Guanarito mammarenavirus: Infectious substances pathogen safety data sheet

Section I – Infectious agent


Guanarito mammarenavirus

Agent type








Guanarito mammarenavirus

Synonym or cross-reference

Also known as GTOV, New World mammarenavirus, and Venezuelan hemorrhagic fever Footnote 1Footnote 2.


Brief description

GTOV is an enveloped, pleomorphic, single-stranded RNA virus. The genome consists of two linear ambisense RNA segments that are 7.1 kb and 3.3 kb in length Footnote 3Footnote 4Footnote 5. GTOV behaves like a negative-sense RNA virus. Virions measure 50 to 200 nm in diameterFootnote 2.


Host cell entry is mediated by transferrin receptor 1 Footnote 6. The GTOV genome encodes four proteins: nucleoprotein (NP), glycoprotein precursor, RNA-dependent RNA polymerase (L protein), and zinc-binding protein (Z protein)Footnote 5. GTOV uses an ambisense coding strategy whereby mRNA for NP and L proteins are transcribed from genomic RNA and mRNA for GP and Z protein are transcribed from anti-genomic RNA Footnote 7. Virus replication occurs in the cytoplasm of host cells Footnote 8. Mature virions are released via budding from the plasma membraneFootnote 8.

Section II – Hazard identification

Pathogenicity and toxicity

GTOV causes systemic infection with hemorrhagic features known as Venezuelan hemorrhagic fever. Initial symptoms (day 0 to 4) are mild and may include fever (93%), malaise (75%), headache (58%), sore throat (36%), and vomiting (34%)Footnote 1. Symptoms usually become more severe as the disease progresses (day 5 to 12) and may include hemorrhagic symptoms (e.g., bleeding gums (53%), hematemesis (16%), petechiae (16%), epistaxis (13%), rectal bleeding (9%)), and convulsions (18%)Footnote 1. Hospitalization is often required within one week from the onset of symptoms. The average time between hospitalization and death is 5 daysFootnote 1. Case-fatality is approximately 26-33%Footnote 1Footnote 9.


Cases of Venezuelan hemorrhagic fever occur within a restricted geographic range in the Venezuelan states of Portuguesa and Barinas, where the disease is endemicFootnote 1Footnote 10. Agricultural workers are most commonly affectedFootnote 1. Incidence is usually highest between November and January in Venezuela, when agricultural activity is at its peakFootnote 1. GTOV was discovered in 1989, and between 1989 and 2006, approximately 618 cases were reported with a mortality rate of approximately 26%Footnote 9. Outbreaks have occurred during 1989-1991 (15 confirmed cases), 1997-1998, 2002-2003, 2011-2012 (86 cases), and 2016 (142 suspected cases) Footnote 11Footnote 12Footnote 13.

Host range

Natural host(s)

Humans, rodentsFootnote 9.

Other host(s)

Guinea pigs and rhesus monkeys have been experimentally infected with GTOV Footnote 14Footnote 15.

Infectious dose


Incubation period

Approximately 1 to 3 weeksFootnote 16.


The primary route of GTOV transmission is via inhalation of aerosolized infectious particles (i.e., excreta and body fluids from infected rodents)Footnote 5Footnote 17. Direct inoculation through broken skin is considered to be a possible route of GTOV transmissionFootnote 2. Person-to-person transmission is believed to be possible (i.e., via direct contact with body fluids from infected individuals), but has not been definitively demonstrated to dateFootnote 1Footnote 2.

Section III – Dissemination


GTOV has been isolated primarily from the cane mouse Zygodontomys brevicauda (prevalence 48%) in Venezuela, but also Alston's cotton rat (Sigmodon alstoni)Footnote 17Footnote 18. The GTOV antibody was found in 1.1% of Z. brevicauda in Cordoba, Colombia, which is adjacent to VenezuelaFootnote 10.


Disease is spread to humans via inhalation of aerosolized infectious material found in excreta and body fluids of GTOV-infected rodentsFootnote 1Footnote 5.



Section IV – Stability and viability

Drug susceptibility/resistance

Ribavirin is effective against other arenaviruses and is used in clinical settingsFootnote 5Footnote 19.

Susceptibility to disinfectants

There is no information specific for GTOV. Other enveloped, single-stranded RNA viruses are inactivated by sodium hypochlorite (1%) and ethanol (70%) Footnote 20.

Physical inactivation

Mammarenaviruses are inactivated below pH 5.5 and above pH 8.5Footnote 2. Other arenaviruses are inactivated by UV and gamma irradiation, and heat (greater than 60 °C for 75 minutes) Footnote 21Footnote 22.

Survival outside host

Data not available for GTOV. Exposure to 24 °C for 2 hours and 32 °C for 3 hours at 30% relative humidity resulted in a 99% titer reduction of other mammarenaviruses Footnote 23Footnote 24.

Section V – First aid/medical


GTOV can be detected using reverse transcription polymerase-chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assayFootnote 16.

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

Treatment is usually supportive to manage bleeding and dehydrationFootnote 1.

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.


No vaccine availableFootnote 14.

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



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

In a retrospective study of 757 people with occupational rodent exposure, antibody against GTOV was detected in a worker who handled rodents in the United States Footnote 25.

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.


Blood, tissue, throat washings, and urineFootnote 1Footnote 26.

Primary hazards

The primary exposure hazard is inhalation of airborne or aerosolized infectious material.

Special hazards


Section VII – Exposure controls/personal protection

Risk group classification

GTOV is a Risk Group (RG) 4 human pathogen and RG4 animal pathogen Footnote 27Footnote 28. GTOV is also a Security Sensitive Biological Agent (SSBA)Footnote 28.

Containment requirements

Containment Level 4 facilities, equipment, and operational practices outlined in the CBS for work involving infectious or potentially infectious materials, animals, or cultures.

Note: There are additional security requirements, such as obtaining a Human Pathogens and Toxins Act Security Clearance, for work involving SSBAs.

Protective clothing

The applicable Containment Level 4 requirements for personal protective equipment and clothing outlined in the CBS to be followed. The use of a positive-pressure suit or use of a Class III biological safety cabinet (BSC) line is required for all work with RG4 pathogens.

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 regulated materials are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are unloaded in a biological safety cabinet. The integrity of positive pressure suits must be routinely checked for leaks. The use of needles, syringes, and other sharp objects to be strictly limited. Open wounds, cuts, scratches, and grazes are to be covered with waterproof dressings. Additional precautions must be considered with work involving animal activities.

Section VIII – Handling and storage


The spill area to be evacuated and secured. Aerosols must be allowed to settle for a minimum of 30 minutes. Spills of potentially contaminated material to be covered with absorbent paper-based material (e.g., paper towels), liberally covered with an effective disinfectant (e.g., 1% sodium hypochlorite), and left to soak for an appropriate amount of time (e.g., 10 minutes) before being wiped up. Following the removal of the initial material, the disinfection process to be repeated. Individuals performing this task must wear PPE, including particulate respirators (e.g., N95 or higher). Disposable gloves, impermeable gowns and protective eye wear are to be removed immediately after completion of the process, placed in an autoclave bag, and decontaminated prior to disposal (CBH).


All materials/substances that have come in contact with the regulated materials must be completely decontaminated before they are removed from the containment zone. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated materials, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination ( CBH).


Containment Level 4: The applicable Containment Level 4 requirements for storage outlined in the CBS are to be followed. Pathogens, toxins, and other regulated materials to be stored inside the containment zone.

Inventory of Risk Group 4 (RG4) pathogens in long-term storage to be maintained and to include:

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with GTOV require a Human Pathogens and Toxins Licence, issued by the Public Health Agency of CanadaFootnote 28. GTOV is a non-indigenous animal pathogen in Canada; therefore, importation of GTOV requires an import permit, issued by the CFIA Footnote 29.

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

Last file update


Prepared by

Centre for Biosecurity, Public Health Agency of Canada.


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


Footnote 1

De Manzione, N., R. A. Salas, H. Paredes, O. Godoy, L. Rojas, F. Araoz, C. F. Fulhorst, T. G. Ksiazek, J. N. Mills, B. A. Ellis, C. J. Peters, and R. B. Tesh. 1998. Venezuelan hemorrhagic fever: clinical and epidemiological studies of 165 cases. Clin. Infect. Dis. 26:308-313.

Return to footnote 1 referrer

Footnote 2

International Committee on the Taxonomy of Viruses. 2019. The Online (10th) Report on the International Taxonomy of Viruses.

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Footnote 3

Charrel, R. N., H. Feldmann, C. F. Fulhorst, R. Khelifa, R. de Chesse, and X. de Lamballerie. 2002. Phylogeny of New World arenaviruses based on the complete coding sequences of the small genomic segment identified an evolutionary. Biochem. Biophys. Res. Commun. 296:1118.

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Footnote 4

Bowen, M. D., K. Thurman, E. Minor, R. F. Meyer, S. A. Malfatti, L. H. Do, K. L. Smith, P. M. McCready, and P. S. G. Chain. 2003. Guanarito virus strain INH-95551 segment L, complete sequence. GenBank: AY358024.2. GenBank.

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Footnote 5

Hallam, S. J., T. Koma, J. Maruyama, and S. Paessler. 2018. Review of Mammarenavirus Biology and Replication. Front. Microbiol. 9:1751.

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Footnote 6

Radoshitzky, S. R., J. Abraham, C. F. Spiropoulou, J. H. Kuhn, D. Nguyen, W. Li, J. Nagel, P. J. Schmidt, J. H. Nunberg, N. C. Andrews, M. Farzan, and H. Choe. 2007. Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses. Nature. 446:92-96.

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Footnote 7

Shao, J., Y. Liang, and H. Ly. 2015. Human hemorrhagic Fever causing arenaviruses: molecular mechanisms contributing to virus virulence and disease pathogenesis. Pathogens. 4:283-306.

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Footnote 8

Burrell, C., C. Howard, and F. Murphy. 2016. Arenaviruses, p. 425. Anonymous Fenner and White's Medical Virology, 5th ed.,. Elsevier. Available at

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Footnote 9

Logue, J., M. Richter, R. F. Johnson, J. H. Kuhn, and W. Weaver. 2019. Overview of Human Viral Hemorrhagic Fevers, p. 39. S. K. Singh and J. H. Kuhn (eds.), Defense Against Biological Attacksvol. II. Springer, Cham.

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Footnote 10

Mattar, S., C. Guzman, J. Arrazola, E. Soto, J. Barrios, N. Pini, S. Levis, J. Salazar-Bravo, and J. N. Mills. 2011. Antibody to arenaviruses in rodents, Caribbean Colombia. Emerg. Infect. Dis. 17:1315-1317.

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Footnote 11

Salas, R., N. de Manzione, R. B. Tesh, R. Rico-Hesse, R. E. Shope, A. Betancourt, O. Godoy, R. Bruzual, M. E. Pacheco, and B. Ramos. 1991. Venezuelan haemorrhagic fever. Lancet. 338:1033-1036.

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Footnote 12

ProMed mail – International Society for Infectious Diseases. 2017. Venezuelan hemorrhagic fever – Venezuela.

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Footnote 13

MD Travel Heath. 2019. Venezuela Travel Health Information. 2019:.

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Footnote 14

Golden, J. W., B. Beitzel, J. T. Ladner, E. M. Mucker, S. A. Kwilas, G. Palacios, and J. W. Hooper. 2017. An attenuated Machupo virus with a disrupted L-segment intergenic region protects guinea pigs against lethal Guanarito virus infection. Sci. Rep. 7:4679-017-04889-x.

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Footnote 15

Tesh, R. B., P. B. Jahrling, R. Salas, and R. E. Shope. 1994. Description of Guanarito virus (Arenaviridae: Arenavirus), the etiologic agent of Venezuelan hemorrhagic fever. Am. J. Trop. Med. Hyg. 50:452-459.

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Footnote 16

Fukushi, S., H. Tani, T. Yoshikawa, M. Saijo, and S. Morikawa. 2012. Serological assays based on recombinant viral proteins for the diagnosis of arenavirus hemorrhagic fevers. Viruses. 4:2097-2114.

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Footnote 17

Milazzo, M. L., M. N. Cajimat, G. Duno, F. Duno, A. Utrera, and C. F. Fulhorst. 2011. Transmission of Guanarito and Pirital viruses among wild rodents, Venezuela. Emerg. Infect. Dis. 17:2209-2215.

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Footnote 18

Tesh, R. B., M. L. Wilson, R. Salas, N. M. De Manzione, D. Tovar, T. G. Ksiazek, and C. J. Peters. 1993. Field studies on the epidemiology of Venezuelan hemorrhagic fever: implication of the cotton rat Sigmodon alstoni as the probable rodent reservoir. Am. J. Trop. Med. Hyg. 49:227-235.

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Footnote 19

Jay, M. T., C. Glaser, and C. F. Fulhorst. 2005. The arenaviruses. J. Am. Vet. Med. Assoc. 227:904-915.

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Footnote 20

Kowalski, W. 2012. Disinfection of the Inanimate Environment, p. 139. W. Kowalski (ed.), Hospital Airborne Infection Control. CRC Press.

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Footnote 21

Elliott, L. H., J. B. McCormick, and K. M. Johnson. 1982. Inactivation of Lassa, Marburg, and Ebola viruses by gamma irradiation. J. Clin. Microbiol. 16:704-708.

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Footnote 22

Mitchell, S. W., and J. B. McCormick. 1984. Physicochemical inactivation of Lassa, Ebola, and Marburg viruses and effect on clinical laboratory analyses. J. Clin. Microbiol. 20:486-489.

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Footnote 23

Stephenson, E. H., E. W. Larson, and J. W. Dominik. 1984. Effect of environmental factors on aerosol-induced Lassa virus infection. J. Med. Virol. 14:295-303.

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Footnote 24

Sinclair, R., S. A. Boone, D. Greenberg, P. Keim, and C. P. Gerba. 2008. Persistence of category A select agents in the environment. Appl. Environ. Microbiol. 74:555-563.

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Footnote 25

Fulhorst, C. F., M. L. Milazzo, L. R. Armstrong, J. E. Childs, P. E. Rollin, R. Khabbaz, C. J. Peters, and T. G. Ksiazek. 2007. Hantavirus and arenavirus antibodies in persons with occupational rodent exposure. Emerg. Infect. Dis. 13:532-538.

Return to footnote 25 referrer

Footnote 26

Fulhorst, C. F., M. D. Bowen, R. A. Salas, G. Duno, A. Utrera, T. G. Ksiazek, N. M. De Manzione, E. De Miller, C. Vasquez, C. J. Peters, and R. B. Tesh. 1999. Natural rodent host associations of Guanarito and pirital viruses (Family Arenaviridae) in central Venezuela. Am. J. Trop. Med. Hyg. 61:325-330.

Return to footnote 26 referrer

Footnote 27

Government of Canada. Jan 2019. ePATHogen - Risk Group Database. Feb 2019:.

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Footnote 28

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

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Footnote 29

Canadian Food Inspection Agency. 2018. Health of Animals Act (HAA) (S.C. 1990, c.21).

Return to footnote 29 referrer

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