Chapare virus: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Chapare virus

Agent type

Virus

Taxonomy

Family

Arenaviridae

Genus

Mammarenavirus

Species

chapareense^{Footnote 1}

Synonym or cross-reference

Commonly known as Chapare virus (CHAPV)^{Footnote 2}, or Chapare Hemorrhagic Fever (CHHF)^{Footnote 3}. Prior to the discovery and initial naming, it was known generically as the ailment it caused, Bolivian Hemorrhagic Fever (BHF)^{Footnote 4Footnote 5}.

Characteristics

Brief description

Chapare virus is part of the Arenaviridae family, which is a family of ambisense RNA viruses with genomes of approximately 10.5 kb^{Footnote 6}. Arenavirid virions are spherical or pleomorphic in shape and between 40 and 200 nm in diameter, with dense lipid envelopes that is covered by glycoprotein projections^{Footnote 6}. Additionally, the virion contains two filamentous nucleocapsids with helical symmetry^{Footnote 7}. The RNA genome of the arenavirids consist of two or three single-stranded (typically ambisense) RNA segments (small [S], medium [M], and large [L])^{Footnote 6Footnote 7}.

Properties

The genus Mammarenavirus is divided into two groups, referred to as Old World (Lassa-lymphocytic choriomeningitis serocomplex) and New World (Tacaribe serocomplex), which is based on their geographic distribution, phylogeny, and antigenic properties^{Footnote 8Footnote 9Footnote 10}. Additionally, the New World category is subdivided into four clades (A, B, C and D). CHAPV falls in clade B under the New World category, which denotes that these arenaviruses utilise human Transferrin Receptor 1 (TfR1) for cell entry^{Footnote 9}.

Virus particles initially enter the host through inhalation of aerosolized particles^{Footnote 2Footnote 9}. It is hypothesized that alveolar macrophages are the first cell types infected due to the route of infection and the infectious particles being present in macrophages early during the infection. Upon attachment to the host cell, CHAPV is endocytosed via the clatherin-dependent pathway^{Footnote 9}. After viral replication and budding, CHAPV continues to circulate throughout the lymphatic system, which aids in spreading the infection to more tissues^{Footnote 9}.

Section II – Hazard identification

Pathogenicity and toxicity

Under the family Arenaviridae, the genus Mammarenavirus encompasses those viruses that infect mammalian hosts^{Footnote 9}. BHF can be caused by two viral agents, the CHAPV and the Machupo virus (MACV)^{Footnote 4}. Both viral agents have similar clinical manifestations. As noted above, CHAPV is classified under clade B of the New World, meaning that CHAPV is one of several arenaviruses that cause severe and fatal hemorrhagic fever^{Footnote 5Footnote 8Footnote 10}.

BHF has three clinical phases referred to as prodromal phase, hemorrhagic phase, and convalescent phase^{Footnote 4}. The disease begins with the prodromal phase which is characterized by non-specific symptoms such as fever, malaise, headache, anorexia, dizziness, arthralgia, myalgia, dehydration, retro-orbital pain, chills, Acute Respiratory Distress Syndrome (ARDS), and lower-back pain^{Footnote 2Footnote 4Footnote 5}. Three to four days later, the disease's severity increases with additional symptoms such as nausea, vomiting, abdominal pain, diarrhea, skin hypersensitivity, leukopenia, thrombocytopenia, upper digestive hemorrhage, and early signs of vascular damage such as petechiae, gingival bleeding, and conjunctival injection. Approximately one third of patients progress to a hemorrhagic phase, which usually takes place 2 weeks after the onset of symptoms, and is characterized by multi-organic hemorrhagic manifestations such as petechiae, subconjunctival hemorrhage, gingival bleeding, epistaxis, hematemesis, melena, relative bradycardia, hypotension, pulmonary edema, hematuria, venepuncture-site hemorrhage, and neurological signs such as tremors, ataxia, muscle spasms, seizures, delirium, and coma. Fatal outcomes occur seven to twelve days after the onset of symptoms, and the most frequent causes of death are pulmonary edema, massive internal bleeding, and hypovolemic shock^{Footnote 2Footnote 4}. The fatality rate is approximately 30%; however, the probability of mortality decreases when patients are treated promptly in the early phases of the disease^{Footnote 4}. Patients who survive the hemorrhagic phase begin to improve after two weeks, which is referred to as the convalescent phase, which can last several weeks or even months before full recovery^{Footnote 2Footnote 4}. During this phase, clinical signs such as fatigue, dizziness, Beau lines in nails, and hair loss can develop^{Footnote 2Footnote 4}.

With the genetically related Lassa virus, pregnant patients tend to have higher mortality (death of the mother and/or fetus) rates and the possibility of further complications including miscarriage, or swollen-baby syndrome in infants (characterized by bleeding, distension, and anasarca)^{Footnote 11}.

Epidemiology

Other than the BHF outbreaks that occurred in the 20th century, for which we have no confirmation that CHAPV was the viral causative agent, there have been two confirmed CHAPV outbreaks, one in 2003-2004 and 2019^{Footnote 4Footnote 5}.

Between December of 2003 and January of 2004, 3 reported cases of hemorrhagic fever occurred in a rural area near the Chapare river, near Cochabamba^{Footnote 5Footnote 12}. Analysis of clinical symptoms and blood samples of one fatal case (22 year old male) along with the subsequent analysis of the complete virus RNA segments sequences identified the virus as a member of the New World clade B arenavirus^{Footnote 5Footnote 12}. The sequence comparison analysis confirmed that the virus was closely related to Sabiá virus, but sufficient differences were found to conclude that the virus represented a newly discovered arenavirus, Chapare virus^{Footnote 5}.

From May to December of 2019, a total of nine cases, four of which had fatal outcomes, were recorded within the La Paz department of Bolivia^{Footnote 3Footnote 5}. The first five cases between May and June of 2019 occurred interconnectedly, 2 of which were agricultural workers and 3 were in health care professionals, with 3 cases resulting in fatal outcomes. The subsequent 4 cases occurred in July and December of 2019, 3 of which were in agricultural workers and 1 was in a child, with 1 case resulting in a fatal outcome. Additionally, of those 4 cases, 2 were pregnant women (16 and 5 weeks gestation). It is unknown whether their pregnancy caused a more severe disease.

Host range

Natural host(s)

The natural hosts include humans as well as rodents^{Footnote 4}.

Other host(s)

For the genetically related MACV and Junin virus (JUNV), experimentally infected hosts include hamsters, mice, horses, cats, rabbits, guinea-pigs, chicken, marmosets, rhesus monkeys, and marsupials^{Footnote 13}.

Infectious dose

Unknown.

Incubation period

Between 3-21 days^{Footnote 4}.

Communicability

The primary transmission method of CHAPV to humans is via inhalation of aerosolized particles from rodents' excrement along with contact to mucous membranes/broken skin^{Footnote 2Footnote 3Footnote 4}. Along with those, another possible route of transmission is via consumption of rodent excreta via contaminated food^{Footnote 4}. Human to human transmission is suspected to have occurred during the 2019 outbreak, including one potential nosocomial transmission^{Footnote 3Footnote 5}. Additionally, rodents contract the virus either via direct contact with other infected rodents, or through environmental exposure to the virus in habitats where the virus is present^{Footnote 3}.

Section III – Dissemination

Reservoir

It is known that rodents are the reservoirs for CHAPV, however, the specific species are unknown^{Footnote 12}. Callomys callosus is suspected to be one possible reservoir, as it was the confirmed reservoir for the Machupo and Latino viruses (both located in Bolivia)^{Footnote 4Footnote 12}. Additionally, during the outbreak of 2019, CHAPV RNA was detected in samples from Oligoryzomys microtis, also known as small-eared pygemy rice rats^{Footnote 3}.

Zoonosis

The virus is transmitted from rodents to humans^{Footnote 3Footnote 8}.

Vectors

There are no known vectors for CHAPV. However, viruses under the Old World category (such as strains of lymphocytic choriomeningitis virus) as well as under the New World category (such as a strain of Tamiami virus and Taracribe virus) have had isolations from arthropods, therefore, arthropod mediated transmission can not be ruled out entirely for CHAPV^{Footnote 8}.

Section IV – Stability and viability

Drug susceptibility/resistance

There are no confirmed drug susceptibilities for CHAPV, however, the use of the antiviral ribavirin (a non-immunosuppressive guanosine analogue that inhibits IMP dehydrogenase) has shown some efficacy for various arenaviruses, including CHAPV, both in vitro and in vivo^{Footnote 4Footnote 5Footnote 14}. While ribavirin has shown favourable results in vivo, further testing in clinical trials is required^{Footnote 4Footnote 5}.

Susceptibility to disinfectants

Similar to all lipid-enveloped viruses, CHAPV is inactivated by compounds such as hypochlorites, phenolics, alcohols (such as ethanol and propanol), formaldehyde (paraformaldehyde and formalin), glutaraldehyde, iodophors, hydrogen peroxide, and peracetic acid^{Footnote 15Footnote 16}. In addition, CHAPV can be inactivated by quaternary ammonium compounds (QACs) such as chlorhexidine digluconate^{Footnote 16}.

Physical inactivation

Similar to other viruses under the Arenaviridae family, CHAPV is rapidly inactivated at 56℃, at pH below 5.5 or above 8.5, or by exposure to UV and/or gamma radiation^{Footnote 14}.

Survival outside host

As CHAPV is a lipid-enveloped virus, it has a generally minimal survival rate outside the host due to the envelope being sensitive to environmental factors such as humidity, as well as the presence of UV light and disinfectants^{Footnote 17Footnote 18}.

Section V – First aid/medical

Surveillance

Mammarenavirus can be identified using enzyme-linked immunosorbent assays (ELISA) to detect antibodies to the virus, virus neutralization tests, fluorescent microscopy assays (IFAs), reverse transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, and PCR^{Footnote 2Footnote 14}.

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.

First aid/treatment

Treatment for CHAPV consists primarily of supportive care such as mechanical ventilation, administration of clotting factor or platelet replacement, as well as correction fluid, electrolyte, and osmotic imbalance^{Footnote 2Footnote 14}. There are no antiviral therapies approved for the treatment of BHF, and the current options, including the usage of ribavirin and passive antibody therapy, need to be further tested in clinical trials specifically for CHAPV^{Footnote 4Footnote 5}.

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 Canadian Biosafety Handbook.

Immunization

There is currently no approved vaccines for CHAPV. However, in Argentina, a vaccine for the genetically related JUNV, referred to as Candid #1, has shown some evidence of cross-reactivity to MACV, and may therefore be effective against CHAPV^{Footnote 5Footnote 14}.

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

Prophylaxis

No known post-exposure prophylaxis.

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

Section VI – Laboratory hazard

Laboratory-acquired infections

No cases of laboratory-acquired infections have been reported.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents.

Sources/specimens

CHAPV RNA was detected by real time RT-PCR in whole blood, serum, and urine samples, as well as in nasopharyngeal, oropharyngeal, and bronchoalveolar-lavage fluid, and additionally in conjunctiva and semen samples^{Footnote 2Footnote 4Footnote 14}.

Primary hazards

Exposure (inhalation or ingestion) to infectious material in animal waste is the primary hazard associated with exposure to CHAPV^{Footnote 4}.

Special hazards

Work with experimentally CHAPV-infected rodents can present a special hazard^{Footnote 3Footnote 5}.

Section VII – Exposure controls/personal protection

Risk group classification

CHAPV is a Risk Group 4 Human Pathogen and Risk Group 2 Animal Pathogen, and is a Security Sensitive Biological Agent (SSBA)^{Footnote 19Footnote 20}.

Containment requirements

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

Note that 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 Canadian Biosafety Standard are 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 BSC. The integrity of positive pressure suits must be routinely checked for leaks. The use of needles, syringes, and other sharp objects are 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 is to be repeated.

For spills outside of a biological safety cabinet (BSC), air supply to positive-pressure suits must be ensured. Positive-pressure suits that have been in contact with the regulated materials must be completely decontaminated by following procedures for gross decontamination of a positive-pressure suit. Plastics to be transferred to a dishpan, which should be moved to the BSC. 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., 5% MicroChem), and left to soak for at least 5 minutes before being wiped up. Following the removal of the initial material, the disinfection process is to be repeated. After disinfection, inform the appropriate internal authority (e.g., containment zone supervisor, BSO) of the incident.

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 (Canadian Biosafety Handbook).

Storage

The applicable Containment Level 4 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Pathogens and other regulated materials to be stored inside the containment zone.

An inventory of RG4 pathogens and SSBAs in long-term storage to be maintained and to include:

• specific identification of the regulated materials
• a mechanism that allows 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 Mammarenavirus chapareense require a Pathogen and Toxin licence issued by the Public Health Agency of Canada (PHAC). M. chapareense is also a terrestrial animal pathogen in Canada; therefore, its importation requires an import permit under the authority of the Health of Animals Regulations (HAR). The PHAC issues a Pathogen and Toxin Licence which includes a Human Pathogen and Toxin Licence and an HAR importation permit.

Note that there are additional security requirements, such as obtaining a Human Pathogen and Toxins Act Security Clearance, for work involving SSBAs.

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

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• National notifiable disease (human)

Last file update

June, 2024

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, directives and standards applicable to the import, transport, and use of pathogens and toxins 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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