Brucellosis: Recommendations for Risk Assessment, Post-Exposure Prophylaxis, and Follow-up of Laboratory Personnel Exposed to Pathogenic Brucella Species

I work with Brucella in the laboratory, am I at risk for acquiring brucellosis?

Brucellosis is the most commonly reported laboratory-associated bacterial infection. A number of factors contribute to the risk of an accidental Brucella exposure. Laboratories may lack experience working with the organism, as it has become less common in the United States due to an aggressive immunization program in cattle. In addition, the organism is often "unknown" when the sample arrives for analysis. Work may be performed on an open bench before it is recognized as a gram-negative rod. Certain characteristics of the bacterium, such as its low infectious dose and the fact that it is easily aerosolized, also contribute to the risk of acquisition of the organisms in a laboratory setting.

Specifically implicated procedures or events related to pathogenic Brucella species include sniffing bacteriological cultures, direct skin contact, mouth pipetting, inoculations, and sprays into eyes, nose, and mouth. Manipulation of Brucella organisms on an open bench without use of the recommended practices has led to infections. Anyone who practiced a specifically implicated procedure (above), anyone who was within five feet of any manipulation of Brucella on an open bench, or anyone present in a laboratory during a Brucella aerosol-generating event is at risk for acquiring brucellosis.

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If my lab learns we have worked with Brucella, how do we determine who is at risk for developing brucellosis?

Related to pathogenic Brucella species, specifically implicated events associated with laboratory-acquired Brucella infections include sniffing bacteriological cultures, direct skin contact, presence when aerosols have been generated (such as during catalase testing), mouth pipetting, inoculations, and sprays into eyes, nose, and mouth. Manipulation on an open bench without use of the recommended practices has led to infections. Any worker present in the laboratory during the work-up and identification of a pathogenic Brucella isolate is considered a Brucella-exposed worker.

High-risk exposure

Individuals who performed a specifically implicated practice (see above), individuals who were near (within five feet) work with Brucella on an open bench, or individuals present in the laboratory during a Brucella aerosol-generating event should be considered as having a high risk exposure.

Low-risk exposure

Others in the lab at the time of manipulation on an open bench, but who do not have high-risk exposures as defined above, have a low-risk exposure.

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What are the recommendations for post-exposure prophylaxis (PEP) to prevent brucellosis?

Interim PEP recommendations

Doxycycline 100 mg orally twice a day plus rifampin 600 mg orally once a day for 21 days.

Note: PEP recommendations for B. abortus RB51 (attenuated vaccine strain) differ from those for fully pathogenic Brucella spp. As RB51 was derived by selection in rifampin-enriched media and is resistant to rifampin in vitro, the use of rifampin for PEP or treatment will not be effective for RB51. Post-exposure prophylaxis for those at high risk of exposure should include doxycycline 100 mg orally twice daily for at least 21 days. For those with contraindication to doxycycline, trimethoprim-sulfamethoxazole may be used.

After a potential laboratory exposure, all individuals classified as high-risk should begin PEP. PEP should be discussed with, and offered to, laboratory workers with low-risk exposures. For women who are pregnant, PEP should be considered in consultation with their obstetricians.

Serial serum specimens should be monitored for all exposed workers. Obtain baseline serum as soon as possible after the exposure has been recognized, and obtain available pre-exposure stored specimens. Arrange for serologic testing (Brucella microagglutination testing) at 2, 4, 6, and 24 weeks. These tests will monitor for the development of infection and can be performed at your state public health laboratory or CDC. Note: RB51 does not induce a measurable antibody response. Monitoring serum specimens in individuals exposed to RB51 will not provide a useful indicator of infection.

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How long should exposed workers be observed for the development of illness?

All exposed individuals, regardless of risk status, should be monitored for the development of symptoms. From the last exposure, temperature should be actively monitored for fever for four weeks. Broader symptoms of brucellosis should be passively monitored for six months from the last exposure. These symptoms include:

Acutely

fever, chills, headache, low back pain, joint pain, malaise, occasionally diarrhea

Sub-acutely

malaise, muscle pain, headache, neck pain, fever, sweats

Chronically

anorexia, weight loss, abdominal pain, join pain, headache, backache, weakness, irritability, insomnia, depression, constipation

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Recommendations for safe laboratory practices for Brucella spp.

• When brucellosis is suspected, clinicians should note "suspect or rule out brucellosis" on the laboratory submission.
• Review laboratory containment methods and microbiological procedures to ensure compliance with recommendations in the Biosafety in Microbiological and Biomedical Laboratories (BMBL), 5th edition.
• Use primary barriers: use safety centrifuge cups, personal protective equipment, and class II or higher Biological Safety Cabinets (BSCs) for procedures with a high likelihood of producing droplet splashes or aerosols.
• Use secondary barriers: restrict access to the laboratory when work is being performed and maintain the integrity of the laboratory’s air handling system by keeping external doors and windows closed.
• Perform all procedures on unidentified isolates carefully to minimize the creation of splashes or aerosols.
• Prohibit sniffing of opened culture plates to assist in the identification of isolates. Manipulate isolates of small gram-negative or gram-variable rods within a BSC.

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Recommendations for surveillance and post-exposure prophylaxis for laboratory exposure to Brucella isolates

1. Determine number of workers exposed to Brucella isolates and classify exposures into high- and low-risk
2. Recommend PEP for workers with high-risk exposures to Brucella:
   • doxycycline 100mg twice daily and rifampin 600mg once daily for 3 weeks
   • trimethoprim-sulfamethoxazole should be considered for those patients with contraindications to doxycycline
   • pregnant workers with high-risk exposures should consider PEP in consultation with their obstetricians
3. Discuss PEP with workers with only low-risk exposures to Brucella
4. Obtain baseline serum samples from all workers as soon as possible after a potential Brucella exposure is recognized. If available, obtain pre-exposure stored specimens.
5. Arrange for sequential serologic testing on all workers exposed to Brucella (e.g. 2, 4, 6, and 24 weeks post exposure) using agglutination test at state public health laboratory or CDC.
6. Arrange for regular (e.g. weekly) active surveillance for development of febrile illness or other signs and symptoms of brucellosis among all workers exposed to Brucella isolates for 6 months following last exposure.

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