Brucella spp., the causative agents for brucellosis, are facultative, intracellular, gram-negative coccobacilli. The main Brucella spp. known to cause human disease are Brucella abortus (including the livestock vaccine strain Brucella abortus RB51), B. melitensis, B. suis , and B. canis .
Brucellosis is a classical bacterial zoonosis since animals are the only source of infection. Humans most commonly acquire the infection through consumption of unpasteurized dairy products (such as raw milk, soft cheese, butter, and ice cream). The bacteria can also enter the body via skin wounds, mucous membranes, or inhalation, so direct contact with infected animal tissues or fluids can be a risk for exposure. Particularly important is direct contact with birthing tissues from infected animals or blood while dressing a carcass during hunting activities. Infection through eating undercooked meat from infected animals can occur, although this is less likely because of lower bacterial loads in muscle. Person-to-person transmission has been reported but is rare.
More than 500,000 new human cases of brucellosis are reported worldwide each year. However, this number is likely an underestimate as brucellosis cases are underreported and often misdiagnosed because symptoms are nonspecific, physicians may lack awareness, and laboratory capacity for diagnosis is limited. B. melitensis is the most frequently reported cause of human illness worldwide, while the most widespread potential source of infection is B. abortus . Human infections occur most frequently among people who have traveled to or who live in areas where the disease is endemic in animals (mainly cattle, sheep, and goats) along the Mediterranean Basin, South and Central America, Eastern Europe, Asia, Africa, and the Middle East. Although not commonly reported in travelers, clinicians should also be aware of the possibility of B. suis or B. canis infection, as these Brucella species are present in animal populations (such as B. suis in feral swine and caribou/reindeer and B. canis in canines) that certain travelers may contact.
The incubation period is usually 2–4 weeks (range, 5 days to 6 months). Initial presentation is nonspecific and includes fever, malaise, arthralgia, myalgia, fatigue, headache, and night sweats. Focal infections are common and can affect most organs in the body. Osteoarticular involvement is the most common brucellosis complication, and reproductive system involvement is the second most common. Although rare, endocarditis can occur and is the principal cause of death among brucellosis patients.
Blood culture is considered the diagnostic gold standard, but isolation rates may vary considerably (25%–80%) depending on stage of infection, previous use of antibiotics, type and volume of clinical specimen, and culture method used. Bacterial growth can be observed within 3–5 days in culture but may take longer; therefore, cultures should be held for ≥10 days before considering the sample culture-negative. To increase recovery of the organism when focal disease is suspected, samples for culture should be collected from the affected area (for example, cerebrospinal fluid, joint aspirate, or urine). Inform the laboratory if brucellosis is suspected when submitting blood, bone marrow, or other clinical specimen for culture, as the bacteria take longer to grow, and laboratory personnel require additional personal protective equipment when handling.
Serologic testing is the most common method for diagnosis. The serum agglutination test (SAT) is the standard method for serologic diagnosis and detects IgM, IgG, and IgA. In general, ELISA tests have good sensitivity and specificity and can detect IgM and IgG. Some limitations to the use of serologic tests must be taken into consideration when diagnosing Brucella infections, as most serologic assays for brucellosis show variable levels of cross-reactivity with other gram-negative bacteria (for example, E. coli O:157, Francisella tularensis , and Yersinia enterocolitica ). Brucella antibodies can persist for more than a year despite successful antibiotic treatment. Last, no validated serologic assays are available to detect antibodies produced against infections caused by B. canis and B. abortus RB51 strain. If infection by either of these organisms is possible or suspected, culture should be performed.
A combined regimen of doxycycline (or oral tetracycline) and rifampin for ≥6 weeks is the recommended treatment for uncomplicated infection. For complicated brucellosis (endocarditis, meningitis, osteomyelitis) an aminoglycoside in combination with tetracycline should be considered, and duration of therapy is often extended for 4–6 months. B. abortus RB51 is resistant to rifampin, so treatment for brucellosis due to this strain should be altered accordingly (for example, doxycycline in combination with trimethoprim-sulfamethoxazole, unless contraindicated). Other agents have been used in various combinations; treatment should be guided by someone with expertise in infectious diseases. Late diagnosis or incorrect therapy can result in relapse.
Avoid unpasteurized dairy products and undercooked meat, especially when traveling to countries where brucellosis is endemic. Wear protective equipment (rubber gloves, goggles or face shields, and gowns or aprons) when dressing or butchering wild animals or when handling birthing products from animals potentially infected with Brucella spp. Clinicians should inform clinical microbiology laboratories when submitting specimens from patients with suspected brucellosis to ensure proper biosafety precautions in the laboratory when handling specimens and specimen derivatives.
For questions on laboratory diagnostics, postexposure guidance, or treatment, please contact the CDC Bacterial Special Pathogens Branch (firstname.lastname@example.org).
CDC website: www.cdc.gov/brucellosis
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María E. Negrón, Rebekah Tiller, Grishma Kharod