November 1944.


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Two U.S. Navy observers18 stated that at least 50 percent of the cases of catarrhal fever in a South Pacific Area showed asthmalike manifestations. An eosinophilia of 8 to 10 percent was a common finding. The significance is obscure unless it is related to the high incidence of allergic disorders in the Tropics.19

Treatment-Treatment of common upper respiratory infections was symptomatic and lacked uniformity. Apart from streptococcal and Vincent's infections, this group is not susceptible to chemotherapy. Nevertheless, it is unquestionable that a great many viral infections were treated with sulfadiazine. The greater the experience of the medical officer, and the better his facilities for laboratory diagnosis, the less unnecessary sulfonamides were administered. The Professional Service Division advised that sulfonamides should not be employed as a routine measure in the absence of definite indications. In doubtful cases, however, it seemed wise to prescribe them. If certain indications were present, such as leukocytosis, symptoms of otitis media, the presence of pneumococci in the sputum, or the clinical features of acute tonsillitis, sulfonamides, and particularly sulfadiazine, were employed.

Sulfadiazine was used in the treatment of recognized streptococcal infections with prompt effect. It was likewise employed in Vincent's infection.

In the winter of 1945, studies were made, in a number of hospitals in England, of the effect of local penicillin therapy, either in the form of a throat spray or more frequently of lozenges containing 500 units of penicillin. Results in streptococcal infections were disappointing. The use of intramuscular penicillin was also reported in a few hospitals. Its effects in streptococcal infection were said to resemble those with sulfadiazine. Local and intramuscular penicillin gave striking results in Vincent's infections in reports from England, but variable results were obtained in a small number of cases of Vincent's angina when penicillin was used intramuscularly in the Mediterranean theater.

INFLUENZA

Introduction

The word "influenza" has been in general English usage since the 16th century to designate irregularly recurring, widespread visitations of respiratory diseases, explosive in character and often associated with considerable mortality. Its recognition, until the introduction of the new serological methods, rested upon epidemiological and not clinical grounds, and one could not speak of an isolated case.

Good clinical descriptions of these outbreaks are available. Worldwide attention was directed to the disease in 1889 because of its high incidence

18Schneierson, S. J., and Wilson, W. A.: Unusual Feature of Respiratory Infections in a South Pacific Area. U.S. Nav. M. Bull. 44: 1010-1012, May 1945.
19Young, C. T., Cook, W. R., and Kawasaki, I. A.: Allergic Rhinitis and Asthma in Hawaii. War Med. 3: 282-290, March 1943.


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and the relatively frequent association with fatal pneumonia during that epidemic. The influenza bacillus, isolated by Pfeiffer from a number of those fatal cases, was regarded for some years as the cause of the disease. Pandemic influenza revisited the world in a more devastating form in 1918, toward the end of the First World War. Incidence was very high, distribution global, and the mortality appalling. In the U.S. Army alone, 24,664 deaths were attributed to the disease, and the number of deaths throughout the world ran into millions.20 This catastrophe gave rise to a most intensive scientific investigation of the disease which revealed that the Pfeiffer bacillus could not be found in many typical cases of influenzal pneumonia. These pneumonias usually had a mixed bacterial flora, among which pneumococci and streptococci were prominent. The conclusion became inescapable that some wholly different agent, not recognizable by ordinary bacteriologic means, was the primary cause of the pandemic; that this agent, while occasionally killing in a few hours, usually produced its lethal effect by paving the way for a secondary bacterial pneumonia; and that the agent was often, though not always, accompanied by Pfeiffer's bacillus. If this agent were not bacterial, it must be in the category of the filterable viruses.

The highest mortality of the 1918 pandemic was in the age group between 20 and 35 years. Susceptibility to the most severe form of the disease seemed to increase with age until about 35 years, when it fell off sharply. This suggests that exposure to the primary agent in 1889 may have increased resistance in 1918 and that the two pandemics were caused by the same virus. 

Before and after the influenza outbreak of 1918, epidemic waves of acute respiratory diseases occurred which were clinically indistinguishable from mild cases in the pandemic. However, in these outbreaks, cases were uncomplicated and mortality was nil. These epidemics were called influenza of the interpandemic type or simply epidemic influenza.

Intensive study of epidemic influenza during the past 15 years was begun in England where the first successful isolation of a virus capable of infecting laboratory animals was achieved. Investigators throughout the world have contributed to the work, the principal ones being Andrewes in England, Francis in the United States, Burnet in Australia, and Smorodintsev in Russia. From these researches, a fairly clear pattern has emerged although there remain distinct gaps in our understanding of the disease.

Two causative agents have been identified. Influenza A virus, the first to be recognized, gives rise to epidemics which, in the Northern Hemisphere, tend to occur biennially in odd-numbered years in the winter months, with larger outbreaks every fourth year. Recent studies have shown that influenza A is a group of which the various agents are related but immunologically distinguishable.

20The Medical Department of the United States Army in the World War. Washington: Government Printing Office, 1925, vol. XV, pt. 2, p. 134.


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Influenza B virus has appeared less regularly and less explosively and has caused less severe epidemics. It was first identified in the United States in 1940, and retrospective study of sera saved from the 1936 epidemic of influenza found them to contain antibodies to this virus. Clinically, it cannot be distinguished from the disease caused by influenza A. Identification may be by isolation of the virus or by demonstrating a rise in titer of antibody to one of the two viruses following an attack. However, in some cases of influenza, identification of neither virus can be made. On the other hand, during an epidemic of one type, a significant proportion of sera may later show evidence of infection by the other type.21

Exceptions to the general statement that epidemic influenza tends to be mild must be noted. For example, in Boston, Mass., in December 1940 and January 1941, 66 cases of staphylococcal pneumonia with 21 deaths occurred with coincident infection with influenza A in many of these.22 The Commission on Acute Respiratory Diseases recorded an outbreak of type I pneumococcal infection in Northville, N.Y., related to influenza B infection.23 In a station such as the Army Air Force Technical School at Sioux Falls, S. Dak., the already constant, rather high incidence of lobar pneumonia rose when influenza appeared.

Active immunity acquired during an attack of influenza appears from clinical and serological evidence to be of short duration. Complete correlation between the level of serological immunity and susceptibility to the disease is not possible although the Commission found some evidence that patients with initially low antibody titer tended to be more severely ill than those with an initially high titer. Reference will be made later to the first large-scale attempt at active immunization of Army personnel with artificially cultivated influenza vaccine.24

What light do these studies of influenza throw upon the pandemic of 1918? Slight epidemiological evidence that the pandemics of 1889 and 1918 were caused by the same agent and that therefore the interpandemic variety is immunologically distinct has been mentioned. On the other hand, Shope's work on swine influenza, a persistent disease which first appeared in 1918, has suggested another hypothesis. The virus of swine influenza is related to, but not identical with, influenza A virus. If it is in reality a survival in another species of the 1918 human influenza, then one may suppose that pandemic and interpandemic influenza are related. These questions may be answered if another pandemic appears. Had such an event transpired during World War II, it would likely not have created the disaster of 1918

21Lush, D., Stuart-Harris, C. H., and Andrewes, C. H.: The Occurrence of Influenza B in Southern England. Brit. J. Exper. Path. 22: 302-304, December 1941.
22Finland, M., Peterson, O. L., and Strauss, E.: Staphylococcic Pneumonia Occurring During an Epidemic of Influenza. Arch. Int. Med. 70: 183-205, August 1942.
23Commission on Acute Respiratory Diseases and the New York State Department of Health: The Relation Between Epidemics of Acute Bacterial Pneumonia and Influenza. Science 102: 561-563, 30 Nov. 1945.
24See footnote 19, p. 9.


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because complications and therefore mortality might have been very favorably affected by chemotherapy and antibiotic treatment.

For a complete account of the epidemiology of influenza during World War II, the reader is referred to the chapter by Dr. Thomas Francis, Jr., in another volume in the history of the Medical Department in World War II.25 In the ensuing paragraphs, only the highlights most relevant to the interests of the Professional Service Division will be presented.

Experience in the Continental United States

Influenza was epidemic in the winter of 1940-41, but the major epidemic took place at the end of 1943. It was explosive in character, but not all parts of the country were simultaneously affected. It is of interest that evidence of infection with influenza A virus was found in three patients in May in a station hospital in Michigan, and on 18 November, at the very beginning of the epidemic, the same virus was recovered from two patients also in Michigan.26 Thereafter, during the epidemic, influenza A appeared in various parts of the country. As in other epidemics, in a number of clinically typical cases, no rise in antibody titer to influenza A virus could be demonstrated, and there were rare cases in which influenza B virus appeared to be involved.

The epidemic was fairly widespread, both in the Army and among civilians, but like other outbreaks of the interpandemic type, the disease was of very short duration, rather mild in character, and generally uncomplicated. Extensive clinical and serological studies were made by the Commission at Fort Bragg.27 Some of the conclusions drawn are as follows: Influenza with typical features-sudden onset, severe malaise, painful eyeballs, flushed face, injected eyes, high fever, and leukopenia-occurred as a clinical entity in only about half the serologically proved cases. Moreover, certain cases of undifferentiated respiratory disease, prevalent at the time, presented the same characteristics. In the aggregate, there were significant differences between undifferentiated respiratory disease and influenza, but individual cases could not be distinguished clinically.

In some areas, the 1943 influenza epidemic assumed a slightly more severe character. An example of this occurred at the Army Air Force Technical School in Sioux Falls where the first definite case was noted on 22 November. Following this, the incidence rose very sharply, the peak being reached between 29 November and 1 December. Respiratory disease admissions per 1,000 per week for the 4 weeks beginning 14 November through the week beginning 5 December were: 7.8, 13.7, 99.0, and 19.6, respectively. Altogether, 11.1 percent of the school population was affected. Age, length

25See footnote 2 (1), p. 2.
26Salk, J. E., Menke, W. J., and Francis, T., Jr.: Identification of Influenza Type A in the Current Outbreak of Respiratory Disease. J.A.M.A. 124: 93, 8 Jan. 1944.
27Commission on Acute Respiratory Diseases: Studies of the 1943 Epidemic of Influenza A. II. Comparison of the Clinical and Laboratory Characteristics of Influenza A and Undifferentiated Acute Respiratory Disease (ARD). Am. J. Hyg. 48: 263-275, November 1948.


13

of service, and duration of stay at the post had no detectable effect upon susceptibility. Clinically, the cases were typical of influenza; throat cultures on 137 patients showed hemolytic streptococci in 17 and pneumococci in 7. There was no evidence that the epidemic engendered the spread of beta hemolytic streptococci.

Associated pneumonitis was said to be present in 5.8 percent of the patients. In these cases, onset and symptoms were similar to the uncomplicated ones, but the disease was more severe, the fever higher and of slightly longer duration (3.2 days average), and there were rales at the bases together with X-ray changes. There was no associated leukocytosis, and sulfonamides did not shorten the duration of fever. Influenzal pneumonia-which this picture most assuredly suggests-has been very uncommonly found elsewhere. In addition, at Sioux Falls, there was a sharp rise (from 1.5 to nearly 5 per 1,000) in the weekly incidence of lobar pneumonia, the peak corresponding precisely with that of influenza.

By 1943, the production of a vaccine made with artificially cultivated influenza virus had been greatly improved, and a quantity of material containing both the A and B viruses was available for testing during the epidemic. Vaccination of man with both the A and B viruses had been shown not only to stimulate the production of antibodies but also to induce considerable immunity against the artificially induced disease.28 The active immunity to type A was apparently of shorter duration than to type B, as those vaccinated with the former 4 months before the test were considerably more susceptible than those vaccinated 2 weeks before. A large-scale trial seemed warranted. By great good fortune, some 6,263 students in the Army Specialized Training Program were vaccinated just before the epidemic. The subsequent incidence of influenza was significantly less than that in 6,211 controls, the ratio being 1:3.2.29

Evidence of influenza B infection was established in local outbreaks in different parts of the continental United States, in the Canal Zone, Alaska, and Hawaii in the spring of 1945. The occurrence of some influenza in the spring was reminiscent of the year 1918, and this led the chairman of the Army Epidemiological Board to recommend that the entire Army be vaccinated. The proposal was approved by The Surgeon General, U.S. Army, and was carried out in October 1945. From this uncontrolled experiment, two conclusions30 could be drawn by comparing disease rates in the Army with those of unvaccinated U.S. Navy personnel. The first was that mass

28(1) Francis, T., Jr., Salk, J. E., Pearson, H. E., and Brown, P. N.: Protective Effect of Vaccination Against Induced Influenza A. Proc. Soc. Exper. Biol. & Med. 55: 104-105, February 1944. (2) Salk, J. E., Pearson, H. E., Brown, P. N., and Francis, T., Jr.: Protective Effect of Vaccination Against Induced Influenza B. Proc. Soc. Exper. Biol. & Med. 55: 106-107, February 1944.
29Commission on Influenza: A Clinical Evaluation of Vaccination Against Influenza; Preliminary Report. J.A.M.A. 124: 982-985, 1 Apr. 1944.
30(1) Francis, T., Jr., Salk, J. E., and Brace, W. M.: The Protective Effect of Vaccination Against Epidemic Influenza B. J.A.M.A. 131: 275-278, 25 May 1946. (2) Hirst, G. K., Vilches, A., Rogers, O., and Robbins, C. L.: The Effect of Vaccination on the Incidence of Influenza B. Am. J. Hyg. 45: 96-101, January 1947.


14

vaccination had exerted a definitely protective effect in lowering mortality, and the second, that influenza B was a better immunizing agent than influenza A.

Experience Overseas

European theater

The history of influenza in the U.S. Army in the European theater is extraordinarily interesting in the light of what might have happened. Since 1931, epidemics had occurred in England in the odd-numbered years with a larger wave every fourth year. Had this schedule been maintained, a moderate outbreak would have occurred in January 1943 and a more severe one in January 1945. The former would not have been serious as hospital facilities in England were more than adequate to care for all troops then stationed there. However, in 1945, hospitals were already filled beyond normal capacity. A sharp epidemic at that time would have been extremely difficult to cope with and its effect upon the military situation would have been grave. It is not known why the epidemic did not occur.

There is seldom a complete explanation of any epidemiological phenomenon. In this instance, the events were as follows: The January 1943 epidemic did not take place; it was delayed 10 months, until November, when a sharp, widespread epidemic developed. The rhythmic pattern of influenza was thus disturbed. Late in 1944, the senior consultant in infectious diseases, European theater, ventured to predict to the surgeon, United Kingdom Base, that influenza would not occur in 1945. Partly as a result of this point of view, many hospitalized patients with trenchfoot were retained for duty in the theater rather than being boarded home in order to increase the number of available hospital beds. It required some fortitude to make the prediction of a healthy winter from the respiratory standpoint, but, mirabile dictu, precisely this came to pass, and the U.S. Army went through the most critical period of the winter campaign with an extraordinarily low noneffective rate due to respiratory disease.

Actually, the prediction was based on fairly sound epidemiological and immunological reasoning. It has been demonstrated that considerable immunity is left by epidemic influenza and that outbreaks of the interpandemic type occur at least 2 years apart. The delay in appearance of influenza in 1943 deflected what would have been an almost intolerable extra burden in 1945 at a time when medical facilities were badly strained.

Observations made by English investigators31 on the behavior of the influenza viruses may be briefly summarized, as follows: Although no epidemic occurred in the winter of 1943, a few sporadic cases of influenza showed rise in antibody titer to influenza B. In the spring and summer. a few cases were noted with influenza A. This is a very unusual time for

31Stuart-Harris, C. H., Glover, R. E., and Mills, K. C.: Influenza in Britain, 1942-43. Lancet 2: 790-793, 25 Dec. 1943.


15

finding evidence of influenza A infection. Then when the widespread epidemic took place in November, influenza A was incriminated in many sections of the country.32

Influenza in the U.S. Army paralleled this disease in the British civilian population. The incidence of all respiratory infections in the U.S. Army in the European theater reached a sudden peak in November 1943, with almost as rapid a fall to a point somewhat above the preepidemic level, and a subsequent slower decline through the winter months. By June, at the time of the invasion, the incidence was extremely low, and it remained low, with much less than the expected seasonal upturn, through the winter of 1945.

The great bulk of the cases on which this curve is based fall into the category called common upper respiratory infection. That the striking peak of November 1943 represents superadded influenza is presumed because of the explosive character of the epidemic, its clinical features, and serological evidence. Tests were not done on a large scale in the Army, but a sufficient number of sera from different parts of the country were examined to show that the Army experience was quite similar to British civilian experience; that is, a majority showed a rise in titer to influenza A virus.

In the Army, as with civilians in England and elsewhere, all influenza encountered during World War II was mild and uncomplicated. The patients were moderately, not severely, prostrated, and the disease was a short one with a febrile course of 2 or 3 days. To all intents and purposes, pneumonia did not occur. Influenzal pneumonia of the 1918 type was not seen. A reported increase in civilian deaths in England was found by the Ministry of Health to be due to an increased mortality caused by such conditions as congestive heart failure, associated with the general rise in the respiratory disease rate. In the U.S. Army, no deaths were attributed to influenzal pneumonia. A few complications, such as otitis and sinusitis were observed, but they were not conspicuous.

As for the clinical features of the epidemic, the familiar symptoms were encountered in many cases. However, the writer was more impressed with the widespread character of the disease than by its uniformity of behavior. As he had observed in other epidemics of influenza, a typical case was hard to define. For example, at an airbase in East Anglia in November 1943, a large number of patients were treated, but many of these had persistent colds caught on their recent transport voyage, and common upper respiratory disease confused the picture of sudden outbreak of influenza.

Mediterranean theater

Maj. (later Lt. Col.) Daniel W. Myers, MC, and Capt. (later Lt. Col.) Edward deS. Matthews, MC, stated in their report on respiratory diseases

32Andrewes, C. H., and Glover, R. E.: Influenza "A" Outbreak of October-December, 1943. Lancet 2: 104-105, 22 July 1944.


16

in the Mediterranean theater: "Influenza was reported 11,094 times in MTOUSA, thus apparently making up 5.9 percent of common respiratory infections; however, it is doubtful whether true influenza was encountered in MTOUSA."33 The authors mention the fallacy of making the diagnosis solely upon clinical criteria, as the same symptoms occurred in other diseases, such as sandfly fever, malaria, and hepatitis, prevalent in the theater. There were no reports of geometric increase in frequency of influenza-like respiratory disease from any organization in this theater and incidence of acute common respiratory diseases remained within expected seasonal range. Because of lack of sufficient indication, influenzal virus studies were not attempted on a large scale. It is noteworthy, however, that by far the highest peak for the annual rate of common respiratory disease (nearly 300) occurred in January 1944 only very slightly after the epidemic of influenza A in England and the United States. It seems unlikely that the Mediterranean theater should have completely escaped so widespread a visitation, and superadded influenza would be a logical explanation for the shape of the curve at that time.

Other oversea theaters

Reported admission rates for influenza in the China-Burma-India theater and the Pacific areas were low throughout the war, and the curves for common respiratory infection show no peaks suggestive of the superadded effect of influenza.

So the history of influenza during World War II stands in happy contrast to that of World War I. Pandemic influenza did not occur. Owing to the prolongation of the epidemic cycle in the middle of the war, only one important outbreak took place and that at a time when it could be handled with ease.

PRIMARY ATYPICAL PNEUMONIA

Introduction

The term "primary atypical pneumonia" would have evoked polite incomprehension in the average medical practitioner about 20 years ago, and today it is one of our commonest diagnoses.

Pneumonias were originally classified on an anatomical basis; this was followed by a combined anatomical-clinical approach and, also, by an endeavor to identify them etiologically. These three phases were often harmonious. Thus, the common type of pneumonia appearing as a primary disease was lobar in distribution; it had well-defined clinical characteristics, and it was due to the pneumococcus. Therefore, "lobar pneumonia" was designated an anatomical, clinical, and etiological entity. As the identifica-

33See footnote 16, p. 8.


17

tion of pneumococcus types became more exact, the qualification "type I lobar pneumonia" or "type VII lobar pneumonia" was added.

Apart from the disruption of the pattern caused by the 1918 pandemic of influenza, lobar pneumonia had maintained a fairly consistent record for many years in the temperate zones as primarily a winter disease with a usual mortality of about 30 percent in cases not specifically treated. It had been subjected to exhaustive research, and a great deal of knowledge had been accumulated as to the mechanisms of recovery and immunity. The biology of the pneumococcus was, perhaps, better understood than that of any other micro-organism. By 1938, specific therapeutic sera had been produced for more than 30 types of pneumococcus.

"Bronchopneumonia" was also originally an anatomical term, but the classification of bronchopneumonias clinically was much less clearly defined. They formed a heterogeneous group. It was known that a number of micro-organisms besides the pneumococcus could cause pulmonary consolidation of peribronchial distribution. Most of these pneumonias, however, were secondary; that is, they occurred as complications of other diseases or surgical operations and in the aged and debilitated. Primary bronchopneumonias were recognized, but generally speaking they were relatively uncommon. Occasionally, the hemolytic streptococcus gave rise to primary bronchopneumonia, either in sporadic cases or in localized epidemics, when it often followed in the wake of measles or epidemic milkborne sore throat. One type of virus pneumonia, psittacosis, was recognized, but was admittedly rare. As for influenzal pneumonia, this, to all intents and purposes, had vanished after the 1918-20 pandemic.

In 1938, two events occurred to change the clinical concept of pneumonia. In the first place, in England, a chemotherapeutic agent, M. & B. 693 or sulfapyridine, was introduced which was highly effective against pneumococcal infections. Intense interest was manifested in whether sulfapyridine would supplant serum therapy as the treatment of choice in lobar pneumonia and if it would constitute a successful treatment of the bronchopneumonias. At almost the same time, an increasing number of primary pneumonias, apparently not caused by the pneumococcus and quite obviously not susceptible to chemotherapy, were being observed. A new disease entity was rapidly suspected.

The principal characteristics of this disease were as follows: It seemed to have a predilection for young adults; the onset was rather gradual; the pulmonary consolidation was patchy and often showed a migratory tendency; there was no associated leukocytosis (at least in the early stages), and the bacterial flora of the sputum was not different from that found in normals; some patients were gravely ill but after a variable febrile period complete recovery took place, with a very low overall mortality; and such slight histological material as was available indicated that the process was an interstitial pneumonitis with a mononuclear type of exudate. Strepto-


18

coccus viridans was at first thought to be the cause, but this hypothesis failed to be substantiated. With no evident bacterial etiology, the disease was then presumed to be due to a filterable virus.

But was it a new disease? Hospital clinical records between 1922 and 1935 contain infrequent descriptions of single cases exactly corresponding with the description just cited. Furthermore, beginning about 1933, occasional notations in medical literature indicate that some observers were aware of benign bronchopulmonary infiltrations simulating tuberculosis, and localized epidemics of an influenza-like disease associated with mild pneumonitis had been described. It is likely that both of these conditions were caused by the same agent or agents of the "new disease." Atypical pneumonias more or less conforming to the same description were likewise described as occurring during the winter of 1917-18.34 The following factors probably caused the delay until 1938 in general recognition of primary atypical pneumonia: The more numerous and severe cases observed in that year, the more exact bacteriological diagnosis of the familiar types of pneumonia, and the introduction of the new chemotherapeutic agents.

Most of the increasing number of papers on primary atypical pneumonia during the ensuing years were clinical descriptions, but the research work was going forward. Broadly speaking, it is now generally agreed that atypical pneumonia is caused by a virus but by far the majority of cases are not due to the identifiable viral agents, such as psittacosis, ornithosis-lymphogranuloma, and rickettsia. Endeavors to transmit the agent to laboratory animals, or to cultivate it, have been, on the whole, disappointing. The most important studies of the etiology of primary atypical pneumonia were performed during World War II by the Commission on Acute Respiratory Diseases under the direction of Dr. Dingle. Briefly, these studies were as follows:

The disease was successfully transmitted from man to man by bacteria-free filtrates under conditions of quarantine.35 A minority of those inoculated developed atypical pneumonia, but others had less severe illnesses which might be called bronchitis or common upper respiratory infection. In other words, there is evidence that under epidemic conditions the virus may produce many cases of nondescript respiratory infection for each one of frank atypical pneumonia. Under experimental conditions, the incubation period was not quite so long as the 2 or 3 weeks which had been estimated from epidemiological studies of the naturally occurring disease.

Two serological reactions which develop during convalescence from atypical pneumonia in the majority of cases have been discovered. One of

34See footnote 1, p. 1.
35(1) Commission on Acute Respiratory Diseases: Transmission of Primary Atypical Pneumonia to Human Volunteers. J.A.M.A. 127: 146-149, 20 Jan. 1945. (2) Commission on Acute Respiratory Diseases: The Present Status of the Etiology of Primary Atypical Pneumonia. Bull. New York Acad. Med. 21: 235-262, May 1945. (3) Commission on Acute Respiratory Diseases: An Experimental Attempt to Transmit Primary Atypical Pneumonia in Human Volunteers. J. Clin. Investigation 24: 175-188, March 1945.


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these phenomena is the cold hemagglutinin;36 the other is the agglutinin for a certain strain of nonhemolytic streptococcus.37 These two agglutinins are not identical, and their significance is not clear. There is general agreement that the particular streptococcus in question is not the cause of the disease.

Experience in the Continental United States

The concept of atypical pneumonia was still a fairly new one in the winter of 1941, and while the disease was recognized in most university clinics, it was not familiar to the profession as a whole. In the summer of 1941, something in the nature of a mild epidemic of pneumonia which did not respond to sulfonamide therapy occurred in southern training camps. At the request of the surgeon, Fourth Corps Area, a small civilian mission 38 was dispatched in October to several southern training camps, notably Camp Claiborne, La. It reached the conclusion that this was an epidemic of atypical pneumonia. The Surgeon General accepted a recommendation from this mission that a permanent commission be instituted for the study of the disease, inasmuch as the Army seemed an ideal milieu for such a study. This commission, established in December 1941, continued to work throughout the war, first at Camp Claiborne, and later at Fort Bragg. It conducted intensive clinical and scientific researches on the subject of atypical pneumonia, as well as other acute respiratory infections.39 Among many noteworthy accomplishments of the Commission on Acute Respiratory Diseases were the successful human transmission experiments.40

The characteristics of the disease as originally seen at Camp Claiborne were briefly described by the chief of medical service of the station hospital and two of his colleagues.41 They reported that 262 cases occurred during a period of 4 months with a camp population of about 27,000. In general, these cases were mild with a short febrile course. A few more severe cases

36(1) Peterson, O. L., Ham, T. H., and Finland, M.: Cold Agglutinins (Autohemagglutinins) in Primary Atypical Pneumonias. Science 97: 167, 12 Feb. 1943. (2) Turner, J. C.: Development of Cold Agglutinins in Atypical Pneumonia. Nature, London 151: 419-420, 10 Apr. 1943.
37Thomas, L., Mirick, G. S., Curnen, E. C., Ziegler, J. E., Jr., and Horsfall, F. L., Jr.: Serological Reactions With Indifferent Streptococcus in Primary Atypical Pneumonia. Science 98: 566-568, 24 Dec. 1943.
38Drs. A. R. Dochez and Y. Kneeland, Jr., of the College of Physicians and Surgeons, Columbia University, New York, N.Y., and Dr. Colin M. MacLeod, of the New York University College of Medicine, New York, N.Y., all members of the recently created Board for the Investigation and Control of Influenza and Other Epidemic Diseases in the Army.
39(1) 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., Jr.: Primary Atypical Pneumonia, Etiology Unknown. War Med. 3: 223-248, March 1943. (2) Commission on Acute Respiratory Diseases: Epidemiology of Atypical Pneumonia and Acute Respiratory Disease at Fort Bragg, North Carolina. Am. J. Pub. Health 34: 335-346, April 1944. (3) 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., Jr.: Primary Atypical Pneumonia, Etiology Unknown. (Parts I, II, and III.) Am. J. Hyg. 39: 67-128, January; 197-268, March; 269-336, May 1944. (4) Dammin, G. J., and Weller, T. H. (in collaboration with Commission on Acute Respiratory Diseases): Attempts to Transmit Primary Atypical Pneumonia and Other Respiratory Tract Infections to the Mongoose. J. Immunol. 50: 107-114, February 1945.
40See footnote 35, p. 18.
41Moore, G. B., Jr., Tannenbaum, A. J., and Smaha, T. G.: Atypical Pneumonia in an Army Camp. War Med. 2: 615-622, July 1942.


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were noted, and two patients died, although there was some question of the diagnosis in one of them. Men over 28 years old were being released from the Army at this time. Occasionally, the routine predischarge X-ray in these individuals showed areas of infiltration resembling tuberculosis which cleared up quite rapidly. This, taken together with the human transmission experiments just cited, suggests that there were probably many "walking cases" of the disease. The rate of 262 cases in 27,000 troops over a period of 4 months may thus not indicate the true communicability. That it may be quite high under special circumstances is indicated by an occasional report. For example, on one occasion about 40 percent of the men out of a single company engaged as "cleanup teams" in a wire operations school contracted the disease.

Shortly after the Commission began its activities, a change in terminology of the pneumonias was made by The Surgeon General, so that thenceforward primary atypical pneumonia was reported as such.43 Clinical recognition of the disease became increasingly accurate in many hospitals, although there is reason to believe that the officially reported incidence was always low. A perusal of the large number of papers submitted to The Surgeon General to be approved for publication convinces one that the clinical characteristics of the disease were fairly uniform. The student is referred to the original articles44 published by the Commission on Acute Respiratory Diseases for the best account of the manifestations and epidemiology of the disease.

The annual incidence of primary atypical pneumonia in Army camps throughout the war was remarkably constant. The highest admission rate in the United States (8.95 per annum per 1,000 average strength) occurred in 1943, although the validity of this may be questioned owing to change in diagnostic criteria. Seasonal variations in admission rates were more marked; with striking exceptions, rates were usually higher in the winter months. Generally speaking, cases of atypical pneumonia showed an immense numerical preponderance over lobar pneumonia, rates for which were exceedingly low. One report, from Truax Army Air Field, Madison, Wis., gives this ratio as approximately 10:1. At Scott Field, Belleville, Ill., 738 cases of atypical pneumonia were seen during a period when 24 lobar pneumonias and 37 bacterial bronchopneumonias occurred.45 At Jefferson Barracks, Mo., 1,862 cases of atypical pneumonia were described as contrasted with 62 lobar pneumonias occurring over the same period of time.46 These

42Idstrom, L. G., and Rosenberg, B.: Primary Atypical Pneumonia. Bull. U.S. Army M. Dept. No. 81, pp. 88-92, October 1944.
43Circular Letter No. 19, Office of the Surgeon General, U.S. Army, 2 Mar. 1942. 
44See footnote 39 (1), (2), and (3), p. 19.
45Owen, C. A.: Primary Atypical Pneumonia. An Analysis of 738 Cases Occurring During 1942 at Scott Field, Ill. Arch. Int. Med. 73: 217-231, March 1944.
46Van Ravenswaay, A. C., Erickson, G. C., Reh, E. P., Siekierski, J. M., Pottash, R. R., and Gumbiner, B.: Clinical Aspects of Primary Atypical Pneumonia: A Study Based on 1,862 Cases Seen at Station Hospital, Jefferson Barracks, Missouri, from June 1, 1942 to August 10, 1943. J.A.M.A. 124: 1-6, 1 Jan. 1944.


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cases of atypical pneumonia were said to be more severe than the average thus far described in the Army. Two deaths resulted. Pleural effusions appeared in 9.7 percent of cases; about one-quarter of these were large.

Between 1942 and 1945, 110,133 admissions for primary atypical pneumonia were reported in the Army in the United States with 101 deaths as compared to 50,807 admissions and 69 deaths overseas. Atypical pneumonia was never of sufficient magnitude to interfere seriously with the huge training program. On the other hand, the rather prolonged course of the disease and the lengthy convalescence often affected the military career of the individual concerned. Because of the rarity of complications and late sequelae, chronic invalidism did not occur.

Experience Overseas

European theater

During the late summer and autumn of 1942, there was a mild epidemic of atypical pneumonia among U.S. troops in the European theater. The incidence of lobar pneumonia was very low; in one hospital, for example, during one of the autumn months, the chief of medical service reported 3 cases which might be called typical pneumonia and 70-odd cases which were atypical. As in cases described in the States among military personnel, these cases were milder on the average than those presented in earlier reports from civilian hospitals. The febrile course was shorter, being perhaps 5 to 7 days instead of 10 to 12, and the tendency to relapse, or prolonged migratory pneumonia, was much less pronounced. Moreover, such bizarre manifestations as erythematous skin lesions, liver involvement, pericarditis, and so forth, which had been noted on rare occasions in civilian outbreaks, were not observed. A true pleuritic pain, so commonly found in lobar pneumonia, is not a feature of atypical pneumonia. Sterile pleural effusions may occur; when they do, they are usually small and often interlobar. Occasionally, however, they may persist for an appreciable period, and in 1942 when this was so they were conventionally considered highly suggestive of tuberculosis. It was pointed out then that a small effusion need not be regarded as tuberculous, and where there was any evidence of associated pneumonitis, past or present, atypical pneumonia was probably the cause.

In the autumn of 1942, a board composed of an epidemiologist, Lt. Col. (later Col.) John E. Gordon, MC; a clinician, Lt. Col. (later Col.) Yale Kneeland, Jr., MC; and a virologist, Maj. (later Col.) Ralph S. Muckenfuss, MC, was appointed to consider the subject of atypical pneumonia. The results of its deliberations were embodied in a circular letter, which outlined the history and clinical features of atypical pneumonia, together with advice as to management. It was pointed out that sulfonamides were ineffective in this disease and that, if the diagnosis could be made with reasonable certainty by a mature clinician with an adequate laboratory at his disposal, sulfonamides were contraindicated. Where the diagnosis was in doubt, or


22

satisfactory laboratory facilities unavailable, sulfonamides in full dosage were recommended for a brief but definitive therapeutic trial. Attention was drawn to the possibly prolonged residual effects of an attack of atypical pneumonia and to the need for a considerable rehabilitation before the soldier returned to duty.

During the winter and summer of 1943, atypical pneumonia was less conspicuous. The phenomenon of cold hemagglutination was described and carefully reported in relation to a fairly large series of cases by a medical officer in the European theater almost simultaneously with independent discovery of the phenomenon in the United States.47 Rare cases of encephalitis complicating the pulmonary lesions were encountered in the theater. In one fatal case, histological evidence was found at autopsy.48 In two others, encephalitis was recognized clinically from symptoms and spinal fluid findings.49

Atypical pneumonia was not generally recognized by the bulk of the British medical profession in 1942, although scientific investigators were aware that a form of pneumonia, presumably of viral origin, had recently come into prominence in America. Contacts between British investigators and American medical officers were soon established. Professor Bedson,50 for example, tested serum from several convalescent U.S. soldiers for antibodies to psittacosis virus with negative results. Dr. C. H. Andrewes tested sera for antibodies to influenza virus, similarly with negative results. The possibility that pigeons imported by the U.S. Army Signal Corps might introduce an ornithosis-like disease in humans into the British Isles seemed remote when it was found that native British birds were already infected.51 It seems highly unlikely that atypical pneumonia was brought into the British Isles de novo by the U.S. Army. In fact, ward rounds in any British Army hospital in the autumn of 1942 convinced one that the disease in a mild form was present. Stimulated in part by American interest in the disease,52 British physicians shortly began to recognize it, and in 1943 an excellent descriptive article53 appeared in the Lancet.

In the autumn of 1943, at a second meeting of the Atypical Pneumonia Board (p. 21), it was recommended that routine cold agglutinin tests be performed in hospitals, that careful records be kept, that a summary be made of the results of the test in a large series of cases, and that informa-

47See footnote 36 (1), p. 19.
48Perrone, H., and Wright, M.: Fatal Case of Atypical Pneumonia With Encephalitis. Brit. M.J. 2: 63-65, 17 July 1943.
49Hein, G. E.: Primary Atypical Pneumonia. Lancet 1: 431-432, 3 April 1943.
50Sir Sam Phillips Bedson, M.D., F.R.C.P., F.R.S., Consulting Advisor in Pathology, Ministry of Health.
51Andrewes, C. H., and Mills, K. C.: Psittacosis (Ornithosis) Virus in English Pigeons. Lancet 1: 292-294, 6 Mar. 1943.
52Brown, J. W., Hein, G. E., Ellman, P., and Joules, H.: Discussion on Atypical Pneumonia. Proc. Roy. Soc. Med. 36: 385-390, June 1943.
53Drew, W. R. M., Samuel, E., and Ball, M.: Primary Atypical Pneumonia. Lancet 1: 761-765, 19 June 1943.


23

tion be obtained as to the frequency of second attacks. Some data were collected, but no important conclusions could be drawn.

The annual admission rate in the European theater for primary atypical pneumonia was 9.23 in 1942, 6.35 in 1943, and only 4.80 in 1944. Apart from the late summer-autumn peak of 1942, these rates were considerably lower than in the United States. This may be partly ascribed to the fact that the virus of atypical pneumonia seems to have been less widespread and virulent in England than in the United States. Seasoning of troops might have played a role also, but one is inclined to doubt that it was very large, since rates in the Mediterranean theater, where the troops were also seasoned, were much higher than at home for the years 1944 and 1945.

An interesting observation was made in the winter of 1945 at the 7th General Hospital in Dorsetshire, England. Two patients were studied who showed extremely high cold agglutinin titers with associated hemolytic crises. One of these episodes followed a definite attack of atypical pneumonia. This phenomenon has since been discussed in considerable detail by Finland and his coworkers.54

Mediterranean theater

Available statistical reports in the Mediterranean theater do not provide a reliable indication of the relative frequencies of lobar and atypical pneumonia before May 1944. From 1 May 1944 to 31 March 1945, inclusive, 7,142 primary pneumonias were reported, of which 5,684, or approximately 80 percent, were classified as atypical pneumonia.55 If this percentage holds for the entire history of the theater, it would seem that the preponderance of atypical pneumonias over bacterial pneumonias was less than in some other areas.

The general situation in regard to pneumonia in the Mediterranean theater as reported in 1945 (p. 8) is described in the following paragraph:

The pneumonia rate in the theater remained at comparatively low levels until January 1944 when a marked increase was noted principally in the troops based in Italy. This increased incidence was manifested by both Base Section and Army troops, the peak level for this season occurring in the Peninsular Base Section during April 1944 when the rate was 38.5 per 1,000 per annum. The rate in Italy remained high until July, the incidence in Army falling more precipitously and at an earlier date than in the Base. In January 1945 a similar rise in pneumonia rates began, the rate in March 1945 reaching a level substantially higher than that in the preceding year. Peninsular Base Section and Fifth U.S. Army troops participated in the rise, and once more the incidence was highest in the Base, attaining the surprising level of 82 per 1,000 per annum in the month of March. It is of interest, though an explanation is not offered, that pneumonia in the Army Air Forces reached its height in February 1945 and fell precipitously in March when Fifth U.S. Army and Peninsular Base rates were still ascending. The case fatality rates showed

54Finland, M., Peterson, O. L., Allen, H. E., Samper, B. A., and Barnes, M. W.: Cold Agglutinins. I. Occurrence of Cold Isohemagglutinins in Various Conditions. II. Cold Isohemagglutinins in Primary Atypical Pneumonia of Unknown Etiology With a Note on the Occurrence of Hemolytic Anemia in These Cases. J. Clin. Investigation 24: 451-457; 458-473, July 1945.
55See footnote 16, p. 8.


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a fall rather than a corresponding rise in the years of greatest incidence. In 1943, 24 deaths occurred in 1,427 pneumonias, a case fatality rate of 1.68 percent. There were 7,489 pneumonias and 35 deaths in 1944, a rate of 0.47 percent. During the first 3 months of 1945, 3,263 pneumonias and 6 pneumonia deaths were encountered, a case fatality of 0.18 percent. The quoted rates included all pneumonia deaths.

If 80 percent of the pneumonia was atypical its incidence was at times very high.

Clinical descriptions of the disease in the Mediterranean theater were generally similar to those published elsewhere. However, several peculiar outbreaks occurred which excited a good deal of interest and were the subject of considerable investigation. The report of Myers and Matthews (p. 8) described these in some detail. One took place in an isolation ward of the 24th General Hospital in the Bizerte area, Tunisia, in the winter of 1943-44. Within a 9-day period, over half the patients and ward personnel (13 in all) contracted mild atypical pneumonia. A tentmate of one of the affected aidmen and a substitute aidman also became ill, the latter 6 days after the first contact. The outbreak appeared to have an unusually short incubation period and a high degree of communicability. Its origin could not be traced.

During the 1944-45 pneumonia season, seven local outbreaks occurred. One, of 82 cases in the personnel of one company, arose in Corsica in December 1944, and the remaining six outbreaks occurred between December and April in separate organizations in a 5-mile radius of North Central Italy. The Corsican cases were as follows:

* * * The usual duration of fever was five days, maximum temperature varying from 100° to 105°, and recovery without serious complications ensued in every case. Diagnosis was established by chest X-ray examination in nearly every instance. Two hundred cold agglutination tests were performed by Capt. Joseph H. Swartz, utilizing the sera from the 82 patients and a 2 percent suspension of washed human group O erythrocytes. In two cases agglutination was observed with a serum dilution of 1:32. In the remainder agglutination did not occur with serum titer greater than 1:8. There were no circumstances incriminating an insect vector.

The extremely high attack rate and the negative cold agglutinin tests suggest that this was not primary atypical pneumonia. The same report gives a description of four localized, sharp epidemics occurring near Pagliana, Italy, and totaling at least 355 cases. These constitute additional evidence of the existence in Italy of a specific and different disease entity. One of the involved units had an attack rate of 27.7 percent. The disease characteristically had an abrupt onset, with an incubation period apparently varying from 17 to 23 days. Cold agglutinins were not found, and it was suspected that the etiological agent might have had an insect vector, a mite, which was found in large numbers in the area used by one of the units involved.

Two more outbreaks, totaling 53 cases, occurred about 10 airline miles north-northeast of Pagliana. These cases again differed in certain noteworthy respects from atypical pneumonia; that is, abruptness of onset, fre-


25

quent appearance of pleuritic pain, and absence of cold agglutinins. Complement fixation tests performed with lymphogranuloma antigen on both human and pigeon serum (from the area) were negative for psittacosis, as were other serological tests (Weil-Felix, influenza A and B, cold agglutinin). Attempts at virus isolation were also made. Preliminary observations suggested that throat washings from acute cases contained a filterable agent which produced fever on guinea pig inoculation and was transmissible in series. A rickettsial agent was finally isolated from the material. Moreover, late followup serological tests on other cases of the disease which developed in troops returning from Italy have shown that the condition was, in fact, Q fever. It seems definitely proved that all the above cases as well as the so-called Balkan grippe occurring among British paratroopers in Greece were Q fever.56

Myers and Matthews noted that true atypical pneumonia in Italy during the winter of 1943-44 took on a rather more severe character than they were accustomed to observe in Army practice. There was a large number of severe cases, reminiscent of those described in the United States in 1938, with cyanosis, dyspnea, and extensive pulmonary involvement. Some of these ended fatally. Another group showed a protracted coarse, with persistence of pulmonary infiltration beyond the expected period. In one group,57 55.8 percent of cases had residual X-ray changes after 3 weeks of illness.

Lt. Col. Tracy B. Mallory, MC, of the 15th Medical General Laboratory, furnished the following description of his findings in the tissues of nine fatal cases:58

Each of the nine cases showed consolidation of more than 75 percent of the total lung substance. Microscopic examination disclosed massive exudation into the alveoli of a protein-rich fluid, almost free of fibrin, and containing mononuclear and red cells but few polymorphonuclear leukocytes. Alveolar wall thickening was observed but was minor in degree. In no case was there evidence of necrotizing bronchiolitis or atelectasis, lesions characteristic of the atypical pneumonia seen in troops in the continental United States during 1942-43. A serous or purulent effusion was not found in any instance.

Four of the nine evidenced other pathological changes unrelated to the pneumonia but of such character and degree as to have contributed to the fatal issue. One exhibited recent vegetations superimposed on an old rheumatic valvulitis, the second had a fresh myocardial infarction, the third a hemoperitoneum associated with a fractured pelvis, and the fourth a fracture of the dorsal spine with paraplegia. Three other cases displayed a well-marked acute myocarditis which was deemed to be a complication of the pneumonia and which undoubtedly played in important part in the outcome.

Summary

In summary, primary atypical pneumonia was by far the most common variety of pneumonia in U.S. troops in the European and Mediterranean

56Commission on Acute Respiratory Diseases: Outbreaks of a Rickettsial Disease Related to Q Fever. Bull. U.S. Army M. Dept. 5 (No. 3): 245-246, March 1946.
57Theodos, P. A., and Zwickel, R. E.: Clinical Aspects of Primary Atypical Pneumonia. M. Bull. North African Theater Op. 2: 104-109, November 1944.
58See footnote 16, p. 8.


26

theaters. Even so, it never became a military medical problem of any real importance. Rates for Europe were lower than in the continental United States, but in the Mediterranean they were sometimes higher. On the whole, the cases were mild and recovery tended to be complete, although an average of about 30 days per patient were lost to duty. Very rarely, the individual might be left with a chronic bronchitis, sometimes of an asthmatic type. Secondary bronchiectasis was almost unknown. Complications were very infrequent. A few of the patients at times seemed to have some secondary bacterial infection. Such secondary infections were usually not very clear cut, but when definite they were controlled by sulfonamides. The death rate was almost nil.

Had the incidence of this condition been higher, it would have been a military problem of some magnitude owing to the rather prolonged disability incurred by the individual. This low incidence probably reflects a considerable degree of immunity in the general population. The virus, too, may be one of rather low communicability, and the long incubation period militates against the explosive type of epidemic spread when individuals are temporarily crowded together, as on transports.

Rates for atypical pneumonia were low throughout the war in the Pacific area. They were also low in the China-Burma-India theater apart from a moderate peak in July and August 1942. In the latter area, the disease picture was stated to conform with that seen in the United States except that an initial shaking chill and pleuritic pain were more commonly encountered. 

An interesting outbreak, late in 1944, was described by the surgeon of an airbase in India. Fourteen persons, all of whom had been in the same hold of a troop transport arriving in Bombay, came down with atypical pneumonia almost simultaneously a few days afterward. About a fortnight later, there were eight secondary cases at the station.

BACTERIAL PNEUMONIA

Introduction

Lobar pneumonia due to the pneumococcus has been so closely studied and so accurately described that it would be presumptuous to review the disease here. Medical records indicate a total of 109,882 admissions for pneumonia other than atypical as occurring in the Army from 1942-45 (table 2). Of these, 970 patients died, giving a case fatality rate of 0.88 percent. This is in contrast to a figure of 160,940 admissions for atypical pneumonia with 198 deaths. How many of these reported cases were actually pneumococcal pneumonia is impossible to state; probably the percentage was a relatively small one. Two generalizations may be made concerning the condition in World War II. First, the incidence was generally lower than anticipated, particularly overseas. This low rate was simultaneously true of the civilian population and probably reflects an inexplicable fluctuation in the character


27

of the disease which had begun some years before World War II. Secondly, and perhaps for the same reason, the individual cases seemed surprisingly mild. One is accustomed to think of lobar pneumonia beginning violently in the classical way, with a rapid development of the complete picture of the disease and bacteremia in about 25 percent of the cases. In the Army, the disease did begin suddenly with the customary symptoms, but the patient usually did not appear as ill as one might expect; the amount of consolidation by X-ray was often astonishingly slight, and bacteremia was extremely uncommon. It is possible that these differences were apparent rather than real, that they were due to prompt recognition and early treatment. Nevertheless, it is the writer's belief that the essential severity of the disease was diminished.

Other varieties of primary bacterial pneumonia were rarely encountered. On the extremely infrequent occasions in which organisms, such as Staphylococcus, Friedländer's bacillus, and H. influenzae, produced pneumonia, they ran true to form. Secondary pneumonias, usually on the surgical wards, were occasionally noted, but on the whole the control of these conditions by antibiotics was satisfactory.

TABLE 2.-Admissions for primary atypical pneumonia, bacterial pneumonia, and other pneumonia, in the U.S. Army, by area and year, 1942-45

[Preliminary data based on sample tabulations of individual medical records] 
[Rate expressed as number of admissions per annum per 1,000 average strength]

Disease category and year


Total Army

United States

Overseas


Number

Rate

Number

Rate

Number

Rate

Primary atypical pneumonia:

 

 

 

 

 

 

    

1942-45

160,940

6.32

110,133

7.47

50,807

4.73

    

1942

19,891

6.13

17,902

6.74

1,989

3.40

    

1943

51,177

7.45

46,375

8.95

4,802

2.84

    

1944

43,022

5.52

25,056

6.31

17,966

4.70

    

1945

46,850

6.18

20,800

7.09

26,050

5.61

Other pneumonia:

 

 

 

 

 

 

    

1942-45

109,882

4.31

81,962

5.56

27,920

2.60

    

1942

27,583

8.51

24,267

9.13

3,316

5.66

    

1943

41,161

5.99

35,735

6.90

5,426

3.21

    

1944

23,473

3.01

14,470

3.64

9,003

2.36

    

1945

17,665

2.33

7,490

2.55

10,175

2.19

    

Bacterial pneumonia:1

 

 

 

 

 

 

         

1942-45

50,943

2.00

37,406

2.54

13,537

1.26

         

1942

10,441

3.22

9,340

3.52

1,101

1.88

         

1943

16,838

2.45

14,690

2.83

2,148

1.27

         

1944

13,014

1.67

8,526

2.15

4,488

1.18

         

1945

10,650

1.41

4,850

1.65

5,800

1.25


1Cases recorded as lobar pneumonia.


28

The hemolytic streptococcus gives rise to an occasional case of primary pneumonia; however, the cases become numerically important only when for some reason the organism is widely distributed in a highly pathogenic state, as is sometimes found in association with a milkborne epidemic. Measles and influenza viruses seemed to "activate" the hemolytic streptococcus in the First World War but during the Second World War measles was unimportant in the Army and influenza of the 1918 type did not occur. These facts probably are related to the low incidence of streptococcal pneumonia. What effect did the widespread use of sulfonamides have in preventing the streptococcus from really getting under way? This complex subject will be considered elsewhere, together with that extraordinarily interesting phenomenon, the appearance of sulfonamide-resistant strains of beta hemolytic streptococci.

Experience in the Continental United States

On summary health reports, statistical data in the Army with regard to the pneumonias are unsatisfactory. After March 1942, the pneumonias were reported under three headings: Primary atypical pneumonia; pneumonia, primary; and pneumonia, secondary. The rates for pneumonia, secondary, were generally very low. Our interest here is in the term "pneumonia, primary."

By definition, this should mean any pneumonia arising de novo, or in the course of minor upper respiratory infection, which a medical officer considers to be bacterial, not viral, in origin. Presumably, these should be mainly pneumococcal, that is to say, lobar pneumonia. As might be expected, medical records based on the consolidated statistical health report (WD MD Form 86ab) contain an enormous amount of error, resulting from the natural limitations of this source of information.

For example, at Camp Lee, Va., between 6 November 1943 and 3 March 1944, 155 cases of pneumonia were reported; 147 designated pneumonia, primary, and 8 atypical pneumonia. This seemed of sufficient interest to warrant further investigation. The Director, Commission on Pneumonia, Army Epidemiological Board, visited Camp Lee and studied records on 97 pneumonia cases admitted since 1 January 1944. In his opinion, 58 of these were atypical pneumonia, and only 8 were lobar pneumonia. The remainder consisted of 6 definitely streptococcal cases, 13 doubtful streptococcal cases, 10 probably bacterial pneumonias from which no organism was isolated, and 2 staphylococcal cases.

There were several reasons for this woeful degree of inaccuracy. One, of course, was the failure of many clinicians to think clearly along etiological lines; another was lack of interest and experience on the part of the laboratory; and last, but not least, was the registrar's habit of making up the statistical health report from the morning report which was usually compiled by a nurse. There is, therefore, little to be gained from a discussion of the overall incidence of so-called pneumonia, primary, as reported on periodic


29

summary reports. In contrast, considerable information is made available from the tabulations of final diagnoses from individual medical records (table 2).

The low incidence and mortality of lobar pneumonia in the Army may be illustrated by two figures which, although not strictly comparable, do give a crude index of affairs. The death rate from lobar pneumonia is given in the official history of the First World War as 2.59 per 1,000 per year, or 259 per 100,000 per year, for the period 1 April 1917 to 31 December 1919. Preliminary Army figures in World War II, 1942-45, give the death rate for the bacterial pneumonia in the United States as less than 2 per 100,000 per year.

Lobar pneumonia was mildly epidemic in the United States at times, but only in certain localities. Epidemic conditions never became generalized. The most conspicuous instances of this were in the Sixth Service Command where the rates for pneumonia were significantly higher than in other service commands. These high rates were entirely contributed by Air Forces personnel, the rate for Army Service Forces being not dissimilar to that in other regions. Accordingly, the matter was investigated by the consultant in medicine of the Sixth Service Command and the director of the Commission on Pneumonia who reported a number of interesting figures. For example, rates for common respiratory disease the week of 20 October 1944 at three airfields were 150, 111, and 83 as compared to 55 and 64 in two service camps. Similarly, the pneumonia rates were 32, 41, and 55, compared to 7 and 3. These reported pneumonias included both lobar pneumonia and atypical pneumonia. The exact proportion of the two varieties was hard to determine. At one field between 1 January and 8 December 1944, 215 cases of primary pneumonia were reported as against 396 atypical pneumonia cases, but when the investigators studied the individual medical records rather than the statistical health report they found that at the three airfields primary pneumonia was being somewhat overdiagnosed at the expense of atypical pneumonia. Nevertheless, it was obvious that lobar pneumonia was unusually prevalent.

At one field, pneumococcus typings had been performed in 160 cases. In these, type VII was present in 18.1 percent of cases, types I and II each in 14.4 percent, so that these three together accounted for nearly half the cases. The prominence of type VII seems a little surprising; whether it was also such a notable offender at the other two fields is unknown.

A careful attempt was made to discover the reasons for this unusual incidence of respiratory infection including pneumonia. In the final analysis, the most striking difference between life at the air station and in the service forces was that the former involved men being together in classrooms all day.

Another interesting example of the behavior of lobar pneumonia was reported at the Army Air Force Technical School, Sioux Falls. Coincident


30

with the peak of a sharp epidemic of influenza in November 1943, and extending for about a fortnight afterward while the influenza was rapidly subsiding, the rate for lobar pneumonia (already rather high) rose to an unprecedented level. For the week of 3 December, it was 4.8 per 1,000. In 72 cases, pneumococci were isolated and typed. Of these, 17 proved to be type II, 9 type V, 6 type I, and 5 type VII. The rest were scattered or untypable. Later in the winter, during a controlled experiment on sulfadiazine prophylaxis at the same station, it was noted that the drug appeared to reduce significantly the incidence of lobar pneumonia, although the result was not as striking as in the case of streptococcal infections.

In harmony with all experience elsewhere, the treatment of lobar pneumonia with sulfadiazine was highly satisfactory, and complications were very infrequent. In this connection, it is interesting to review the role of serum therapy. At a conference on pneumonia held at the Office of the Surgeon General in January 1944, the subject of classification was discussed at length. Therapy was also considered, and it was agreed that antipneumococcus serum may be lifesaving in cases of drug-resistant pneumonia. Shortly thereafter, a remarkable variation in the actual use of antipneumococcus serum in various hospitals was uncovered in a survey by the Professional Service Division. A good many hospitals had never used serum while in others it had been employed surprisingly often. The opinion of all the service command consultants in medicine was then sought. The great majority agreed that serum was necessary in only very exceptional instances and that it could, if necessary, be obtained from local sources. In other words, the consensus was that antipneumococcus serum could be discontinued in the Army drug lists; in this, the Chief Consultant in Medicine, Office of the Surgeon General, and the National Research Council concurred on 15 May 1944. The advent of penicillin as an addition to sulfonamides had much to do with influencing this view, which would have been considered mildly revolutionary a few years earlier. The efficacy of treatment of lobar pneumonia with sulfonamides alone is shown by a report of 454 cases over a period of 3 years with only 4 deaths.59 In the last year of this study, 92 cases were treated without a single death.

An important study of immunization against lobar pneumonia by injection of specific capsular polysaccharides was started in September 1944 at the Sioux Falls Army Air Force Technical School60 where the pneumonia rate had been very high; over 1,500 cases had occurred in the preceding 2 years. Of these, 34.9 percent were due to type II pneumococcus. More than 8,000 men were injected with a single dose of a mixture containing polysaccharides derived from pneumococcus types I, II, V, and VII with a strik-

59Adamson, W. B.: Lobar Pneumonia. Air Surgeon's Bull. (No. 11) 1: 21, November 1944.
60MacLeod, C. M., Hodges, R. G., Heidelberger, M., and Bernhard, W. G.: Prevention of Pneumococcal Pneumonia by Immunization With Specific Capsular Polysaccharides. J. Exper. Med. 82: 445-465, December 1945.


31

ing subsequent immunity to pneumonia caused by these types as compared with a similar control group. The carrier rate of these four types was also significantly reduced, but no effect was noted against infection with, or the carrier rate of, other types.

Hemolytic streptococcal pneumonia was comparatively uncommon. Some cases were seen, however, which conformed to the pattern set in the First World War; that is, an abrupt onset of the pneumonia with symptoms of pleurisy and the rapid development of a massive effusion. Such effusions were characteristically thin but, of course, infected. The opportunity to use local penicillin therapy was seized, but the cases were not sufficiently numerous to draw any final conclusions as to its efficacy. Early in 1944, one station hospital in the Third Service Command reported 5 such cases, together with 10 other pneumonias, believed to be streptococcal, which did not have associated empyema. At about the same time, six cases were present in another hospital in the same service command. These numbers, however, were quite unusual. Other varieties of bacterial pneumonia were occasionally encountered, but not with sufficient frequency to merit particular comment.

Bacterial pneumonia never became a serious problem in the United States, and its response to sulfonamides and antibiotics completely changed its significance as compared with the First World War.

Experience Overseas

European theater

The incidence of bacterial pneumonia in the European theater was extremely low, and the mortality almost nil. This small fatality rate can be ascribed, in part at least, to early diagnosis and satisfactory response to treatment.

Empyema following lobar pneumonia was very inconspicuous in the Second World War. When it occurred, it was ordinarily the result of delay in the institution of treatment, the pneumonia at times having been unsuspected. Other complications were exceedingly rare.

The typing of pneumococci was always difficult overseas. This was no doubt in part due to lack of training of laboratory technicians. However, it also appeared to be a fact that the available typing serum was weak.

There were a number of scattered cases of bronchopneumonia in the European theater, particularly in the spring of 1944, in which the differential diagnosis between atypical and bacterial infection was in doubt. Clinically, these cases resembled atypical pneumonia, but the sputum was more purulent than one expects in that disease and contained a pathogenic organism. These cases occasionally showed a moderate, although not a dramatic, response to sulfonamides. They may have represented instances of secondary infection superimposed on a pneumonia originally of viral origin.


32

Mediterranean theater

Preliminary data on pneumonia in the Mediterranean theater indicate that there were 17,715 admissions for these diseases during the period 1942-45. Of these, 12,908 were reported as primary atypical pneumonia, and 2,443 (approximately 14 percent) were regarded as bacterial pneumonia. There were 74 deaths, and of these, 28 were due to bacterial pneumonia. Presumably, the bulk of the bacterial pneumonias were pneumococcal, and pneumococcal lobar pneumonia is estimated to have caused about one-third of the deaths from pneumonia that occurred in the theater.

Other types of bacterial pneumonia were occasionally noted in the Mediterranean theater but in insufficient numbers to warrant discussion. A small number of cases in which a green streptococcus was cultivated from blood and sputum are recorded. Str. viridans pneumonia was a clinical rarity, but had been previously observed. It is possible to speculate on the relation of this condition to atypical pneumonia, with the streptococcus in the role of secondary invader, but no proof of such relationship exists.

The standard treatment of lobar pneumonia was sulfadiazine, which yielded satisfactory results. Penicillin was tried in a limited number of cases and found to be effective. Occasionally, in a severe case, both agents were used. Serum therapy was only recommended in very exceptional cases.

MEASLES

Introduction

Measles (rubeola) is a highly communicable virus disease with a stereotyped clinical pattern which is universally familiar. Susceptibility to measles is considered to be almost universal, and one attack, in the majority of persons, confers lifelong immunity. In urban communities, it is more or less epidemic in the early spring of each year with a greater number of cases in alternate years. Approximately 102,000 cases of measles occurred in the U.S. Army in the First World War, with 2,370 deaths. Associated infections were a cause of serious illness, prolonged invalidism, and death. In World War II, by contrast, the total number of cases was 60,809, with only 33 deaths, in spite of the fact that the Army was about four times as large and the duration of the war twice as long. The seasonal peak for measles during World War II occurred in late winter or early spring, but during World War I peak incidence due to mobilization occurred in the late fall of 1917. This is of sufficient importance to warrant considerable discussion.

Uncomplicated measles is almost never fatal. The gravity of the condition lies in complications caused by certain micro-organisms. Bacterial infections due to pneumococcus, C. diphtheriae, H. influenzae, Mycobacterium tuberculosis, and most particularly the hemolytic streptococcus, are described. 

The most frequent and serious complications of measles are pneumonia and otitis media. In the First World War, there were 93,629 admissions due


33

to measles among enlisted men in the continental United States and Europe of which bronchopneumonia and lobar pneumonia were complications of measles in 6,283 cases, with 2,186 deaths. Similar data for the entire Army are not available. Suppurative pleurisy, undoubtedly secondary to pneumonia, occurred in 645 cases with 268 deaths. There were 3,926 instances of otitis media, but only 122 of these patients died. Careful studies of the bacteriology of these complications indicated that the hemolytic streptococcus was the causative agent in nearly every case. One may ask how this secondary infection comes about. Does it occur in a carrier of streptococcus who becomes infected with measles? Does one catch the streptococcus along with the virus of measles or does one become secondarily infected as a result of living in a highly contaminated environment after contracting the measles? It seems likely that all these mechanisms play a part. At one hospital in the First World War, for instance, the carrier rate for hemolytic streptococcus rose steadily on measles wards from 11 percent on admission to 57 percent in patients who had been on the ward from 8 to 16 days. If noncarriers of streptococcus with measles were carefully segregated from carriers at the time of admission, the difference in complications was striking, the rate being 6.4 percent in the noncarriers as opposed to 36.8 percent in the carriers. While the mechanism of secondary infection might not always be clear in the individual case, it is safe to conclude that, during a measles epidemic in a training camp, the hemolytic streptococcus became widely distributed.

Following a measles epidemic with much complicating pneumonia, primary streptococcal pneumonia made its appearance in some camps. The cases were severe, with a high incidence of early suppurative pleurisy, and a high case fatality rate. This disease also spread to the civilian population. It seems likely that rapid passage from individual to individual through the mediation of measles enhanced the essential infectivity and virulence of the hemolytic streptococcus.

Epidemiological studies of measles in the First World War also have an interesting bearing on more recent events. In such a station as Camp Pike, Ark., which drew its recruits from the rural regions of Alabama, Arkansas, Louisiana, Mississippi, and Tennessee, the rate was enormously higher than in camps drawing from urban areas. Thus, the admission rate for measles among white enlisted men at Camp Pike was 164.67 per 1,000 per year, compared to 7.27 at Camp Dix, N.J. For white and colored enlisted men combined, the admission rates were 142.05 per 1,000 per year for Camp Pike and 7.73 for Camp Dix. Moreover, as might be expected, the incidence of measles was highest in recruits less than 2 months in camp. Thus, it was essentially a disease of country boys coming for the first time in their lives into a densely crowded environment.

The only tenable explanation of the much lower rates for measles in the Second World War is that the number of susceptibles was much smaller. There is no question that a great change in habits of life occurred in rural


34

America between the two World Wars. In 1910, rural districts were fairly well isolated; it was the "horse and buggy era"; the facilities of travel were limited; people stayed on the farm. By 1935, all this had changed. There was a moving picture house in nearly every village; schools were larger, and education was more centralized. As a result, the country boy growing up in this decade had far more opportunity for exposure to the exanthemata of childhood with a consequent reduction in susceptibility rate at the time of induction into the Army. Although there is no firm statistical basis for this conclusion, one cannot avoid feeling that it must be correct.

Complications of measles were much less conspicuous in World War II. Undoubtedly, this was related to the low incidence of the disease. Where cases are sporadic, rather than epidemic, the widespread dissemination of virulent streptococci is unlikely to take place. Moreover, the use of sulfadiazine in cases with threatened or actual complications unquestionably served to modify the picture. Part of the small number of deaths were probably due to secondary infection; some may have occurred as a result simply of overwhelming virus infection or complicating encephalitis.

An average of about 13 days was lost to duty for each case of measles.

Experience in the Continental United States

Most of the measles in the Army took place in the United States for the reasons just mentioned; that is, that it is essentially a disease of unseasoned troops first entering military life. Actually, 54,388 cases occurred in the United States as contrasted with 6,421 overseas. The largest number and the highest rates were reported in 1943, although in the civilian population the absolute numbers of cases were about the same in 1942, 1943, and 1944. As in the First World War, the disease was seasonal, but the peaks were much lower. In other words, while the total number of cases was considerable, measles never became a really serious military problem.

The relative insignificance of complications is illustrated by a report of 400 cases of measles at the Station Hospital, Fort Sill, Okla., in which otitis media occurred but 6 times.61 Three hundred of these were given sulfonamides, but 100 control cases were untreated. No difference was noted in the clinical course of the treated as opposed to the control cases.

Suppression or modification of measles following exposure by the injection of convalescent serum or immune globulin are established procedures in pediatric practice. Measles in the Army, however, never was sufficiently serious to warrant the generalized use of these measures. Similarly, no attempt was made to apply the principles of active immunization, although interesting preliminary studies, under the direction of the Commission on Measles

61Haerem, A. T.: Treatment of Measles and Mumps With Three Well-Known Sulfonamides. Mil. Surgeon 92: 306-309, March 1943.


35

and Mumps, Army Epidemiological Board, indicated the immunizing value of artificially cultivated measles virus.62

Experience Overseas

Measles rates in the European theater were low, a total of 2,554 cases being reported. The disease was sporadic, and nothing in the nature of a real epidemic ever developed. Clinically, the cases presented no unusual features. Sulfadiazine was administered to most of the patients for several days during the acute phase. Only one death was attributed to the disease.

Between 1 January 1943 and 31 March 1945, 612 cases of measles with no deaths were reported in the Mediterranean theater.

MUMPS

Introduction

Of the so-called communicable diseases of childhood, mumps (epidemic parotitis) was the most common in the U.S. Army. There were 103,055 cases recorded between 1942-45 compared with approximately 237,000 during the First World War, for a much smaller number of men over a shorter period of time. This marked reduction was greater than that for measles, the comparable figures being 60,809 and 102,000, respectively.

No exact explanation of the reason for this is possible, but a plausible hypothesis suggests itself. As has already been pointed out in the section on measles, a change in the living habits of rural America probably permitted more exposure in childhood and resulted in fewer susceptibles of military age. Measles is more highly communicable than mumps; therefore, when measles occurs under conditions of military life, where opportunity for spread of epidemic disease is excellent, it is likely that a higher percentage of the nonimmunes will contract measles than mumps. Thus, the proportionate decline in the incidence of the two diseases during the two World Wars might be expected to be greater in measles, the highly communicable disease, than in mumps, the disease of lesser communicability.

Complications

Mumps is a specific virus infection with a particular tendency to localization in the parotid glands. In the majority of cases, these are the only organs clinically affected. However, a number of other glands and structures are ordinarily spoken of as complications, although they are probably better regarded as additional manifestations of the virus infection. Generally speak-

62(1) Stokes, J., Jr., O'Neil, G. C., Shaffer, M. F., Rake, G., and Maris, E. P.: Studies on Measles. IV. Results Following Inoculation of Children With Egg-Passage Measles Virus. J. Pediat. 22: 3-18, January 1943. (2) Maris, E. P., Rake, G., Stokes, J., Jr., Shaffer, M. F., and O'Neil, G. C.: Studies on Measles. V. Results of Chance and Planned Exposure to Unmodified Measles Virus in Children Previously Inoculated With Egg-Passage Measles Virus. J. Pediat. 22: 17-19, January 1943.


36

ing, these complications are troublesome, but not particularly serious. Mumps is essentially a nonfatal disease, and in the First World War the only deaths occurred as a result of infrequent secondary infections, such as pneumonia. At that time, the case fatality rate where mumps was the primary cause of admission was 0.08 percent. As there were only five deaths from mumps reported for the entire U.S. Army during the Second World War, it can be seen that even the cited low figure was markedly reduced.

Perhaps the most striking of these so-called complications is orchitis which develops as a rule when the parotitis is subsiding. Rarely it is said to be the only manifestation of mumps. In a recent study of the disease in civilian life, orchitis is stated to occur in 18 percent of cases of mumps, and in about one-sixth of these the condition is bilateral.63 In over 50 percent, some atrophy is said to result, but ensuing sterility is claimed to be rare, probably because the cases are unilateral, and even in bilateral cases with atrophy a sufficient amount of spermatogenic tissue is left intact. The authors of this paper recommend surgical decompression in severe cases, a procedure which was tried at times in the Army during World War II with allegedly good results.64 It seems likely that comparatively few cases are sufficiently severe to require such an operation. It is reported to cause remarkable relief, however, in patients with very marked swelling, intolerable pain, and high fever.

Pancreatitis may be another complication of mumps. How often it occurs is impossible to say. The clinical diagnosis is occasionally made on the basis of the appearance of upper abdominal pain, nausea, and vomiting during the course of mumps. Unfortunately, there would appear to be no means of laboratory confirmation, for a study at Camp Adair, Oreg.,65 showed that the level of blood diastase was elevated in 73 percent of cases of mumps. Only 15 percent of these had any symptoms of pancreatitis, and it was assumed that the diastase originated in the affected salivary glands rather than in the pancreas. In any event, pancreatitis is an unpleasant rather than a serious complication.

The virus of mumps can also cause meningoencephalitis which manifests itself as a rule by headache, some stiffness of the neck, and increased cell count in the spinal fluid. Although more severe central nervous system manifestations can occur, this complication is usually a rather mild one of short duration. Complete recovery is the rule.

In World War I, mumps was third in order of importance as a cause for noneffectiveness; in World War II, with less than half the number of cases, it was obviously less important. However, as the average number of days lost

63Wesselhoeft, C., and Vose, S. N.: Surgical Treatment of Severe Orchitis in Mumps. New England J. Med. 227: 277-280, 20 Aug. 1942.
64
(1) McGuinness, A. C., and Gall, E. A.: Mumps at Army Camps in 1943. War Med. 5: 95-104, February 1944. (2) Nixon, N., and Lewis, D. B.: Mumps Orchitis; Surgical Treatment. Air Surgeon's Bull. 2: 152-154, May 1945.
65Zelman, S.: Blood Diastase Values in Mumps and Mumps Pancreatitis. Am. J.M. Sc. 207: 461-464, April 1944.


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to duty for each case was about 18 during World War II, it remained one of the major causes of noneffectiveness among the acute infections, being surpassed only by hepatitis, common respiratory diseases, the pneumonias, gonococcal infections, malaria, syphilis, and dermatophytosis. Mumps usually begins in the late autumn, and there is a slow development of the epidemic during the winter and spring. It is not as explosive as measles. On the other hand, the incidence may rise sharply when a unit with sporadic mumps is closely packed in together for a long period of time, as happens on a transport on a protracted sea voyage.66

Experience in the Continental United States

As with other so-called childhood communicables, the greatest incidence of mumps occurs in the first months of Army service. Mumps occurred at some time in all Army camps and, at times, was sufficiently prevalent to be called epidemic. One such epidemic at Camp McCoy, Wis., was reported in detail by McGuinness and Gall. During a 7-month period, 1,378 cases were treated in the station hospital. The slow evolution of the epidemic is noteworthy, the peak of 194 cases not being reached until the 17th week. One group of soldiers was predominantly from the rural areas of the South. This group, roughly equal in size to the other group from the industrialized North, contributed 84 percent of the cases. Nearly half the companies in the northern group had but one case each, whereas in one southern company 19 percent of the men contracted the disease. Orchitis occurred in slightly over 36 percent of the cases in this epidemic as compared to 15 percent of some 250 to 300 cases in an epidemic in two large camps in the Fourth Service Command. This relationship was borne out elsewhere; that is, the larger the epidemic, the higher the incidence of complicating orchitis. Orchidotomies were performed in 83 cases at Camp McCoy with what were described as good results. An attempt to ward off orchitis by enforcing 2 weeks of bed rest was a failure. The complication appeared to be as frequent as in ambulatory patients. Of the entire series of mumps cases, one-third were moderate in degree, and one-third severe. Clinical meningoencephalitis was uncommon.

Other interesting observations were made elsewhere in regard to orchitis. For example, no relationship between incidence of this complication and preceding gonorrhea67 could be found. Generally speaking, treatment with convalescent serum was found ineffective in preventing orchitis,68 except in a small series treated with serum drawn from convalescent orchitis cases. Here, there was an apparent reduction in incidence to 4.2 percent from an average of about 20 percent.

66Dermon, H., and Le Hew, E. W.: A Mumps Epidemic in a Small Task Force. Am. J.M. Sc. 208: 240-247, August 1944.
67See footnote 66.
68Bailey, W. H., and Haerem, A. T.: Some Observations on the Efficacy of Convalescent Serum in Mumps. Mil. Surgeon 90: 134-139, February 1942.


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No advance in treatment of uncomplicated mumps was recorded. At one station hospital in the Third Service Command, atropinizing did not appear to ameliorate symptoms69 in a small series of cases.

On the whole, it may be stated that, while not infrequently bothersome, mumps did not constitute a very serious military problem.

Experience Overseas

As in measles, mumps was more common in the United States than overseas, although the difference was less marked. About nine times as many cases of measles were reported at home as abroad; about four times as many cases of mumps were reported. This difference is presumably due to the lower communicability of mumps. The disease tended to be mild in the European theater. It was somewhat more common in Negroes than in white troops. A number of complications, particularly orchitis, was observed, but they did not prove very troublesome. It was the writer's impression that bed rest had little influence on the likelihood of development of orchitis.

Routine lumbar punctures were done on a number of consecutive cases of mumps, at the 30th General Hospital,70 Nottinghamshire, England, and in about half of them the spinal fluids showed pleocytosis. On the other hand, only 10 percent of the cases showed clinical evidence of meningoencephalitis. This indicates that the central nervous system is affected by the virus much more often than was formerly believed but that in most cases the infection is asymptomatic. In this connection, it is worth remarking that a very occasional case of mild encephalitis without mumps was seen in an individual from a unit in which the disease was epidemic. It was suggested that such cases were actually mumps meningoencephalitis without parotitis. This may well be true, although there was, of course, no way of verifying the diagnosis.

The question of length of quarantine of patients was considered by the infectious disease board. The board suggested that isolation of the individual case could be terminated as soon as all evidence of swelling had disappeared and there was no fever or other manifestations. This resulted in considerable shortening of hospital stay for the mild cases and, as far as one could tell, produced no untoward consequences.

From 1 January 1943 to 31 March 1915, inclusive, approximately 1,700 cases of mumps were reported in the Mediterranean theater.

INFECTIOUS MONONUCLEOSIS

Introduction

Infectious mononucleosis is a fairly common disease which affects males somewhat more than females and which shows a predilection for people under

69Potter, H. W., and Bronstein, L. H.: Some Clinical Characteristics of Mumps, and the Effect of Belladonna in Treatment; A Study Made at the Station Hospital, Fort George G. Meade, Maryland. Ann. Int. Med. 21: 469-474, September 1944.
70Kirkland, H. B., and Brown, J. W.: Mumps Complicated by Meningo-encephalitis. ETO Med. Bull. 9: 9-10, September 1943.


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30 years old. A survey at Harvard University, Cambridge, Mass., in 1944, indicated that it caused 1.5 percent of all student admissions to the infirmary.71 Therefore, one would expect to encounter it quite often in the Army.

It was frequently recognized in the U.S. Army, but it is probable that the reported incidence is considerably below the actual. Infectious mononucleosis presents itself in a number of clinical forms and is often sufficiently vague in character to escape detection unless one is on the alert. The classical form with sore throat, enlargement of the upper deep cervical lymph glands, palpable spleen, and rather prolonged fever, is easily recognized, either immediately or during a workup to exclude such conditions as syphilis or Hodgkin's disease. On the other hand, it is probable that nearly 20 percent of patients have no abnormal lymph gland enlargement. In some cases, the presenting feature is an ulcerative throat infection of the Vincent's type, from which Vincent's organisms are obtained. There may be an associated stomatitis. A small percentage of patients will have jaundice, which may be confused with infective hepatitis of the ordinary type. Some cases show a skin eruption which may be purpuric or resemble German measles. Mumps also may be simulated. Evidence of meningoencephalitis is found on rare occasions. Lastly, some of the cases are extremely mild and therefore likely to be dismissed as undifferentiated respiratory infection.

In connection with jaundice, a study at the Station Hospital, Boca Raton Army Air Field, Fla., is worthy of mention.72 Serial liver function tests performed in 15 consecutive cases of infectious mononucleosis showed some evidence in every case of deranged liver function, although clinical jaundice was not present in any of the cases. Since World War II, it has become recognized that the cephalin flocculation reaction is almost invariably positive in mononucleosis. It has, in fact, become a useful ancillary aid in diagnosis.

The etiological agent of infectious mononucleosis is still unknown, but is not believed to be any of the several microbes which have been described in the past. It may well be a filterable virus, although transmission experiments have usually been unsuccessful. Nor has the mode of transmission been established. It is apparently infectious, and occasional, localized epidemics with a high incidence have been described. The communicability would seem to be usually rather low as many of the cases are sporadic, without history of contact. Moreover, cases are treated on an open ward in most hospitals, and the disease does not appear to spread under these circumstances. If it is true that infection is widespread but that most of the cases are subclinical, then the phenomenon of apparent low communicability would be explained.

Infectious mononucleosis is a benign disease with a mortality that may be considered nil, though death may result from conditions complicating the

71Contratto, A. W.: Infectious Mononucleosis; A Study of 196 Cases. Arch. Int. Med. 73: 449-459, June 1944.
72Cohn, C., and Lidman, B. I.: Hepatitis Without Jaundice in Infectious Mononucleosis. J. Clin. Investigation 25: 145-151, January 1946.


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disease, as has been recorded in several reports.73 The disease may persist for several weeks and require considerable additional time before convalescence is complete. Sixty percent of a series of cases in the Army spent more than 3 weeks in the hospital.

Experience in the Continental United States

During 1944, it became clear that in certain areas in the Fourth and Eighth Service Commands infectious mononucleosis was being more frequently reported than formerly and was presumably mildly epidemic. An extensive clinical study at a station hospital in the Eighth Service Command reviewed the findings in some 556 cases occurring over a period of about a year.74 Several points of interest were noted in this excellent report. The disease was found in more than the anticipated number of Negroes, in whom it was formerely thought to be rare. Skin manifestations occurred in 16 percent of all the cases, a higher figure than has been commonly recorded. In 23 percent of 223 patients on whom cardiograms were taken, some abnormality was noted, usually of the T-waves. Six percent of the patients were jaundiced, but unequivocal meningoencephalitis occurred only once. The authors also noted 14 cases in which there was radiographic evidence of pneumonitis, a complication which has received scanty attention in the literature. The rest of the clinical manifestations conformed to the varied picture which has already been described. The blood counts were typical, and heterophile antibody titers of 1:112 or higher were noted in most of the cases. Very few had titers below 1:56. False-positive Kahn tests were only noted in 8 of 263 cases, and the incidence of other false serological reactions, that is, Weil-Felix, Widal, cold agglutination, was exceedingly low.

In contrast, what was described as an epidemic of 91 cases of infectious mononucleosis in the Caribbean Defense Command occurred in the autumn of 1944. Of these, 48.7 percent showed an exanthem, and the titer of heterophile antibodies was remarkably low, in the majority being below 1:28. A Weil-Felix reaction of above 1:160 was found in half the cases. Moreover, there were numerous other transient serological reactions, such as the Kahn, Widal, and cold agglutinin tests, a finding which has been noted in typhus. Histological studies of a few excised glands were made at the U.S. Army Medical Museum, Washington, D.C., and the findings were not typical in all of them. Altogether, there is a strong suspicion that this outbreak may have been rickettsial in nature.

In summary, it may be stated that while infectious mononucleosis was fairly common, it was not a serious medical problem in the continental United States. It is estimated from sample tabulations that about 21,000

73(1) Bernstein, A.: Infectious Mononucleosis. Medicine 19: 85-159, February 1940. (2) Custer, R. P., and Smith, E. B.: Pathology of Infectious Mononucleosis. Blood 3: 830-857, August 1948.
74Wechsler, H. F., Rosenblum, A. H., and Sills, C. T.: Infectious Mononucleosis; Report of an Epidemic in an Army Post. Ann. Int. Med. 25: 113, July; 236, August 1946.


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cases occurred in the total U.S. Army during the period 1942-45, of which about 15,000 were in the continental United States.

Experience Overseas

Sporadic cases of infectious mononucleosis were observed in the European theater throughout World War II where the case rate was about one-half that in the United States. At one time, the disease was mildly epidemic in an area of East Anglia, where a considerable number of cases was reported among Army Air Force personnel, and also among the personnel of the 2d Evacuation Hospital. In one of these, a most unusual complication occurred, spontaneous rupture of the spleen. The patient recovered following splenectomy. This epidemic was not of sufficient magnitude significantly to affect military operations.

As might be expected in any disease with such varied manifestations, very unusual clinical cases were observed. One patient, for instance, had a severe thrombocytopenic purpura during the acute phase of the disease.75 The writer saw a patient who was nearly exsanguinated owing to hemorrhage from an ulcerative pharyngitis. He recovered following transfusions and penicillin therapy. This indicates that the associated Vincent's infection in mononucleosis may be a dangerous complication. No useful purpose is served in multiplying these remembered clinical curiosities.

RUBELLA

Rubella (German measles) is the mildest of the exanthemata of childhood. Unlike the others, it is almost wholly uncomplicated, and the mortality rate is usually stated as nil. The disease is highly communicable, but the symptoms are so trifling and the resulting disability of such short duration that its only importance is its nuisance value. Clinically, it may cause some difficulty in differential diagnosis as it can be mistaken for other diseases, such as measles, infectious mononucleosis, drug eruptions, scarlet fever, or even syphilis.

Although the diagnosis is purely clinical, it seems probable that German measles in its usual form is recognized with some accuracy by clinicians of wide experience. However, the differential diagnosis between it and measles may be difficult for others less experienced. This point is brought up because of certain peculiarities in its reported behavior during World War II. In the first place, unlike measles and mumps, rates were higher than in World War I. This is difficult to explain unless the low rates for the First World War resulted from marked under reporting of a trifling malady. Secondly, seven deaths were ascribed to German measles, and the average days lost to duty (9) was not much lower than the number lost owing to measles (13 days).

75Lloyd, P. C.: Acute Thrombocytopenic Purpura in Infectious Mononucleosis; Report of a Case. Am. J.M. Sc. 207: 620-624, May 1944.


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Lastly, there was a striking peak in the incidence of German measles in 1943, the year of the highest rate for measles. All these facts create the suspicion that cases of measles were being reported as German measles. The most important differentiating points are the different modes of onset of the two diseases, and the exanthem of true measles.

There were 135,830 cases of German measles reported in World War II, of which 125,530 occurred in the United States. If these figures are accurate, it caused more noneffectiveness than measles. It was an inconsequential malady, of extremely benign character, and presented no clinical features worthy of discussion. However, the interesting observation made in Australia during the Second World War that German measles occurring in the first 2 months of pregnancy is associated with a high incidence of congenital malformations of the newborn76 was obviously devoid of military significance.

Part II. Chronic Respiratory Diseases

CHRONIC BRONCHITIS

"Chronic bronchitis" is a rather loose diagnostic term which does not usually indicate a clear-cut pathological or, for that matter, clinical entity. One variety is the chronic cough of older men, usually more marked in winter. Some of these individuals may have occasional wheezing rales; in others, there are no noteworthy physical signs. X-rays of the chest may show some exaggeration of the bronchial markings, but often the diagnosis is a presumptive one based on the observation of a chronic cough. As the individual grows older, he may develop varying degrees of emphysema with its attendant effects on respiratory physiology. Cigarette smoking and chronic disorders of the upper respiratory tract are most assuredly contributing factors to the condition. Because of the age distribution of Army personnel, this type of chronic bronchitis was more often seen on the officers wards. In some climates, it tended to get worse. It was the writer's impression, for instance, that elderly officers coughed more in England than they had at home. Dampness, unheated billets, and excessive smoking undoubtedly contributed to this. It has also been remarked that in a tropical climate, such as Panama, soldiers with a history of recurrent acute bronchitis tend to develop chronic bronchitis.77

The management of these cases was largely a matter of appraisal. In the author's experience, it was almost always impossible to persuade an officer stationed overseas to stop smoking. If the condition were deemed

76Swan, C., Tostevin, A. L., Moore, B., Mayo, H., and Black, G. H. B.: Congenital Defects in Infants Following Infectious Diseases During Pregnancy, With Special Reference to the Relationship Between German Measles and Cataract, Deaf-Mutism, Heart Disease and Microcephaly, and to Period of Pregnancy in Which Occurrence of Rubella is Followed by Congenital Abnormalities. M.J. Australia 2: 201-210, 11 Sept. 1943.
77Cohen, A. G.: An Early Form of Chronic Bronchitis in Panama. War Med. 5: 105-108, February 1944.


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incompatible with any kind of duty, the patient was boarded home. At times, it was possible to effect a change in his working and living conditions. On the whole, however, there was little in the way of medical treatment which could be offered. Diagnosis of chronic bronchitis was sometimes used as a handy means of returning home elderly officers who had outlived their usefulness in an oversea theater.

A just appraisal of the importance of chronic bronchitis in the Army is difficult. It never seemed to be a major problem, and yet preliminary data based on sample tabulations indicate that the disease was responsible for about 34,000 admissions during the period 1942-45. Nearly half of these occurred overseas. The figure seems extraordinarily high and, perhaps, indicates that the diagnosis was freely used to designate any case of chronic cough.

Mustard gas is a recognized cause of chronic bronchitis. Had this or other irritating inhalants been employed in any of the campaigns, the disease might well have become a major problem. During World War II, virtually the only individuals at risk were those engaged in the manufacture of mustard gas. A few cases were reported.78

Asthma-The dividing line between chronic bronchitis and asthma is often not very clear cut. In younger individuals, chronic bronchitis is often of an asthmatic character; that is, it may be really a manifestation of asthma of the endogenous or intrinsic type. These asthmatic bronchitides tended to get worse overseas.79 Moreover, it is interesting to note that, in one series of 28 asthmatics whose initial attack occurred in the Army, in 23 it developed overseas.80 This is presumably related to heavy pollination in certain tropical areas. At the same time, intrinsic asthma was aggravated during the tropical rainy season.

The management of asthma in the Army is fraught with discouragement. In civilian practice, one can perform an exhaustive study and, depending upon the findings, endeavor to modify the external environment or to exert influence on the patient, by either improving his respiratory disease status or actually rendering him less sensitive. None of these is feasible during a military campaign, save in very exceptional instances. The clinical management of asthma, apart from symptomatic treatment, consists principally in appraisal. By observing the patient over a considerable period of time, the medical officer tries to answer the following questions: Is this man capable of full duty? Of limited duty? Should he be boarded home from an oversea theater or, if at home, separated from the service?

Most medical officers believed that very few asthmatics, no matter how mild their disease, were fit for combat duty. Exertion and dust, for in-

78Morgenstern, P., Koss, F. R., and Alexander, W. W.: Residual Mustard Gas Bronchitis; Effects of Prolonged Exposure to Low Concentrations of Mustard Gas. Ann. Int. Med. 26: 27-40, January 1947.
79See footnote 19, p. 9.
80Alford, R. I.: Disposition of Soldiers With Bronchial Asthma. J. Allergy 15: 196-202, May 1944.


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stance, tended to produce some shortness of breath in these individuals even when the asthma did not seem to be clinically active. On the other hand, many such individuals could be retained on a limited duty status either overseas or at home. It must be added, however, that this was partly dependent on the man's willingness to serve. Asthma undoubtedly has a psychosomatic aspect, and if a relatively mild asthmatic wished to get himself sent home from an oversea theater, he usually succeeded in doing so. Mild asthma often got worse overseas. Thus, asthma was one of the leading medical causes for return to the Zone of Interior. The disposition of asthmatics in the United States may be indicated by a report of 100 consecutive patients, of whom 71 were discharged from the service.

BRONCHIECTASIS

In young individuals, bronchiectasis may be a progressive and disabling disease. The likelihood of such a person being accepted for military service is extremely remote, and it has been stated that bronchiectasis was the most common form of chronic nontuberculous lung disease discovered on induction examination. However, bronchiectasis of a milder type, essentially cylindrical rather than saccular, may be discovered in a soldier who has previously been in reasonably good health. The pathogenesis of the condition is somewhat obscure, but the lesions may arise apparently as a result of sinusitis, following pneumonia, or in older individuals as a consequence of chronic bronchitis. Bronchiectasis by itself does not necessarily produce any physical signs or X-ray changes. It is likely, therefore, that the disease is overlooked on occasion. Undoubtedly, if more bronchographic studies were performed, it would be more frequently recognized.

Bronchiectasis has been termed the most common chronic pulmonary disease in the U.S. Army.81 As evidence of this, the authors reported 95 cases investigated bronchographically, mostly for slowly resolving pneumonia. Of these, 37 showed frank and 24 minimal bronchiectasis. No bronchiectasis was found in 34 patients. Two other reports might be cited, both from station hospitals in the Third Service Command: At Fort Belvoir, Va., 33 cases were discovered during the course of a year82-14 were said to be severe, 9 moderate, and 10 minimal. At Fort Eustis, Va., the diagnosis was made 40 times over a 15-month period;83 9 patients were studied because of chronic cough, and the rest were admitted with a diagnosis of atypical pneumonia. When resolution failed to occur in 4 to 6 weeks, bronchographic studies revealed the true condition. Only 23 of the entire series

81Evans, W. A., Jr., and Galinsky, L. J.: The Diagnosis of Bronchiectasis in Young Adults; Prebronchographic Roentgen Manifestations Observed Among Military Personnel. Am. J. Roentgenol. 51: 537-547, May 1944.
82Thompson, T. E., Jr., Cawley, F. C., and Seltzer, A.: A Study of Bronchiectasis at Station Hospital, Fort Belvoir, Virginia. M. Ann. District of Columbia 13: 93-97, March 1944.
83Grier, G. S., III: Importance of Bronchography in Cases of Unresolved Pneumonia. Arch. Int. Med. 73: 444-448, June 1944.


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gave a long history of chronic cough. These patients did not show the typical textbook picture of severe bronchiectasis with wasting, foul sputum, clubbed fingers, and so forth. The disease was obviously in a much milder, or earlier, stage. The author of this study did not believe that these slowly resolving pneumonias were primary atypical pneumonia but rather that they were of the variety long recognized as occurring in conjunction with symptomatic flareups of bronchiectasis. Some internists believe that chronic bronchiectasis is at times a rare sequel of severe atypical pneumonia. For instance, the disease was believed to follow atypical pneumonia in no less than 17 of 33 cases admitted during a 9-month period to the Percy Jones General Hospital, Battle Creek, Mich.84 However, a review of the case reports given in this paper leaves serious doubts as to the diagnosis of atypical pneumonia. Flareups of pneumonitis are a common feature of bronchiectasis, and the differentiation of these from primary atypical pneumonia is extremely difficult. Van Ravenswaay and his associates85 stated that bronchiectasis occurred as a sequel to atypical pneumonia at Jefferson Barracks in 11 of 1,862 cases. This question is not yet entirely settled. On the other hand, dilated bronchi, which later reverted to normal, have been shown in a few patients convalescing from atypical pneumonia.86 The condition was termed "pseudobronchiectasis."

It is estimated that the disease caused more than 6,000 admissions in the period 1942-45, four-fifths of them in the continental United States. When the diagnosis was established, it was ordinarily a cause for separation from the service.

A certain number of cases were treated surgically during World War II. For example, in 1943, 25 lobectomies were performed at Fitzsimons General Hospital, Denver, Colo., with 2 deaths.

LUNG ABSCESS

The possibility that a person with a chronic lung abscess could pass the induction X-ray and physical examination is so slight that cases of this condition observed in the U.S. Army presumably developed in the service. Acute lung abscess is by no means uncommon in civilian practice; such cases follow a fairly well recognized clinical pattern, and a considerable percentage, perhaps nearly half, recover spontaneously without surgical drainage. The remainder will become chronic if not drained. Acute abscesses of this type coming on de novo, so to speak (in the absence of such predisposing factors as dental extraction and tonsillectomy) were very rarely encountered in the Army. The reason for this is not entirely clear unless it be the generally low incidence of bacterial pneumonias. Lung abscess

84Kay, E. B.: Bronchiectasis Following Atypical Pneumonia. Arch. Int. Med. 75: 89-104, February 1945.
85see footnote 46, p. 20.
86Blades, B., and Dugan, D. J.: Pseudo Bronchiectasis Following Atypical Pneumonia. Bull. U.S. Army M. Dept. No. 70, pp. 60-68, November 1943. 


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developing after surgical procedures also seemed unexpectedly rare. It is the writer's impression that many of the lung abscesses seen in the Army were in battle casualties.

The disease is estimated to have been responsible for about 500 admissions in the 1942-45 period, with 16 deaths.

SPONTANEOUS PNEUMOTHORAX

The sudden appearance of air in the pleural cavity not due to penetrating wounds of the chest wall or endotracheal trauma is known as spontaneous pneumothorax. It was formerly thought to be related to tuberculosis. Now, however, while it is known that spontaneous pneumothorax may occasionally occur as a complication of frank pulmonary tuberculosis, it is also recognized that the great majority of cases take place as a result of rupture of a subpleural bleb and have no relationship with tuberculosis whatsoever. Interestingly enough, rupture often takes place quite independently of physical exertion.

In many instances, pneumothorax is a recurrent disease. Recurrences were formerly thought to be uncommon, but it now seems likely that if more frequently recognized by general practitioners their incidence would rise. For example, a report from the Station Hospital, Seymour Johnson Field, Goldsboro, N.C.,87 points to a highly suggestive history of one or more previous episodes in five out of seven carefully studied cases.

Spontaneous pneumothorax is most frequently encountered in relatively young males and gives rise to characteristic physical signs only if the amount of escaped air is large enough. Roentgen examination, however, as a rule is unequivocal; and if chest X-rays are routinely taken of individuals giving a suggestive clinical history (there is almost invariably some sudden chest pain at the onset followed by varying degrees of dyspnea), the condition should not be overlooked. Pneumothorax is rarely complete; in probably three-fourths of the cases, the collapse is less than 50 percent, so that the number of cases not detectable with assurance on physical examination is high. Following spontaneous pneumothorax, fluid may occasionally appear, but these effusions are small.

In the usual course of events, there is a single leakage of air which will be absorbed in the course of time. On the other hand, there may be recurrent leakages during the reexpansion period, or the pneumothorax may be permanent due to an open fistula. Such cases require the attention of the thoracic surgeon. Another clinical variety is the so-called tension pneumothorax wherein so much air escapes (often aided by a valve effect in the rent pleura) that dangerously high intrathoracic pressures are produced. Fortunately, this is a rare happening, but when it occurs, it may constitute a real medical emergency. The patient is extremely dyspneic and cyanotic,

87Pease, P. P., Steuer, L. G., and Chapman, A.: Spontaneous Pneumothorax in Soldiers. Bull. U.S. Army M. Dept. No. 82, pp. 102-107, November 1944.


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and his gasping respirations only serve to aggravate the situation. In such instances, the quick release of air by means of a needle plunged through the chest wall is lifesaving. Lastly, the rare phenomenon of hemopneumothorax might be mentioned. Here, bleeding occurs from the torn pleura, sometimes on a large scale.

There were 3,831 admissions for spontaneous pneumothorax to U.S. Army hospitals between 1942 and 1945. It was about twice as common at home as overseas. The vast majority of these cases were of the uncomplicated benign type, and in about 10 percent was the condition a cause for separation from military service. Recurrence was the reason for most of the discharges. The average duration of hospitalization was in the neighborhood of 2 months, so that neither in terms of man-days lost nor manpower permanently lost did the disease constitute a serious medicomilitary problem. The four deaths attributed to the condition were presumably due to tension pneumothorax.

In 1944, at the suggestion of the National Research Council, a booklet on spontaneous pneumothorax was prepared for general distribution by Dr. James J. Waring.88 In this, he advocated conservative therapy, with emphasis on hospitalization, bed rest, and the avoidance of air transport. Dr. Waring also discussed the indications for thoracotomy, chemical pleuritis in the recurrent cases, and the disadvantages of these procedures. In general, he advised an individualized approach to each case.

PULMONARY FIBROSIS

Diffuse fibrosis of the lungs may follow granulomatous diseases, such as tuberculosis, fungus infections, sarcoidosis, and beryllium poisoning. It is also a serious occupational hazard of those exposed to the inhalation of silica dust. The preinduction X-ray screening of U.S. Army personnel in World War II made it highly improbable that individuals with any significant degree of pulmonary fibrosis would be accepted for military service. Moreover, the conditions leading to its development were not a feature of army life, so that, apart from a certain amount secondary to chronic pulmonary tuberculosis, it was never a feature of medicomilitary practice. It might be added that the only generalized fungus infection with a fairly high incidence in the Army, coccidioidomycosis, is not a recognized cause of diffuse pulmonary fibrosis.

Peculiar instances of rapidly progressive pulmonary fibrosis whose etiology is entirely obscure have been recorded in the literature. Notable among these is the report of Hamman and Rich.89 It is of interest that four

88Waring, J. J.: Spontaneous Pneumothorax. Office of Medical Information, Division of Medical Sciences, National Research Council, July 1944.
89(1) Hamman, L., and Rich, A. R.: Acute Diffuse Interstitial Fibrosis of the Lungs. Bull. Johns Hopkins Hosp. 74: 177-212, March 1944. (2) Eder, H., Hawn, C. V., and Thorn, G. W.: Report of a Case of Acute Interstitial Fibrosis of the Lungs. Bull. Johns Hopkins Hosp. 76: 163-171, April 1945.


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cases thought to resemble those described by Hamman and Rich were observed in the U.S. Army in New Guinea in 1944. Of these, one patient finally recovered while two were evacuated and lost to followup study. One came to autopsy.

PULMONARY EMPHYSEMA

Chronic pulmonary emphysema was occasionally noted in the U.S. Army in the older age groups, particularly among officers. It was less common than in civilian practice, probably owing to the generally higher standards of health prevailing in the Army. It was said to be responsible for about 750 admissions in the period of 1942-45, most of them in the continental United States.

MALIGNANT DISEASE OF THE LUNGS

The incidence of malignant disease generally in the U.S. Army is very low, owing to the age group involved. Moreover, a survey of 15 million Army man-years in the 20- to 40-year age group made in 1944-45 indicated that the incidence in this group was lower than among civilians.90 The reason for this difference is not apparent. In any case, cancer occurs with expected frequency in the older age group, again particularly among officers.

As a measure of the importance of malignant disease of the lungs in military medicine, the following is cited: Bronchogenic carcinoma is estimated to have been recognized 200 times during the period 1942-45. There were 91 cases of all forms of malignant diseases of the lungs identified at Letterman General Hospital, San Francisco, Calif., between 1944 and 1950. This represented almost exactly 1 per 1,000 admissions.91

90Lindsey, D., and Cohart, E. M.: Incidence of Cancer in American Males; 15,000,000 Man-Years of Aggregate Experience, United States Army, 1944-45. Cancer 3: 945-959, November 1950.
91For the surgical aspects of diseases of the chest see Blades, Brian B., Carter, B. Noland, and DeBakey, Michael E.: Surgical Aspects of Diseases of the Chest. In Medical Department, United States Army. Surgery in World War II. Thoracic Surgery. Volume II, ch. XI. [In preparation.]-J. B. C., Jr.

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