Update on Brucellosis: The Latest STD?
By Carol Kemper, MD, FACP
Dr. Kemper is Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center.
Dr. Kemper does research for Abbott Laboratories and Merck. Infectious Disease Alert editor Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, does research for the National Institutes of Health and is a consultant and advisory board member for Merck. Peer reviewer Timothy Jenkins, MD, Assistant Professor of Medicine, University of Colorado, Denver, Denver Health Medical Center, reports no financial relationships to this field of study.
This article originally appeared in the September 2010 issue of Infectious Disease Alert.
Brucellosis is the most common zoonosis worldwide, resulting in an estimated half million cases annually. Infection usually occurs from ingestion of contaminated dairy products, aerosolization, or mucocutaneous contact with conjunctiva, abraded skin, or open infected tissues. Sexual transmission has seldom been documented in humans, although it is common in farm animals, and the organism has been found in both semen and vaginal fluids. One can imagine that disseminated infection could result in infection in genital secretions, which is indirectly supported by the fact that genital infection does occur, and infection within families is common (up to 50%).
The first article describes the apparent sexual transmission of Brucella spp. between two married couples.1 The first patient was a 55-year-old man who had traveled to Israel, where he consumed unpasteurized goat milk. About two weeks later, he developed fever and rigors, and blood cultures yielded B. melitensis biovar 1. He received a combination of rifampin and doxycycline for two weeks and quickly recovered. Four weeks following the man's diagnosis, his wife, who had not traveled, presented with fever and rigors, and blood cultures yielded the same organism. Semen samples, obtained from the husband at that time (toward the end of his treatment course), failed to yield an organism, but PCR was positive for Brucella spp. Despite the same treatment regimen, and initial response, the wife relapsed with recurrent infection four weeks later. Culture of semen was negative, but PCR remained positive.
The second case describes a 65-year-old man who presented with fever, chills, cervical discitis and osteomyelitis, and epididymo-orchitis. Blood cultures grew B. melitensis. He responded well to treatment. He recalled eating unpasteurized cheese purchased in a small village in Israel. About four weeks later, his wife, who had not traveled with him and had no history of exposure to unpasteurized dairy, developed fever and chills. Blood cultures grew B. melitensis.
Both cases are highly suggestive of sexual transmission from husband to wife. The persistence of the organism in semen in the first case, at least as demonstrated by persistently positive PCR, raises concern that persistence of the organism in genital secretions may present an ongoing risk to sexual partners, despite apparent response to treatment. Persistence of infection is, in part, what makes certain species of Brucella particularly difficult to treat.
At least 10 different species of Brucella have been identified, each with apparent differences in host specificity, virulence, and in the ability to cause persistent infection, including more commonly B. melitensis (in goats), B. abortus (in cattle), and B. suis (in pigs). An increasing number of cases is being reported from Israel, Iraq, Iran, Kyrgyzstan, and Mongolia, as well as the U.S.-Mexican border. Two newer species have been identified within the past decade, including B. microti, which was first described in an outbreak in the Czech Republic in 2001. The reservoir for this organism in the wild appears to be the common vole.
Laboratory work with B. microti indicates that it may be more virulent than other species of Brucella, but may lack the ability to persist in tissues as other species.2 Jimenez de Bagues and colleagues infected human and murine macrophages with both B. microti and B. suis. At 24 hours of cell culture, B. microti demonstrated a significantly increased capacity for intracellular replication compared with B. suis. In vivo inoculation of different mice strains showed that the bacterial load in liver and spleen peaked at day 3 for B. microti, compared with day 7 for B. suis. Intraperitoneal inoculation of 105 B. microti resulted in death in 82% of Babl/c mice within 4-7 days. However, sublethal doses of B. microti resulted in total protection from subsequent lethal doses of organism suggesting that naturally occurring immunity in the wild may be important in preventing spread of the organism. Furthermore, B. microti had a lower residual capacity for persistence of infection in spleen tissue.
Interestingly, genetic sequencing studies suggest that all of the Brucella species share a high degree of homology and, specifically, B. microti appears to be nearly identical to B. suis enough so that it has been proposed that all of these organisms should be grouped into one species (tentatively named B. melitensis). However, genetic analyses do not seem to adequately explain the observed differences in host specificity and possibly virulence between the various organisms.
References
- Meltzer E, et al. Sexually transmitted brucellosis in humans. Clin Infect Dis. 2010:51:e12-15.
- Jimenez de Bagues MP, et al. The new species of Brucella microti replicates in macrophages and causes death in murine models of infection. J Infect Dis. 2010;202:3-10.
- Accompanying editorial by J. Glenn Morris, Jr., and F.S. Southwick. Brucella, voles, and emerging pathogens. J Infect Dis. 2010;202:1-2.
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