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MACHUPO VIRUS

PATHOGEN SAFETY DATA SHEET – INFECTIOUS SUBSTANCES

SECTION I – INFECTIOUS AGENT

NAME: Machupo virus

SYNONYM OR CROSS REFERENCE: Viral hemorrhagic fever (VHF), Bolivian hemorrhagic fever (BHF), South American hemorrhagic fever, Arenavirus, black typhus, Ordog Fever(1).

CHARACTERISTICS: The Machupo virus was first isolated in 1959 and is a New World Arenavirus from the Arenaviridae family. It is spherical and pleomorphic, with a diameter of 50 – 300 nm (average of 120 nm), and has a RNA genome that is single stranded and bi-segmented. Ribosomes located inside the virus give it its characteristic sandy appearance under electron microscopy, and it is enclosed in a dense lipid- containing envelop, with 8 – 10 nm long club-shaped projections(1,2).

SECTION II – HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: Dominant clinical features of viral haemorrhage include microvascular damage and changes in vascular permeability, fever, myalgia (muscle pains), and prostration(3). Initial symptoms may include conjunctival injection, mild hypertension, flushing, bleeding gums and cavities, headache, arthralgia, and petechial haemorrhages. Symptoms can further develop into shock and generalized mucous membrane haemorrhage, epistaxis, haematemesis, melena, haematuria, accompanied by neurological damage such as tremor, seizures, and coma(4). The case fatality rate during the 1960's outbreak was 22%.

EPIDEMIOLOGY: Occurrence is concentrated in Bolivia and surrounding areas. The prevalence of the Machupo virus is limited to the location of its specific rodent hosts, which are commonly found in tropical grasslands and temperate forest regions, eastern Bolivian plains, northern Paraguay, and western Brazil(4). An outbreak in Bolivia of over 1000 cases was reported during 1962 – 1964, which co-occurred with an increase of the Calomys (vesper mouse) rodent population, and the mortality rate was 18%. Another outbreak solely based on nosocomial transmission was observed in 1971 in Cochabamba, Bolivia(5). The incidence rate is highest during harvest seasons between March and June(1).

HOST RANGE: Rodents are the primary and most common hosts in nature(1). Humans, ticks, and mosquitoes can also become infected.

INFECTIOUS DOSE: 1 – 10 organisms by aerosol transmission are sufficient to cause clinical infection in humans(3).

MODE OF TRANSMISSION: The spread of the virus is primarily by aerosol transmission of dust particles from infected rodents excreta or secreta(1). Nosocomial transmission has also been observed.

INCUBATION PERIOD: 4 – 21 days(3).

COMMUNICABILITY: Although rare, person-to-person spread of the virus is possible through nosocomial transmission(1,4,6).

SECTION III – DISSEMINATION

RESERVIOR: Rodents, primarily the Calomys callosus (large vesper mouse)(6).

ZOONOSIS: Yes – virus is most commonly transmitted to humans through bite wounds of ticks that inhabit infected rodents(1), mosquitoes(1), or through inhalation of microareosols from infected rodents(7).

VECTORS: Ticks and mosquitoes are the main vectors(1).

SETION IV – STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: Ribavirin treatment for Bolivian hemorrhagic fever caused by the Machupo virus has been used successfully in a very small number of infected humans, although more detailed studies are required to determine its efficacy(2,3,8). Ribavirin is recommended for treating persons infect with the closely related Lassa Fever virus, and Ribavirin has shown some promise for treating human infections with other arenaviruses, including Junin virus and Sabia virus(2,9,10).

SUSCEPTIBILITY TO DISINFECTANTS: Susceptible to 1% sodium hypochlorite, phenolic disinfectants, and 2% glutaraldehyde(11).

PHYSICAL INACTIVATION: The virus can be inactivated by heating at 56 C, at pH below 5.5 or above 8.5, and by UV and gamma irradiation(11).

SURVIVAL OUTSIDE HOST: The hemorrhagic fever viruses cannot survive in dry environments, but can survive up to 2 weeks in blood specimens outside the host(12).

SECTION V – FIRST AID / MEDICAL

SURVEILLANCE: Monitor for symptoms. Viral haemorrhage and Machupo infection should be suspected in cases of severe febrile illness with evidence of vascular damage. Diagnosis can be confirmed by serology (i.e. ELISA), PCR, and definitive virus isolation techniques(3).

Note: All diagnostic methods are not necessarily available in all countries.

FIRST AID/TREATMENT: Administer appropriate drug therapy. Treatment using Ribavirin is most effective when administered within 7 days from the onset of symptoms, as was found against the Lassa virus. Rapid, non-traumatic hospitalization can prevent damage to capillary beds, which can be fragile in the presence of infection, thus intravenous lines, catheters, and other invasive devices should be avoided(3). Patients are generally dehydrated, respond poorly to fluid infusions, and may develop pulmonary oedema.

IMMUNIZATION: Animal protection studies have shown that the live attenuated vaccine Candid #1 used for the Junin virus can also be effective against the Machupo virus(13). Candid #1 has been tested on human volunteers and has passed safety and immunogenicity tests in the U.S. The treatment was administered in 6500 agricultural workers in Argentina during two epidemic seasons, and its efficacy was found to be around 84% or higher with no serious side effects.

PROPHYLAXIS: Avoiding contact with rodents(13). Ribavirin has been used as a prophylactic in at-risk populations to prevent Lassa virus infections(2).

SECTION VI – LABORATORY HAZARDS

LABORATORY-ACQUIRED INFECTIONS: As of 1980, 6 cases have been reported, one of which resulted in death, with aerosol transmission as the suspected source(14,15).

SOURCES/SPECIMENS: Infected blood or blood products, and excreta or secreta of infected organisms(1,12).

PRIMARY HAZARDS: Accidental parenteral inoculation, contact with mucous membranes, and aerosols that carry the virus(1,12).

SPECIAL HAZARDS: Contact with feces or microaerosols carrying the virus released by infected animals(1).

SECTION VII – EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 4(16).

CONTAINMENT REQUIREMENTS: Containment Level 4 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, or cultures.

PROTECTIVE CLOTHING: Personnel entering the laboratory must remove street clothing, including undergarments, and jewellery, and change into dedicated laboratory clothing and shoes, or don full coverage protective clothing (i.e., completely covering all street clothing). Additional protection may be worn over laboratory clothing when infectious materials are directly handled, such as solid-front gowns with tight fitting wrists, gloves, and respiratory protection. Eye protection must be used where there is a known or potential risk of exposure to splashes(17).

OTHER PRECAUTIONS: All activities with infectious material should be conducted in a biological safety cabinet (BSC) in combination with a positive pressure suit, or within a class III BSC line. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are loaded or 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 should be strictly limited. Open wounds, cuts, scratches, and grazes should be covered with waterproof dressings. Additional precautions should be considered with work involving animal activities(17).

SECTION VIII - HANDLING AND STORAGE

SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (30 min)(17).

DISPOSAL: Decontaminate all materials for disposal from the containment laboratory by steam sterilization, chemical disinfection, incineration or by gaseous methods. Contaminated materials include both liquid and solid wastes(17).

STORAGE: In sealed, leak-proof containers that are appropriately labelled and locked in a Containment Level 4 laboratory(17).

SECTION IX – REGULATORY AND OTHER INFORMATION

REGULATORY INFORMATION: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.

UPDATED: September 2010.

PREPARED BY: Pathogen Regulation Directorate, Public Health Agency of Canada.

Although the information, opinions and recommendations contained in this Pathogen Safety Data Sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.

Copyright ©
Public Health Agency of Canada, 2010
Canada

REFERENCES:

  1. LeDuc, J. W. (1989). Epidemiology of hemorrhagic fever viruses. Reviews of Infectious Diseases, 11 Suppl 4 , S730-5.
     
  2. Charrel, R. N., & de Lamballerie, X. (2003). Arenaviruses other than Lassa virus. Antiviral Research, 57 (1-2), 89-100.
     
  3. Franz, D. R., Jahrling, P. B., Friedlander, A. M., McClain, D. J., Hoover, D. L., Bryne, W. R., Pavlin, J. A., Christopher, G. W., & Eitzen, E. M.,Jr. (1997). Clinical recognition and management of patients exposed to biological warfare agents. JAMA : The Journal of the American Medical Association, 278 (5), 399-411.
     
  4. Warrell, D. A., Cox, T. M., Firth, J. D., & Benz, J., E.J. (Eds.). (2005). Oxford Textbook of Medicine . Oxford: Oxford Univeristy Press.
     
  5. Lennette, E. H., & Smith, T. F. (Eds.). (1999). Laboratory Diagnosis of Viral Infections (3rd ed.). New York, NY: Marcel Dekker Inc.
     
  6. Buchmeier, M., Adam, E., & Rawls, W. E. (1974). Serological evidence of infection by Pichinde virus among laboratory workers. Infection and Immunity, 9 (5), 821-823.
     
  7. Charrel, R. N., & de Lamballerie, X. (2010). Zoonotic aspects of arenavirus infections. Veterinary Microbiology, 140 (3-4), 213-220. doi:10.1016/j.vetmic.2009.08.027
     
  8. Kilgore, P. E., Ksiazek, T. G., Rollin, P. E., Mills, J. N., Villagra, M. R., Montenegro, M. J., Costales, M. A., Paredes, L. C., & Peters, C. J. (1997). Treatment of Bolivian hemorrhagic fever with intravenous ribavirin. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America, 24 (4), 718-722.
     
  9. Enria, D. A., Briggiler, A. M., Levis, S., Vallejos, D., Maiztegui, J. I., & Canonico, P. G. (1987). Tolerance and antiviral effect of ribavirin in patients with Argentine hemorrhagic fever. Antiviral Research, 7 (6), 353-359.
     
  10. Canonico, P. G., Kende, M., Luscri, B. J., & Huggins, J. W. (1984). In-vivo activity of antivirals against exotic RNA viral infections. The Journal of Antimicrobial Chemotherapy, 14 Suppl A , 27-41.
     
  11. Laboratory Safety Manual (1993). (2nd ed.). Geneva: World Health Organization.
     
  12. Burke, R. (2007). Counter-Terrorism for Emergency Responders (2nd ed.). Florida, USA: Taylor and Francis Group, LLC.
     
  13. Charrel, R. N. (2004). Viral Infections. Textbook of Pediatric Infectious Diseases (pp. 2372). Philadelphia, Pennsylvania: Elsevier, Inc.
     
  14. Scherer, W. F., Eddy, G. A., & Monath, T. P. (1980). Laboratory safety for arboviruses and certain other viruses of vertebrates. American Journal of Tropical Medicine and Hygiene, 29 (6), 1359-1381.
     
  15. Pike, R. M. (1976). Laboratory-associated infections: summary and analysis of 3921 cases. Health Laboratory Science, 13 (2), 105-114.
     
  16. Human pathogens and toxins act. S.C. 2009, c. 24, Second Session, Fortieth Parliament, 57-58 Elizabeth II, 2009. (2009).
     
  17. Public Health Agency of Canada. (2004). In Best M., Graham M. L., Leitner R., Ouellette M. and Ugwu K. (Eds.), Laboratory Biosafety Guidelines (3rd ed.). Canada: Public Health Agency of Canada.