Biosafety concerns related to Brucella and its potential use as a bioweapon

Authors: Olsen, Steven; Boggiatto, Paola; White, David; McNunn, Tonia

Submitted to: Applied Biosafety
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/28/2018
Publication Date: 4/16/2018
Citation: Olsen, S.C., Boggiatto, P.M., White, D.M., McNunn, T.B. 2018. Biosafety concerns related to Brucella and its potential use as a bioweapon. Applied Biosafety. 23(2)77-90. https://doi.org/10.1177/1535676018771983.
DOI: https://doi.org/10.1177/1535676018771983

Interpretive Summary: Three species of Brucella (B. abortus, B. suis, and B. melitensis) are currently considered potential bioweapons and are regulated under the Biological Select Agent and toxins (BSAT) list. Classification as BSAT is associated with increased research costs due to the need to meet security and safety requirements. During biennial reviews of the BSAT list, a number of biological, clinical, and epidemiologic properties of Brucella were identified for which a consensus opinion could not be reached. In this review, some of the identified issues are reviewed in light of published scientific reports. This information will be of interest to researchers in brucellosis, regulatory personnel, employees of agencies tasked with public safety or security, and people with an interest in biosafety.

Technical Abstract: Brucellosis is endemic throughout the world and causes approximately 500,000 new human infections worldwide annually. Brucella melitensis is the most virulent species in humans and is associated with the majority of human infections under field and laboratory conditions. In the U.S., billions have been invested in regulatory programs in livestock in the U.S. in an effort to protect public health by elimination of brucellosis from reservoir hosts. Human disease is almost exclusively associated with exposure to infected reservoir hosts or consumption of products (i.e. unpasteurized milk products) from infected livestock. Emerging threats from wildlife reservoirs pose a significant risk to the investment made in regulatory programs as well as a growing risk to public health. Currently there are few registered facilities capable of addressing research needs related to brucellosis in livestock or wildlife. Although frequently reported as being infectious at dosages between 10 and 100, these estimates were based on studies that calculated the numbers of bacteria delivered into the pulmonary parenchyma and do not include other routes of exposure that may have contributed to infection. More relevant data would suggest that infection in humans and animals would require environmental delivery of at least 104 or 105 CFU dosages of virulent strains of Brucella. Advances in medical care have led to mortality no longer being a significant risk associated with human infection, but there are clinical risks associated with infection during pregnancy. Antibiotic treatment is highly effective but relapse does occur in some patients after treatment. Pulmonary infection is not associated with more severe clinical symptoms and antibiotic treatment of pulmonary infection is highly effective. Although considered a high risk for laboratory infections, the incidence of laboratory infections appear to be declining and in many instances are directly related to improper biosafety practices. Regulatory programs in livestock and endemic infection in many countries result in high numbers of samples and more frequent microbiologic isolations at clinical laboratories which likely contribute to a higher risk for laboratory infection with brucellosis as compared to other zoonotic agents. Research costs associated with any agent listed as a BSAT are higher than for work with non-BSAT agents with increased costs related to security and regulatory issues; with the result that listing of a pathogen as a BSAT negatively impacts research activities. As biannual review of the BSAT list is required, we suggest that discussions related to retention or removal of Brucella from the BSAT list are enhanced by illuminating the issues surrounding the clinical, biological and epidemiological properties of the agent.