BMBL Section VII

Biosafety Documents

BMBL Table of Contents

SALS recommends that work with the 184 arboviruses included in the alphabetical listings of Tables 3 and 4 be conducted at the equivalent of Biosafety Level 3 practices, safety equipment, and facilities. These recommendations are based on the following criteria: for Table 3 (pages 193-194), SALS considered the laboratory experience inadequate to assess risk, regardless of the available information regarding disease severity. For the agents listed on Table 4 (pages 194-195), SALS recorded overt laboratory-associated infections transmitted by the aerosol route in the absence or non-use of protective vaccines; and considered that the natural disease in humans is potentially severe, life threatening, or causes residual damage. Arboviruses were also classified BSL-3 if they cause diseases in domestic animals in countries outside the USA.

Laboratory or laboratory animal-associated infections have been reported with the following BSL-3 agents:^(1)(2)(3)

* Export permit required by Department of Commerce

** An importation or domestic transfer permit for this agent can be obtained from USDA/APHIS/VS.

Large quantities and high concentrations of Semliki Forest virus are commonly used or manipulated by molecular biologists under conditions of moderate or low containment. Although antibodies have been demonstrated in individuals working with this virus, the first overt (and fatal) laboratory-associated infection with this virus was reported in 1979. Because the outcome of this infection may have been influenced by an unusual route of exposure or high dosage, a compromised host, or a mutated strain of the virus, this case and its outcome are not typical. More recently, SFV was associated with an outbreak of febrile illness among European soldiers stationed in Bangui.(4) The route of exposure was not determined in the fatal laboratory infection; for the natural infections, mosquitoes were the probable vector. SALS continues to classify SFV as a BSL-3 virus, with the caveat that most activities with this virus can be safety conducted at Biosafety Level 2.

Some viruses (e.g., Akabane, Israel turkey meningoencephalitis) are listed in BSL-3, not because they pose a threat to human health, but because they are exotic diseases of domestic livestock or poultry.

Laboratory Hazards: The agents listed in this group may be present in blood, cerebrospinal fluid, urine, and exudates, depending on the specific agent and stage of disease. The primary laboratory hazards are exposure to aerosols of infectious solutions and animal bedding, accidental parenteral inoculation, and contact with broken skin. Some of these agents (e.g., VEE) may be relatively stable in dried blood or exudates. For five BSL-3/4 viruses, attenuated strains exist which may be handled at BSL-2, as listed in Table 2.

Recommended Precautions: Biosafety Level 3 practices, safety equipment, and facilities are recommended for activities using potentially infectious clinical materials and infected tissue cultures, animals, or arthropods.

A licensed attenuated live virus is available for immunization against yellow fever. It is recommended for all personnel who work with this agent or with infected animals, and those qualified to enter rooms where the agents or infected animals are present. Indeed, but for this vaccine, the aerosol infectivity and high case fatality of yellow fever virus would make its classification BSL-4. For Venezuelan equine encephalomyelitis, investigational (IND) vaccine TC-83 provides excellent protection against many epizootic strains. This protection may extend to other VEE strains of the complex, including Everglades, Mucambo, Tonate, and Cabassou viruses. TC-83 vaccine should be used as part of a comprehensive safety program and may be particularly important in protecting those working with infected animals and virus concentrates. The administration of the vaccine and the use of its inactivated counterpart (C-84) should be determined by personnel experienced in the use of these vaccines within the constraints of the IND. Likewise, an inactivated IND vaccine is available for Rift Valley Fever virus, and a live attenuated Junin virus vaccine (Candid #1) is available. These IND vaccines may be obtained from the U.S. Army Medical Research and Materiel Command, after consultation with USAMRIID (telephone 301-619-2833).

SALS has lowered the biohazard classification of Junin virus to BSL-3, provided that all at-risk personnel are immunized and the laboratory is equipped with HEPA-filtered exhaust. SALS has also lowered the biohazard classification of the Central European tick-borne encephalitis (CETBE) viruses to BSL-3, provided all at-risk personnel are immunized. An inactivated IND vaccine for CETBE is available from USAMRIID and is recommended for all laboratory and animal care personnel working with the agent or infected animals, and for all personnel entering laboratories or animal rooms when the agent is in use.

Enhanced Biosafety Level 3 Containment: Situations may arise for which enhancements to Biosafety Level 3 practices and equipment are required. An example of such a situation would be a BSL-3 laboratory performing diagnostic testing on specimens from patients with hemorrhagic fevers thought to be due to dengue or yellow fever. When the origin of these specimens is Africa, the Middle East, or South America, the potential is present for such specimens to contain etiologic agents, such as arenaviruses, filoviruses or other viruses that are usually manipulated in a Biosafety Level 4 laboratory. Enhancements to BSL-3 laboratories might include one or more of the following three categories: a) enhanced respiratory protection of personnel against aerosols; b) HEPA filtration of dedicated exhaust air from the laboratory; c) decontamination of laboratory liquid effluent. Additional appropriate training for all animal care personnel should be considered.

Biocontainment of Infectious Unknowns: Decisions regarding biohazard classification for materials containing unidentified infectious virus should be based on all available information regarding the agent. Viruses isolated from infected human patients should be handled at the BSL-3 level with enhanced precautions, as detailed in the hantavirus agent summary, or preferably at BSL-4, unless there is confidence that the agent is not infectious via the aerosol route. All unknown samples should be handled at BSL-3, unless there is evidence of aerosol transmission (which would require BSL-4 containment.) SALS will continue to evaluate infectivity and virulence data for all viruses registered in the Catalogue of Arboviruses and Certain Other Viruses of Vertebrates and for newly emerging viruses prior to registration.

Transfer of Agents: For a permit to import these agents, contact CDC.

References

1. Hanson, R.P., et al. 1967. (3)

2. Pike, R.M. 1976 (4)

3. Subcommittee on Arbovirus Laboratory Safety for Arboviruses and Certain Other Viruses of Vertebrates. 1980. (4)

4. Mathiot, C.C., et al. 1990. An Outbreak of Human Semliki Forest Virus Infections in Central African Republic. Am J Trop Med Hyg 42:386-393.

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This page last reviewed June 17, 1999

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