Guanarito mammarenavirus: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Guanarito mammarenavirus

Agent type

Virus

Taxonomy

Family

Arenaviridae

Genus

Mammarenavirus

Species

Guanarito mammarenavirus

Synonym or cross-reference

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

Characteristics

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 diameter^{Footnote 2}.

Properties

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 membrane^{Footnote 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 days^{Footnote 1}. Case-fatality is approximately 26-33%^{Footnote 1Footnote 9}.

Epidemiology

Cases of Venezuelan hemorrhagic fever occur within a restricted geographic range in the Venezuelan states of Portuguesa and Barinas, where the disease is endemic^{Footnote 1Footnote 10}. Agricultural workers are most commonly affected^{Footnote 1}. Incidence is usually highest between November and January in Venezuela, when agricultural activity is at its peak^{Footnote 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, rodents^{Footnote 9}.

Other host(s)

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

Infectious dose

Unknown.

Incubation period

Approximately 1 to 3 weeks^{Footnote 16}.

Communicability

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 transmission^{Footnote 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 date^{Footnote 1Footnote 2}.

Section III – Dissemination

Reservoir

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 Venezuela^{Footnote 10}.

Zoonosis

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

Vectors

None.

Section IV – Stability and viability

Drug susceptibility/resistance

Ribavirin is effective against other arenaviruses and is used in clinical settings^{Footnote 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 8.5^{Footnote 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

Surveillance

GTOV can be detected using reverse transcription polymerase-chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay^{Footnote 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 dehydration^{Footnote 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.

Immunization

No vaccine available^{Footnote 14}.

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

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.

Sources/specimens

Blood, tissue, throat washings, and urine^{Footnote 1Footnote 26}.

Primary hazards

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

Special hazards

None.

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

Spills

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).

Disposal

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).

Storage

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:

• specific identification of the pathogens, toxins, and other regulated materials; and
• a means to allow for the detection of a missing or stolen sample in a timely manner.

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 Canada^{Footnote 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:

• Human Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• Transportation of Dangerous Goods Regulations

Last file update

2019

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.

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