New World Arenaviruses (Junin, Machupo, Guanarito, and Sabia viruses)
Boston University
Research Occupational Health Program (ROHP)
617-358-7647
Agent
New World arenaviruses (Junin virus, Machupo virus, Guanarito virus, and Sabia virus) are segmented negative-sense RNA viruses that belong to the family Arenaviridae, occurring in South America. All viruses are of zoonotic origin and transmitted mainly by contact with infected rodents. Person to person transmissions occur with less frequency and are associated with exposure in nosocomial settings. The infections caused by these pathogens can range from self-limited febrile illness to severe hemorrhagic fever with unique clinical features pronounced in each particular virus (discussed below).
Disease/Infection
Junin virus (Argentine hemorrhagic fever),
Machupo virus (Bolivian hemorrhagic fever),
Guanarito virus (Venezuelan hemorrhagic fever),
Sabia virus (Brazilian hemorrhagic fever)
Pathogenicity
Most patients improve after 1-2 weeks, but approximately one-third of untreated cases become severe and life-threatening. Mortality is up to 30% untreated. Drops to 1-2% with transfusion of convalescent plasma in Argentine hemorrhagic fever.
Risk Group/BSL
Risk group 4
Biosafety level: BSL4
Modes of Transmission
| Transmission | |
| Skin Exposure (Needlestick, bite, or scratch): | Yes |
| Mucous Membrane Splash to Eye(s), Nose or Mouth: | Yes |
| Inhalation: | Transmission via aerosolization of infected fluids or feces. |
| Ingestion: | Unlikely in laboratory setting |
Host Range/Reservoir
Rodents. Humans are accidental hosts.
Symptoms
South American hemorrhagic fevers resemble Lassa fever, but hemorrhages and neurological signs are more likely to be seen in severe cases.
Initial or mild presentation: fever, headache, anorexia, malaise and myalgia, lower back pain, nausea or vomiting, diarrhea, dizziness, sore throat, hyperesthesia of the skin, rash and lymphadenopathy.
Severe presentations: Hypovolemia, multi organ failure. Hemorrhagic features including: petechiae, gum bleeding, gastrointestinal tract or vaginal bleeding are also possible.
Pharyngitis, vomiting and diarrhea more common in Guanarito virus infections.
Erythema, petechiae, facial edema and shock more common in Junin or Machupo virus infections.
Late onset neurological syndrome after a symptom-free period in 10% of patients given convalescent plasma.
Incubation Period
Argentine hemorrhagic fever (Junin virus): 6 to 14 days.
Bolivian hemorrhagic fever (Machupo virus): 7 to 16 days
High dose exposures can reduce incubation days to around 2.
Viability
Arenaviruses can be inactivated by most detergents and disinfectants including 1% sodium hypochlorite and 2% glutaraldehyde. The viruses are also susceptible to ultraviolet light and gamma irradiation, and they can be inactivated by temperatures of 56°C (133°F) and by pH less than 5.5 or greater than 8.5.
Survival Outside Host
Junin virus: Unknown.
Machupo virus: up to 2 weeks in blood specimen.
Information for Lab Workers
Laboratory PPE
One-piece positive pressure ventilated suit with life support system is utilized. Long sleeve scrubs will be worn under the positive pressure suit with inner gloves providing added protection against outer glove tear.
Containment
All work with infectious virus must be performed in BSL-4/ABSL-4 containment.
PRIMARY HAZARDS:
- Accidental parenteral inoculation, respiratory exposure to infectious droplets, and/or direct contact with broken skin or mucous membranes.
SPECIAL HAZARDS:
- Work with, or exposure to, infected non-human primates, rodents, or their carcasses represents a risk of human infection; use of sharps when handling virus-containing material.
In Case of Exposure/Disease
Immediately after exposure, lab workers should follow the HIGH AND MAXIMUM CONTAINMENT MEDICAL INCIDENT RESPONSE PLAN (ERP C.1) as provided on site and during training.
- For all lab exposures which involve BSL-4 pathogens (needle sticks, punctures, cuts, scratches, etc.) and for all medical events which require immediate evaluation and treatment (traumatic injury, heart attack, stroke, seizure, etc.):
- Medical Campus: call or have a coworker call the Control Center at 617-414–6666. You will be referred to or transported to the appropriate health care location by the emergency response team.
- The Control Center operator will activate a communication tree which includes the BU Research Occupational Health Program (ROHP) Officer will help guide the response.
- To reach the ROHP directly use the 24/7 hour number (617-358-7647 (ROHP)).
- You will be connected with the BU Research Occupational Health Program (ROHP) medical officer. ROHP will refer you the appropriate health care location.
- Under any of these scenarios, always inform the physician of your work in the laboratory and the agent(s) that you work with.
- Present the Medical Surveillance Card that every BSL-4 researcher has been provided by ROHP, this wallet size card identifies the agents that the researcher works with; provide the ID card to the treating physician.
Vaccination
Argentine hemorrhagic fever (Junin virus): A live attenuated vaccine is available in endemic areas.
Animal models show some protection against Bolivian hemorrhagic fever (Machupo virus) with this vaccine but not Venezuelan hemorrhagic fever (Guanarito virus) or Brazilian hemorrhagic fever (Sabia virus).
There are no FDA approved vaccinations for either virus.
Information for First Responders/Medical Personnel
Public Health Issues
After exposure: Immediately after an exposure to a BSL-4 New World arenavirus, the lab worker is not considered infectious. He/she can be cared for with standard PPE. On campus exposures will be escorted directly from NEIDL triage room to the Special Pathogens Unit (SPU) at Boston Medical Center (BMC) where lab workers will be received by a team of physicians and nurses. In case of a lab worker presenting to BMC ED or other outside medical facility, either the exposed or the caring physicians should immediately contact ROHP for further instructions.
In case of (suspected) illness: Lab worker should contact ROHP directly and when possible, transport will be arranged to bring the patient to BMC’s Patient Isolation Unit. Patient should prevent close contact with household members pending evaluation, if possible. If the worker presents to BMC ED or other outside medical facility, caring physicians should contact ROHP for further instructions and ROHP will consult infectious diseases specialists at SPU.
Person-to-person transmission is reported via close personal contact with an infected individual or their body fluids during the late stages of the infection. PPE requirements for care of this patient are listed below.
PPE: SPU staff use advanced PPE including coveralls, fluid proof aprons, PAPR’s, and double gloves. CDC recommendations: Airborne, Droplet Precautions plus Contact Precautions, with face/eye protection, emphasizing safety sharps and barrier precautions when blood exposure likely. Avoid aerosol-generating procedures.
Other guidance for outside providers: No blood work should be drawn until contact is made with ROHP.
Specimen should be handled with extreme care and enclosed in appropriate shatter-proof and leak-proof packing for transport to lab. Diagnostic laboratory staff should be notified of suspicion of infection, and tests should be performed under proper containment. Please contact ROHP immediately for further details.
Public health officials will be notified.
Diagnosis/Surveillance
These viruses can be detected by PCR in bodily fluids. Acute and convalescent serologies are to be drawn.
Potential alternate diagnoses with similar presentation should be considered, such as influenza or other respiratory viruses.
First Aid/Post Exposure Prophylaxis
The administration of convalescent serum or oral ribavirin is considered in exposures.
Additional medical countermeasures maybe available post exposure through CDC and public health bodies and will be done in coordination with the SPU program.
Treatment
Treatment is aggressive supportive care, and is directed at maintaining renal function and electrolyte balance, addressing coagulopathy and combating hemorrhage and shock. Ribavirin maybe considered.
Transfusion of convalescent serum may be beneficial in Argentine hemorrhagic fever (Junin virus) particularly when started early and can decrease the mortality rate from 20-30% to 1-2%. May also be effective in Bolivian hemorrhagic fever (Machupo virus). No treatments are FDA approved for any of the agents.
Medical countermeasures maybe available during treatment through CDC and public health bodies and will be done in coordination with the SPU program.
Survivors of diseases caused by New World arenaviruses may shed virus for weeks after infection in urine and semen.
References
Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition. US Government Printing Office, Washington, 2007.
Iowa State University, Viral Hemorrhagic Fevers Caused by Arenaviruses, http://www.cfsph.iastate.edu/Factsheets/pdfs/viral_hemorrhagic_fever_arenavirus.pdf
Public Health Agency of Canada. Material Safety Data Sheets. Infectious Substances. Junin Virus, Machupo virus. https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/machupo-virus.html
https://www.canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/junin-virus.html
Siegel JD, Rhinehart E, Jackson M, Chiarello L. 2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Health Care Settings. American journal of infection control 2007 Dec;35(10 Suppl 2):S65-164.