Laboratory-acquired Infections Beyond Bioterrorism
Special Report
Ellen Jo Baron, PhD, D(ABMM), Professor Pathology and Medicine, Stanford University Medical School Director, Clinical Microbiology Laboratory, Stanford University Medical Center, is Associate Editor for Infectious Disease Alert.
Dr. Baron reports no financial relationships relevant to this field of study.
Threats to laboratory workers come in many varieties, ranging from earthquakes to fires. But one threat that has acquired enhanced visibility in this age of bioterrorism is the threat of a laboratory-acquired infection. Exposure to a harmful biological agent can occur in many ways. The most common occurs when the clinical laboratory worker inadvertently handles a specimen or an isolate from a patient with a transmissible infectious disease without using appropriate precautions.
Our laboratory has had its share of such incidents. A few years ago, we isolated a small, gram-negative coccobacillus from a blood culture from a patient from Mexico. Although the physician knew that the patient had been feeling ill for several months, he did not notify the laboratory of his suspicions. In fact, the initial Gram stain prepared from blood culture broth was reported as gram-variable to gram-positive rods, which led all of us astray. Two days later (another clue), the very small, translucent colonies, growing only on blood and chocolate agar, were examined during laboratory plate "rounds." We even passed the Petri dish around for everyone to have a "sniff." In hindsight, this was a bad idea for several reasons, the least of which was that it had no identifiable smell. The isolate was actually Brucella melitensis. A literature review revealed that this organism often appears as gram-variable or gram-positive short rod-like shapes in the blood culture Gram stain. Seven people were placed on prophylactic rifampin and doxycycline. One of our infectious diseases fellows reacted so badly to this regimen that she had to stay home for several days. None of us were happy about it. We subsequently published our experience with recommendations for other laboratories.1
Deliberate release of biologically harmful infectious agents is not limited to terrorists. Our own clinical laboratory credentialing agency, the College of American Pathologists, recently sent out an attenuated, but still virulent, strain of Brucella in 2006 as a proficiency testing sample, necessitating post-exposure prophylaxis in multiple workers.2 They were quite contrite when the story hit the newspapers; especially because they had sent out a potentially deadly avian influenza virus (H2N2) just a year before that generated a lot of bad publicity, particularly considering that the strain had not been included in the flu vaccine since 1968. Proficiency samples sent in the recent past (2006) have contributed to serious infections in laboratory scientists who handled them.3 Although most of us thought that by working in a laminar-flow biological safety cabinet we were immune from acquisition, a study published in 2004 refuted that assumption. Rusnak and colleagues examined the laboratory-acquired infections of workers at the Fort Detrick Biological Weapons laboratory from 1943 to 1989. Their findings were surprising.4 Rates of laboratory-acquired infections, including brucellosis, tularemia, Q fever, and other scary diseases did not diminish appreciably with the introduction of the biological safety cabinet (BSC) in 1949. In fact, infection rates among lab workers only dropped after they either received an effective vaccine for the agent with which they were working, or when studies of that agent were curtailed. This is a sobering realization for those of us trusting BSCs as our primary protection. Whether the lack of efficacy was due to inefficiency of early BSCs, improper utilization (still very common in almost every clinical laboratory that I visit), or actual lack of protection by laminar flow cabinets, is not known. However, even if protection is not complete, BSCs are still recommended for handling transmissible pathogens.
More important than use of BSCs for known high-risk agents is the fact that the initial interaction with a dangerous pathogen in the laboratory will invariably come before its identity is suspected. Activities that place workers at risk include performing routine tasks on the workbench, such as preparing a Gram stain, catalase test, or preparing a suspension of an isolate, and inoculating the carrier for an automated identification/susceptibility testing instrument. What about sniffing plates; are they an important component of daily organism identification? Although "sniffing" has been implicated in laboratory-acquired infections, results from the only published study on this practice would argue otherwise. Barkham and Taylor used a vacuum suction device pulling 40 L/min placed 2 cm above agar plates with colonies of Staphylococcus aureus, Neisseria meningitidis, Pseudomonas aeruginosa, Streptococcus pneumoniae, and others. They sampled the air for 4 minutes per plate. Only 5 of 9 strains grew on the sample plates, and the number of organisms was between 6 and 13 cfu/cubic meter. They concluded that between 6000 and 7000 strong sniffs would be needed before a technologist would sniff one colony-forming unit of bacteria from the plates.5 It is sobering to realize that there are virtually no scientific studies examining the relative risk of various laboratory activities on laboratory-acquisition of infection.
A survey of microbiology laboratories was conducted in 2006.6 For the survey, 88 facilities responded, 53 large institution laboratories, and the rest were small hospital laboratories. Exposures were common, but actual infections in workers were rare. Not surprisingly, many more infections and exposures occurred in the larger facilities, which manipulated more cultures per year and were, thus, more likely to encounter a dangerous pathogen. When relative risk statistics were applied to the survey responses, Brucella was determined to be the most dangerous pathogen for microbiologists. In the age group encompassing the majority of laboratory workers, 25-64, clinical microbiologists have an astounding 641 times greater risk of acquiring brucellosis than did the general population. Neisseria meningitidis, particularly problematic because of its high morbidity and mortality, poses a 25 times greater risk to diagnostic microbiology lab workers that to others. Although Shigella was the most common laboratory-acquired infectious agent in this survey, the chances of developing shigellosis are exactly the same whether you work in a laboratory or not.
A number of recommendations can begin to address the problem. First, a national surveillance system for clinical laboratory-acquired infections should be initiated so that we can begin to understand the breadth of the problem and develop a baseline. The reported incidents are thought to be only the tip of the iceberg. Second, an environment of safety must be developed in microbiology laboratories so that careful handling is not reserved for those isolates that are suspicious and so all workers will be empowered to speak up about lapses in safety practices. Vaccines against the meningococci should be given to laboratory workers in the same manner as hepatitis vaccine is offered to all healthcare workers. Engineering controls, personal protective equipment, and laboratory design should be consistent with safe working behavior. Rules for handling any suspicious cultures before risky activities should be mandated, such as working in the BSC, taping plates with harmful potential, not using automated instruments (for which identifications of many bioterrorism agents is incorrect anyway), and limiting sniffing of colonies until safe handling is assured. Physicians and pathologists need to be constantly reminded to inform the laboratory if they suspect one of the transmissible agents. In California, for example, Coccidioides is a particular risk for laboratory workers, and advance knowledge allows proper precautions to be instituted before a potentially disastrous exposure occurs. Access to laboratories needs to be controlled, and hospital administrations need to support appropriate design, space, and sufficient personnel to work safely. Need for human resources in the form of more training time is also clear, and programs must be developed to fill the gaps that will occur as many experienced clinical laboratory microbiologists leave the field in the next several years. Finally, guidelines for laboratory safety should be based on evidence and science, and studies to determine the actual risk of daily activities should be supported. Would proper use of a functioning BSC protect workers? Currently, even this most basic information has not been determined in a scientific experiment.
Fortunately, the CDC has convened a "blue ribbon" committee to begin to develop a framework for actions that will enhance clinical laboratory safety. This group will collaborate with an ongoing government group that is working on similar guidelines for research laboratories. Expect some changes.
References
- Yagupsky P, Baron EJ. Laboratory exposures to brucellae and implications for bioterrorism. Emerg Infect Dis 2005;11:1180-1185.
- Centers for Disease Control and Prevention. Update: potential exposures to attenuated vaccine strain Brucella abortus RB51 during a laboratory proficiency test — United States and Canada, 2007. MMWR. 2008;57:36-39.
- Centers for Disease Control and Prevention. Laboratory-acquired brucellosis — Indiana and Minnesota, 2006. MMWR. 2008;57:39-42.
- Rusnak JM, et al. Risk of occupationally acquired illnesses from biological threat agents in unvaccinated laboratory workers. Biosecur Bioterror. 2004;2:281-293.
- Barkham T, Taylor MB. Sniffing bacterial cultures on agar plates: a useful tool or a safety hazard? J Clin Microbiol. 2002;40:3877.
- Baron EJ, Miller JM. Bacterial and fungal infections among diagnostic laboratory workers: evaluating the risks. Diagn Microbiol Infect Dis. 2008;60:241-246.
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