LABORATORY-ACQUIRED INFECTIONS

S. EDWARD SULKINIDepartment of Microbiology, The University of Texas Southwestern Medical School, Dallas, Texas

Although numerous individual case reports anda few instances of institutional outbreaks oflaboratory-acquired infections had appeared inthe literature, the magnitude of this problem as itrelates to the occupational health of laboratoryworkers did not become evident until the resultsof an extensive survey conducted in 1950 becameavailable. Prior to that time only an occasionalreport concerned itself with consideration of theneed for adequately protecting personnel whocome in daily contact with disease-producingagents. By means of a questionnaire circularizedto several laboratories in the United States,Meyer and Eddie (26) in 1941 assembled perti-nent information regarding laboratory infectionsdue to brucellae. From published reports andpersonal communications, Sulkin and Pike (34)in 1949 collected data regarding the occurrence ofviral infections contracted in laboratories in theUnited States and elsewhere in the hope thatsuch information would indicate where the great-est need for caution exists in work with viruses.To obtain more information regarding the oc-currence of laboratory infections, the NationalInstitutes of Health sponsored a survey whichwas conducted about 10 years ago. Questionnairesmailed to nearly 5,000 laboratories in the UnitedStates revealed over 1,300 instances of presumedlaboratory-acquired infection, with 39 deaths(35). Since that time an effort has been made tomaintain a file of laboratory-acquired infectionsas they are reported in the literature and as theyare called to our attention. A section on this sub-ject in Diagnostic Procedures and Reagents, pub-lished by the American Public Health Associa-tion, contains a summary of 2,262 cases with 96deaths (36). Since that manuscript was prepared,86 additional cases (with 11 deaths) have come toour attention bringing the total to 2,348 cases,with 107 fatalities.

1 Chairman, Committee on Laboratory Infec-tions and Accidents, American Public HealthAssociation. To further the work of this Com-mittee, investigators are urged to report instancesof laboratory infections and accidents to theauthor of this article.

Since many laboratories do not keep records ofinstances of laboratory infection, much informa-tion was given from memory and some fromhearsay only. Furthermore, some commerciallaboratories were unable to provide informationbecause of a company policy not to release suchdata, although a few freely provided the informa-tion requested. Also there is little doubt thatnumerous laboratory-acquired infections of amild nature have escaped diagnosis entirely.These facts indicate that the number of caseswhich have come to our attention represents per-haps only a modest fraction of those which haveactually occurred. Moreover, an analysis of thedata which have become available unfortunatelydoes not provide information concerning thenumber of organisms required to produce recog-nizable illness under a variety of circumstances.A great variety of disease-producing agents is

involved representing bacteria, viruses, fungi,rickettsiae, and protozoa. The highest proportionof deaths occurred among those persons infectedwith viruses with a case fatality rate of 7.3% ascompared with 4.0% for bacterial, 2.6% forrickettsial, and 2.3% for fungal infections. Nofatalities occurred among the cases of parasiticinfections.The diseases most frequently encountered were

brucellosis, tuberculosis, and hepatitis, which to-gether accounted for about one-third of all in-fections. There are many agents with which rela-tively few persons have laboratory contact, yetthe number of infections caused by them has beenlarge. For example, tularemia, psittacosis, typhus,Q fever, and coccidioidomycosis occur as insti-tutional outbreaks or as scattered cases in labora-tories where the organisms producing thesediseases are studied intensively.

Laboratory infections are not confined to thepersonnel most closely associated with the in-fectious agents. Although professional and tech-nical workers, research assistants, and graduatestudents experience about three-fourths of theillnesses, office workers, janitors, and dishwashersbecame infected as a result of activities in thelaboratories with which they were associated.

203

on July 6, 2020 by guesthttp://m

mbr.asm

.org/D

ownloaded from

S. EDWARD SULKIN

In an attempt to analyze the data which havebecome available to us, the cases have beenclassified according to the proved or probablesource of the infection. If one removes the knownaccidents which are preventable in the sense thatmost accidents can be prevented, it becomes clearthat a major proportion of the remaining infec-tions result from aerogenic transmission of theagent. An effort will be made to limit the remain-ing portion of this discussion to those areas whichrelate to the subject of this Conference.The exact source of a laboratory-acquired in-

fection is frequently obscure. Often it is knownonly that an individual had been working with aparticular agent or that he had been in contactwith infected animals or ectoparasites. In othersituations it is known that the atmosphere of alaboratory had become contaminated with patho-genic organisms. This potential source of infectionhas been more fully appreciated since workers atFort Detrick (29, 41) have designed atmosphericsampling devices which show that such commonand simple procedures as removing stoppers,pipetting fluids, and flaming inoculating needlesmay produce aerosols near the laboratory bench.This subject will be discussed more fully byWedum (42).

In analyzing the data which have become avail-able to us, a category labeled "aerogenic trans-mission" was reserved for those cases in whichthis source appeared to be most likely, eventhough the actual mode of transmission in manyof those infections which were listed as havingresulted from "work with the agent" may wellhave been aerogenic. In some instances the evi-dence for aerogenic transmission was fairly welldocumented. For example, a fatal case of typhoidfever resulted from opening a lyophilized culture,and two cases of typhus and one of rickettsialpoxapparently resulted from the use of the WaringBlendor. In many more instances aerogenictransmission was listed as the probable source ofa laboratory-acquired infection although thiscould not always be clearly established. It maybe assumed that most laboratory infections whichdo not result from poor technique or accidentsare generally connected with inhalation of in-fectious material. Contamination of the air mayarise from many sources. One of these is theXWaring Blendor, which has come into wide usefor the emulsification of infected tissues. Althoughrelatively few laboratory infections are directly

attributable to use of the W1'aring Blendor, specialprecautions are indicated.

Tuberculosis, which ranks second among thebacterial diseases, has been a matter of specialconcern because of the large numbers of personswho handle tuberculous materials in clinical,research, and teaching institutions and becauseof the severity and prolonged course of the dis-ease. Since the onset is insidious and since thereare numerous opportunities to acquire the dis-ease outside the laboratory, it is usually impos-sible to trace the source to any given incidentthat might have resulted in infection. Conse-quently, in most instances, only circumstantialevidence points to the origin of infection in thelaboratory. The potential hazard of acquiringtuberculosis is considered to be so great thatseveral medical schools no longer permit classesto studv materials containing living tuberclebacilli.Long (21), reporting 10 years ago on the hazard

of acquiring tuberculosis in the laboratory,noted, "Probably the danger of infectious aero-sols from bacillary suspensions is now of greatermoment than ever, since culture media designedfor subsurface growth and maximum dispersionof bacilli favor the presence of organisms in ex-tremely minute droplets, of the size most likelyto penetrate to the deepest recesses of the lungsand set up pulmonary infection." This commentis just as pertinent today as it was 10 years ago.Other sources of laboratory-acquired tuberculosisare well recognized and include secretions frominfected animals, dust from dried contaminatedmaterials, and aerosols produced by overenergeticdischarge of suspensions of tubercle bacilli fromhypodermic needles and pipettes.

Evidence of aerogenic spread of tubercle bacilliin animal rooms was presented 30 years ago byLurie (22). Spontaneous tuberculosis occurredfrom time to time in presumably normal guineapigs housed in the same room with tuberculousanimals. Infection in these animals was usuallyby the way of the respiratory tract and the fre-quency increased with the duration and intensityof exposure. In studies reported later, Wells andLurie (43) showed that normal rabbits almostinvariably become infected if exposure is allowedto continue for several months. Animals wereexposed in specially designed chambers to air-borne infection from tuberculous rabbits. Theseobservations indicate the dangers to which lab-

204 [VO)L. 25

on July 6, 2020 by guesthttp://m

mbr.asm

.org/D

ownloaded from

LABORATORY-ACQUIRED INFECTIONS

oratory workers and animal caretakers may beexposed. Their studies further indicated thatproper use of ultraviolet light will sterilize theatmosphere. The foregoing facts, together withthe recent studies of Riley and his associatesdiscussed elsewhere in the proceedings of thisConference (30), indicate that emphasis uponmeasures to prevent contamination of the airwould certainly be effective in limiting the oc-currence of tuberculous infection among labo-ratory workers.

It has long been known that the physical prox-imity of normal animals to animals infected withcertain viruses is sufficient to cause infection inthe former. This pertains to a number of virusesand may not only present a hazard to those work-ing in the immediate area but also complicateinterpretation of laboratory data resulting fromthe use of such animals. Contact infections havebeen demonstrated among normal animals whichhave been in association with those infected withthe viruses of poliomyelitis (4, 15, 47), influenza(14, 32), distemper (6, 14), psittacosis (19), andlymphocytic choriomeningitis (37), to mention afew. White mice may harbor the virus of lympho-cytic choriomeningitis as an inapparent infection.Infected animals eliminate the agent throughnasal secretions, urine, and feces, and aerosolsmay carry the virus not only to normal animalsbut to workers and caretakers. Laboratory ani-mals may also serve as a large reservoir of lepto-spires which are shed in the urine. Leptospiraballum is commonly found among laboratorywhite mice (46) and natural infection with Lepto-spira icterohaemorrhagiae has occurred amongwhite rats and guinea pigs (23, 39). White ratsmay become inapparent carriers of leptospires asa result of inadequate "wild" rodent control inthe normal animal colony. In Europe Leptospiragrippotyphosa has been isolated from naturallyinfected hamsters (28) and in the United Statesa new strain of leptospires, belonging in the Lepto-spira hebdomadis subgroups and designatedLeptospira mini georgia, has been isolated fromnaturally infected raccoons, opossums, and astriped skunk (8). A laboratory infection with L.ballum was traced by Wolff, Bohlander, and Ruys(44) to the urine of laboratory white mice and re-cently Stoenner and MacLean (33) reported in-fection of eight laboratory employees who hadclose contact with Swiss albino mice which wereinfected with this organism. Through a labora-

tory accident it was demonstrated that the re-cently characterized leptospire, L. mino georgia,was infective for man (10). At least 16 laboratory-acquired infections with B virus have occurredsince this agent was first demonstrated in 1932; 10of these occurred in 1957 and 1958 probably as aresult of increased use of monkey tissues forcultivation in vitro of poliovirus and for safetytesting of vaccine. Although many of these in-fections resulted from monkey bites or handling ofthese animals, there is the suggestion that somepersons might have acquired their infectionthrough aerogenic means.

Precautions that may have to be taken to limitthe occurrence of laboratory infections are wellillustrated in the case of Q fever, which involvedmany laboratory workers in the first few years ofstudy of its causative agent. The relatively stableCoxiella burnetii is excreted in the urine of infectedlaboratory animals and the inhalation of driedcage litter may have accounted for one of theinstitutional epidemics of Q fever (16). In at leastone laboratory where this agent has been handledextensively, procedures likely to produce in-fectious aerosols are avoided. Infected animalsare housed in separate quarters. Triethylene gly-col aerosols are maintained in work rooms andanimal houses to help disinfect the atmosphere,and in addition all personnel are immunized withvaccine. The result has been the virtual elimina-tion of Q fever infections in this laboratory (25).The opening of sealed glass ampoules which

contain lyophilized active viral or rickettsial ma-terial constitutes a serious inhalation hazard inthe laboratory. Special techniques have beenrecommended for opening such ampoules. Thecircumstances leading to a case of psittacosis werecarefully reconstructed by Rosebury, Ellingson,and Meiklejohn (31) to show how a leaking am-poule containing a suspension of yolk-sac virushad contaminated the worker's hand and sur-rounding atmosphere.The cases of infection among laboratory per-

sonnel apparently resulting from the handling ofinfected chick embryos attest to the potentialcontagiousness of such material. Chick embryocultivated virus was thought to be the source ofinfection in two cases of Western equine enceph-alomyelitis (9, 12), in four cases of Venezuelanequine encephalomyelitis (18), and in a case ofEastern equine encephalomyelitis (27). Amongthe cases of psittacosis, of particular interest is a

19611 205

on July 6, 2020 by guesthttp://m

mbr.asm

.org/D

ownloaded from

S. EDWARD SULKIN

laboratory worker who had handled infectedbirds and mice for several years without infec-tion but who became ill with proved psittacosisafter working with a suspension of virus fromchick membranes (2). Five laboratory infectionswith the agent of lymphogranuloma venereumoccurred among persons working with infectedchick embryos (11). It was pointed out that onefactor that contributes to the danger in handlinginfected embryonic egg tissues may be the highconcentration of virus in such material (24).An analysis of the circumstances leading to

certain of the laboratory infections has providedimportant information regarding the transmissionof these diseases. For example, since contami-nated dust from mouse cages was apparentlyresponsible for several infections with the virus ofVenezuelan equine encephalomyelitis, it seemedlikely that infection was by the respiratory route(20). The possibility of direct transmission ofthe equine encephalomyelitis viruses suggestedby these observations is of interest since it indi-cates that under these circumstances the diseasemay be transmitted to man in the absence ofknown arthropod vectors. The same may besaid for a case of encephalitis which occurred ina person working with the St. Louis encephalitisvirus (40).

Those agents which are the chief offenders incausing infections among laboratory personnelare likely to show the greatest possibilities for usein biological warfare. The agents most ofteninvolved in laboratory-acquired infections are amatter of record and are generally recognizedto be hazardous. One thing that may be over-looked is the fact that laboratory infections donot always follow the pathways of transmissionestablished for the naturally occurring disease.For example, the typhoid bacillus has certainlybeen considered as a potential agent of biologicalwarfare. Those concerned with the means ofdefense in biological warfare would probablythink first of contaminated food and water sup-plies in connection with the transmission of ty-phoid fever. The survey, however, revealed atleast one case in which the infection was trans-mitted aerogenically when a worker opened atube containing lyophilized culture. Although theactual route of infection in this case was prob-ably by way of the gastrointestinal tract, theincident suggests that an effective degree ofatmospheric contamination might be produced

by means of such material. A number of labora-tory-acquired cases of brucellosis have occurredamong persons exposed only to atmospherecontaminated by brucella organisms. In tula-remia there are instances in which there is notonly circumstantial evidence for aerogenic trans-mission but also the pneumonic nature of theinfection points to this route. In neither bru-cellosis nor tularemia is aerogenic infectionthought to be important in the natural trans-mission of the disease.

Laboratory infections due to at least threeviruses have evidently been transmitted by unnat-ural means. Of 17 cases of encephalitis recorded,none was thought to have been transmittedby an arthropod. The means of transmissionwas largely unknown, but, since many of thesecases occurred in persons who worked with theagent, aerogenic transmission is a distinct pos-sibilitv. There have been 2 cases of enceph-alitis, however, in which there had been nodirect contact with the virus but only briefcontact with potentially contaminated atmos-phere. Of 14 cases of yellow fever, only 1 wasthought to be due to the bite of an infectedmosquito. Three individuals had been workingwith dried virus preparations which wouldprovide ideal circumstances for aerogenic trans-mission. It is of interest that laboratory-acquiredyellow fever was more common before introduc-tion of the lyophile process, when individualsworked with dried infectious tissues often inopen containers. Lymphogranuloma venereum,which occurs naturally as a venereal disease,has been responsible for five cases of respiratoryinfection in laboratory workers who had director indirect contact with contaminated materials.About one-seventh of all laboratory infections

which have come to our attention have beencaused by rickettsial agents. Of all of the rickett-sial diseases, Q fever is the only one naturallytransmitted in the absence of an arthropodvector. Of course, the fact that an agent islikely to cause infections in the laboratory doesnot mean that it fulfills all of the qualificationswhich have been established for the ideal biologi-cal warfare agent. Most laboratory infectionsrepresent specialized situations and are usuallydue to exposure to fairly fresh material.

All of the above-mentioned agents could beprepared in almost unlimited quantities, butthere might be difficulty in maintaining the

206 [VOL. 25

on July 6, 2020 by guesthttp://m

mbr.asm

.org/D

ownloaded from

LABORATORY-ACQUIRED INFECTIONS

virulence of such an agent as the virus of yellowfever under conditions of laboratory propagation.On the other hand, it is well known that typhusrickettsiae will survive in dried louse feces forconsiderable periods of time and the same mightbe true for preparations of yolk-sac material.These and other examples should be of interestto those concerned with protection against bio-logical warfare because they suggest that evenin the absence of some of the links in the usualchain of transmission a given agent might be apotential danger if properly dispersed in theenvironment.

In several instances a disease was first recog-nized in man as a result of infection amonglaboratory personnel. The first human infectionwith the virus of Aujeszky's disease (pseudo-rabies) occurred in a laboratory worker (38).Six cases of laboratory-acquired infection withlouping-ill virus were the only known humancases until two naturally acquired cases werereported in 1948 (5), and the first infections withthe Newcastle disease virus among human beingswere laboratory infections involving the eyes(1, 3). The first known human case of Q feverin the United States was a scientist visiting alaboratory where studies with the causativeagent, Coxiella burnetii, were in progress (7).More than 60 cases of Q fever due to laboratory-propagated strains of this microorganism hadoccurred in the United States before the diseasewas found to occur naturally among packinghouse workers. Soon after Rickettsia akari, thecause of rickettsialpox, was isolated in New YorkCity in 1946, four cases of rickettsialpox occurredamong laboratory workers. Also shortly after thediscovery of the Coxsackie viruses in 1948, whentheir relationship to human disease was notcompletely understood, several workers acquiredlaboratory infections which presented the clinicalfeatures later to be ascribed to this group ofviruses. A laboratory infection with adenovirustype 8 with resulting typical clinical epidemickeratoconjunctivitis firmly established the etio-logical relationship of this virus to this clinicalsyndrome (17). A laboratory infection withECHO virus (type 9), with resulting asepticmeningitis, occurred after the virus had beenthrough several extra-human passages in monkeykidney tissue cultures (13). Like other membersof the Russian spring-summer complex of viruses,the recently described Kayasanur Forest disease

virus has proved to be highly infectious tolaboratory workers (45). Clinically apparentinfections have occurred in several laboratoryworkers in India, New York, and Washington.There have been no fatalities. Of special interestis the fact that the benign course of the infec-tion in persons with prior antigenic experiencewith group B arborviruses (visceral manifesta-tions rather than central nervous system involve-ment) suggested that this new member of theRussian spring-summer complex may be one ofthe safer of these viruses to handle in the labora-tory even though the infection rate has been high.

Although the significance of the recently iso-lated bat salivary gland virus in human infectionremains to be determined, there is evidence thatit may be pathogenic for man, producing systemicillness with complicating orchitis or ovaritis. Atleast five laboratory-acquired infections have oc-curred since this virus, related to the St. Louisencephalitis complex of viruses, was isolated in1956. In these and many of the other instances oflaboratory infections cited, it is possible thatthe infection was acquired by aerogenic means.

ACKNOWLEDGMENTS

I wish to express my appreciation to my col-leagues, Robert M. Pike and Mary LouiseSchulze, without whose co-operation materialcontained in this report could not have beenassembled.

This work was aided by a grant from the U. S.Public Health Service.

LiTERATURE CITED1. ANDERSON, S. G. 1946. Note on two laboratory

infections with virus of Newcastle disease offowls. Med. J. Australia 1:371.

2. Anonymous. 1936. Psittacosis and tularemia:report of cases-infection of two laboratoryworkers in California; recovery. Calif. andWestern Med. 44:79-80.

3. BURNET, F. M. 1943. Human infection withvirus of Newcastle disease of fowls. Med. J.Australia 2:313-314.

4. CRAIG, D. E., AND T. FRANCIS, JR. 1958.Contact transmission of poliomyelitis virusamong monkeys. Proc. Soc. Exptl. Biol.Med. 99:325-329.

5. DAVIDSON, G., C. NEUBAUER, AND E. W.HURST. 1948. Meningo-encephalitis in mandue to louping-ill virus. Lancet 2:453-457.

6. DUNKIN, G. W., AND P. P. LAIDLAW. 1926.

20719611

on July 6, 2020 by guesthttp://m

mbr.asm

.org/D

ownloaded from

S. EDWARD SULKIN

Studies in dog-distemper. I. Dog-distemperin the ferret. J. Comp. Pathol. Therap. 39:201-212.

7. DYER, R. E. 1938. Filter-passing infectiousagent isolated from ticks: human infection.Public Health Repts. (U. S.) 53:2277-2282.

8. GALTON, M. M., G. W. GORMAN, AND E. B.SHOTTS, JR. 1960. A new leptospiral sub-serotype in the Hebdomadis group. PublicHealth Repts. (U. S.) 75:917-921.

9. GOLD, H., AND B. HAMPIL. 1942. Equine en-

cephalomyelitis in laboratory technicianwith recovery. Ann. Internal Med. 16:556-569.

10. GOLEY, A. F., A. D. ALEXANDER, J. F. THIEL,AND V. E. CHAPPELL. 1960. A case of humaninfection with Leptospira mini Georgia.Public Health Repts. (U. S.) 75:922-924.

11. HARROP, G. A., G. RAKE, AND M. F. SHAFFER.1941. Group of laboratory infections ascribedto lymphogranuloma venereum. Trans. Am.Clin. Climatol. Assoc. 56:154-159.

12. HELWIG, F. C. 1940. Western equine encepha-lomyelitis following accidental inoculationwith chick embryo virus: report of fatalhuman case with necropsy. J. A. M. A. 115:291-292.

13. HENNESSEN, W. 1957. Study of virus of epi-demic meningitis, ECHO 9. Z. Hyg. In-fektionskrankh. 144:125-147.

14. HORSFALL, F. L., JR., AND J. H. BAUER. 1940.Individual isolation of infected animals ina single room. J. Bacteriol. 40:569-580.

15. HOWE, H. A., AND D. BODIAN. 1944. Polio-myelitis by accidental contagion in thechimpanzee. J. Exptl. Med. 80:383-390.

16. HUEBNER, R. J. 1947. Report of an outbreakof Q fever at the National Institutes ofHealth. II. Epidemiological features. Am. J.Public Health 37:431-440.

17. JAWETZ, E., L. HANNA, M. SONNE, AND P.THYGESON. 1959. A laboratory infection withadenovirus type 8. Am. J. Hyg. 69:13-20.

18. KOPROWSKI, H. AND H. Cox. 1947. Humanlaboratory infection with Venezuelan equineencephalomyelitis virus: report of fourcases. New Engl. J. Med. 236:647-654.

19. LAZARUS, A. S., AND K. F. MEYER. 1939. Thevirus of psittacosis. I. Propagation anddevelopmental cycle in the egg membrane,purification and concentration. J. Bacte-riol. 38:121-151.

20. LENNETTE, E. H., AND H. KOPROWSKI. 1943.Human infection with Venezuelan equineencephalomyelitis virus: report of eightcases of infection acquired in laboratory.J. A. M. A. 123:1088-1095.

21. LONG, E. R. 1951. The hazard of acquiringtuberculosis in the laboratory. Am. J. Pub-lic Health 41:782-787.

22. LURIE, M. B. 1930. Air-borne contagion oftuberculosis in an animal room. J. Exptl.Med. 51:743-751.

23. MASON, N. 1937. Leptospiral jaundice occur-

ring naturally in a guinea-pig. Lancet 1:564-565.

24. MCKEE, C. M., G. RAKE, AND M. F. SHAFFER.1940. Complement fixation test in lympho-granuloma venereum. Proc. Soc. Exptl.Biol. Med. 44:410-413.

25. MEIKLEJOHN, G., AND E. H. LENNETTE. 1950.Q fever in California: observations on vac-

cination of human beings. Am. J. Hyg.52:54-64.

26. MEYER, K. F., AND B. EDDIE. 1941. Laboratoryinfections due to Brucella. J. InfectiousDiseases 63:23-32.

27. OLITSKY, P. K., AND I. M. MORGAN. 1939.Protective antibodies against equine en-

cephalomyelitis virus in serum of laboratoryworkers. Proc. Soc. Exptl. Biol. Med. 41:212-215.

28. POPOVA, E. MI., AND N. I. AMOSENKOVA. 1957.Reservoirs of leptospiral infection in thenorthwest regions of the U. S. S. R.: resultsof an investigation on leptospiral infectionsof murine rodents. J. Microbiol. Epidemiol.Immunobiol. 28:44-49.

29. REITMAN, M., AND A. G. WEDUM. 1956. Micro-biological safety. Public Health Repts.(U. S.) 71:659-665.

30. RILEY, R. L. 1961. Airborne pulmonary tuber-culosis. Bacteriol. Rev. 25:243-248.

31. ROSEBURY, T., H. V. ELLINGSON, AND G.MEIKLEJOHN. 1947. Laboratory infectionwith psittacosis virus treated with penicillinand sulfadiazine, and experimental databearing on mode of infection. J. InfectiousDiseases 80:64-77.

32. SMITH, W., C. H. ANDREWES, AND P. P. LAID-LAW. 1933. A virus obtained from influenzapatients. Lancet 2:66-68.

33. STOENNER, H. G., AND D. MACLEAN. 1958.Leptospirosis ballmin contracted from Swissalbino mice. A. MI. A. Arch. Internal Med.191:606-610.

34. SULKIN, S. E., AND R. MI. PIKE. 1949. Viralinfections contracted in the laboratory. NewEngl. J. Mled. 241:205-213.

35. SULKIN, S. E., AND R. M. PIKE. 1951. Surveyof laboratory-acquired infections. Am. J.Public Health 41:769-781.

36. SULKIN, S. E., R. Ml. PIKE, E. R. LONG, C. E.SMITH, M. MI. SIGEL, AND A. G. WEDUM. 1961.

208 [VOL. 25

on July 6, 2020 by guesthttp://m

mbr.asm

.org/D

ownloaded from

LABORATORY-ACQUIRED INFECTIONS

Laboratory infections and accidents. InDiagnostic procedures and reagents. 4thed. Am. Public Health Assoc., New York.

37. TRAUB, E. 1936. The epidemiology of lympho-cytic choriomeningitis in white mice. J.Exptl. Med. 64:183-200.

38. TUNgMAN, Z. M. 1938. La maladie d'Aujeszkyobserv6e chez l'homme. Ann. inst. Pasteur60:95-98.

39. VAN THIEL, P. H. 1948. The leptospiroses.Univ. Pers. Leiden, Leiden. 231 p.

40. VON MAGNUS, H. 1950. Laboratory infectionwith St. Louis encephalitis virus. ActaPathol. Microbiol. Scand. 27:276-282.

41. WEDUM, A. G. 1953. Bacteriological safety.Am. J. Public Health 43:1428-1437.

42. WEDUM, A. G. 1961. Control of laboratory air-borne infection. Bacteriol. Rev. 25:210-216.

43. WELLS, W. F., AND M. B. LURIE. 1941. Experi-

mental air-borne disease: quantitative na-

tural respiratory contagion of tuberculosis.Am. J. Hyg. 34:21-40.

44. WOLFF, J. W., H. BOHLANDER, AND A. C. Ruys.1949. Researches on leptospirosis ballum:the detection of urinary carriers in labora-tory mice. Anthonie van Leeuwenhoek. J.Microbiol. Serol. 15:1-13.

45. WORK, T. H. 1958. Russian spring-summervirus in India. Progr. Med. Virol. 1:248-277.

46. YAGER, R. H., W. S. GOCHENOUR, JR., A. D.ALEXANDER, AND P. W. WETMORE. 1953.Occurrence of Leptospira ballum in ruralhouse mice and in an opposum. Proc. Soc.Exptl. Biol. Med. 84:589-590.

47. ZARAFONETIS, C., S. E. SULKIN, AND C. H.TERRY. 1947. Poliomyelitis (Lansing) con-

tact infection in mice. J. Bacteriol. 53:367.

19611 209

on July 6, 2020 by guesthttp://m

mbr.asm

.org/D

ownloaded from