Laboratory-associated infections with hepatitis A or E viruses do not appear to be an important occupational risk among laboratory personnel. However, the disease is a documented hazard in animal handlers and others working with chimpanzees and other nonhuman primates which are naturally or experimentally infected (153). Hepatitis E virus appears to be less of a risk to personnel than hepatitis A virus, except during pregnancy, when infection can result in severe or fatal disease. Workers handling other recently captured, susceptible primates (owl monkeys, marmosets) may also be at risk.
LABORATORY HAZARDS: The agents may be present in feces, saliva, and blood of infected humans and nonhuman primates. Ingestion of feces, stool suspensions, and other contaminated materials is the primary hazard to laboratory personnel. The importance of aerosol exposure has not been demonstrated. Attenuated or avirulent strains of hepatitis A viruses have been described resulting from serial passage in cell culture.
RECOMMENDED PRECAUTIONS: Biosafety Level 2 practices, safety equipment, and facilities are recommended for activities with known or potentially infected feces from humans or nonhuman primates. Animal Biosafety Level 2 practices and facilities are recommended for activities using naturally or experimentally infected nonhuman primates. Animal care personnel should wear gloves and take other appropriate precautions to avoid possible fecal-oral exposure. A licensed inactivated vaccine against hepatitis A is available in Europe; it is available as an investigational vaccine in the U.S., and is recommended for laboratory personnel. Vaccines against hepatitis E are not available for use in humans.
Hepatitis B has been one of the most frequently occurring laboratory-associated infections, (153) and laboratory workers are recognized as a high risk group for acquiring such infections (170). Individuals who are infected with hepatitis B virus are at risk of infection with hepatitis D (delta) virus, which is defective and requires the presence of hepatitis B virus for replication.
Hepatitis C infection can occur in the laboratory situation. The prevalence of antibody to hepatitis C is slightly higher in medical care workers than in the general population. Epidemiologic evidence indicates that hepatitis C is spread predominantly by the parenteral route (94, 128).
LABORATORY HAZARDS: Hepatitis B virus may be present in blood and blood products of human origin, in urine, semen, cerebrospinal fluid, and saliva. Parenteral inoculation, droplet exposure of mucous membranes, and contact exposure of broken skin are the primary laboratory hazards. The virus may be stable in dried blood or blood components for several days. Attenuated or avirulent strains have not been identified.
Hepatitis C virus has been detected primarily in blood and serum, less frequently in saliva and rarely or not at all in urine or semen. It appears to be relatively unstable to storage at room temperature, repeated freezing and thawing, etc.
RECOMMENDED PRECAUTIONS: Biosafety Level 2 practices, containment equipment and facilities are recommended for all activities utilizing known or potentially infectious body fluids and tissues. Additional primary containment and personnel precautions, such as those described for Biosafety Level 3, may be indicated for activities with potential for droplet or aerosol production and for activities involving production quantities or concentrations of infectious materials. Animal Biosafety Level 2 practices, containment equipment and facilities are recommended for activities utilizing naturally or experimentally infected chimpanzees or other nonhuman primates. Gloves should be worn when working with infected animals and when there is the likelihood of skin contact with infectious materials. Licensed recombinant vaccines against hepatitis B are available and are highly recommended for laboratory personnel (46). Vaccines against hepatitis C and D are not yet available for use in humans.
B-virus is a naturally occurring alphaherpesvirus infecting free-living or captive Macaca mulatta, M. fasicularis, and other members of the genus. It is associated with acute vesicular oral lesions, as well as latent and often recrudescent infection (193). Human infection has been documented in 25 instances, usually with a lethal outcome or serious sequelae from encephaliti (7, 92, 145).
Although B-virus presents a potential hazard to laboratory personnel working with the agent, laboratory-associated human infections with B-virus have, with rare exceptions, been limited to those having direct contact with macaques. Primary macaque cell cultures, including commercially-prepared rhesus monkey kidney cells, occasionally are inapparently infected with B-virus and have been implicated in one human case (92).
Sixteen fatal cases of human infections with B-virus have been reported (193).
LABORATORY HAZARDS: The highest risk of acquiring B-virus from macaques is through the bite of an infected monkey with active lesions. Contamination of broken skin or mucous membranes with oral, ocular, or genital secretions from animals with lesions, or experiencing clinically silent virus shedding, is also dangerous. Stability of viral infectivity on cages and other surfaces is not known, but the potential hazard must be recognized. The importance of aerosol exposure is thought to be minimal. Attenuated or avirulent strains have not been identified.
The agent also may be present in thoracic and abdominal viscera and nervous tissues of naturally infected macaques. These tissues, and the cultures prepared from them, are potential hazards (196).
RECOMMENDED PRECAUTIONS: Biosafety Level 2 practices and facilities are recommended for all activities involving the use or manipulation of tissues, body fluids, and primary tissue culture materials from macaques. Additional practices and personnel precautions, such as those detailed for Biosafety Level 3, are recommended for activities involving the use or manipulation of any material known to contain Herpesvirus simiae. In vitro propagation of the virus for diagnosis may be conducted under the same guidelines, but it would be prudent to confine manipulations of positive cultures which would contain high-titered virus to a Class 3 biosafety cabinet or BSL-4 facility, depending on the judgement of the laboratory director.
Biosafety Level 4 practices and facilities are recommended for activities involving the propagation and manipulation of production quantities or concentrates of H. simiae.
The wearing of gloves, masks, and laboratory coats is recommended for all personnel working with non-human primates -- especially macaques and other Old World species -- and for all persons entering animal rooms where non-human primates are housed. Any macaque colony not known to be free of B-virus infection should be presumed to be naturally infected. Guidelines are available for safely working with macaques and should be consulted (39, 150). Animals with oral lesions suggestive of active B-virus infection should be isolated and handled with extreme caution. Studies with animals experimentally infected with H. simiae should be conducted at ABSL-3.
Vaccines are not available for use in humans. Human to human transmission has only occurred in one case, suggesting that precautions should be taken with vesicle fluids, oral secretions, and conjunctival secretions of infected persons (92).
Antiviral drugs have shown promise in the therapy of rabbits infected with H. simiae, and anecdotal observations suggest this may extend to man (7, 92). Because of the seriousness of infection with this virus, experienced medical personnel should be available for consultation to manage incidents involving exposure to the agent or suspected infections.
The herpesviruses are ubiquitous human pathogens and are commonly present in a variety of clinical materials submitted for virus isolation. While few of these viruses are demonstrated causes of clinical laboratory-associated infections, they are primary as well as opportunistic pathogens, especially in immunocompromised hosts. Herpes simplex viruses 1 and 2 and varicella virus pose some risk via direct contact and/or aerosols; cytomegalovirus and Epstein-Barr virus pose relatively low infection risks to laboratory personnel. The risk of laboratory infection from herpesviruses 6 and 7 is not known. Although this diverse group of indigenous viral agents does not meet the criteria for inclusion in agent-specific summary statements (i.e., demonstrated or high potential hazard for laboratory-associated infection; grave consequences should infection occur), the frequency of their presence in clinical materials and their common use in research warrants their inclusion in this publication.
LABORATORY HAZARDS: Clinical materials and isolates of herpesviruses may pose a risk of infection following ingestion, accidental parenteral inoculation, droplet exposure of the mucous membranes of the eyes, nose, or mouth, or inhalation of concentrated aerosolized materials. Clinical specimens containing the more virulent Herpesvirus simiae (B-virus) may be inadvertently submitted for diagnosis of suspected herpes simplex infection. This virus has also been found in cultures of primary rhesus monkey kidney cells. Cytomegalovirus may pose a special risk during pregnancy because of potential infection of the fetus.
RECOMMENDED PRECAUTIONS: Biosafety Level 2 practices, containment equipment, and facilities are recommended for activities utilizing known or potentially infectious clinical materials or cultures of indigenous viral agents which are associated or identified as a primary pathogen of human disease. Although there is little evidence that infectious aerosols are a significant source of laboratory-associated infections, it is prudent to avoid the generation of aerosols during the handling of clinical materials or isolates, or during the necropsy of animals. Primary containment devices (e.g., biological safety cabinets) constitute the basic barrier protecting personnel from exposure to infectious aerosols.