AN EXPLOSIVE OUTBREAK OF PRIMARY ATYPICAL PNEUMONIA IN A COLLEGE COMMUNITY'

ROBERT A. SNYDER, M.D., HARRY B. HARDING, M.D., OPAL E. HEPLER, M.D. and LEONA B. YEAGER, M.D.2

N October, 1951, the Garrett Biblical be caused by Pasteurella tularensis. There I Institute of Northwestern University remained a larger group ,,·ith unproven at Evanston, Illinois, experienced an ex­ etiology, which has been labeled variously plosive outbreak of a severe respiratory "acute pneumonitis," "virus pneumonia," infection, with marked pulmonary infil­ "atypical bronchopneumonia," etc., but tration in almost every case. Through is more widely called "primary atypical the facilities of the virus laboratory of pneumonia. " North\\'estern University Medical School, Despite thorough investigations in a the pneumonitis was proven serologi­ number of excellent laboratorie, con­ cally to be primary atypical pneumonia. clusive evidence of the etiologic agent in It is our purpose, in this paper, to primary atypical pneumonia is still lack­ review briefly the history of primary ing. At least five seemingly different atypical pneumonia, to describe the clin­ infectious agents have been impEcated. ical features of the Garrett cases, to dis­ The experiments of Stokes et al. (4), cuss the laboratory differentiation of this Weir and Horsfall (5), Blake et al. (6), epidemic, and, finally, to summarize the and Eaton and cO\\'orkers (7) are "'ell information obtained from a standard documented and need not be revie\\"ed in epidemiological approach to this outbreak. detail. In 1946, the Commission on Acute Respiratory Diseases, working at Fort REVIEW OF LITERATURE Bragg, North Carolina (8), succeeded in Arrasmith (1 ), Bowen (2), and Allen transferring primary atypical pneumonia (3) were among the first to call attention to 16 out of 60 patients, using pooled to certain penumonias, occurring both specimens from typical cases. Twenty­ sporadically and in small epidemics, which six others developed an upper respiratory failed to conform to the accepted picture infection without pneumoni a. The of either lobar or bronchopneumonia. workers concluded that primary atypical Later, as the sulfonamides and penicillin pneumonia was caused or initiated by a became widely and effectively used against filter-passing agent, presumably a vim. the bacterial pneumonias, these so-called Though we still lack the abiEty to atypical pneumonias were further deline­ demonstrate the etiologic agent, there ated. In certain instances, the etiology remain two serologic tests, quite inde­ of these atypical pneumonias could be pendent of each other, which are useful clearly established as due to viruses or adjuncts to the diagnosis of primary rickettsiae such as those of psittacosis, atypical pneumonia. The one most .\\·idely influenza, Q fever, and lymphocytic chor­ used is the demonstration of cold ag­ iomeningitis. A few cases were found to glutinins (9, 10), these being present, de­ 'From the Student Health Service of Northwestern Uni· pending upon the severity of the case, versity; the Departments of l\1edicine. Bacteriology, and in 20 to 90 per cent (11) of the con­ Pathology of Northwestern University Medical School; and the Departments of Medicine and Pathology of valescent sera from these patients. Evanston Hospital. Received for puhlication, September 23, 1952. This test was highly useful in the Gar­ This investigation was supported in part by a research rett outbreak and \\·ill be discussed more grant from the National Institutes of Health, U. S. Public Health Service. fully later in this paper. The second 'The authors wish to gratefully acknowl edge the tech· nical assistance of Edna Murmann, M.s .. Nathalie Schmidt, serologic test is the demonstration of M.S., Jeanne Doucette, M.S., and Mary Robinson, B.S. agglutinins against a non-hemolytic strep- 327 328 QUA RTERLY BULLETIN, N.V. M.S.

tococcu , de ignated Streprococcus MG. Mirick and Thomas (12), in 1945, iso­ TABLE I lated this microorganism from the lungs Frequency of Occurrence of Symptoms and of fatal cases of primary atypical pneu­ Signs in Nineteen Patients with a Clinical monia, and suggested it I\"aS implicated Diagnosis of Primary Atypical Pneumonia Fever ...... 19 in the cause of this disease. About 50 per Cough ...... 19 cent of the cases of pri mary atypical Headache...... 18 pneumonia develop these agglutinins. Myalgia...... 15 Ri,'ers (13) suggests three explanations Sore Throat ...... , ...... 14 Chills ...... 11 for th is phenomenon. Fir t, there may Sputum ...... 11 be a coincidental immunologic relation- Anorexia ...... 7 hip betll"een the bacterium and some Rhinit is...... 6 other infectious agent. Second, the reac­ Hoarseness ...... 6 Photophobia...... 4 tion may be caused by a secondary in­ Xausea ...... 2 "asion of the microorganism. Third, the Insomnia ...... ~. . . . . 0 agglutination may result from a double Vomiting...... 0 infection ini tiated by the streptococcus Clinical Laboratory Findings and some other infectious agent, presum­ Leucocytosis...... 1 ably a I·irus. Lymphocytosis (over 50% by diffe rential count) . . 0 THE EPJDEMIC A'l' THE GARRE'!"!' X-ray pneu moni ti * ...... 14 BIBLICAL INSTl'ru,),E *T\\'o patient · exhibited rales \\'ithout The Garrett outbreak of primary sho\\'ing infi ltration on x-ray examination. atypieal pneumonia con isted of 19 cases, all of them clinically imilar and charac­ ing 3 to 4 lI"eeks after they became am­ teri ·tic of the generally accepted picture bulatory. of this disease. Fourteen of them lI'ere X-ray clearing u ually \\"a present developed lI'ithin a 4-day interval, be­ \\·ithin 5 to 10 days. Two cases, hOIl'ever, ginning October 14, follo ll'ed by 5 econd­ continued to have sli ght infiltration long ary cases ol'er a period of 5 days. T he after they lI'ere well. Five representative secondary Irave lasted hom October 20 x-rays are included (fi g, 1). th rOlwh October 24. T he frequency of Due to the small number of cases, no . igns and symptoms is listed in Ta,b[e 1. conclusions \I'ere reached as to the effi­ All illnesses began lI'ith a rapidly develop­ cacy of treatment. T he duration of illness ing upper respiratory infection, accom­ \\'as remarkably similar lI'hether aureo­ panied by a 101l"-grade fever, headache, mycin, chloromycetin, terramycin , or no malai,'e, and generalized aching. Within treatment I\'as used. Three persons wi th 2 to 3 days mriously productive cough severe bilateral involvement lI'ere ill del'eloped, Irhile the fever ranged up to longer than the others and did not seem 103 F. As is usual in this disea,'e, phys­ to reo pond to any of t he antibiotics, ical findings in the che t lI'ere at I"ari ance T hus Ire did not confirm the general im­ lI"ith the x-ray findings. Of 14 persons pre sion one deri ves from reading the Irith marked x-ray find ings, 5 presented literatUl'e, namely, that aureomycin is an only slight physical find ings of pneu­ effective drug in primary atypical pneu­ monitis, lI·hereas examination of 2 other monia (14), patients in the epidemic revealed defin ite phy ical finding of pneumonia Iri th ab­ LABORATORY STUDIES 'ent or slight x-ray el" idence. Both of At the time the outbreak began, the the, 'e latter indil'iduals developed cold nature of the causal agent was, of course, agglutinins lI·ith titers of diagnostic sig­ unkno\\·n. The cl ini cal picture and the nificance. The duration of illness was 10 x-ray findings of the first 15 cases, ho\\'­ days on the average. Temperature con­ eyer, strongly indicated the probable tinued, u 'ually 101l'-grade, but in 3 in­ diagnosis of primary atypical pneumonia. stance. was high (103 to 104 F.) during Therefore microbiological laboratory in­ the height of the pneumonitis. Almost vestigation Irere conducted as follows: all patients noted persistent fatigue, last- 1. Bacteri ological examination of spu- SNYDER ET AL.- PRIMARY ATYPICAL PNEUMONIA 329

Fig. 1. Typical x-my films jTOm patients in Gar1'elt epidemic. A , Patient, C. K. Film taken October 14, 1951. Note injiltmtion in right lower lobe w'ea and increased hilar markings. B, Patient J. J . Film taken October 22, 1951 . There is a circulw' a1'ea of increased density in region of fifth and sixth 1'ib (on left). C, Patient J. S. Film taken October 22, 19.51 . Note clouding and increased density in left costophrenic angle. Note also the increased hilar mw·kings. D, Patient M. J . Film taken October 29, 1951. The moltled lesion in right hmg W'W is quite prominent. E, Patient J. M u. Lesions may be seen in both lung bases . tum samples in the acute phase of each stained by Gram's method. Portions of patie~t 's illness for predominating micro­ each specimen \rere then inoculated onto orgamsms. Loeffler's serum medium, eosin methylene 2. A survey for virus complement-fix­ blue agar, chocolate agar, rabbit blood ing antibodies in the acute and conval­ agar, and thioglycollate medium. Growth escent phases of each patient's illness. appearing on these media \ras identified 3. A determination of cold-agglutinin by appropriate methods (15). Table II titers in the acute and convalescent phases summarizes the species of organisms of each patient's illness. found in this investigation together ,,·i th their frequency of occurrence on the Bacteriological Examinations: above media. Since in no instance "'as a predominating pathogen found, these Sputum specimens4 obtained in the acute phase from 11 of the patients in­ results would indicate that the organisms volved in the epidemic were examined for isolated from these patients lacked eti­ the presence of predominating micro­ ologic significance. organi!';ms. Direct films were made and Complement Fixation Studies : 4Twelve specimens of sputum , including the above 11, were examined October 25, 1951 b.l'chick-embr.l'o inocu­ Using 14 different viral and rickettsial lation for the presence of virus by Mr. Richard Morrisey antigens, 392 separate tests were made on of the Illinois State Public Health Laboratories . Neg­ ative results were obtained from these inoculations. blood specimens obtained from 11 patients 330 QUARTERLY BULLETIN, N.U.M.S.

ings (see above), and clinical course of TABLE II t he disease all indicate that these patients Frequency of Occurrence of Various Organ­ \\-ere suffering from primary atypical isms in Sputum Specimens from Eleven pneumonia and not from influenza. Al­ Patients with a Diagnosis of Primary Atypical though one cannot rule out the possi­ Pneumonia bility of a concurrent influenza, it is more Number probable that the antibody response in of Times this instance was of the anamnestic type. Organism Recovered A consideration of this evidence indi­ Micrococcus pyogenes vaL aureus . . . . 6 cates therefore that the Garrett epidemic Micrococcus pyogenes var. albus 8 was not due to viruses of the influenza Candida albicans . . . . . 1 group. Actin omyces sp...... 1 Streptococcus salivarius ...... 6 The responses to mumps antigen Hemophilus influenzae ...... 1 (Table III) are next in frequency of occur­ Serratia marcescens ...... 1 rence. The dropping or low level response Proteus vulgaris ...... 3 in these instances, as well as the scattered Bacillus subtilis ...... 5 low level responses to five other antigens (Table III), indicates their lack of sig­ (Table III). The technique employed nificance. for these tests has been published else­ where (16). Cold Hemagglutination Tests: The acute phase sera were tested at The basis for this test was the obser­ the time they were received. These sera vation by Clough and Richter (18), in were saved and run again at. the time the 1918, that the serum from a case which convalescent phase sera were tested, em­ they had diagnosed as "bronchopneu­ ploying identical antigen dilutions and monia" contained agglutinins for human the same hemolytic system for both the group 0 erythrocytes. These are oper­ acute and convalescent phase sera. The ative at temperatures ranging from 0 C. convalescent phase specimen was sub­ to 10 C. At 37 C. the reaction dis­ sequently tested a second time. In this appears. Peterson (19) and others have ,,-ay, a true measurement of a rise in established the fact that this phenome­ antibody titer could be made (if such non occurs in primary atypical pneu­ occurred) upon the specimens from each monia. Sera from 10 patients were exam­ patient. Table III presents a summary ined by techniques as outlined by Feller of the results of these tests. In t.abulat­ (20). A total of 34 tests were conducted ing these findings, reactions of 1 plus or so as to compare acute and convalescent less \rere disregarded because of their lack phase sera against the same erythrocyte of significance. system on t he same days. The results The almost universal response of sera of these tests are reported in Table IV. from these patients to influenza group According to Feller (20), a titer of 1:32 antigens and the paucity of reaction with or higher is suggestive of virus pneumonia other viral and ri ckettsial antigens, al­ (primary atypical pneumonia). Cold ag­ though noteworthy, is not to be inter­ glutinins appear at the end of the first preted as indicating a serologic diagnosis week of illness and usually reach their of influenza. As determined from a recent maximum in 2 to 4 weeks, declining in 4 survey conducted by hro of us (17), it to 6 weeks. Feller (20) states that high is a common occurrence to find measur­ titers of 1 :128 to 1 :1024 or more are not able titers of influenza antibody in sera often seen except in primary atypical from persons \rho are not suffering from pneumonia. A fourfold or greater in­ this disease. Table III indicates that crease in titer occurring during the course there \rere fourfold increases in titer to of illness is significant, as well as a marked influenza B antigen in specimens of serum decrease in titer from a high level in the from patients F. C. and C. Ie These re­ convalescent phase. The decrease must sults are usually considered diagnostic. occur 6 to 8 weeks after onset. In both of these instances, however, cold­ In our studies (Table IV) it will be no­ agglutinin studies (see below), x-ray find- ted that the serum of J. M. gave titers of SNYDER ET AL.- PRIMARY ATYPICAL PNEUMONIA 331

TABLE III Summary of Complement Fixation Studies on Eleven Patients with a Clinical Diagnosis of Primary Atypical Pneumonia

Reciprocal of Highest Titer Showing Positive Complement-Fixation (by Antigens)

Patient Date

2 1 4 4 1 4 32 32 I .. .. I ...... I ...... I . . 8 8 32 2 ...... ---1------1- .------4------1 1 2 2 4 2 2 8 8 2 2 4 16 4 2 2 -.-. -4- .-. 32-.-. -.-. -.-. -.-. -.-. -.-.1- 4-.-. -.-...... ~ ...... --- 1------1---.-. - .-. -.-. -.-. -.-. 321616- 8 -.-.1-.-. -.-. -.-. ___ 1______1____ . ._ __4___ 2_ ~ _._.___ . .__ ._ .___ . .__ ._. _ __. '_1_ ' .__ ._. ___.._ 2 8 8 2 8 32 2 ---1------11 ------__ 2 88 2 8 8 - - -1------1------. . 4 32 8 64 2 2 16 64 4 2 ---1------1------____ 4 484 4 4 8 4 - --11------1------2

------1------___ ---- -_ 2 2 32 2 16 8 ---1------1------448 4 2 16 8 8 16

*J. M. was the original contact for the Garrett outbreak

1 :512 on two occasions. This would be or greater increase in ti tel' ; in one in­ expected, since his was the first case and stance there was a twofold increase in he was convalescent at the time the first titer from 1 :1 6 to 1 :32 in 11 days. We blood specimen was drawn. Seven of those subsequently tested exhibited serum believe these results establish a serologic titers of 1 :32 or better. diagnosis of primary atypical pneumonia In four instances there was a fourfold for this epidemic. 332 QUARTERLY BULLETIN, N.U.M.S.

14 cases, all but one was from the Garrett Table IV Biblical Institute. Although the facil­ Summary of Cold Hemagglutination Studies ities of this institute lie wit.hin the bound­ on Ten Patients with a Clinical Diagnosis of aries of the N orth\\'estern University cam­ Primary Atypical Pneumonia pus, its curriculum is distinct, and there is little, if any, intermingling of t he Date of GalTett students with the other North­ Patient Specimen Result \\'estern students. The only non-Garrett -- I student, and t he onl y \\'oman, in the ini­ J. Mu. 10-1 9-5 1 Pas. in 1-16 10-30-51 Pas. in 1-32 tial group wi th pneumonia \ras a student, -- I B. B., enrolled in the school of Liberal C. K. 10-19-51 Po . in 1-32 Arts. In questioning her, it \\'as di scov­ 11- 2-51 Pas. in 1-128 ered that she lived in the same rooming -- I J. M .* 10-24--51 Pas. in 1-512 house as a Garrett student, took meals Il- l-51 Pas. in 1-512 \rith him, and that, furthermore, he \\'as -- just recovering from "virus pneumonia." J, S. 10-26-51 Pas. in 1-32 This student, J . M., \\'as questioned and 11- 1-51 Pas. in 1-128 -- proved to be very cooperative and anxious W. P , 10-19-51 Pas. in 1-32 to delineate his role in the outbreaks, I 10-30-51 Pas. in 1-1024 He stated that on October 2, 1952, the -- first day of classes at GalTett, he was R. O. W. 10-19-51 Xegative -- quite ill \\·ith a se\'ere upper respiratory F. C. 10-31-51 Pas. in 1-32 infection, but attended the morning ses­ -- sions anyway for fear of missing valu able J . C. 10-26-51 Pas. in 1-16 orientation. He went to three classes, 11-2!J-51 Pas. in 1-128 -- but, unfortunately, no seating plan was It. D. 10-24-51 Pas. in 1-32 in effect, so his immediate seating neigh­ -- bors \rere unknO\\·n. By aftemoon, he M . B, 11-20-51 l'\egative \\'as too ill to continue, so he stayed at 1- 4-52 Xegative home and \\'as seen by a local physician *J, M. was the original contact for the \\'ho subsequently made a diagnosis of Garrett outbreak "virus pneumonia." Our first 14 cases, 13 of them having attended the same sessions as this student on October 2, developed their illnesses from October 14 EPIDEMIOLOGY to 17, setting the incubation period at Primary atypical pneumonia is de­ from 12 to 15 days. As further circum­ scribed usually as an endemic disease stantial evidence, J, M.'s father and occurring sporadicall y. N umerou small mother, and one other student \\'ho lived explosi\'e outbreaks ha\"e been reported, in the same rooming house as J. M., de­ usually occulTing in army camps, insti­ veloped the disease coincident in time t utions, schools, 01' hospitals, although no wi th our first 14 cases. As \\'as shown epidemic has ever reached major propor­ above, t he serum of J. M. \\'as positive tion s. Troen (21) has recently described for cold agglutinins in a dilution of 1 :512 an outbreak occurring in a . S. Army on two occasions, establishing his illness install ation in Kobe, Japan, in which 33 as serologically identical to all the others. patients de\'eloped the disease \\'ithin a We have presumptive evidence, then, that 5-day period, there bein g only 12 addi­ J. M. infected at least 17 other persons, tional econdary cases. In t he Garrett a good record fo r a disease thought not outbreak, 14 of the individuals became to be easily communicated. ill \\"i thin a 4-day period, all of these This set of circumstances provides a developing typical radiologic pulmonary good opportunity to review and utilize infiltration. This, of course, led to spec­ orderly procedure for epidemiological in­ ulation that there must be a single source, vestigations. The foll owing outline (16) and through a fortunate circumstance, for investigating this epidemic \\'as fol­ this source \\'as uncovered . Of the original lo\\'ed and proved very useful: SNYDER ET AL.-PRIMARY ATYPICAL PNEUMONIA! 333

1. VerificaMon of the diagnosis. DISTRIBUTION by DATE of ONSET of 19 CASES In this series, the clinical picture, of PRIMARY ATYPICAL PNEUMONIA physical findings, and x-ray confir­ 8 OCCURRING at GARRETT BIBLICAL INSTITUTE mations were so identical and char­ acteristic that there was little doubt ~ 6 ...3 5 as to the nature of the problem. o Later, the serologic studies con­ • firmed the clinical impression. .z 4 g 3 2. Verification of existence of epidemic. :z The first.-vear class of Garret.t Bib­ lical Institute, in which all the cases

occurred, numbered 118. The ap­ 14 15 16 11 18 19 20 21 22 23 24 pearance of 14 cases of pneumonia Octobar 1951 within 3 days in this school group Chm·t 1 left little doubt that an epidemic *19 cases were actually concerned in the Ga1'l'etl existed. outbreak propel'. J . M ., the twentieth person, was the source of the epidemic. 3. Orientation of epidemic as to time by determining the chronological dis­ tions. It was feared a general epi­ tribution of dates of onset, and demic migh t ensue and permeate the construction of an epidemic curve. other schools of the University. This would be a difficult procedure Therefore, in order to cover all pos­ in certain circumstances, but infor­ sibilities, 78 of the 118 Garrett fresh­ mation was readily at hand here men were vaccinated with Lederle's (Chart 1). influenza vaccine (FMJ, PR8, Cup­ 4. Orientation as to place. pett and Lee strains), beginning on The place was well localized; in this October 22, 1951. Only 5 second­ instance involving only the rooming ary cases were discovered, and none house of J. M. and that part of the after October 24. The Institute de­ Garrett Biblical Institute housing cided to diminish contacts by hold­ the first-year class. However, it was ing no classes (from Thursday until found that J. M. had just come from Tuesday) during the height of the an outlying community where epi­ outbreak, although this \\'as not demic pneumonitis existed. officially recommended. 5. Orientation of epidemic as to per­ 8. Determining what additional infor­ sons, age, sex, occupation. mation is necessary to test the hy­ All patients were young adults, pre­ pothesis. dominantly males, and all (with The hypothesis, in this case, was one exception) first-year students supported (as pre\'iously stated) by at Garrett. the pORitive cold-agglutinin tests with significant rises in titer \~hi ch 6. Tentative hypothesis on basis of pre­ were obtained from 8 of 10 patIents liminary analysis. tested. a. This resulted in the explanation already given above. 9. Conduct a detailed case analysis. This was done first in the instances b. Mode of transmission was deter­ of J. M. and B. B. and subsequently mined to be a single exposure for the remainder of the individuals from person to person, probably involved. The data, hO\\'ever, are so by droplet nuclei. detailed as to prevent their publi­ 7. Search fo r additional cases which mny cation here. not have been recognized or reported. 10. Try to identify Ihe group splected for The entire enrollment of the Garrett the attack and determine th e common Biblical Institute was alerted and source of exposure. cooperated wel! in voluntarily re­ porting any upper respirat,ol'Y infec- This \\'as done, as is indicated above. 334 QUARTERLY BULLETIN, N.U.M.S.

CONCLUSIONS ently Transmissable to Rats, Science, 96:518- 519, 1942. 8. Commission on Acute Respiratory Diseases Our study of an epidemic of acute re­ l Epidemiology of Atypical Pneumonia and spiratory disease "'hich occulTed at the Acute Respiratory Disease at Fort Bragg, Garrett Biblical Institute of North\\'est­ North Carolina, Am. J . Pub. Health, 34:335- ern Uni\'ersity, Evanston, Illinois, during 346, 1946. October, 1951 , \\'as one of acute primary 9. Peterson, V. L., Horn, T . H. and Finland, M.: Development of Cold Agglutinins in Primary atypical pneumonia because: Atypical Pneumonia, Science, 97:167, 1943. 10. Finland, M. and Barnes, M . W.: Cold 1. The symptomatology \\'as typical. Agglut inins. VII. Tests for Cold Isohemo­ agglutinins in Pneumonia and Other Acute 2. Typical x-ray e\'idence was obtained Respiratory Infectious Cases over a FolU"­ Year Period, Am ..J. M . Sc., 221 :152-157, 195 1. in 14 cases. 11. Rivers, T. M.: Viral and Rickettsial Infec­ tions of Man, Philadelphia, J . B. Lippincott, 3. Positi\'e cold-agglutinin tests were p. 288, 1948. obtained in 8 of 10 cases tested. 12. Thomas, L., Mirick, G. S., Curnen, B. C., Ziegler, J. E ., Jr. and Horsfall , F. L., Jr.: 4. N egatiye vil"Us complement-fixation Studies on Primary Atypical Pneumonia. II. Observat.ions Concernin g t he Relationship of studies corroborated these findings. a ?\ on-hemolytic Streptococcus to the Dis­ ease, .I. Clin. Investigation, 24:227-240, 1945. 5. The epidemiological survey sup­ 13. R ivers, T. M.: Viral and Rickettsial I nfec­ ported this evidence as: a, there \\'as tions of Man, Philadelphia, J. B. Lippincott, a single source of exposure; b, an p. 292, 1948. 14. Schoenback, E. B. and Bryer, M. S.: Treat­ apparent single exposure occurred in ment of Primary Atypical Pneumon ia wi t h most ca es; c, the malady was trans­ Au reomycin, J.A.M.A., 139:275-280, 1949. mitted from person to person; el, oral 15. Department of Bacteriology, Nort hwestern and nasal discharges \\" ere involved; University Medical School, Manual of Diag­ nostic Methods, 1951. e, the incubation period \\"as estab­ 16. Schmidt, N., Harding, H. B., Hepler, O. E. lished at 12 to 15 days. and Mllrmann, E. M.: Inhibition of Com­ plement Fixation by Certain Human Sera When Tested against Psittacosis and Lym­ phogranuloma Venereum Antigens, J. Infect. REFERENCE. Dis., Fall , 1952. 17. Harding, H . B., Hepler, O. E., Schmidt, N. I. Arrasmith, T. M., Jr.: Influenzal Pneumonia and Murmann, E.: A Summary of Two Years' - A Clinical Report, \\' ith Special Reference Experi ence with Virus Complement Fixation to Diagno is, C. S. Xav. M. Bull., 28:769- Tests in Relation to Hospital and Clinic 783, 1930. Patients, Unpublished Data. 2. Bowen, A.: Acute Influenzal Pneumonitis, 18. Clough, M. C. and Richter, 1. M.: A Study Am. J . Roentgenol., 34 :1 68-174, 1935. of an Autoagglutination Occ urring in Human 3. Allen, M. H . : Acute Pneumonitis, Ann. Int. Serum, Bull. Johns Hopkins H osp., 29 :86- Med., 10:441-446, 1936-37. 93, 1918. 4. Stokes, J ., Jr., Kenny, A. S. ancl Shaw, B. R.: 19. Peterson, O. L., Ham, T . H. and Finland, M .: New Filterable Agent Associated with Respir­ Cold Agglutinins (A utohemagglutinins) in atory Infections, Tr. & Stud., ColI. Physi­ Primary Atypical Pneumoni as, Science, 97: cians, Philadelphia, 6:329-333, 1939. 167, 1943. 5. Weir, J . M. and Horsfall, F. L., Jr.: The 20. Fell er, A. E .: Primary Atypical Pneumonja, Recovery From Patients with Acute Pneu­ Section in Diagnostic Procedures for Virus monitis of a Virus Causing Pneumonia in the and Rickettsial Diseases, A. P.H.A., pp. 125- Mongoose, J. Expel'. Med., 72:595-610, 1940. 138, 1948. 6. Bla ke, F. A., Howard, M . E. and Tatlock, H.: 21. Troen, P.: Explosive Outbreak of an Atypical Feline Vil'lls Pneumonia and its Possible Re­ Pneumonia ("K-8 Fever"), Arch. Int. Med., lation to Some Cases of Primary Atypical 87 :258-269, 1952. Pneumonia in Man, Yale J . BioI. & Med., 22. Densen, P. M.: Epidemiology, Section in 15: 139-166, 1942. Rosenau's Preventive Medicine and Hygiene, 7. Eaton, M. D., Meiklejohn, G., Von Herick, Edited by Kenneth F. Maxcy, New York, W. a nd Talbot, J . C.: An Infectiou Agent Appleton-Century-Crofts, Inc., pp. 1289- from Cases of Atypical Pneumonia Appar- 1307, 1951.