Over 37 bacterial species account for approximately 43% of LAIs, making bacteria the most frequent cause of LAIs in diagnostic laboratories (10). The risk of transmission of M. tuberculosis and Mycobacterium bovis in healthcare facilities and clinical laboratories has long been recognized (28). Since 1953, the tuberculosis case rate in the United States has declined nearly tenfold, from 53 cases per 100,000 to 5.6 per 100,000 in 2001, and decreased 40% compared with the most recent peak year of 1992 (http://www.cdc.gov/tb/statistics/reports/2008/default.htm). Historical surveys have demonstrated an incidence of tuberculosis among laboratory workers up to nine times greater than in the general population (29,30). The greatest risk of laboratory-acquired mycobacterial infection is associated with exposure to aerosols generated during handling of liquid specimens, preparation of frozen sections, and performing autopsies, although a few LAI mycobacterial infections have been attributed to direct parenteral inoculation (7,31). The relatively low inoculum of M. tuberculosis required to establish infection in humans (32) makes unprotected exposure to this microorganism in the laboratory quite risky. Although respiratory specimens are most frequently implicated as the source of laboratory-acquired mycobacterial infection, the presence of acid-fast bacilli in specimens other than respiratory secretions (e.g., gastric aspirates, cerebrospinal fluid (CSF), urine, exudates, and tissue) may also result in healthcare-associated transmission to healthcare workers (HCWs) and autopsy personnel (33).

Historically, the second most frequent of the bacterial causes of LAI have been Brucella spp., which have caused approximately 24% of all reported LAIs and 11% of LAI-associated laboratory worker deaths in the United States (34,35,36,37,38,39,40). Brucella spp. are highly infectious and often cause infections in multiple research or clinical laboratory workers following a single laboratory accident (36,37,40). While protocols for proper handling of known Brucella isolates in clinical microbiology laboratories are typically in place, misidentification of this microorganism frequently occurs, leading to laboratory staff exposures (36,41). Brucella spp. are believed to be transmitted in the laboratory primarily via aerosolization or direct contact. Often, however, it has been impossible to determine the mechanism of transmission. Rare cases of person-to-person transmission have been reported, and in some instances, individuals with very low risk exposure (nonlaboratorians that have made short visits to the laboratory) have contracted brucellosis (20). F. tularensis is rarely encountered in the clinical laboratory. However, like Brucella spp., it is a fastidious, slow-growing gram-negative coccobacillus that may be difficult to identify early enough to prevent accidental exposures (42).

Bacillus anthracis is a gram-positive spore-forming rod that is a rare cause of human infections in the United States. B. anthracis represents a unique risk among potential LAI agents, because the spores it produces are extraordinarily hardy and contaminated surfaces (or hands) are difficult to disinfect with routine procedures. Laboratory-acquired
anthrax has most recently been documented in a laboratory worker handling specimens from the 2001 bioterrorismrelated anthrax outbreak that occurred in the United States (43,44). In this case, the lab worker acquired cutaneous anthrax from exposure to microorganisms present on the surface of contaminated vials.

Burkholderia pseudomallei, the microorganism responsible for melioidosis, is cited as a rare cause of LAIs but has been associated with a fatal outcome (45). Direct contact with microbiologic cultures or specimens, ingestion, autoinoculation, and exposure to infectious aerosols and droplets all have been implicated in transmission of B. pseudomallei. N. meningitidis is another infrequent cause of LAIs that has been associated with fatal outcomes (46). In a recent survey, 16 worldwide cases of probable laboratory-acquired N. meningitidis, with eight fatal outcomes, were identified between 1985 and 2001, including six US cases between 1996 and 2000 (47). All cases (16/16) occurred among clinical microbiologists who, in most cases (15/16), performed isolate manipulation without respiratory protection (47).

The agent of whooping cough, Bordetella pertussis, has caused at least 12 LAIs in the past 30 years, with six probable cases in the United States from 1996 to 2001 (2,5). The source isolates for the US cases were recovered from blood or CSF in five of the six cases and middle ear fluid in the sixth case.

The enteric bacterial pathogens, Salmonella species and Shigella species, are commonly reported causes of LAIs, while many additional cases likely go unreported (2,13,19,21,48). In older surveys, Salmonella typhi has caused more reported fatalities than any other LAI, while in more recent studies Shigella sp. was identified as the most frequent bacterial cause of LAIs (11,13,15,19). Infections generally occur from handling laboratory specimens and microbiologic cultures or occasionally from ingestion of intentionally contaminated food (49). Gastroenteritis resulting from Vibrio species, Campylobacter species, enterotoxigenic E. coli and Clostridium difficile are infrequently reported (15,50, 51, 52 and 53).

The agent of Q fever, C. burnetii, is rare in the United States, so the risk for diagnostic laboratory-acquired Q-fever infection in this country is minor compared with that in many other parts of the world. The microorganism is present in blood, urine, feces, milk, and tissue specimens and resists drying. Most LAIs from C. burnetii arise from aerosols generated in animal research laboratories, although there are a few reports of parenteral and mucous membrane transmissions (2,21,54).

Before 1960, psittacosis was “among the most commonly reported laboratory-associated infections,” but only sporadic cases have been reported in the past 20 years (2,21). Psittacosis case fatality rates are high compared with those of infections resulting from other agents. Chlamydia psittaci, the agent of psittacosis, may be present in tissues, feces, nasal secretions, and blood specimens. Few infections occur from exposure to Chlamydia trachomatis and generally result from mucous membrane exposure.

Leptospira interrogans, the cause of leptospirosis, can be present in urine, blood, and tissues of infected patients. Ingestion, accidental parenteral inoculation, and contact of skin or mucous membranes with cultures or infected specimens have all led to infection in laboratory workers. Likewise, LAI with syphilis has been documented, and its agent, Treponema pallidum, can be present not only in blood but also in cutaneous, mucous membrane, and other lesions. Laboratory spread of this microorganism follows from parenteral inoculation, contact of mucous membranes or broken skin with infectious clinical materials, and possibly infectious aerosols. Accidental parenteral inoculations are likely sources for laboratory-acquired rickettsial infections, but several infections with typhus have been associated with aerosols or infected airborne particles, and cases of Rocky Mountain Spotted Fever probably have occurred by this route as well (19,48). LAIs from Rickettsia typhi, Rickettsia coronii, and Orientia tsutsugamushi have also been reported (2,55). Because most diagnostic clinical laboratories do not perform cultures for rickettsia, these infections are more likely to be a risk in research laboratories.

The blood-borne viruses (HIV, HBV, HCV) pose the infection risk of greatest concern to hospital workers (6,7,56,57). As of September 2007, the Centers for Disease Control and Prevention (CDC) had received reports of 57 HCWs in the United States with documented occupationally acquired HIV seroconversion, and 140 additional reports classified as possible occupational transmission (http://www.cdc. gov/ncidod/dhqp/bp_hcp_w_hiv.html). These individuals include 19 laboratory workers (16 clinical laboratory workers and 3 nonclinical laboratory technicians). Forty-eight of the fifty seven documented seroconversions were from percutaneous exposures, five were mucocutaneous, two were both, and two had an unknown route of exposure. Forty-nine HCWs were exposed to HIV infected blood, three to concentrated virus, one to visibly bloody fluid, and four to unspecified fluid. Twenty-six of these individuals had developed acquired immunodeficiency syndrome as of the date of the report.