LYMPHOCYTIC CHORIOMENINGITIS VIRUS

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Lymphocytic choriomeningitis virus ⁽¹⁾.

SYNONYM OR CROSS REFERENCE: LCMV ^(2-13), LCM ^(14-18), benign (or serous) lymphocytic meningitis ⁽¹⁴⁾, and Armstrong’s disease ⁽¹⁵⁾.

CHARACTERISTICS: As member of the family Arenaviridae, genus Arenavirus ^{(9, 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 genome ^{(6, 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 projections ⁽¹⁵⁾.

SECTION II - HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: Acquired LCM (Postnatal): LCMV infection in immunocompetent adults may be asymptomatic (nearly one third of all infections ^{(2, 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 throat ^{(2, 8, 9, 15, 19)}. The illness can progress to include meningitis or meningoencephalitis ^{(6, 8, 14)}, and other less common neurologic symptoms such as paralysis, sensorineural hearing loss ^{(2, 6, 8)}, and Guillain-Barré type syndrome ⁽⁸⁾. Uncommon non-neurologic manifestations of illness include pancreatitis ⁽²⁾, orchitis ^{(2, 8)}, arthritis, pericarditis, parotitis ⁽⁸⁾ pneumonitis, and rash ⁽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 cases ^{(5, 6, 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 infection ⁽¹²⁾. In some cases, infection may result in abortion ^{(2, 9)}, hydrocephalus, chorioretinitis, and/or mental retardation of the infant ⁽⁶⁾. The mortality rate of infants diagnosed with congenital LCMV is approximately 35% ⁽¹⁶⁾. Among survivors of congenital LCMV infection, two thirds have long-term neurologic abnormalities, including microcephaly, mental retardation, cerebral palsy, seizures, and visual impairment ^{(2, 8, 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 aetiologies ^{(7, 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 encephalitis ⁽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 humans ⁽¹⁵⁾. The largest outbreak occurred between 1973 and 1974 in the United States with 181 cases and no deaths ⁽¹⁹⁾. Other recognised outbreaks have been recorded in Germany and France ⁽⁹⁾. The number of acquired LCM cases is underestimated since most cases are mild or asymptomatic and such individuals rarely seek medical attention ⁽¹²⁾. Greater awareness and improved methods of detection may be contributing to increased prevalence ⁽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 worldwide ^{(3, 6, 21)}, 63% of them since 1993 ⁽⁶⁾. It is not known whether the actual number of cases is significantly higher than this since only the most severe cases are reported ⁽¹³⁾, and congenital LCM can produce a spectrum of pathological effects from minimal to severe ⁽¹²⁾.

HOST RANGE: Humans ^{(2-4, 6, 8, 9, 12-17)}, mice ^{(2, 3, 6, 14, 15)}, hamsters ^{(3, 4, 15, 17, 18)}, guinea pigs, rats, monkeys, dogs, rabbits, and chickens ⁽¹⁷⁾.

INFECTIOUS DOSE: Unknown.

MODE OF TRANSMISSION: Mice infected in utero asymptomatically shed LCMV in their faeces, urine, saliva, breast milk, and semen ^{(2, 3, 8, 14, 15)}, and transmit the virus to humans (and other rodents, such as hamsters) by direct contact ^{(2, 3)}, through damaged skin ⁽¹⁴⁾ or mucous membranes ^{(14, 15)}, inhalation of aerosolised virus ^{(2, 3, 8, 14)}, ingestion of virus contaminated food ^{(8, 9, 14, 15)} or dust ^{(9, 14)}, through rodent bites ^{(8, 15)}, or by contact with infected fomites ^{(2, 14)}. Transmission is also possible through organ transplantation from LCMV infected donors ^{(4, 7)}, and vertically from an infected mother to her foetus ⁽³⁾.

INCUBATION PERIOD: Approximately 8 to 13 days ^{(9, 14)} and 15 to 21 days before any meningeal symptoms appear ^{(14, 15)}.

COMMUNICABILITY: No evidence of human-to-human transmission ⁽¹⁴⁾, with the exception of vertical transmission from an infected mother to her foetus during pregnancy ⁽³⁾, and through solid organ transplantation from infected donors ^{(4, 7)}.

SECTION III - DISSEMINATION

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

ZOONOSIS: Yes, LCMV is spread mainly through contact with contaminated rodent secretions/excretions ^{(2, 5, 14, 15, 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 transmission ⁽¹⁵⁾.

SECTION IV – STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: Ribavirin has been shown to inactivate arenaviruses in vitro and may improve symptoms under clinical conditions ^{(5, 7, 21)}.

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

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

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

SECTION V - FIRST AID / MEDICAL

SURVEILLANCE: Monitor for symptoms. Diagnosis is confirmed by serology, ELISA ^{(2-4, 8, 9, 15)}, RT-PCR ^{(3, 4, 15)}, Western blot ^{(9, 15)}, immunohistochemical staining ^{(4, 17)}, neutralisation assay ⁽¹⁷⁾, immunofluorescent antibody test ^{(8, 9)}, and viral culture from blood or cerebrospinal fluid ^{(4, 9)}. The widely available complement fixation test, however, is deemed to be insensitive and its use is no longer recommended ^{(6, 8)}.

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

FIRST AID/TREATMENT: Treatment is symptomatic and generally supportive ^{(12, 15)}. Ribavirin is effective in vitro, and may be effective for treatment of LCM ^{(5, 7, 21)}.

IMMUNIZATION: None ⁽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 1978 ⁽²²⁾, including 3 outbreaks between 1973 and 1975 among laboratory workers who had handled hamsters that had tumour grafts containing LCMV ^{(18, 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 LCMV ⁽²³⁾.

SOURCES/SPECIMENS: Blood ^{(1, 14, 18)}, cerebrospinal fluid ^{(1, 8, 14, 18)}, urine ^{(1, 17, 18)}, transplantable tumours ^{(15, 18)}, secretions of the nasopharynx ^{(8, 14, 15, 18)}, faeces ^{(8, 14, 15)}, and infected tissues from animals and humans ⁽⁵⁾.

PRIMARY HAZARDS: Aerosols ⁽⁵⁾, and direct contact of mucous membranes with virus ^{(14, 15)}.

SPECIAL HAZARDS: Transplantable tumour lines represent a potential hazard ^{(14, 15)}.

SECTION VII - EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 3 ⁽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 splashes ⁽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 activities ⁽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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