《微生物生物学》课程教学资源（书籍文献）Biosafety In Microbiology And Biomedical Laboratory，Fourth Edition April，999

HHS Publication No.(CDC)(99-xxxx) Biosafety in Microbiological and Biomedical Laboratories U.S.Department of Health and Human Services Public Health Service Centers for Disease Control and Prevention and National Institutes of Health Fourth Edition April 1999

HHS Publication No. (CDC) (99-xxxx) Biosafety in Microbiological and Biomedical Laboratories U.S. Department of Health and Human Services Public Health Service Centers for Disease Control and Prevention and National Institutes of Health Fourth Edition April 1999 U.S. GOVERNMENT PRINTING OFFICE WASHINGTON: 1999

Editors: ab2noMa d ph n Public He 1600 Cifton Road N.E Control and Prevention Atlanta,Georgia 30333 RobertW.McKinney,Ph.D Director,Division ofafety Health Room 1C0: Bethesda,Marylnd 20892

i Editors: Jonathan Y. Richmond, Ph.D. Director, Office o f Health a nd Safe ty Public Health Service Centers for Disease Control and Prevention 1600 Clifton Road N.E. Atlanta, Georgia 30333 Robert W. McKinney, Ph.D. Director, Division of S afety Public Health Service Nationa l Institutes of H ealth Building 31, Room 1C02 Bethesda, Maryland 20892

GUEST EDITORS Centers for Disease Control and Prevention RobertB.Craven,M.D. Arbovirus Disease Branch National Center for Infectious Disease Mark L.Eberhard,Ph.D. Chief National Center for Infectious Diseases Thomas Foks,Ph.D. Chief lV and Retr rology Branch Laboratory Research National Center for Infectious Diseases Bradford Kay.Dr.P.H. Senior Labo oratory Advisor rlogy and National Center for Infectious Diseases Richard C.Knudsen,Ph.D. Chief DW.J.Mahy.c. Director Disease of Viral and Rickettsial National Center for Infectious Diseases

ii GUEST EDITORS Centers for Disease Control and Prevention Robert B. Craven, M.D. Chief, Epidemiology Section Arbovirus Disease Branch National Center for Infectious Diseases Mark L. Eberhard, Ph.D. Chief Biology and Diagnostics Branch Division of Parasitic Diseases National Center for Infectious Diseases Thomas Folks, Ph.D. Chief HIV and Retrovirology Branch Division of AIDS, STD, and Laboratory Research National Center for Infectious Diseases Bradford Kay, Dr.P.H. Senior Laboratory Advisor Division of Bacteriology and Mycotic Diseases National Center for Infectious Diseases Richard C. Knudsen, Ph.D. Chief Laboratory Safety Branch Office of Hea lth and Safety Brian W . J. Mahy, Sc.D., Ph.D. Director Division of Viral and Rickettsial Diseases National Center for Infectious Diseases

C.J.Peters.M.D. Chief al Path National Center for Infectious Diseases Margaret A.Tipple,M.D. Chief National Institutes of Health John Bennett,MD. Chief.Mycobgy Section or Allergies and David Hackstadt,Ph.D. ain Laboratory Deborah E.Wilson,Dr.P.H. Chief,Occupational Health and Safety INDIVIDUAL GUEST EDITORS Jonathan Crane,A.LA. Architect Atlanta,GA PeterJ.Gerone,Sc.D. Director,Tulane Regional Primate Medical Center Covington,Louisiana .D.V.M Consultant Cary.NC

iii C.J. Peters, M.D. Chief Special Pathogens Branch National Center for Infectious Diseases Margaret A. Tipple, M.D. Chief External Activities Program Office o f Health a nd Safe ty National Institutes of He alth John Bennett, M.D. Chief, Mycology Section National Institute for Allergies and Infectious Diseases David Hackstadt, Ph.D. Microbiologist Rocky Mou ntain Laboratory Deborah E. Wilson, Dr.P.H. Chief, Occupational Health and Safety Branch Division of Safety INDIVIDUAL GUEST EDITORS Jonathan Crane, A.I.A. Architect Atlanta, GA Peter J. Gerone, Sc.D. Director, Tulane Region al Prima te Research Center Tulane University Medical Center Covington, Louisiana Thom as Ha mm , D.V.M ., Ph.D. Consultant Cary, NC

DebraL.Hunt,Dr.PH. Peter Jahring.Ph.D. Senior Research Scier ntist rMaryand Thomas Kost,Ph.D. icn Doparmont esearch TECHNICAL EDITOR Marie J.Murray Wl iv

iv Debra L. Hunt, Dr.P.H. Director, Biological Safety and Infection Control Duke University Medical Center Durham, North Carolina Peter Jahrling, Ph.D. Senior Research Scientist Disease Assessment Division USAM RIID Frederick, Maryland Thomas Kost, Ph.D. Section Head Molecular Sciences Department Glaxo Wellcome, Inc. Research Triangle Park, NC TECHNICAL EDITOR Marie J. Murray Writer-Editor Atlanta, GA

TABLE OF CONTENTS SECTION I .1 les of Biosafe ty .8 Table 1 Summary of re 17 Levels for Infectious Agents. .52 SECTION IV Vertebrate Animal Biosafety Level Criteria .53 Tabl ded Biosafet Naturally Infected Vertebrate Animals Are used.75 76 SECTION VI d Biosafety Leveks for Infectious Agents and Infected Animals .84 SECTION VII onVIL-C: un ge Ag Section VIl Rick ettsial Agen ts Section VIG:Arboviuses and Relat ed to Biosafe e12 183 s assianed to Biosafety Level 2 186

v TABLE OF CONTENTS SECTION I Introduction . . 1 SECT ION II Principles of Biosafe ty . . 8 SECT ION III Laborato ry Bio safe ty Level C riteria . 17 Tab le 1. Sum ma ry of R ecomm ended Biosafety Levels for Infectious Agents. . 52 SECT ION IV Vertebra te An imal Biosafety L evel Criteria . 53 Tab le 1. Sum ma ry of R ecomm ended Biosafety Levels for Activities in Which Experimentally or Naturally Infected Vertebrate Animals Are Used . 75 SECTION V Risk Assessment . . 76 SECTION VI Recommended Biosafety Levels for Infectious Agents and Infected Animals . . 84 SECT ION VII Agent Summ ary State ments . 88 Section VII-A: Bac terial Agen ts . 88 Section VII-B: Fun gal Agen ts . 118 Section VII-C: Pa rasitic Age nts . 127 Section VII-D: Prions . . 134 Section VII-E: Rick ettsial Agen ts . 148 Section VII-F: Viral Agents (other than arboviruses) . 153 Section VII-G: Arboviruses and Related Zoonotic Viruses . . 183 Arbo virus es Assigned to Biosafe ty Leve l 2 . 183 Table 1 . Arbovirus es and Arenav iruses Assigned to Bios afety L evel 2 . 186

.189 viruses and Certain Other Viruses 189 ,193 Table 194 i5.Arbovruses.Arenavruses and19 avirus Filoviruses Assigned to Biosafety Level 4.197 APPENDIX A mary conanment:Biological Safety Cabinets.200 nparison of Safety .205 Figure 2a.Class ll,Type A Biological Safety .207 gical Safety .208 Figure 2c ClasslI.Type B2 Biological Safety Figure 2d. Table-top Model Figure 3.Class lll Biological Safety Cabinet .211 APPENDIX B Imm uno prop hyla xis .212 APPENDIX C Transportation and Tran sfer of Biological Agents.214 Figure 1.Pack 219 Figure 2. nd la Clinical Specimens .219 APPENDIX D Restricted Animal Pathogens. 220 vi

vi Table 2. Vaccine Strains of BSL-3/4 Viruses W hich May Be Handled at Biosa fety Level-2 . 189 Arboviruses and Arenaviruses Assigned to Bios afety L evel 3 . . 189 Table 3. Arboviruses and Certain Other Viruses Assigned to Biosafety Level 3 (on the basis of insufficient experience) . 193 Table 4. Arboviruses and Certain Other Viruses Assigned to Biosafety Level 3 . 194 Arboviruses, Arenaviruses, and Filoviruses Ass igned to Biosafe ty Leve l 4 . 196 Table 5. Arboviruses, Arenaviruses and Filovir uses As signed to Biosafety L evel 4 . . 197 APPENDIX A Primary Contain ment: Biological Sa fety Cab inets . 200 Tab le 1. C om paris on of Biological Safe ty Cabine ts . . 205 Figu re 2a . Clas s II, Type A Biological Safe ty Cabinet . . 207 Figu re 2b . Clas s II, Type B1 Biologica l Safe ty Cabinet . . 208 Figu re 2c . Clas s II, Type B2 Biologica l Safe ty Cabinet . . 209 Figure 2d. Table-top Model . 210 Figure 3. Class III Biological Safety Cabinet . 211 APPENDIX B Imm unoprop hylaxis . . 212 APPENDIX C Trans portation a nd Tran sfer of Biolo gical Age nts . 214 Figure 1 . Packin g and La beling of Infectious Substances . 219 Figure 2 . Packin g and La beling of Clinical Specimens . 219 APPENDIX D Restricted Animal Pathogens . 220

APPENDIX E Resources for Information.222 APPENDIX F Laboratory Securty and Emergency Response for Microbiolgical and Biomedical Laboratories.224 APPENDIX G Integrated Pest Management .230 APPENDIX H Working With Human and Other Primate Cells and Tissues 234 APPENDIX I Guidelines for Work With Toxins of Biological Origin.237 .243

vii APPENDIX E Resources for Information . 222 APPENDIX F Laboratory Security and Emergency Response for Microbiological and Biomedical Laboratories . 224 APPENDIX G Integrated Pest Management . 230 APPENDIX H Working With Human and Other Primate Cells and Tissues . . 234 APPENDIX I Guid elines for W ork W ith Toxins of Biologica l Origin . 237 INDEX Index . . 243

PREFACE ctious agents in various laboratory They are intended to itie However.the application of these recommendation s to a ts a 00n than used as a universal and generic code applicable to all situations. thtdom ofthechagemade in this four In response to global concem about emerging and re- infomio tom A considerable increase n the design and construction of ories hasoc urred been incorporated.particularly in Sections lll and IV. chis an approp riate conta inment. England.In response,an appendix has been added to

viii PREFACE This publication describes the combinations of standard and special microbiological practices, safety equipment, and facilities constituting Biosafety Levels 1-4, which are recommended for work with a variety of infectious agents in various laboratory settings. Thes e recom men dations a re adviso ry. They are intended to provide a voluntary guide or code of practice as well as goals for upgrading operations. They also are offered as a guide and referenc e in the cons truction of new labor atory f acilities and in the reno vation of e xisting fac ilities. However, the application of these recommendations to a particular laboratory operation should be based on a risk assessment of the special agents and activities, rather than used as a universal and generic code applicable to all situations. Since the publication of the third edition of Bios afety in Microbiological and Microbiological Laboratories, a number of events have occurred that influenced some of the changes made in this fourth edition. C In response to global concern about emerging and re￾emerging infectious diseases, the section on Risk Assessment has been enlarged to provide the laboratorian with additional information to make such determinations easier. C A considerable increase in the design and construction of biomedical and microbiological laboratories has occurred, particularly at Biosafety Levels 3 and 4. In response, clarification of and additions to the “Facilities” sections have been incorporated, particularly in Sections III and IV, as an expansion of our performance-based approach to achieving approp riate conta inme nt. C Interest in prion diseases increased significantly with the identificatio n of b ovine spon giform e ncephalopathy (BSE) in Englan d. In respo nse, an appen dix has b een ad ded to

address the varied biosafety concerns ass ociated with working with these agents Several laboratorv-associated infections have occurred involving both known and previously unknown agents.In have Each Agent Summary Statement now contains information oratory to anothe Finally.growing concerns about bioterrorism have caused eaoheeo8isn attention on the increased security needs of our microbiological laboratories We also acknowledge the contrbutions of many in the science community who have pro ovided id im pro ng this for its thoughtful comments and suggestions

ix addres s the varie d biosaf ety conce rns ass ociated w ith working with these agents . C Several laboratory-associated infections have occurred involving bo th know n and pr eviously un know n agen ts. In response, various Agent Summary Statements have been modified or added to this edition. C Concern has increased regarding the national and international transfer of infectious microorganisms. Each Agent Summary Statement now contains information regardin g the req uirem ents to ob tain appro priate perm its before transferring the agents from one laboratory to another. C Finally, growing concerns about bioterrorism have caused conside rable intere st in biosaf ety matte rs in rece nt years. In response, an additional appendix is designed to help focus attention on the increased security needs of our microbiological laboratories. We also acknowledge the contributions of many in the science com mu nity wh o hav e pro vided ideas for im prov ing this publication. In particular, we are indebted to the Technical Review Committee of the American Biological Safety Association for its thoughtful comments and suggestions