BMBL Section VII - A Agent Summary Statements

Bacterial Agents E through R

Agent: Escherichia coli (Cytotoxin-producing (VTEC/SLT) organisms)

Cytotoxin-producing (VTEC/SLT) strains of Escherichia coli (also called enterohemorrhagic strains) are a demonstrated hazard to laboratory personnel in the United States and elsewhere.(39)(40)(41) Hemolytic uremic syndrome occurs in a small proportion of patients (usually children) and is responsible for most deaths associated with infections with these organisms. Domestic farm animals (particularly bovines) are significant reservoirs of the organisms. However, experimentally infected small animals are also sources of infection in the laboratory.

Laboratory Hazards: Enterohemorrhagic E. coli is usually isolated from feces. A variety of foods contaminated with the organisms may serve as vehicles of spread, and include uncooked ground beef and unpasteurized dairy products. It may rarely be found in blood of infected humans or animals. Ingestion is the primary laboratory hazard. The importance of aerosol exposure is not known.

Recommended Precautions: Biosafety Level 2 practices, containment equipment, and facilities are recommended for all activities utilizing known or potentially infectious clinical materials or cultures. Animal Biosafety Level 2 facilities and practices are recommended for activities with experimentally or naturally infected animals. Vaccines are currently not available for use in humans. The reader is advised to consult the current related recommendations of the ACIP published in the CDC Morbidity and Mortality Weekly Report (MMWR) for the existence of recommendations for vaccination against enterohemorrhagic strains of E. coli.

Transfer of Agent: For a permit to import this agent, contact CDC.

Agent: Francisella tularensis

Tularemia has been a commonly reported laboratory-associated bacterial infection.(42) Almost all cases occurred at facilities involved in tularemia research. Occasional cases have been related to work with naturally or experimentally infected animals or their ectoparasites. Although not reported, cases have occurred in clinical laboratories. Work with cultures of F. tularensis requires special security considerations due to their potential use for purposes of biological terrorism.

Laboratory Hazards: The agent may be present in lesion exudates, respiratory secretions, cerebrospinal fluid, blood, urine, tissues from infected animals, and fluids from infected arthropods. Direct contact of skin or mucous membranes with infectious materials, accidental parenteral inoculation, ingestion, and exposure to aerosols and infectious droplets have resulted in infection. Infection has been more commonly associated with cultures than with clinical materials and infected animals. The human 25% to 50% infectious dose is approximately 10 organisms by the respiratory route.(43)

Recommended Precautions: Biosafety Level 2 practices, containment equipment, and facilities are recommended for activities with clinical materials of human or animal origin containing or potentially containing Francisella tularensis. Biosafety Level 3 and Animal Biosafety Level 3 practices, containment equipment, and facilities are recommended, respectively, for all manipulations of cultures and for experimental animal studies.

Note:

Vaccination for F. tularensis is available and should be considered for personnel working with infectious materials or infected rodents. Vaccination is recommended for persons working with the agent or infected animals, and for persons working in or entering the laboratory or animal room where cultures or infected animals are maintained.(44) The reader is advised to consult the current recommendations of the Advisory Committee on Immunization Practices (ACIP) published in the CDC Morbidity and Mortality Weekly Report (MMWR) for recommendations for vaccination against F. tularensis.

Transfer of Agent: For a permit to import this agent, contact CDC. Contact the Department of Commerce for a permit to export this agent. Laboratory registration with CDC is required before sending or receiving this select agent.

Agent: Helicobacter pylori

Since its discovery in 1982, Helicobacter pylori has received increasing attention as an agent of gastritis.(45) The main habitat of H. pylori is the human gastric mucosa. Human infection with H. pylori may be long in duration with few or no symptoms, or may present as an acute gastric illness. Both experimental and accidental laboratory-acquired human infections with H. pylori have been reported.(46)(47) The agent may be present in gastric or oral secretions and stool. Transmission, while incompletely understood, is thought to be by the fecal-oral or oral-oral route.

Laboratory Hazards: The agent may be present in gastric and oral secretions and stool. Ingestion is the primary known laboratory hazard. The importance of aerosol exposures is unknown.

Recommended Precautions: Biosafety Level 2 practices, containment equipment, and facilities are recommended for activities with clinical materials and cultures known to contain or potentially containing the agents. Animal Biosafety Level 2 practices, containment equipment, and facilities are recommended for activities with experimentally or naturally infected animals. Vaccines are currently not available for use in humans.

Transfer of Agent: For a permit to import this agent, contact CDC.

Agent: Leptospira interrogans - all serovars

Leptospirosis is a well-documented laboratory hazard. Pike reported 67 laboratory-associated infections and 10 deaths,(48) and three additional cases have been reported elsewhere.(49) An experimentally infected rabbit was identified as the source of an infection with L. interrogans serovar icterohemorrhagiae.(50) Direct and indirect contact with fluids and tissues of experimentally or naturally infected mammals during handling, care, or necropsy is a potential source of infection. In animals with chronic kidney infections, the agent is shed in the urine in enormous numbers for long periods of time.

Laboratory Hazards: The agent may be present in urine, blood, and tissues of infected animals and humans. Ingestion, accidental parenteral inoculation, and direct and indirect contact of skin or mucous membranes with cultures or infected tissues or body fluids--especially urine--are the primary laboratory hazards. The importance of aerosol exposure is not known.

Recommended Precautions: Biosafety Level 2 practices, containment equipment, and facilities are recommended for all activities involving the use or manipulation of known or potentially infectious tissues, body fluids, and cultures, and for the housing of infected animals. Gloves are recommended for the handling and necropsy of infected animals, and when there is the likelihood of direct skin contact with infectious materials. Vaccines are not currently available for use in humans.

Transfer of Agent: For a permit to import these agents, contact CDC. An importation or domestic transfer permit for this agent can be obtained from USDA/APHIS/VS.

Agent: Listeria monocytogenes

Listeria monocytogenes poses a potential hazard to laboratory personnel. The gram-positive, non-spore-forming, aerobic bacilli are hemolytic and catalase-positive.(51) Bacteria have been isolated from soil, dust, human food, animals, and asymptomatic humans.(52)(53) Most cases of listeriosis have arisen from eating contaminated food products, most notably soft cheeses, raw meat, and unwashed raw vegetables.(54) Although healthy adults and children can contract a Listeria infection, they do not usually become seriously ill. At risk of severe illness are pregnant women, newborns, and persons with impaired immune function.

Laboratory Hazards: Listeria monocytogenes may be found in feces, CSF, and blood, as well as food and environmental materials.(55)(56) Naturally or experimentally infected animals are a source of exposure to laboratory workers and animal care personnel, and other animals. Ingestion is the most likely mode of exposure, but Listeria can also cause eye and skin infections following a direct exposure. Listeria monocytogenes infections in pregnant women occur most often in the third trimester and may precipitate labor. Transplacental transmission of L. monocytogenes poses a grave risk to the fetus and may result in disseminated abscesses contributing to a mortality rate of nearly 100%.(57)

Recommended Precautions: Biosafety Level 2 practices, containment equipment, and facilities are recommended for activities with clinical specimens and cultures known or suspected to contain the agent. Gloves and eye protection should be worn while handling infected cultures. Animal Biosafety Level 2 practices, containment equipment and facilities are recommended for activities with experimentally or naturally infected animals. Vaccines are not currently available for use in humans.(58) Pregnant women who work with Listeria monocytogenes in the clinical or research laboratory setting should be fully informed of the potential hazards associated with the organism, including potential risks to the fetus.

Transfer of Agent: An importation or domestic transfer permit for this agent can be obtained from USDA/APHIS/VS.

Agent: Legionella pneumophila; other Legionella-like agents

A single documented nonfatal laboratory-associated case of legionellosis, due to presumed aerosol or droplet exposure during animal challenge studies with Pontiac Fever agent (L. pneumophila), has been recorded.(59) Human-to-human spread has not been documented.

Experimental infections are readily produced in guinea pigs and embryonate chicken eggs.(60) Challenged rabbits develop antibodies but not clinical disease. Mice are refractory to parenteral exposure. Unpublished studies at the Centers for Disease Control and Prevention have shown that animal-to-animal transmission did not occur in a variety of experimentally infected mammalian and avian species.

Laboratory Hazards: The agent may be present in pleural fluid, tissue, sputum, and environmental sources (e.g., cooling tower water). Because the natural mode of transmission appears to be airborne, the greatest potential hazard is the generation of aerosols during the manipulation of cultures or of other materials containing high concentrations of infectious microorganisms (e.g., infected yolk sacs and tissues).

Recommended Precautions: Biosafety Level 2 practices, containment equipment, and facilities are recommended for all activities involving the use or manipulation of known or potentially infectious clinical materials or cultures, and for the housing of infected animals. Biosafety Level 3 practices with primary containment devices and equipment (e.g., biological safety cabinets, centrifuge safety cups) are used for activities likely to generate potentially infectious aerosols and for activities involving production quantities of microorganisms. Note:  Vaccines are not currently available for use in humans.

Transfer of Agent: For a permit to import this agent, contact CDC.

Agent: Mycobacterium leprae

Inadvertent parenteral human-to-human transmission of leprosy has been reported following an accidental needle stick in a surgeon(61) and the use of a presumably contaminated tattoo needle.(62) There are no cases reported as a result of working in a laboratory with biopsy or other clinical materials of human or animal origin. While naturally occurring leprosy or leprosy-like diseases have been reported in armadillos(63)and in nonhuman primates,(64)(65) humans are the only known important reservoir of this disease.

Laboratory Hazards: The infectious agent may be present in tissues and exudates from lesions of infected humans and experimentally or naturally infected animals. Direct contact of the skin and mucous membranes with infectious materials and accidental parenteral inoculation are the primary laboratory hazards associated with handling infectious clinical materials.

Recommended Precautions: Biosafety Level 2 practices, containment equipment, and facilities are recommended for all activities with known or potentially infectious clinical materials from infected humans and animals. Extraordinary care should be taken to avoid accidental parenteral inoculation with contaminated sharp instruments. Animal Biosafety Level 2 practices, containment equipment, and facilities are recommended for animal studies utilizing rodents, armadillos, and nonhuman primates. Vaccines are not currently available for use in humans.

Transfer of Agent: For a permit to import this agent, contact CDC.

Agent: Mycobacterium spp. other than M. tuberculosis, M. bovis or M. leprae

Pike reported 40 cases of nonpulmonary "tuberculosis" thought to be related to accidents or incidents in the laboratory or autopsy room.(66) Presumably, these infections were due to mycobacteria other than M. tuberculosis or M. bovis. A number of mycobacteria that are ubiquitous in nature are associated with diseases other than tuberculosis or leprosy in humans, domestic animals, and wildlife. Characteristically, these organisms are infectious but not contagious. Clinically, the diseases associated with infections by these "atypical" mycobacteria can be divided into three general categories:

1. Pulmonary diseases resembling tuberculosis, which may be associated with infection by M. kansasii, M. avium complex, and rarely, by M. xenopi, M. malmoense, M. asiaticum, M. simiae, and M. szulgai.
2. . Lymphadenitis, which may be associated with infection by M. scrofulaceum, M. avium complex, and rarely, by M. fortuitum and M. kansasii.
3. 3. Skin ulcers and soft tissue wound infections, which may be associated with infection by M. ulcerans, M. marinum, M. fortuitum, and M. chelonei.

Laboratory Hazards: The agents may be present in sputa, exudates from lesions, tissues, and in environmental samples (e.g., soil and water). Direct contact of skin or mucous membranes with infectious materials, ingestion, and accidental parenteral inoculation are the primary laboratory hazards associated with clinical materials and cultures. A potential infection hazard to laboratory personnel is also posed by the infectious aerosols created during the manipulation of broth cultures or tissue homogenates of these organisms associated with pulmonary disease.

Recommended Precautions: Biosafety Level 2 practices, containment equipment, and facilities are recommended for activities with clinical materials and cultures of Mycobacterium spp. other than M. tuberculosis or M. bovis. Animal Biosafety Level 2 practices, containment equipment, and facilities are recommended for animal studies with mycobacteria other than M. tuberculosis, M. bovis, or M. leprae. Vaccines are not currently available for use in humans.

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

Agent: Mycobacterium tuberculosis, M. bovis

Mycobacterium tuberculosis and M. bovis (including BCG) infections are a proven hazard to laboratory personnel as well as others who may be exposed to infectious aerosols in the laboratory.(67)(68)(69)(70)(71) The incidence of tuberculosis in laboratory personnel working with M. tuberculosis has been reported to be three times higher than that of those not working with the agent.(72) Naturally or experimentally infected nonhuman primates are a proven source of human infection (e.g., the annual tuberculin conversion rate in personnel working with infected nonhuman primates is about 70/10,000 compared with a rate of less than 3/10,000 in the general population).(73) Experimentally infected guinea pigs or mice do not pose the same problem since droplet nuclei are not produced by coughing in these species; however, litter from infected animals may become contaminated and serve as a source of infectious aerosols.

Laboratory Hazards: Tubercle bacilli may be present in sputum, gastric lavage fluids, cerebrospinal fluid, urine, and in lesions from a variety of tissues.(74) Exposure to laboratory-generated aerosols is the most important hazard encountered. Tubercle bacilli may survive in heat-fixed smears,(75) and may be aerosolized in the preparation of frozen sections and during manipulation of liquid cultures. Because of the low infective dose of M. tuberculosis for humans (i.e., ID50 <10 bacilli)and, in some laboratories, a high rate of isolation of acid-fast organisms from clinical specimens (>10%),(76) sputa, and other clinical specimens from suspected or known cases of tuberculosis must be considered potentially infectious and handled with appropriate precautions.

Recommended Precautions: Biosafety Level 2 practices and procedures, containment equipment, and facilities are required for non-aerosol-producing manipulations of clinical specimens such as preparation of acid-fast smears. All aerosol-generating activities must be conducted in a Class I or II biological safety cabinet. Use of a slide-warming tray, rather than flame-drying, is recommended. Liquification and concentration of sputa for acid-fast staining may also be conducted safely on the open bench by first treating the specimen (in a Class I or II safety cabinet) with an equal volume of 5% sodium hypochlorite solution (undiluted household bleach) and waiting 15 minutes before centrifugation.(77)(78) Biosafety Level 3 practices, containment equipment, and facilities are required for laboratory activities in the propagation and manipulation of cultures of M. tuberculosis or M. bovis, and for animal studies utilizing nonhuman primates experimentally or naturally infected with M. tuberculosis or M. bovis. Animal studies utilizing guinea pigs or mice can be conducted at Animal Biosafety Level 2.(79)

Note: Skin testing with purified protein derivative (PPD) of previously skin-tested-negative laboratory personnel can be used as a surveillance procedure. An attenuated live vaccine (BCG) is available but is not used in the United States for laboratory personnel. The reader is advised to consult the current recommendations of the Advisory Committee on Immunization Practices (ACIP) published in the CDC Morbidity and Mortality Weekly Report (MMWR) for current vaccination recommendations.

Transfer of Agent: For a permit to import these agents, contact CDC. An importation or domestic transfer permit for M. Bovis can be obtained from USDA/APHIS/VS.

Agent: Neisseria gonorrhoeae

Laboratory-associated gonococcal infections have been reported in the United States.(80)

Laboratory Hazards: The agent may be present in conjunctival, urethral and cervical exudates, synovial fluid, urine, feces, and cerebrospinal fluid. Accidental parenteral inoculation and direct or indirect contact of mucous membranes with infectious clinical materials are the known primary laboratory hazards. The importance of aerosols is not determined.

Recommended Precautions: Biosafety Level 2 practices, containment equipment, and facilities are recommended for all activities involving the use or manipulation of clinical materials or cultures. Gloves should be worn when handling infected laboratory animals and when there is the likelihood of direct skin contact with infectious materials. Additional primary containment and personnel precautions, such as those described for Biosafety Level 3, may be indicated for aerosol or droplet production, and for activities involving production quantities or concentrations of infectious materials. Vaccines are not currently available for use in humans.

Transfer of Agent: For a permit to import this agent, contact CDC.

Agent: Neisseria meningitidis

Meningococcal meningitis is a demonstrated but rare hazard to laboratory workers.(81)(82) (83)

Laboratory Hazards: The agent may be present in pharyngeal exudates, cerebrospinal fluid, blood, and saliva. Parenteral inoculation, droplet exposure of mucous membranes, infectious aerosol and ingestion are the primary hazards to laboratory personnel.

Recommended Precautions: Biosafety Level 2 practices, containment equipment, and facilities are recommended for all activities utilizing known or potentially infectious body fluids, tissues, and cultures. Additional primary containment and personnel precautions, such as those described for Biosafety Level 3, may be indicated for activities with a high potential for droplet or aerosol production and for activities involving production quantities or concentrations of infectious materials.

Note: Vaccines for N. meningitidis are available and should be considered for personnel regularly working with infectious materials. The reader is advised to consult the current recommendations of the Advisory Committee on Immunization Practices (ACIP) published in the CDC Morbidity and Mortality Weekly Report (MMWR) for recommendations for vaccination against N. meningitidis.

Transfer of Agent:  For a permit to import this agent, contact CDC.