Brucella

Etiology

Brucella abortus (cattle), Brucella melitensis (goats and sheep), Brucella suis (swine), and Brucella canis (dogs) are the most common organisms responsible for human disease. These organisms are small, aerobic, non–spore-forming, nonmotile, gram-negative coccobacillary bacteria. Brucella spp. are fastidious in their growth but can be grown on various laboratory media, including blood and chocolate agars.

Epidemiology

Brucellosis is endemic in many parts of the world and is especially prevalent in the Mediterranean basin, Persian Gulf, Indian subcontinent, and parts of Mexico and Central and South America. There are approximately 500,000 new cases annually worldwide, although accurate estimates of the prevalence of disease are lacking because of underreporting and underdiagnosis. Childhood brucellosis accounts for 10–30% of cases. B. melitensis is the most prevalent species causing human brucellosis and is most often carried by sheep, goats, camels, and buffalo. Because of improved sanitation and animal vaccination, brucellosis has become rare in industrialized countries where recreational or occupational exposure to infected animals is a major risk factor for the development of disease. A history of travel to endemic regions or consumption of exotic food or unpasteurized dairy products may be an important clue to the diagnosis of human brucellosis. In the United States, >50% of cases occur in California, Florida, and Texas; hunting feral swine in these states is a recently recognized risk factor. All age-groups can be infected by Brucella, and infections are more common in males, likely because of more frequent occupational and environmental exposures.

Pathogenesis

Modes of transmission for these organisms include inoculation through cuts or abrasions in the skin, inoculation of the conjunctiva, inhalation of infectious aerosols, or ingestion of contaminated meat or dairy products. Infected livestock are the most common source of human infection. In children the primary means of infection is through eating or drinking unpasteurized or raw dairy products. Individuals in endemic areas with occupational exposures to animals, such as farmers and veterinarians, are at highest risk. Laboratory workers are more often exposed to infected aerosols. The risk for infection depends on the nutritional and immune status of the host, the route of inoculum, and the species of Brucella. For reasons that remain unclear, it has been suggested that B. melitensis and B. suis are more virulent than B. abortus or B. canis.

The major virulence factor for Brucella appears to be its cell wall lipopolysaccharide (LPS). Strains containing smooth LPS have been demonstrated to have greater virulence and are more resistant to killing by polymorphonuclear leukocytes. These organisms are facultative intracellular pathogens that can survive and replicate within the mononuclear phagocytic cells (monocytes, macrophages) of the reticuloendothelial system. Even though Brucella spp. are chemotactic for entry of leukocytes into the body, the leukocytes are less efficient at killing these organisms than other bacteria despite the assistance of serum factors such as complement. Brucella spp. possess multiple strategies to evade immune responses and establish and maintain chronic infection. Specifically, during chronic stages of infection, organisms persist within the liver, spleen, lymph nodes, and bone marrow and result in granuloma formation.

Antibodies are produced against the LPS and other cell wall antigens, providing a means of diagnosis and probably playing a role in long-term immunity. The major factor in recovery from infection appears to be development of a cell-mediated response, resulting in macrophage activation and enhanced intracellular killing. Specifically, sensitized T lymphocytes release cytokines (e.g., interferon-γ, tumor necrosis factor-α), which activate the macrophages and enhance their intracellular killing capacity.