NIH Guidelines - Risk Groups

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NIH Guidelines
for Research Involving
Recombinant DNA Molecules
APPENDIX B.�� CLASSIFICATION OF HUMAN ETIOLOGIC AGENTS ON THE
BASIS OF HAZARD
This appendix includes those biological agents known to infect
humans as well as selected animal agents that may pose theoretical
risks if inoculated into humans.� Included are lists of
representative genera and species known to be pathogenic; mutated,
recombined, and non-pathogenic species and strains are not
considered.� Non-infectious life cycle stages of parasites are
excluded.
This appendix reflects the current state of knowledge and should
be considered a resource document.� Included are the more
commonly encountered agents and is not meant to be allinclusive.� Information on agent risk assessment may be found in
the Agent Summary Statements of the CDC/NIH publication, Biosafety
in Microbiological and Biomedical Laboratories (see
HYPERLINK
"http://www4.od.nih.gov/oba/rac/guidelines_02/NIH_Guidelines_Apr_0
2.htm" \l "_SECTION_V._FOOTNOTES" Sections V-C, V-D, V-E, and VF , Footnotes and References of Sections I through IV.� Further
guidance on agents not listed in Appendix B may be obtained
through:�
HYPERLINK "http://www.cdc.gov/" \n Centers for
Disease Control and Prevention , Biosafety Branch, Atlanta,
Georgia 30333, Phone:� (404) 639-3883, Fax:� (404) 639-2294;
National Institutes of Health, Division of Safety, Bethesda,
Maryland 20892, Phone:� (301) 496-1357; National Animal Disease
Center, U.S. Department of Agriculture, Ames, Iowa 50010, Phone:�
(515) 862-8258.�
A special committee of the American Society for Microbiology will
conduct an annual review of this appendix and its recommendation
for changes will be presented to the Recombinant DNA Advisory
Committee as proposed amendments to the NIH Guidelines.
Appendix B - Table 1.
Basis for the Classification of Biohazardous Agents by Risk Group
(RG)
Risk Group 1 (RG1) Agents that are not associated with disease in
healthy adult humans
Risk Group 2 (RG2) Agents that are
associated with human disease which is rarely serious and for
which preventive or therapeutic interventions are often
available Risk Group 3 (RG3) Agents that are associated with
serious or lethal human disease for which preventive or
therapeutic interventions may be available (high individual risk
but low community risk) Risk Group 4 (RG4) Agents that are likely
to cause serious or lethal human disease for which preventive or
therapeutic interventions are not usually available (high
individual risk and high community risk)
Appendix B-I.�� Risk Group 1 (RG1) Agents
RG1 agents are not associated with disease in healthy adult
humans.� Examples of RG1 agents include asporogenic Bacillus
subtilis or Bacillus licheniformis (see
HYPERLINK
"http://www4.od.nih.gov/oba/rac/guidelines_02/APPENDIX_C.htm" \l
"_Appendix_C-IV-A._Exceptions" \n Appendix C-IV-A , Bacillus
subtilis or Bacillus licheniformis Host-Vector Systems,
Exceptions); adeno- associated virus (AAV) types 1 through 4; and
recombinant AAV constructs, in which the transgene does not encode
either a potentially tumorigenic gene product or a toxin molecule
and are produced in the absence of a helper virus.� A strain of
Escherichia coli (see
HYPERLINK
"http://www4.od.nih.gov/oba/rac/guidelines_02/APPENDIX_C.htm" \l
"_Appendix_C-II-A._Exceptions" \n Appendix C-II-A , Escherichia
coli K-12 Host Vector Systems, Exceptions) is an RG1 agent if it
(1) does not possess a complete lipopolysaccharide (i.e., lacks
the O antigen); and (2) does not carry any active virulence factor
(e.g., toxins) or colonization factors and does not carry any
genes encoding these factors.
Those agents not listed in Risk Groups (RGs) 2, 3 and 4 are not
automatically or implicitly classified in RG1; a risk assessment
must be conducted based on the known and potential properties of
the agents and their relationship to agents that are listed.
Appendix B-II.�� Risk Group 2 (RG2) Agents
RG2 agents are associated with human disease which is rarely
serious and for which preventive or therapeutic interventions are
often available.
Appendix B-II-A.�� Risk Group 2 (RG2) - Bacterial Agents
Including Chlamydia
--Acinetobacter baumannii (formerly Acinetobacter calcoaceticus)
--Actinobacillus
--Actinomyces pyogenes (formerly Corynebacterium pyogenes)
--Aeromonas hydrophila
--Amycolata autotrophica
--Archanobacterium haemolyticum (formerly Corynebacterium
haemolyticum)
--Arizona hinshawii - all serotypes
--Bacillus anthracis
--Bartonella henselae, B. quintana, B. vinsonii
--Bordetella including B. pertussis�
--Borrelia recurrentis, B. burgdorferi
--Burkholderia (formerly Pseudomonas species) except those listed
in Appendix B-III-A (RG3))
--Campylobacter coli, C. fetus, C. jejuni
--Chlamydia psittaci, C. trachomatis, C. pneumoniae
--Clostridium botulinum, Cl. chauvoei, Cl. haemolyticum, Cl.
histolyticum, Cl. novyi, Cl. septicum, Cl. tetani
--Corynebacterium diphtheriae, C. pseudotuberculosis, C. renale
--Dermatophilus congolensis
--Edwardsiella tarda
--Erysipelothrix rhusiopathiae
--Escherichia coli - all enteropathogenic, enterotoxigenic,
enteroinvasive and strains bearing K1 antigen, including E. coli
O157:H7
--Haemophilus ducreyi, H. influenzae
--Helicobacter pylori
--Klebsiella - all species except K. oxytoca (RG1)
--Legionella including L. pneumophila
--Leptospira interrogans - all serotypes
--Listeria
--Moraxella
--Mycobacterium (except those listed in
HYPERLINK
"http://www4.od.nih.gov/oba/rac/guidelines_02/APPENDIX_B.htm" \l
"_Appendix_B-III-A._Risk" Appendix B-III-A (RG3)) including M.
avium complex, M. asiaticum, M. bovis BCG vaccine strain, M.
chelonei, M. fortuitum, M. kansasii, M. leprae, M. malmoense, M.
marinum, M. paratuberculosis, M. scrofulaceum, M. simiae, M.
szulgai, M. ulcerans, M. xenopi
--Mycoplasma, except M. mycoides and M. agalactiae which are
restricted animal pathogens
--Neisseria gonorrhoeae, N. meningitidis
--Nocardia asteroides, N. brasiliensis, N. otitidiscaviarum, N.
transvalensis
--Rhodococcus equi
--Salmonella including S. arizonae, S. cholerasuis, S.
enteritidis, S. gallinarum-pullorum, S. meleagridis, S. paratyphi,
A, B, C, S. typhi, S. typhimurium
--Shigella including S. boydii, S. dysenteriae, type 1, S.
flexneri, S. sonnei
--Sphaerophorus necrophorus
--Staphylococcus aureus
--Streptobacillus moniliformis
--Streptococcus including S. pneumoniae, S. pyogenes
--Treponema pallidum, T. carateum
--Vibrio cholerae, V. parahemolyticus, V. vulnificus
--Yersinia enterocolitica
Appendix B-II-B.�� Risk Group 2 (RG2) - Fungal Agents
--Blastomyces dermatitidis
--Cladosporium bantianum, C. (Xylohypha) trichoides
--Cryptococcus neoformans
--Dactylaria galopava (Ochroconis gallopavum)
--Epidermophyton
--Exophiala (Wangiella) dermatitidis
--Fonsecaea pedrosoi
--Microsporum
--Paracoccidioides braziliensis
--Penicillium marneffei
--Sporothrix schenckii
--Trichophyton
Appendix B-II-C.�� Risk Group 2 (RG2) - Parasitic Agents
--Ancylostoma human hookworms including A. duodenale, A.
ceylanicum
--Ascaris including Ascaris lumbricoides suum
--Babesia including B. divergens, B. microti
--Brugia filaria worms including B. malayi, B. timori
--Coccidia
--Cryptosporidium including C. parvum
--Cysticercus cellulosae (hydatid cyst, larva of T. solium)
--Echinococcus including E. granulosis, E. multilocularis, E.
vogeli
--Entamoeba histolytica
--Enterobius
--Fasciola including F. gigantica, F. hepatica
--Giardia including G. lamblia
--Heterophyes
--Hymenolepis including H. diminuta, H. nana
--Isospora
--Leishmania including L. braziliensis, L. donovani, L. ethiopia,
L. major, L. mexicana, L. peruvania, L. tropica
--Loa loa filaria worms
--Microsporidium
--Naegleria fowleri
--Necator human hookworms including N. americanus
--Onchocerca filaria worms including, O. volvulus
--Plasmodium including simian species, P. cynomologi, P.
falciparum, P. malariae, P. ovale, P. vivax
--Sarcocystis including S. sui hominis
--Schistosoma including S. haematobium, S. intercalatum, S.
japonicum, S. mansoni, S. mekongi
--Strongyloides including S. stercoralis
--Taenia solium
--Toxocara including T. canis
--Toxoplasma including T. gondii
--Trichinella spiralis
--Trypanosoma including T. brucei brucei, T. brucei gambiense, T.
brucei rhodesiense, T. cruzi
--Wuchereria bancrofti filaria worms
Appendix B-II-D.�� Risk Group 2 (RG2) � Viruses
Adenoviruses, human - all types
Alphaviruses (Togaviruses) - Group A Arboviruses
--Eastern equine encephalomyelitis virus
--Venezuelan equine encephalomyelitis vaccine strain TC-83
--Western equine encephalomyelitis virus
Arenaviruses
--Lymphocytic choriomeningitis virus (non-neurotropic strains)
--Tacaribe virus complex
--Other viruses as listed in the reference source (see
HYPERLINK
"http://www4.od.nih.gov/oba/rac/guidelines_02/NIH_Guidelines_Apr_0
2.htm" \l "_SECTION_V._FOOTNOTES" Section V-C , Footnotes and
References of Sections I through IV)
Bunyaviruses
--Bunyamwera virus
--Rift Valley fever virus vaccine strain MP-12
--Other viruses as listed in the reference source (see
HYPERLINK
"http://www4.od.nih.gov/oba/rac/guidelines_02/NIH_Guidelines_Apr_0
2.htm" \l "_SECTION_V._FOOTNOTES" \n Section V-C , Footnotes and
References of Sections I through IV)
Caliciviruses
Coronaviruses
Flaviviruses (Togaviruses) - Group B Arboviruses
--Dengue virus serotypes 1, 2, 3, and 4
--Yellow fever virus vaccine strain 17D
--Other viruses as listed in the reference source (see
HYPERLINK
"http://www4.od.nih.gov/oba/rac/guidelines_02/NIH_Guidelines_Apr_0
2.htm" \l "_SECTION_V._FOOTNOTES" \n Section V-C , Footnotes and
References of Sections I through IV)
Hepatitis A, B, C, D, and E viruses
Herpesviruses - except Herpesvirus simiae (Monkey B virus) (see
HYPERLINK
"http://www4.od.nih.gov/oba/rac/guidelines_02/NIH_Guidelines_Apr_0
2.htm" \l "_Appendix_B-IV-D._Risk" \n Appendix B-IV-D , Risk
Group 4 (RG4) - Viral Agents)
--Cytomegalovirus
--Epstein Barr virus
--Herpes simplex types 1 and 2
--Herpes zoster
--Human herpesvirus types 6 and 7
Orthomyxoviruses
--Influenza viruses types A, B, and C
--Other tick-borne orthomyxoviruses as listed in the reference
source (see
HYPERLINK
"http://www4.od.nih.gov/oba/rac/guidelines_02/NIH_Guidelines_Apr_0
2.htm" \l "_SECTION_V._FOOTNOTES" \n Section V-C , Footnotes and
References of Sections I through IV)
Papovaviruses
--All human papilloma viruses
Paramyxoviruses
--Newcastle disease virus
--Measles virus
--Mumps virus
--Parainfluenza viruses types 1, 2, 3, and 4
--Respiratory syncytial virus
Parvoviruses
--Human parvovirus (B19)
Picornaviruses
--Coxsackie viruses types A and B
--Echoviruses - all types
--Polioviruses - all types, wild and attenuated
--Rhinoviruses - all types
Poxviruses - all types except Monkeypox virus (see
HYPERLINK
"http://www4.od.nih.gov/oba/rac/guidelines_02/APPENDIX_B.htm" \l
"_Appendix_B-III-D._Risk" \n Appendix B-III-D , Risk Group 3
(RG3) - Viruses and Prions) and restricted poxviruses including
Alastrim, Smallpox, and Whitepox (see
HYPERLINK
"http://www4.od.nih.gov/oba/rac/guidelines_02/NIH_Guidelines_Apr_0
2.htm" \l "_SECTION_V._FOOTNOTES" Section V-L , Footnotes and
References of Sections I through IV)
Reoviruses - all types including Coltivirus, human Rotavirus, and
Orbivirus (Colorado tick fever virus)
Rhabdoviruses
--Rabies virus - all strains
--Vesicular stomatitis virus - laboratory adapted strains
including VSV-Indiana, San Juan, and Glasgow
Togaviruses (see Alphaviruses and Flaviviruses)
--Rubivirus (rubella)
Appendix B-III.��� Risk Group 3 (RG3) Agents
RG3 agents are associated with serious or lethal human disease for
which preventive or therapeutic interventions may be available.
Appendix B-III-A.�� Risk Group 3 (RG3) - Bacterial Agents
Including Rickettsia
--Bartonella
--Brucella including B. abortus, B. canis, B. suis
--Burkholderia (Pseudomonas) mallei, B. pseudomallei
--Coxiella burnetii
--Francisella tularensis
--Mycobacterium bovis (except BCG strain, see
HYPERLINK
"http://www4.od.nih.gov/oba/rac/guidelines_02/APPENDIX_B.htm" \l
"_Appendix_B-II-A._Risk" Appendix B-II-A , Risk Group 2 (RG2) Bacterial Agents Including Chlamydia), M. tuberculosis
--Pasteurella multocida type B -"buffalo" and other virulent
strains
--Rickettsia akari, R. australis, R. canada, R. conorii, R.
prowazekii, R. rickettsii, R, siberica, R. tsutsugamushi, R. typhi
(R. mooseri)
--Yersinia pestis
Appendix B-III-B.�� Risk Group 3 (RG3) - Fungal Agents
--Coccidioides immitis (sporulating cultures; contaminated soil)
--Histoplasma capsulatum, H. capsulatum var.. duboisii
Appendix B-III-C.�� Risk Group 3 (RG3) - Parasitic Agents
None
Appendix B-III-D.�� Risk Group 3 (RG3) - Viruses and Prions
Alphaviruses (Togaviruses) - Group A Arboviruses
--Semliki Forest virus
--St. Louis encephalitis virus
--Venezuelan equine encephalomyelitis virus (except the vaccine
strain TC-83, see
HYPERLINK
"http://www4.od.nih.gov/oba/rac/guidelines_02/APPENDIX_B.htm" \l
"_Appendix_B-III-D._Risk" Appendix B-II-D (RG2))
--Other viruses as listed in the reference source (see
HYPERLINK
"http://www4.od.nih.gov/oba/rac/guidelines_02/NIH_Guidelines_Apr_0
2.htm" \l "_SECTION_V._FOOTNOTES" \n Section V-C , Footnotes and
References of Sections I through IV)
Arenaviruses
--Flexal
--Lymphocytic choriomeningitis virus (LCM) (neurotropic strains)
Bunyaviruses
--Hantaviruses including Hantaan virus ���
--Rift Valley fever virus
Flaviviruses (Togaviruses) - Group B Arboviruses
--Japanese encephalitis virus
--Yellow fever virus
--Other viruses as listed in the reference source (see
HYPERLINK
"http://www4.od.nih.gov/oba/rac/guidelines_02/NIH_Guidelines_Apr_0
2.htm" \l "_SECTION_V._FOOTNOTES" \n Section V-C , Footnotes and
References of Sections I through IV)
Poxviruses
--Monkeypox virus
Prions
--Transmissible spongioform encephalopathies (TME) agents
(Creutzfeldt-Jacob disease and kuru agents)(see
HYPERLINK
"http://www4.od.nih.gov/oba/rac/guidelines_02/NIH_Guidelines_Apr_0
2.htm" \l "_SECTION_V._FOOTNOTES" \n Section V-C , Footnotes and
References of Sections I through IV, for containment instruction)
Retroviruses
--Human immunodeficiency virus (HIV) types 1 and 2
--Human T cell lymphotropic virus (HTLV) types 1 and 2
--Simian immunodeficiency virus (SIV)
Rhabdoviruses
--Vesicular stomatitis virus
Appendix B-IV.�� Risk Group 4 (RG4) Agents
RG4 agents are likely to cause serious or lethal human disease for
which preventive or therapeutic interventions are not usually
available.
Appendix B-IV-A.�� Risk Group 4 (RG4) - Bacterial Agents
None
Appendix B-IV-B.�� Risk Group 4 (RG4) - Fungal Agents
None
Appendix B-IV-C.�� Risk Group 4 (RG4) - Parasitic Agents
None
Appendix B-IV-D.�� Risk Group 4 (RG4) - Viral Agents
Arenaviruses
--Guanarito virus
--Lassa virus
--Junin virus
--Machupo virus
--Sabia
Bunyaviruses (Nairovirus)
--Crimean-Congo hemorrhagic fever virus
Filoviruses
--Ebola virus
--Marburg virus
Flaviruses (Togaviruses) - Group B Arboviruses
--Tick-borne encephalitis virus complex including Absetterov,
Central European encephalitis, Hanzalova, Hypr, Kumlinge, Kyasanur
Forest disease, Omsk hemorrhagic fever, and Russian spring-summer
encephalitis viruses
Herpesviruses (alpha)
--Herpesvirus simiae (Herpes B or Monkey B virus)
Paramyxoviruses
--Equine morbillivirus
Hemorrhagic fever agents and viruses as yet undefined
Appendix B-V.��� Animal Viral Etiologic Agents in Common Use
The following list of animal etiologic agents is appended to the
list of human etiologic agents.� None of these agents is
associated with disease in healthy adult humans; they are commonly
used in laboratory experimental work.
A containment level appropriate for RG1 human agents is
recommended for their use.� For agents that are infectious to
human cells, e.g., amphotropic and xenotropic strains of murine
leukemia virus, a containment level appropriate for RG2 human
agents is recommended.
Baculoviruses
Herpesviruses
--Herpesvirus ateles
--Herpesvirus saimiri
--Marek's disease virus
--Murine cytomegalovirus
Papovaviruses
--Bovine papilloma virus
--Polyoma virus
--Shope papilloma virus
--Simian virus 40 (SV40)
Retroviruses
--Avian leukosis virus
--Avian sarcoma virus
--Bovine leukemia virus
--Feline leukemia virus
--Feline sarcoma virus
--Gibbon leukemia virus
--Mason-Pfizer monkey virus
--Mouse mammary tumor virus
--Murine leukemia virus
--Murine sarcoma virus
--Rat leukemia virus
Appendix B-V-1.�� Murine Retroviral Vectors
Murine retroviral vectors to be used for human transfer
experiments (less than 10 liters) that contain less than 50% of
their respective parental viral genome and that have been
demonstrated to be free of detectable replication competent
retrovirus can be maintained, handled, and administered, under BL1
containment.
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