APPENDIX B. CLASSIFICATION
OF HUMAN ETIOLOGIC AGENTS ON THE BASIS OF HAZARD
Appendix B-I. Risk Group 1 (RG1) Agents
Appendix B-II. Risk Group 2 (RG2) Agents
Appendix B-II-A. Risk Group 2 (RG2) - Bacterial Agents Including
Chlamydia
Appendix B-II-B. Risk Group 2 (RG2) - Fungal Agents
Appendix B-II-C. Risk Group 2 (RG2) - Parasitic Agents
Appendix B-II-D. Risk Group 2 (RG2) - Viruses
Appendix B-III. Risk Group 3 (RG3) Agents
Appendix B-III-A. Risk Group 3 (RG3) - Bacterial Agents Including
Rickettsia
Appendix B-III-B. Risk Group 3 (RG3) - Fungal Agents
Appendix B-III-C. Risk Group 3 (RG3) - Parasitic Agents
Appendix B-III-D. Risk Group 3 (RG3) - Viruses and Prions
Appendix B-IV. Risk Group 4 (RG4) Agents
Appendix B-IV-A. Risk Group 4 (RG4) - Bacterial Agents
Appendix B-IV-B. Risk Group 4 (RG4) - Fungal Agents
Appendix B-IV-C. Risk Group 4 (RG4) - Parasitic Agents
Appendix B-IV-D. Risk Group 4 (RG4) - Viral Agents
Appendix B-V. Animal Viral Etiologic Agents in Common Use
Appendix B-V-1. Murine Retroviral Vectors
List of Tables
Appendix B - Table 1. Basis for the Classification of
Biohazardous Agents by Risk Group (RG)
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
all-inclusive. 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 Sections
V-C, V-D, V-E, and V-F, Footnotes and References of Sections I through
IV. Further guidance on agents not
listed in Appendix B may be obtained through:
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) |
RG1 agents are not
associated with disease in healthy adult humans. Examples of RG1 agents include asporogenic Bacillus subtilis
or Bacillus licheniformis (see 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 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.
RG2 agents are associated with human disease which is rarely
serious and for which preventive or therapeutic interventions are often
available.
--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 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
--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
--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
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 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 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 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 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 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 Appendix B-III-D, Risk
Group 3 (RG3) - Viruses and Prions) and restricted poxviruses including
Alastrim, Smallpox, and Whitepox (see 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)
RG3 agents are associated with serious or lethal human
disease for which preventive or therapeutic interventions may be
available.
--Bartonella
--Brucella including B. abortus, B. canis,
B. suis
--Burkholderia (Pseudomonas) mallei, B. pseudomallei
--Coxiella burnetii
--Francisella tularensis
--Mycobacterium
bovis (except BCG strain, see 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
--Coccidioides immitis (sporulating cultures;
contaminated soil)
--Histoplasma capsulatum, H. capsulatum var.. duboisii
None
Alphaviruses (Togaviruses) - Group A Arboviruses
--Semliki Forest virus
--St. Louis encephalitis virus
--Venezuelan equine encephalomyelitis virus (except the
vaccine strain TC-83, see Appendix B-II-D
(RG2))
--Other viruses
as listed in the reference source (see 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 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 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
RG4 agents are likely to cause serious or lethal human
disease for which preventive or therapeutic interventions are not usually
available.
None
None
None
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
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
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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