Mucambo virus: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Mucambo virus

Agent type

Virus

Taxonomy

Family

Togaviridae

Genus

Alphavirus

Species

Mucambo virus

Synonym or cross-reference

Also known as Venezuelan equine encephalitis (VEE) virus subtype IIIA Footnote 1 and previously referred to as a strain of VEE virus Footnote 2.

Characteristics

Brief description

Mucambo virus (MUCV) is a member of the Venezuelan equine encephalitis (VEE) complex of virusesFootnote 1. MUCV is an arbovirus that can cause self-limiting febrile illness in humans and is considered to be an enzootic VEE complex virusFootnote 3Footnote 4.

Properties

MUCV is a spherical, enveloped virus measuring 65-70 nm in diameterFootnote 1. The nucleocapsid core contains a single-stranded positive-sense RNA genome approximately 11.4 kb in length.Footnote 1Footnote 5.

Section II – Hazard identification

Pathogenicity and toxicity

MUCV causes subclinical infection or self-limiting febrile illness in humans, indicating that MUCV exhibits reduced virulence in humans relative to closely phylogenetically related viral species of the VEE complex.Footnote 3Footnote 6Footnote 7. Symptoms include fever, headache, and malaise lasting 2 to 3 daysFootnote 3. No MUCV-associated human fatalities have been reported.

In natural settings, enzootic strains of the VEE complex, including MUCV, are generally avirulent for horsesFootnote 4; however, horses experimentally inoculated with MUCV developed febrile illness and viremiaFootnote 2. Macaques experimentally infected with MUCV via the aerosol route developed fever and clinical signs of mild encephalitis, including loss of balance and muscle controlFootnote 8. The viremic period was short, lasting about 2 daysFootnote 8. Symptoms resolved after approximately 10 days and all macaques fully recoveredFootnote 8.

Epidemiology

MUCV has been found in several restricted geographic foci within South America, including parts of BrazilFootnote 9Footnote 10, TrinidadFootnote 11, SurinameFootnote 7, and PeruFootnote 12Footnote 13. MUCV disease incidence in humans is sporadic, with only seven MUCV isolates recovered from humans prior to 1992Footnote 3. In MUCV-endemic areas in the Brazilian Amazon, prevalence of MUCV antibodies in humans ranges from 0% to 34% (average 6%)Footnote 6. MUCV is generally avirulent for equinesFootnote 4Footnote 14.

Host range

Natural host(s)

MUCV has been isolated from humansFootnote 3, non-human primatesFootnote 15, and rodentsFootnote 9Footnote 10. Serological evidence indicates that horsesFootnote 16, opossumsFootnote 9, wild birdsFootnote 10, and batsFootnote 17 are occasionally infected in regions where MUCV is prevalent.

Other host(s)

Experimental hosts include hamstersFootnote 18 and guinea pigsFootnote 4Footnote 14.

Infectious dose

Unknown.

Incubation period

The incubation period for VEE complex viruses in humans is approximately 2 to 5 daysFootnote 4. The incubation period for non-human primates infected with MUCV via the aerosol route is approximately 3 daysFootnote 8.

Communicability

In natural settings, MUCV is primarily transmitted to humans and other mammals via bites from infected mosquitoesFootnote 9. In laboratory settings, MUCV is highly infectious via the aerosol routeFootnote 19Footnote 20 and infection may occur through direct contact of virus with damaged skin or mucous membranesFootnote 21Footnote 22.

Section III – Dissemination

Reservoir

MUCV is maintained in a transmission cycle involving mosquitoes and rodentsFootnote 11Footnote 12Footnote 23. Rodents including Oryzomys capitoFootnote 6, Oecomys spp.Footnote 9, and Proechimys spp.Footnote 9 have been implicated in MUCV transmission in the Amazon region.

Zoonosis

There is no evidence of MUCV transmission between humans and non-arthropod animals.

Vectors

Mosquitoes, primarily Culex (Melanoconion) portesi, become carriers of MUCV when they feed on viremic MUCV-infected hostsFootnote 6Footnote 11Footnote 24.

Section IV – Stability and viability

Drug susceptibility/resistance

There are no approved drugs to treat illnesses caused by MUCV or other VEE complex viruses. Sorafenib, an FDA-approved drug used to treat carcinoma, inhibited replication of VEE complex viruses in vitroFootnote 25. Pyrimethamine, an anti-malarial drug, and Prest-392 (Ketanserin tartrate hydrate) showed antiviral activity against VEE virus in vitroFootnote 26.

Susceptibility to disinfectants

Ethanol (60-80%)Footnote 27Footnote 28, quaternary ammonium compoundsFootnote 28Footnote 29, peracetic acidFootnote 30, sodium hydroxide (100-500 mM)Footnote 31, glutaraldehyde (0.1%)Footnote 32, and free chlorine (1 ppm)Footnote 33 are effective against MUCV.

Physical inactivation

Togaviruses are inactivated by UV irradiationFootnote 31Footnote 32 and heat treatment at 65 °C for 15 minutesFootnote 31Footnote 34

Survival outside host

Alphaviruses are highly stable over a wide range of relative humidities (18 to 90%) and temperatures (-40 to 24 °C) in aerosol formFootnote 35. Alphaviruses are also stable on dry surfaces. In darkness, the viral load on a glass surface decreased by 90% after approximately 4 daysFootnote 36.

Section V – First aid/medical

Surveillance

Illness caused by MUCV is clinically indistinguishable from other febrile illnesses such as dengue feverFootnote 23. MUCV can be detected in tissue samples and in blood during the viremic phase of illness using reverse transcription polymerase chain reaction (RT-PCR) and sequencingFootnote 37. Serological tests including plaque reduction neutralization assay, enzyme-linked immunosorbent assay (ELISA), hemagglutination inhibition, and complement fixation have been used in the diagnosis of illnesses caused by alphavirusesFootnote 38. RT-PCR followed by electrospray ionization mass spectrometry has also been used to detect MUCV in mosquito samplesFootnote 13.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (CBH).

First aid/treatment

Illness caused by MUCV is usually mild and self-limitingFootnote 6. Treatment is mainly supportive to manage symptoms.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.

Immunization

There are currently no licenced vaccines for VEE complex viruses, including MUCV. Alphavirus vaccine research has identified promising candidatesFootnote 20. Investigational vaccine products (e.g., live-attenuated TC-83 strain) have been administered to at-risk personnel working with VEE complex virusesFootnote 21Footnote 39.

Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.

Prophylaxis

None.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.

Section VI – Laboratory hazard

Laboratory-acquired infections

Prior to 1970, two laboratory workers developed febrile illness caused by MUCVFootnote 19. The likely route of exposure was inhalation of infectious aerosolsFootnote 19.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.

Sources/specimens

Blood, cerebrospinal fluid, brain tissue, throat washingsFootnote 8Footnote 12.

Primary hazards

Inhalation of aerosolized infectious material, bite of an infected animal/arthropod, exposure of mucous membranes or broken skin to infectious material, and parenteral inoculation are primary exposure hazards for MUCVFootnote 21.

Special hazards

None.

Section VII – Exposure controls/personal protection

Risk group classification

MUCV is a Risk Group (RG) 3 human pathogen and Risk Group 1 animal pathogenFootnote 40Footnote 41.

Containment requirements

Containment Level 3 facilities, equipment, and operational practices outlined in the CBS for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 3 requirements for personal protective equipment and clothing outlined in the CBS to be followed. At minimum, use of full body coverage dedicated protective clothing, dedicated protective footwear and/or additional protective footwear, gloves when handling infectious materials or animals, face protection when there is a known or potential risk of exposure to splashes or flying objects, respirators when there is a risk of exposure to infectious aerosols, and an additional layer of protective clothing prior to work with infectious materials or animals.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.

Other precautions

All activities involving open vessels of pathogens are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. The use of needles, syringes, and other sharp objects to be strictly limited. Additional precautions must be considered with work involving animals or large scale activities.

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing protective clothing, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (CBH).

Disposal

Regulated materials, as well as all items and waste to be decontaminated at the containment barrier prior to removal from the containment zone, animal room, animal cubicle, or post mortem room. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Storage

Containment Level 2, CL3, prions: The applicable Containment Level 3 requirements for storage outlined in the CBS are to be followed. Primary containers of regulated materials removed from the containment zone to be stored in a labelled, leak-proof, impact-resistant secondary container, and kept either in locked storage equipment or within an area with limited access.

SSBA: Containers of security sensitive biological agents (SSBA) stored outside the containment zone must be labelled, leakproof, impact resistant, and kept in locked storage equipment that is fixed in place (i.e., non-movable) and within an area with limited access.

An inventory of RG3 and RG4 pathogens, and SSBA toxins in long-term storage, to be maintained and to include:

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with MUCV require a Human Pathogens and Toxins Licence , issued by the Public Health Agency of Canada.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

Last file update

2020

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright © Public Health Agency of Canada, 2023, Canada

References

Footnote 1

Chen, R., S. Mukhopadhyay, A. Merits, B. Bolling, F. Nasar, L. L. Coffey, A. Powers, and S. C. Weaver. 2018. ICTV virus taxonomy profile: Togaviridae. J. Gen. Virol. 99:761-762.

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Footnote 2

Shope, R. E., O. R. Causey, De Andrade, Amelia Homobono Paes, and M. Theiler. 1964. The Venezuelan equine encephalomyelitis complex of group A arthropod-borne viruses, including Mucambo and Pixuna from the Amazon region of Brazil. Am. J. Trop. Med. Hyg. 13:723-727.

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Footnote 3

Vasconcelos, Pedro Fernando da Costa, Rosa, Amélia Paes de Andrade Travassos da, N. Dégallier, Rosa, Jorge Fernando Soares Travassos da, and Pinheiro Filho, Francisco de Paula. 1992. Clinical and ecoepidemiological situation of human arboviruses in Brazilian Amazonia. Ciência e Cultura. 44:117-124.

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Footnote 4

Weaver, S. C., C. Ferro, R. Barrera, J. Boshell, and J. Navarro. 2004. Venezuelan equine encephalitis. Annual Reviews in Entomology. 49:141-174.

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Footnote 5

Kinney, R. M., M. Pfeffer, and J. Meissner. 2018. Mucambo virus strain Mucambo BeAn 8, complete genome GenBank: AF075253.1.

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Footnote 6

Vasconcelos, Pedro Fernando da Costa, Travassos da Rosa, Jorge Fernando Soares, Travassos da Rosa, Amélia Paes de Andrade, N. Dégallier, and F. d. P. Pinheiro. 1991. Epidemiologia das encefalites por arbovírus na Amazônia brasileira. Revista do Instituto De Medicina Tropical De São Paulo. 33:465-476.

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Footnote 7

De Haas, R. A., and W. C. Timers. 1976. Infection rate of arboviruses in Dutch recruits returning from Surinam. Trop. Geogr. Med. 28:137-140.

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Footnote 8

Reed, D. S., C. M. Lind, L. J. Sullivan, W. D. Pratt, and M. D. Parker. 2004. Aerosol infection of cynomolgus macaques with enzootic strains of Venezuelan equine encephalitis viruses. J. Infect. Dis. 189:1013-1017.

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Footnote 9

Araújo, P. A., M. O. Freitas, J. O. Chiang, F. A. Silva, L. L. Chagas, S. M. Casseb, S. P. Silva, J. P. Nunes-Neto, J. W. Rosa-Júnior, and B. S. Nascimento. 2019. Investigation about the occurrence of transmission cycles of arbovirus in the tropical forest, Amazon region. Viruses. 11:774.

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Footnote 10

Souza-Lopes, O., and L. Sacchetta. 1978. Isolation of Mucambo virus, a member of the Venezuelan equine encephalitis virus complex in the State of Sâo Paulo, Brasil. Rev. Inst. Med. Trop. Sao Paulo. 20:82-86.

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Footnote 11

Auguste, A. J., S. M. Volk, N. C. Arrigo, R. Martinez, V. Ramkissoon, A. P. Adams, N. N. Thompson, A. A. Adesiyun, D. D. Chadee, and J. E. Foster. 2009. Isolation and phylogenetic analysis of Mucambo virus (Venezuelan equine encephalitis complex subtype IIIA) in Trinidad. Virology. 392:123-130.

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Footnote 12

Weaver, S. C., and A. D. Barrett. 2004. Transmission cycles, host range, evolution and emergence of arboviral disease. Nature Reviews Microbiology. 2:789-801.

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Footnote 13

Eshoo, M. W., C. A. Whitehouse, S. T. Zoll, C. Massire, T. D. Pennella, L. B. Blyn, R. Sampath, T. A. Hall, J. A. Ecker, and A. Desai. 2007. Direct broad-range detection of alphaviruses in mosquito extracts. Virology. 368:286-295.

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Footnote 14

Calisher, C. H., and K. C. Maness. 1974. Virulence of Venezuelan equine encephalomyelitis virus subtypes for various laboratory hosts. Appl. Microbiol. 28:881-884.

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Footnote 15

Pedersen, C. E., Jr, D. R. Slocum, and N. H. Levitt. 1972. Chromatography of Venezuelan equine encephalomyelitis virus strains on calcium phosphate. Appl. Microbiol. 24:91-95.

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Footnote 16

Fernandez, Z., R. Richartz, A. Travassos da Rosa, and V. T. Soccol. 2000. Identification of the encephalitis equine virus, Parana, Brazil. Rev. Saude Publica. 34:232-235.

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Footnote 17

Price, J. L. 1978. Serological evidence of infection of Tacaribe virus and arboviruses in Trinidadian bats. Am. J. Trop. Med. Hyg. 27:162-167.

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Footnote 18

Jahrling, P. B., and F. Scherer. 1973. Histopathology and distribution of viral antigens in hamsters infected with virulent and benign Venezuelan encephalitis viruses. Am. J. Pathol. 72:25-38.

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Footnote 19

de Mucha-Macías, J., and I. Sánchez-Spíndola. 1965. Two human cases of laboratory infection with Mucambo virus. Am. J. Trop. Med. Hyg. 14:475-478.

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Footnote 20

Hu, W., R. Steigerwald, M. Kalla, A. Volkmann, D. Noll, and L. P. Nagata. 2018. Protective efficacy of monovalent and trivalent recombinant MVA-based vaccines against three encephalitic alphaviruses. Vaccine. 36:5194-5203.

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Footnote 21

Chosewood, L. C., and D. E. Wilson. 2009. Biosafety in microbiological and biomedical laboratories. US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institutes of Health.

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Footnote 22

Sidwell, R. W., L. P. Gebhardt, and B. D. Thorpe. 1967. Epidemiological aspects of Venezuelan equine encephalitis virus infections. Bacteriol. Rev. 31:65-81.

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Footnote 23

Aguilar, P. V., J. G. Estrada-Franco, R. Navarro-Lopez, C. Ferro, A. D. Haddow, and S. C. Weaver. 2011. Endemic Venezuelan equine encephalitis in the Americas: hidden under the dengue umbrella. Future Virology. 6:721-740.

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Footnote 24

Haas, R. A., and A. E. Arron-Leeuwin. 1975. Arboviruses isolated from mosquitos and man in Surinam. Trop. Geogr. Med. 27:409-412.

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Footnote 25

Lundberg, L., A. Brahms, I. Hooper, B. Carey, S. Lin, B. Dahal, A. Narayanan, and K. Kehn-Hall. 2018. Repurposed FDA-Approved drug sorafenib reduces replication of Venezuelan equine encephalitis virus and other alphaviruses. Antiviral Res. 157:57-67.

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Footnote 26

Ferreira-Ramos, A. S., C. Li, C. Eydoux, J. M. Contreras, C. Morice, G. Quérat, A. Gigante, M. P. Pérez, M. Jung, and B. Canard. 2019. Approved drugs screening against the nsP1 capping enzyme of Venezuelan equine encephalitis virus using an immuno-based assay. Antiviral Res. 163:59-69.

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Footnote 27

Kampf, G. 2018. Efficacy of ethanol against viruses in hand disinfection. J. Hosp. Infect. 98:331-338.

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Footnote 28

Rutala, W. A., and D. J. Weber. 2008. Guideline for disinfection and sterilization in healthcare facilities, 2008.

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Footnote 29

Armstrong, J. A., and E. J. Froelich. 1964. Inactivation of viruses by benzalkonium chloride. Appl. Microbiol. 12:132-137.

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Footnote 30

Evans, D., P. Stuart, and D. Roberts. 1977. Disinfection of animal viruses. Br. Vet. J. 133:356-359.

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Footnote 31

Ibrahim, M., D. Angelini, A. Prugh, T. Sickler, T. Biggs, J. Harris, and M. Ziemski. 2019. Methods for Inactivation of Venezuelan Equine Encephalitis Virus. AD1074319.

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Footnote 32

Lawrence, R. M., J. D. Zook, and B. G. Hogue. 2016. Full inactivation of alphaviruses in single particle and crystallized forms. J. Virol. Methods. 236:237-244.

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Footnote 33

Wade, M. M., A. E. Chambers, J. M. Insalaco, and A. W. Zulich. 2010. Survival of viral biowarfare agents in disinfected waters. International Journal of Microbiology. 2010:412694.

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Footnote 34

Lelie, P., H. Reesink, and C. Lucas. 1987. Inactivation of 12 viruses by heating steps applied during manufacture of a hepatitis B vaccine. J. Med. Virol. 23:297-301.

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Footnote 35

Ehrlich, R., and S. Miller. 1971. Effect of relative humidity and temperature on airborne Venezuelan equine encephalitis virus. Appl. Microbiol. 22:194-199.

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Footnote 36

Sagripanti, J., A. M. Rom, and L. E. Holland. 2010. Persistence in darkness of virulent alphaviruses, Ebola virus, and Lassa virus deposited on solid surfaces. Arch. Virol. 155:2035-2039.

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Footnote 37

Wang, E., S. Paessler, P. V. Aguilar, A. S. Carrara, H. Ni, I. P. Greene, and S. C. Weaver. 2006. Reverse transcription-PCR-enzyme-linked immunosorbent assay for rapid detection and differentiation of alphavirus infections. J. Clin. Microbiol. 44:4000-4008.

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Footnote 38

Calisher, C. H., A. O. El-Kafrawi, M. I. Al-Deen Mahmud, A. P. Travassos da Rosa, C. R. Bartz, M. Brummer-Korvenkontio, S. Haksohusodo, and W. Suharyono. 1986. Complex-specific immunoglobulin M antibody patterns in humans infected with alphaviruses. J. Clin. Microbiol. 23:155-159.

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Footnote 39

Pittman, P. R., R. S. Makuch, J. A. Mangiafico, T. L. Cannon, P. H. Gibbs, and C. J. Peters. 1996. Long-term duration of detectable neutralizing antibodies after administration of live-attenuated VEE vaccine and following booster vaccination with inactivated VEE vaccine. Vaccine. 14:337-343.

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Footnote 40

Government of Canada. 2020. ePATHogen - Risk Group Database.

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Footnote 41

Public Health Agency of Canada. 2019. Human Pathogens and Toxins Act (HPTA) (S.C. 2009, c.24).

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