Author(s): María Negrón, Rebekah Tiller, Grishma Kharod

Infectious Agent

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.

Epidemiology & Transmission

Over 500,000 new human cases of brucellosis—a bacterial zoonosis—are reported worldwide each year. This number is likely an underestimate, however, because cases are underreported and often misdiagnosed because clinical symptoms are nonspecific, physicians might lack awareness, and laboratory capacity for diagnosis is limited. B. melitensis is the most frequently reported cause of brucellosis worldwide, but the most widespread potential source of infection is B. abortus.

Human infections occur most frequently among travelers to, or people living in, areas where the disease is endemic in animals—primarily cattle, goats, and sheep—in Africa, Central and South America, Asia, eastern Europe, along the Mediterranean Basin, and the Middle East. In North America, Brucella spp. are endemic to the feral swine population and wildlife around the Greater Yellowstone Area.

Humans most commonly acquire Brucella through consumption of unpasteurized dairy products (e.g., raw milk, and butter, soft cheese, or ice cream made from raw milk) from infected animals. 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 an exposure risk. Activities such as carcass dressing and assisting birthing animals can increase the risk for contact with infective tissues and fluids.

Travelers’ brucellosis can be caused by B. suis or B. canis infection because certain travelers might have contact with animal populations infected with these Brucella species (e.g., B. suis in feral swine and caribou or reindeer, and B. canis in dogs). Consumption of undercooked meat from infected animals can lead to infection, but this exposure risk is less likely because bacterial loads are lower in muscle. Person-to-person transmission has been reported but is rare. Exposure to Brucella during pregnancy can increase the risk for miscarriage, so travelers who are or might be pregnant should take extra precautions.

Clinical Presentation

The incubation period of brucellosis is usually 2–4 weeks (range 5 days–6 months). Initial clinical presentation is nonspecific and includes arthralgia, fatigue, fever, headache, malaise, myalgia, and night sweats. Focal infections are common and can affect most organs in the body. Osteoarticular involvement is the most common brucellosis complication, as is reproductive system involvement. Although rare, endocarditis can occur and is the principal cause of death among patients with brucellosis.

Diagnosis

Blood culture is considered the diagnostic gold standard, but isolation rates can vary considerably (25%–80%) depending on stage of infection, previous use of antimicrobial drugs, type and volume of clinical specimen, and culture method used. Bacterial growth in culture can be observed within 3–5 days but might take longer; therefore, laboratories should hold cultures for ≥10 days before considering a sample negative.

To increase recovery of the organism, collect samples during a febrile episode and prior to starting antimicrobial drugs; when focal disease is suspected, collect samples for culture from the affected area (e.g., cerebrospinal fluid, joint aspirate). Inform the laboratory that brucellosis is suspected when submitting blood, bone marrow, or other clinical specimens for culture because the bacteria take longer to grow, and laboratory personnel require additional personal protective equipment when handling the clinical specimens and culture.

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. The Bacterial Special Pathogens Branch at the Centers for Disease Control and Prevention (CDC) performs a modified version of the SAT, known as the Brucella microagglutination test (BMAT). In general, ELISA tests have good sensitivity and specificity and can detect IgM or IgG, and US commercial diagnostic laboratories have the capacity to perform these assays.

Because most Brucella serologic assays show variable levels of cross-reactivity with other gram-negative bacteria (e.g., Escherichia coli O:157, Francisella tularensis, Yersinia enterocolitica), consider the limitations of serologic testing for diagnosing brucellosis. In addition, Brucella antibodies can persist for >1 year despite successful antibiotic treatment. Finally, no validated serologic assays are available to detect antibodies produced against infections caused by B. canis and B. abortus RB51 strain in humans. If infection with either of these organisms is possible or suspected, perform a culture on a specimen taken prior to the start of antimicrobial drug therapy.

For diagnostic support and specimen submission guidance, contact the local, territorial, tribal, or state public health department. CDC’s Bacterial Special Pathogens Branch (bspb@cdc.gov) can coordinate testing needs in conjunction with the public health department; CDC-specific guidance on specimen submission can be found at the CDC Test Directory (www.cdc.gov/laboratory/specimen-submission/list.html; enter Brucella in the search bar).

Treatment

A combined regimen of doxycycline (or oral tetracycline) and rifampin for ≥6 weeks is recommended for the treatment of uncomplicated infection. For complicated brucellosis (endocarditis, meningitis, osteomyelitis), consider adding an aminoglycoside in combination with doxycycline and extend the duration of therapy to 4–6 months. B. abortus RB51 is resistant to rifampin; modify treatment for brucellosis caused by this strain accordingly (e.g., doxycycline in combination with trimethoprim-sulfamethoxazole, unless contraindicated). Other antimicrobial agents have been used in various combinations; treatment should be guided by a clinician with expertise in infectious diseases. Incorrect or incomplete therapy, or late diagnosis, can result in relapse.

Prevention

Travelers should avoid unpasteurized dairy products, undercooked meat, and potentially contaminated meat products in countries where brucellosis is endemic. People who dress or butcher wild animals or who handle birthing products from animals potentially infected with Brucella spp. should wear appropriate protective equipment, including rubber gloves, goggles or face shields, and gowns. Inform clinical microbiology laboratories when submitting specimens from patients with suspected brucellosis to ensure proper biosafety precautions in the laboratory handling of specimens and specimen derivatives.

For questions on laboratory diagnostics, post-exposure guidance, or treatment, contact the local, territorial, tribal, or state public health department, or CDC’s Bacterial Special Pathogens Branch (bspb@cdc.gov).

CDC website: Brucellosis