SECTION I Introduction Microbiological laboratories are special often unique wor environments that may pose identifiable infectious disease risks to persons in or nea -associated ca ei,oeyehad:hoa2glener,bnucetostsand the United States.and concluded that the "han dling of cultures or number of cases v were att buted to carelessness or poor tech- nique in the handling of infectious materia In 1949,Sulkin and Pike published the firstin a series of veys of borato cated nfections. ey summ the cases.the probable tion was considered to be associated with the handling of infected Bruc ou umbered all othe 「e tularemia,typhoid,and streptoco cal infection ccounted for 2y% of all ntectons anc for 31 of inte a6eL8fneg地mghegereelaiedomouihppetng and syringe This survey was updated in 1965.5.adding 641 new or previ- ously is ty nia
1 SECTION I Introduction Microbiological laboratories are special, often unique work environments that may pose identifiable infectious disease risks to person s in or near them . Infec tions have been contracte d in the laboratory throughout the history of microbiology. Published repo rts ar ound the turn o f the c entu ry des cribe d labo rator y- -associated cases of typhoid, cholera, glanders, brucellosis, and tetanus.1, In 194 1, Me yer an d Eddie2, published a survey of 74 labor atory- associated bruce llosis infec tions that h ad oc curred in the United States, and concluded that the "handling of cultures or specimens or the inhalation of dust containing Bruc ella organis ms is emine ntly danger ous to lab oratory wo rkers." A number of cases were attributed to carelessness or poor technique in the handling of infectious materials. In 1949, Sulkin and Pike3, published the first in a series of surveys of laboratory-associated infections. They summarized 222 viral infections, 21 of which were fatal. In at least a third of the cases, the probable source of infection was considered to be assoc iated with the handling o f infected anima ls and tissu es. Known accidents were recorded in 27 (12%) of the reported cases. In 1951, Sulkin and Pike4, published the second of the series, based on a que stion naire sent to 5,0 00 lab orato ries. O nly one-third of the 1,342 cases cited had been reported in the literature. Brucellosis outnumbered all other reported laboratory-acquired infections and, together with tuberculosis, tularemia, typhoid, and streptococcal infection, accounted for 72% of all bacterial infections and for 31% of infections caused by all agents. The overall case fatality rate was 3%. Only 16% of all infections reported were associated with a documented accident. The majority of these were related to mouth pipetting and the use of needle and syringe. This survey was updated in 1965, 5, addin g 641 new or pre viously unreported cases, and again in 1976,6, summarizing a cumulative total of 3,921 cases. Brucellosis, typhoid, tularemia
Introduction firmed source of infection for the more than 80%of the reported cases in which the infected person had"worked with the agent." In 1967.Hanson etal'.reported 428 overt laboratory-associ ated infections with arb oviruses.In some instances,the ablity of di ease t Exposure to was considered the most common source of infection. In 1974.Skinholj published the results of a survey which showed that in Danish population.Similarly.a1976 survey by Harrington and hannon general populaton.Hepatitis and s higelosis were also showr al ris tion-associated infections in Britain. Although thes that bh handle,actual rate es of intection are typ ally not avai ab eu6i6ne,sngeiosa.anghopatisBhenoosnesnsa In contrast to the documented occurrenc e of laboratory- ea ratory personne ora to the community For example,although 109 labora on tro m1947-197. ondary
Introduction 2 tuberculosis, hepatitis, and Venezuelan equine encephalitis were the m ost c om mo nly rep orted infec tions . Few er tha n 20% of all cases were as sociated with a kno wn acc ident. Exp osure to infectious aerosols was considered to be a plausible but unconfirmed source of infection for the more than 80% of the reported cases in which the infected p erson h ad "work ed with the agent." In 1967, Hanson et al7, repo rted 4 28 ov ert lab orato ry-as soc iated infections with arboviruses. In some instances, the ability of a given arbovirus to produce human disease was first confirmed as the re sult of uninte ntional infec tion of labor atory pers onnel. Exposure to infectious aerosols was considered the most common source of infection. In 1974, Skinh olj8, published the results of a survey which showed that personnel in Danish clinical chemistry laboratories had a reported incidence of hepatitis (2.3 cases per year per 1,000 employees) seven times higher than that of the general population. Similarly, a 1976 survey by Harrington and Shannon9, indicated that medical laboratory workers in England had "a five times increased risk of acquiring tuberculosis compared with the general population." Hepatitis B and shigellosis were also shown to be continuing occupational risks. Along with tuberculosis, these were the three most commonly reported occupation-associated infections in Britain. Although these reports suggest that laboratory personnel were at increased risk of being infected by the agents they handle, a ctual rates of infection are typically not av ailable. However, the studies of Harrington and Shannon9 and of Skinhoj10, indicate that laboratory personnel had higher rates of tuberculosis, shigellosis, and hepatitis B than does the general population. In contrast to the documen ted occurrence of laboratory- acquired infections in laboratory personnel, laboratories working with infectious agents have not been shown to represent a threat to the community. For example, although 109 laboratory-associated infections were recorded at the Centers for Disease Control and Prevention from 1947-1973,11, no secondary
Introduction ience, with no secondary cases occurring in laboratory and non-lat laboratory-ass 76 dise wife of a pmary case was presumed to have been months after hs dismissal from the d in 1978. Th regreearerreportsfsikcasesofQfee or among ns from with the ac se of afever ir ina visitor to a laboraory. andwo cases of fever in animal ca er to hi hasbeenreperted,apparentydueocontactothenmuswh hese cases are re ve o ne spor personnel working with infectious agents. In his 1979 review,20.Pike concluded that"the kn techniques,and the tions are availab le the United States,ho no single ment.and oer eideratonsotecommendationsorheg d scope of The booklet.Clas sifica Agents on the Basis of Ha zard, served as a general reference ry ac nd th infec ag ents nd laboratory activities into four classes or levels.served as a basic format for earlie 0io6 continues to specifcally describe combinaions of microbiological practice s,laboratory facilities,and safety equipn nent and to ation with ectious i humans 3
Introduction 3 cases were rep orted in fam ily mem bers or c omm unity contac ts. The National Anim al Disease Center reported a sim ilar experience,12, with no secondary cases occurring in laboratory and non-laboratory contacts of 18 laboratory-associated cases occurring from 196 0-1975. A seconda ry case of Marburg disease in the wife of a primary case was presumed to have been transmitted sexually two months after his dismissal from the hospital. 13, Three se condary c ases of s ma llpox w ere re porte d in two laboratory associated outbreaks in England in 197314, and 1978.15, There were earlier reports of six cases of Q fever among personnel of a commercial laundry that cleaned linens and uniform s from a laborato ry working with the ag ent,16, one case of Q fe ver in a visito r to a la bora tory,17, and two cases of Q fever in house hold con tacts of a rickettsiolo gist.18, One case of M onk ey B virus transmission from an infected animal care giver to his wife has be en repo rted, app arently due to contac t of the virus with broken skin.19, The se cases are repre sentative of the spor adic nature and infrequency of com munity infections in laboratory personnel working with infectious agents. In his 1979 review,20, Pike concluded that "the knowledge, the techniques, and the equipment to prevent most laboratory infections are a vailab le." In th e Un ited States , however, no s ingle code of practice, standards, guidelines, or other publication provided detailed descriptions of techniques, equipment, and other considerations or recommendations for the broad scope of laboratory activities conducted with a variety of indigenous and exotic infe ctious ag ents. Th e book let, Clas sifica tion of Etiolo gic Agents on the Basis of Ha zard, 21, served as a general reference for som e labo rator y activities utilizing inf ectio us ag ents . This booklet, and the concept of categorizing infectious agents and labor atory a ctivities into four class es or levels , serv ed as a bas ic format for earlier editions of Biosafety in Microbiological and Biomedical Laboratories (BMBL). This fourth edition of the BMBL continues to specifically describe combinations of microbiological practice s, laborato ry facilities, and s afety equip men t, and to recommend their use in four categories or biosafety levels of laboratory operation with selected agents infectious to humans
Introduction and are consistent with the general criteria originally used in as- activities utilgzing small laboratory Re a98ohRelaD098yguai8no6raena6e dof the agent Since the eary 1980s.laboratories have applied these funda mental quidelnes in activities associated with maninulations the human imm unodeficiency virus(HIV).Even before lating a bloodborne pathogen were suita e for safe laboratory Precautions and this pubication have become the basis for the 8esAapn986loodongegh0geaseceantheecen In the late 1980s onsi Medical Waste Tracking Act of 1988 The principes estab. arlier volum es of ne B BL tC and lin g pote the National Research Council's Biosafety n the Laboraory ib8asacteosiorheHanaingand0sposa16linioceiols the re-emergence pncipeswhehsoeko6nsuresaepacc8s.PtocereSgand thisarborne pathogen. recombinant DNA technologies are being applied routinely in he laboratory to modify the genetic microorganisms.At
Introduction 4 The descriptions of Biosafety Levels 1-4 parallel those in the NIH Guidelines for Research Involving Recombinant DNA, 22,23, and are consistent with the general criteria originally used in assigning agents to Classes 1-4 in Classifica tion of Etiologic Agents on the Basis of Hazard. 24, Four biosafety levels are also described for infectious disease activities utilizing small laboratory anim als. R ecomm endations for biosa fety lev els fo r spe cific agents are made on the basis of the potential hazard of the agent and of th e laborato ry’s function or activity. Since the early 1980s, laboratories have applied these fundamental guidelines in activities associated with manipulations involving the human imm unodeficiency virus (HIV). Even before HIV was identified as the causative agent of Acquired Immunodeficiency Syndrome (AIDS), the principles for manipulating a bloodborne pathogen were suitable for safe laboratory work. Guidelines were also prom ulgated for health care workers under the rubric of Universal Precautions.25, Indeed, Universal Precautions and this publication have become the basis for the safe handling of blood and body fluids, as described in the recent OSH A publica tion, Bloodborne Pathogen Standard. 26, In the late 1980s, considerable public concern was expressed about medical wastes, which led to the promulgation of the Medical Waste Tracking Act of 1988. 27, The principles established in the e arlier volum es of the B MBL for hand ling po tentia lly infectious wastes as an occupational hazard were reinforced by the National Research Council's Biosafety in the Laboratory: Prudent Practices for the Handling and Disposal of Infectious Materials.28, As this edition goes to press, there is growing concern about the re-emergenc e of M. tub ercu losis and w orke r safety in laboratory and health care settings. The BMBL’s underlying principles, which seek to ensure safe practices, procedures and facilities, are applicable to the control of this airborne pathogen, including its multi-drug-resistant strains.29,30, In addition, recombinant DNA technologies are being applied routinely in the laboratory to modify the genetic composition of various microorganisms. A thorough risk assessment must be
Introduction dwhen addressing these activities and their inherent manipulations of etiologic agents in laboratory settings and animal fac Although r nat repor nd xists o indivdual and can pe used in conunction with othe available scientific information. References: 1 Wedum.A.G.History of MicrobiologicalS eey,1975.18h ike RM Viral Infections Contracted inthe g ey of laborabry-acquired Continui Pike. .mdocea. Lab Sc13:105-114 1967.Arbovirus ntectionsof ers.Science 158:12 8. aboratories.I brucon.H. 8met3828mea isnBritish medical 1979
Introduction 5 1. Wedum, A.G. History of Microbiological Safety. 1975. 18th Biological Safety Conference. Lexington, Kentucky. 2. Meyer, K.F., Eddie, B. 1941. Laboratory infections due to Brucella. J Infect Dis 68:24-32. 3. Sulkin, S.E., Pike, R.M. 1949. Viral Infections Contracted in the Laboratory. New Engl J Med 241(5):205-213. 4. Sulkin, S.E., Pike, R.M. 1951. Survey of laboratory-acquired infections. Am J Public Health 41(7):769-781. 5. Pike, R.M., Sulkin, S.E., Schulze, M.L. 1965. Continuing importance of laboratory-acquired infections. Am J Public Health 55:190-199. 6. Pike, R.M. 1976. Laboratory-associated infections: Summary and analysis of 3,921 cases. Hlth Lab Sci 13:105-114. 7. Hanson, R.P., Sulkin, S.E., Buescher, E.L., et al. 1967. Arbovirus infections of laboratory workers. Science 158:1283-1286. 8. Skinholj, P. 1974. Occupational risks in Danish clinical chemical laboratories. II Infections. Scand J Clin Lab Invest 33:27-29. 9. Harrington, J.M., and Shannon, H.S. 1976. Incidence of tuberculosis, hepatitis, brucellosis and shigellosis in British medical laboratory workers. Br Med J 1:759-762. 10. Skinholj, P. 1974. (8) 11. Richardson, J.H. 1973. Provisional summary of 109 laboratoryassociated infections at the Centers for Disease Control, 1947- 1973. Presented at the 16th Annual Biosafety Conference, Ames, conducted when addressing these activities and their inherent unknowns. Experience ha s dem onstrate d the pru dence of the Bios afety Level 1-4 practices, procedures, and facilities described for manipulations of etiologic agents in laboratory settings and animal facilities. Although no national reporting system exists for reporting laboratory-associated infections, anecdotal information suggests that strict adherence to these guidelines does contribute to a healthier and safer work environment for laboratorians, their co-workers , and the surrounding community. To further reduce the potential for laboratory-associated infections, the guidelines presented here should be considered minimal guidance for containment. They must be customized for each individual laboratory and can be used in conjunction with other available scientific information. References: