Members of the genus Brucella are primarily pathogens of animals (domestic and feral). Thus, brucellosis (undulant fever) is a zoonosis (a disease of animals that may be transmitted to humans under natural conditions). Different species of Brucella are each associated with particular animal species: Brucella abortus (cattle), Brucella melitensis (goats and sheep), Brucella suis (swine), Brucella canis (dogs), and Brucella ovis (sheep). All but B. ovis are known to cause disease in humans. The brucellae are aerobic, facultatively intracellular parasites that can survive and multiply within host phagocytes. Cells of the genus Brucella are unencapsulated, small coccobacilli arranged singly or in pairs (see Figure 2). LPS is the major virulence factor as well as the major cell wall antigen.

A. Epidemiology

 Brucellosis is a chronic, lifelong infection in animals. Organisms localize in reproductive organs (male and female) and are shed in large numbers in milk, urine, the placenta and other tissues discharged during delivery or spontaneous abortion. The primary manifestations of infection in animals are sterility and abortion. Transmission to humans characteristically occurs as a result of either direct contact with infected animal tissue or ingestion of unpasteurized milk or milk products (Figure 1).

Fig1. Transmission of Brucella.

B. Pathogenesis

Brucellae typically enter the body through cuts and abrasions in the skin or through the gastrointestinal (GI) tract. Drugs that decrease gastric acidity may increase the likelihood of transmission via the GI route. Inhalation of infected aerosols can also lead to disease among abattoir workers. Once the organisms gain entry, they are transported via the lymphatic system to the regional lymph nodes, where they multiply. The organisms are then carried by the blood to organs that are involved in the reticuloendothelial system, including the liver, spleen, kidneys, bone marrow, and other lymph nodes.

 C. Clinical significance

The incubation period for Brucella infections ranges from 5 days to several months but typically lasts several weeks. Symptoms are nonspecific and flulike (malaise, fever, sweats, anorexia, GI symptoms, headache, and back pains) and may also include depression. Symptom onset may be abrupt or insidious. Objective clinical findings are often few and mild, in contrast to the patient’s subjective evaluation. Untreated, patients may develop an undulating pattern of fever (temperatures repeatedly rise then fall, hence the name “undulant fever,” the traditional name for brucellosis). Subclinical infections occur. Manifestations of brucellosis may involve any of a variety of organ systems, including the GI tract and the skeletal, neurologic, cardiovascular, and pulmonary systems. In industrialized countries, brucellosis is largely an occupational disease, occurring in ranchers, dairy farmers, abattoir workers, and veterinarians.

D. Laboratory identification

 Because the nonspecific symptoms may not point to a diagnosis of brucellosis, a detailed history is often crucial, including the patient’s occupation, exposure to animals, travel to countries where brucella infection is prevalent, and ingestion of potentially contaminated foods. The organism can be cultured from blood and other body fluids or from tissue specimens. Multiple blood specimens should be cultured. For plated materials, colonies may appear in 4 to 5 days, whereas longer times are required for blood cultures, and these are routinely examined for up to 1 month before being declared negative.

 E. Treatment

 Combination therapy involving doxycycline and rifampin is generally recommended for brucellosis (Figure 2). Prolonged treatment (for example, 6 weeks) is generally necessary to prevent relapse and reduce the incidence of complications.

Fig2. Summary of Brucella disease. 1 Indicates first-line drugs.

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