Pathogen Safety Data Sheets: Infectious Substances – Lymphocytic choriomeningitis virus

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Lymphocytic choriomeningitis virus^{Footnote 1}.

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

CHARACTERISTICS: As member of the family Arenaviridae, genus Arenavirus^{Footnote 9Footnote 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^{Footnote 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 projections^{Footnote 15}.

SECTION II - HAZARD IDENTIFICATION

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

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

INFECTIOUS DOSE: Unknown.

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

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

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

SECTION III - DISSEMINATION

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

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

SECTION IV – STABILITY AND VIABILITY

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

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

PHYSICAL INACTIVATION: LCMV is inactivated by UV light^{Footnote 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 host^{Footnote 9}. LCMV will retain its infectivity for at least 206 days if stored in 50% glycerine and 0.85% saline at 4-10°C^{Footnote 1}.

SECTION V - FIRST AID / MEDICAL

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

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

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

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

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

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

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

SECTION VII - EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 3^{Footnote 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^{Footnote 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^{Footnote 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

REFERENCES: