Section VII - A Agent Summary Statements

Bacterial Agents B through C

Agent: Bacillus anthracis

Numerous cases of laboratory-associated anthrax, occurring primarily at facilities conducting anthrax research, have been reported.(1)(2) No laboratory-associated cases of anthrax have been reported in the United States since the late 1950s when human anthrax vaccine was introduced. Any work with B. anthracis requires special security considerations due to its potential use for purposes of biological terrorism. Naturally and experimentally infected animals pose a potential risk to laboratory and animal care personnel.

Laboratory Hazards: The agent may be present in blood, skin lesion exudates, cerebrospinal fluid, pleural fluid, sputum, and rarely, in urine and feces. Direct and indirect contact of the intact and broken skin with cultures and contaminated laboratory surfaces, accidental parenteral inoculation, and rarely, exposure to infectious aerosols are the primary hazards to laboratory personnel.

Recommended Precautions: Biosafety Level 2 practices, containment equipment, and facilities are recommended for activities using clinical materials and diagnostic quantities of infectious cultures. Animal Biosafety Level 2 practices, containment equipment, and facilities are recommended for studies utilizing experimentally infected laboratory rodents. Biosafety Level 3 practices, containment equipment, and facilities are recommended for work involving production quantities or concentrations of cultures, and for activities with a high potential for aerosol production.

Note: A licensed vaccine is available through the Centers for Disease Control and Prevention; however, immunization of laboratory personnel is not recommended unless frequent work with clinical specimens or diagnostic cultures is anticipated (e.g., animal disease diagnostic laboratory).  In these facilities immunization is recommended for all persons working with the agent, all persons working in the same laboratory room where the cultures are handled, and persons working with infected animals.

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

Agent: Bordetella pertussis

Bordetella pertussis, a human respiratory pathogen of worldwide distribution, is the causative agent of whooping cough. The disease is typically a childhood illness; however, the agent has increasingly been associated with adult illness.(3)(4)(5) Several outbreaks in health-care workers have been reported in the literature.(6)(7) Adolescents and adults with atypical or undiagnosed disease can serve as reservoirs of infection and transmit the organism to infants and children.(8) Eight cases of infection with B. pertussis in adults have been documented at a large research institution. The individuals involved did not work directly with the organism, but had access to common laboratory spaces where the organism was manipulated. One case of secondary transmission to a family member was documented.(9) A similar incident occurred at a large Midwestern university resulting in two documented cases of laboratory-acquired infection and one documented case of secondary transmission.(10) Other laboratory-acquired infections with B. pertussis have been reported, as well as adult-to-adult transmission in the workplace.(11) (12) Laboratory-acquired infections resulting from the manipulation of clinical specimens or isolates have not been reported. The attack rate of this airborne infection is influenced by intimacy and frequency of exposure of susceptible individuals.

Laboratory Hazards: The agent may be present in respiratory secretions, but is not found in blood or tissue. Since the natural mode of transmission is by the respiratory route, the greatest potential hazard is aerosol generation during the manipulation of cultures or concentrated suspensions of the organism.

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. Animal Biosafety Level 2 should be used for the housing of infected animals. Primary containment devices and equipment (e.g., biological safety cabinets, centrifuge safety cups, or specially designed safety centrifuges) should be used for activities likely to generate potentially infectious aerosols. Biosafety Level 3 practices, procedures, and facilities are appropriate when engaged in large scale production operations.

Note: Pertussis vaccines are available but are not currently recommended for use in adults. 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 pertussis vaccination in adults.

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

Agent: Brucella (B. abortus, B. canis, B. melitensis, B. suis)

Brucellosis continues to be the most commonly reported laboratory-associated bacterial infection.(13)(14)(15) B. abortus, B. canis, B. melitensis, and B. suis have all caused illness in laboratory personnel.(16)(17)(18) Hypersensitivity to Brucella antigens is also a hazard to laboratory personnel. Occasional cases have been attributed to exposure to experimentally and naturally infected animals or their tissues.

Laboratory Hazards: The agent may be present in blood, cerebrospinal fluid, semen, and occasionally urine. Most laboratory-associated cases have occurred in research facilities and have involved exposure to Brucella organisms grown in large quantities. Cases have also occurred in the clinical laboratory setting from sniffing bacteriological cultures.(19) Direct skin contact with cultures or with infectious clinical specimens from animals (e.g., blood, uterine discharges) are commonly implicated in these cases. Aerosols generated during laboratory procedures have caused large outbreaks.(20)(21) Mouth pipetting, accidental parenteral inoculations, and sprays into eyes, nose, and mouth have also resulted in infection.

Recommended Precautions: Biosafety Level 2 practices are recommended for activities with clinical specimens of human or animal origin containing or potentially containing pathogenic Brucella spp. Biosafety Level 3 and Animal Biosafety Level 3 practices, containment equipment, and facilities are recommended, respectively, for all manipulations of cultures of the pathogenic Brucella spp. listed in this summary, and for experimental animal studies.

Note: While human Brucella vaccines have been developed and tested in other countries with limited success, at the time of this publication no human vaccine is available in the United States.(22)

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

Agent: Burkholderia pseudomallei (Pseudomonas pseudomallei)

Two laboratory-associated cases of melioidosis have been reported: one associated with a massive aerosol and skin exposure;(23) the second resulting from an aerosol created during the open-flask sonication of a culture presumed to be Ps. cepacia. (24)

Laboratory Hazards: The agent may be present in sputum, blood, wound exudates and various tissues depending on the infection's site of localization. Direct contact with cultures and infectious materials from humans, animals, or the environment, ingestion, autoinoculation, and exposure to infectious aerosols and droplets are the primary laboratory hazards. The agent has been demonstrated in blood, sputum, and abscess materials and may be present in soil and water samples from endemic areas.

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. Gloves should be worn when handling infected animals, during their necropsy, 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 activities with a high potential 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: Contact the Department of Commerce for a permit to export this agent.

Agent: Campylobacter (C. jejuni/C. coli, C. fetus subsp. fetus)

C. jejuni/C. coli gastroenteritis is rarely a cause of laboratory-associated illness, although laboratory-acquired cases have been documented.(25)(26)(27) Numerous domestic and wild animals, including poultry, pets, farm animals, laboratory animals, and wild birds are known reservoirs and are a potential source of infection for laboratory and animal care personnel. Experimentally infected animals are also a potential source of infection.(28)

Laboratory Hazards: Pathogenic campylobacters may occur in fecal specimens in large numbers. C. fetus subsp. fetus may also be present in blood, exudates from abscesses, tissues, and sputa. Ingestion or parenteral inoculation of C. jejuni constitute the primary laboratory hazards. The oral ingestion of 500 organisms caused infection in one individual.(29) The importance of aerosol exposure is not known.

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

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

Agent: Chlamydia psittaci, C. pneumoniae, C. trachomatis

Psittacosis, lymphogranuloma venereum (LGV), and trachoma infections were at one time among the most commonly reported laboratory-associated bacterial infections.(30) In cases reported before 1955,(31) the majority of infections were psittacosis, and these had the highest case fatality rate of laboratory-acquired infectious agents. Contact with and exposure to infectious aerosols in the handling, care, or necropsy of naturally or experimentally infected birds are the major sources of laboratory-associated psittacosis. Infected mice and eggs are less important sources of C. psittaci. Laboratory animals are not a reported source of human infection with C. trachomatis.

Laboratory Hazards: C. psittaci may be present in the tissues, feces, nasal secretions and blood of infected birds, and in blood, sputum, and tissues of infected humans. C. trachomatis may be present in genital, bubo, and conjunctival fluids of infected humans. Exposure to infectious aerosols and droplets, created during the handling of infected birds and tissues, are the primary hazards to laboratory personnel working with psittacosis. The primary laboratory hazards of C. trachomatis are accidental parenteral inoculation and direct and indirect exposure of mucous membranes of the eyes, nose, and mouth to genital, bubo, or conjunctival fluids, cell culture materials, and fluids from infected eggs. Infectious aerosols may also pose a potential source of infection.

Recommended Precautions: Biosafety Level 2 practices, containment equipment, and facilities are recommended for activities involving the necropsy of infected birds and the diagnostic examination of tissues or cultures known to contain or potentially infected with C. psittaci or C. trachomatis. Wetting the feathers of infected birds with a detergent-disinfectant prior to necropsy can appreciably reduce the risk of aerosols of infected feces and nasal secretions on the feathers and external surfaces of the bird. Animal Biosafety Level 2 practices, containment equipment, and facilities and respiratory protection are recommended for personnel working with naturally or experimentally infected caged birds. Gloves are recommended for the necropsy of birds and mice, the opening of inoculated eggs, and when there is the likelihood of direct skin contact with infected tissues, bubo fluids, and other clinical materials. Biosafety Level 3 facilities and practices are indicated for activities with high potential for droplet or aerosol production and for activities involving large quantities or concentrations of infectious materials.

Note: Vaccines are not currently available for use in humans.

Transfer of Agent: Contact the Department of Commerce for a permit to export these agents.

Agent: Clostridium botulinum

While there is only one report(32) of botulism associated with the handling of the agent or toxin in the laboratory or working with naturally or experimentally infected animals, the consequences of such intoxications must still be considered quite grave. Work with cultures of C. botulinum requires special security considerations due to their potential use for purposes of biological terrorism.

Laboratory Hazards: C. botulinum or its toxin may be present in a variety of food products, clinical materials (serum, feces), and environmental samples (soil, surface water). Exposure to the toxin of C. botulinum is the primary laboratory hazard. The toxin may be absorbed after ingestion or following contact with the skin, eyes, or mucous membranes, including the respiratory tract.(33) Accidental parenteral inoculation may also represent a significant exposure to toxin. Broth cultures grown under conditions of optimal toxin production may contain 2x106 mouse LD50 per mL.(34)

Recommended Precautions: Biosafety Level 2 practices, containment equipment, and facilities are recommended for all activities with materials known to contain or potentially containing the toxin. A pentavalent (ABCDE) botulism toxoid is available through the Centers for Disease Control and Prevention, as an investigational new drug (IND). This toxoid is recommended for personnel working with cultures of C. botulinum or its toxins. Solutions of sodium hypochlorite (0.1%) or sodium hydroxide (0.1N) readily inactivate the toxin and are recommended for decontaminating work surfaces and spills of cultures or toxin. Additional primary containment and personnel precautions, such as those recommended for Biosafety Level 3, are indicated for activities with a high potential for aerosol or droplet production, and those involving production quantities of toxin. Animal Biosafety Level 2 practices, containment equipment, and facilities are recommended for diagnostic studies and titration of toxin.

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

Agent: Clostridium tetani

Although the risk of infection to laboratory personnel is negligible, five incidents related to exposure of personnel during manipulation of the toxin have been recorded.(35)

Laboratory Hazards: Accidental parenteral inoculation and ingestion of the toxin are the primary hazards to laboratory personnel. Because it is uncertain if tetanus toxin can be absorbed through mucous membranes, the hazards associated with aerosols and droplets remain unclear.

Recommended Precautions: Biosafety Level 2 practices, containment equipment, and facilities are recommended for activities involving the manipulation of cultures or toxin. While the risk of laboratory-associated tetanus is low, the administration of an adult diphtheria-tetanus toxoid at 10-year intervals further reduces the risk to laboratory and animal care personnel of toxin exposures and wound contamination, and is therefore highly recommended.(36) 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 adult vaccination against C. tetani.

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: Corynebacterium diphtheriae

 Laboratory-associated infections with C. diphtheriae have been documented. Laboratory animal-associated infections have not been reported.(37)

Laboratory Hazards: The agent may be present in exudates or secretions of the nose, throat (tonsil), pharynx, larynx, wounds, in blood, and on the skin. Inhalation, accidental parenteral inoculation, and ingestion are the primary laboratory hazards.

Recommended Precautions: Biosafety Level 2 practices, containment equipment, and facilities are recommended for all activities utilizing known or potentially infected clinical materials or cultures. Animal Biosafety Level 2 facilities are recommended for studies utilizing infected laboratory animals. While the risk of laboratory-associated diphtheria is low, the administration of an adult diphtheria-tetanus toxoid at 10-year intervals may further reduce the risk of toxin exposures and work with infectious materials to laboratory and animal care personnel.(38) 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 C. diphtheriae.

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