Pathogen Safety Data Sheets: Infectious Substances – Lymphocytic choriomeningitis virus

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Lymphocytic choriomeningitis virusFootnote 1.

SYNONYM OR CROSS REFERENCE: LCMVFootnote 2-Footnote 13, LCMFootnote 14-Footnote 18, benign (or serous) lymphocytic meningitisFootnote 14, and Armstrong’s diseaseFootnote 15.

CHARACTERISTICS: As member of the family Arenaviridae, genus ArenavirusFootnote 9,Footnote 15, LCMV is an enveloped, round, oval, or pleomorphic virion, measuring roughly 110 nm to 130 nm in diameter with a bipartite single-stranded RNA genomeFootnote 6,Footnote 15. The virion interior contains granules resembling grains of sand, which are characteristic of the family Arenaviridae, while the surface has hollow golf-club shaped projectionsFootnote 15.

SECTION II - HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: Acquired LCM (Postnatal): LCMV infection in immunocompetent adults may be asymptomatic (nearly one third of all infectionsFootnote 2,Footnote 8 or limited to a non-specific, self-limited viral syndrome with symptoms such as fever, cough, malaise, myalgia, headache, photophobia, nausea, vomiting, adenopathy, and sore throatFootnote 2,Footnote 8,Footnote 9,Footnote 15,Footnote 19. The illness can progress to include meningitis or meningoencephalitisFootnote 6,Footnote 8,Footnote 14, and other less common neurologic symptoms such as paralysis, sensorineural hearing lossFootnote 2,Footnote 6,Footnote 8, and Guillain-Barré type syndromeFootnote 8. Uncommon non-neurologic manifestations of illness include pancreatitisFootnote 2, orchitisFootnote 2,Footnote 8, arthritis, pericarditis, parotitisFootnote 8 pneumonitis, and rashFootnote 2. Acquired LCMV infection is usually non-fatal, with a mortality rate of less than 1%, and recovery from even severe disease occurs without sequelae in most casesFootnote 5,Footnote 6,Footnote 14.

Congenital LCM: LCMV infection can produce a spectrum of pathologic effects, from minimal to severe, depending on the developmental stage of the foetus at the time of infectionFootnote 12. In some cases, infection may result in abortionFootnote 2,Footnote 9, hydrocephalus, chorioretinitis, and/or mental retardation of the infantFootnote 6. The mortality rate of infants diagnosed with congenital LCMV is approximately 35%Footnote 16. Among survivors of congenital LCMV infection, two thirds have long-term neurologic abnormalities, including microcephaly, mental retardation, cerebral palsy, seizures, and visual impairmentFootnote 2,Footnote 8,Footnote 16.

Transplantation associated LCM: Recently LCMV infection has been identified in individuals who received solid organ transplants from donors who died of apparent non-infectious aetiologiesFootnote 7,Footnote 20. These cases were uniformly fatal with the exception of one recipient who underwent ribavirin treatment when LCMV infection was suspected.

EPIDEMIOLOGY: The first identified Arenavirus, LCMV was isolated in 1933 from a woman thought to have St. Louis encephalitisFootnote 1. Unlike other Arenaviruses, which have limited geographic distribution, LCMV is found in Europe, the Americas, and Asia, primarily in areas where mice co-habitate with humansFootnote 15. The largest outbreak occurred between 1973 and 1974 in the United States with 181 cases and no deathsFootnote 19. Other recognised outbreaks have been recorded in Germany and FranceFootnote 9. The number of acquired LCM cases is underestimated since most cases are mild or asymptomatic and such individuals rarely seek medical attentionFootnote 12. Greater awareness and improved methods of detection may be contributing to increased prevalenceFootnote 6. Approximately 5% of humans show evidence of previous infection with LCMV (5). Congenital LCM was first recognised in 1955, and since then there have been 54 reported cases worldwideFootnote 3,Footnote 6,Footnote 21, 63% of them since 1993Footnote 6. It is not known whether the actual number of cases is significantly higher than this since only the most severe cases are reportedFootnote 13, and congenital LCM can produce a spectrum of pathological effects from minimal to severeFootnote 12.

HOST RANGE: HumansFootnote 2-Footnote 4,Footnote 6,Footnote 8,Footnote 9,Footnote 12-Footnote 17, miceFootnote 2,Footnote 3,Footnote 6,Footnote 14,Footnote 15,, hamstersFootnote 3,Footnote 4,Footnote 15,Footnote 17,Footnote 18, guinea pigs, rats, monkeys, dogs, rabbits, and chickensFootnote 17.

INFECTIOUS DOSE: Unknown.

MODE OF TRANSMISSION: Mice infected in utero asymptomatically shed LCMV in their faeces, urine, saliva, breast milk, and semenFootnote 2,Footnote 3,Footnote 8,Footnote 14,Footnote 15, and transmit the virus to humans (and other rodents, such as hamsters) by direct contactFootnote 2,Footnote 3, through damaged skinFootnote 14 or mucous membranesFootnote 14,Footnote 15, inhalation of aerosolised virusFootnote 2,Footnote 3,Footnote 8,Footnote 14, ingestion of virus contaminated foodFootnote 8,Footnote 9.Footnote 14,Footnote 15 or dustFootnote 9,Footnote 14, through rodent bitesFootnote 8,Footnote 15, or by contact with infected fomitesFootnote 2,Footnote 14. Transmission is also possible through organ transplantation from LCMV infected donorsFootnote 4,Footnote 7, and vertically from an infected mother to her foetusFootnote 3.

INCUBATION PERIOD: Approximately 8 to 13 daysFootnote 9,Footnote 14 and 15 to 21 days before any meningeal symptoms appearFootnote 14,Footnote 15.

COMMUNICABILITY: No evidence of human-to-human transmissionFootnote 14, with the exception of vertical transmission from an infected mother to her foetus during pregnancyFootnote 3, and through solid organ transplantation from infected donorsFootnote 4,Footnote 7.

SECTION III - DISSEMINATION

RESERVOIR: Primarily the house mouse (Mus. musculus)Footnote 2,Footnote 5,Footnote 14-Footnote 16, but the Syrian hamster is also a possibilityFootnote 17.

ZOONOSIS: Yes, LCMV is spread mainly through contact with contaminated rodent secretions/excretionsFootnote 2,Footnote 5,Footnote 14,Footnote 15,Footnote 18.

VECTORS: LCMV has been isolated from fleas, Culicoides flies, several species of Aedes mosquitoes, ticks and cockroaches, but it is deemed unlikely that arthropods play a role in LCMV transmissionFootnote 15.

SECTION IV – STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: Ribavirin has been shown to inactivate arenaviruses in vitro and may improve symptoms under clinical conditionsFootnote 5,Footnote 7,Footnote 21.

SUSCEPTIBILITY TO DISINFECTANTS: Bleach (sodium hypochlorite) or other common household disinfectants will inactivate LCMVFootnote 11.

PHYSICAL INACTIVATION: LCMV is inactivated by UV lightFootnote 10 and heat (55°C for at least 20 minutes)Footnote 1.

SURVIVAL OUTSIDE HOST: Unless it is preserved at -80°C, LCMV is quickly inactivated outside its hostFootnote 9. LCMV will retain its infectivity for at least 206 days if stored in 50% glycerine and 0.85% saline at 4-10°CFootnote 1.

SECTION V - FIRST AID / MEDICAL

SURVEILLANCE: Monitor for symptoms. Diagnosis is confirmed by serology, ELISAFootnote 2-Footnote 4,Footnote 8,Footnote 9,Footnote 15, RT-PCRFootnote 3,Footnote 4Footnote 15, Western blotFootnote 9,Footnote 15, immunohistochemical stainingFootnote 4,Footnote 17, neutralisation assayFootnote 17, immunofluorescent antibody testFootnote 8,Footnote 9, and viral culture from blood or cerebrospinal fluidFootnote 4,Footnote 9. The widely available complement fixation test, however, is deemed to be insensitive and its use is no longer recommendedFootnote 6,Footnote 8.

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

FIRST AID/TREATMENT: Treatment is symptomatic and generally supportiveFootnote 12,Footnote 15. Ribavirin is effective in vitro, and may be effective for treatment of LCMFootnote 5,Footnote 7,Footnote 21.

IMMUNIZATION: NoneFootnote 14.

PROPHYLAXIS: None.

SECTION VI - LABORATORY HAZARD

LABORATORY-ACQUIRED INFECTIONS: LCMV infection is a well known occupational risk for those working with rodents, especially hamsters and mice. 76 cases were reported up until 1978Footnote 22, including 3 outbreaks between 1973 and 1975 among laboratory workers who had handled hamsters that had tumour grafts containing LCMVFootnote 18,Footnote 19. Further cases have occurred since then, notably in an outbreak associated with nude mice, in which 9% of 82 animal care workers were found to be seropositive for LCMVFootnote 23.

SOURCES/SPECIMENS: BloodFootnote 1,Footnote 14,Footnote 18, cerebrospinal fluidFootnote 1,Footnote 8,Footnote 14,Footnote 18, urineFootnote 1,Footnote 17,Footnote 18, transplantable tumoursFootnote 15,Footnote 18, secretions of the nasopharynxFootnote 8,Footnote 14,Footnote 15,Footnote 18, faecesFootnote 8,Footnote 14,Footnote 15, and infected tissues from animals and humansFootnote 5.

PRIMARY HAZARDS: AerosolsFootnote 5, and direct contact of mucous membranes with virusFootnote 14,Footnote 15.

SPECIAL HAZARDS: Transplantable tumour lines represent a potential hazardFootnote 14,Footnote 15.

SECTION VII - EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 3Footnote 24. This risk group applies to the species as a whole, and may not be representative of all strains and clonal isolates.

CONTAINMENT REQUIREMENTS: Containment Level 3 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, or cultures. These containment levels apply to the species as a whole, and may not be representative of all strains and clonal isolates.

PROTECTIVE CLOTHING: Personnel entering the laboratory should remove street clothing 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 splashesFootnote 25.

OTHER PRECAUTIONS: All activities with infectious material should be conducted in a biological safety cabinet (BSC) or other appropriate primary containment device in combination with personal protective equipment. 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 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 animals or large scale activitiesFootnote 25.

SECTION VIII - HANDLING AND STORAGE

SPILLS: Allow aerosols to settle and, wear protective clothing, gently cover spill with paper towels and apply an appropriate disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up.

DISPOSAL: Decontaminate all materials for disposal by steam sterilisation, chemical disinfection, and/or incineration.

STORAGE: In sealed containers that are appropriately labelled.

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 2011

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, 2011

Canada

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