Chapter 254. Brucellosis

Brucellosis is a worldwide zoonosis of wild and domestic animals and is most commonly found in countries of the Mediterranean basin, the Arabian Gulf, the Indian subcontinent, and parts of Mexico and Central and South America. Human infections are caused by four species: Brucella melitensis which is the most common infection in the United States and is acquired from goats and sheep, B abortus, B suis, and B canis. The organisms are intracellular gram-negative coccobacilli that infect humans by ingestion, inhalation, or inoculation of the skin or conjunctivae.1,2 In countries where brucellosis is endemic, the most common risk factor for infection is consumption of unpasteurized milk.2-4 The typical patient seen in the United States tends to be an Hispanic male from California or Texas who acquired B melitensis from contaminated goat’s milk or goat cheese that was imported from or ingested in Mexico. Brucellosis can be an occupational hazard for veterinarians and other individuals involved in the livestock industry. This changed markedly with immunization of herds and improved sanitation in meat-processing plants so that infections ascribable to B abortus (cattle) and B suis (swine) have essentially disappeared. Brucellosis is rare in the United States and is infrequently seen in children. In 2006, only 14 of 121 cases reported to the Centers for Disease Control were in patients under age 15.5

Clinical Manifestations

Brucellosis is a disease of protean manifestations. Symptoms typically develop 2 to 3 weeks after exposure and can be acute or insidious. Fever is an almost invariable component of the illness and may wax and wane over a prolonged period of time in untreated patients, hence the name, undulant fever. The classical triad of brucellosis consists of fever, arthralgia or arthritis, and organomegaly, often associated with night sweats, malaise, weight loss, and anorexia. Physical examination findings may be scarce and include joint tenderness, splenomegaly or hepatomegaly, and rarely arthritis.4,6,7 Congenital brucellosis has been described, and the infection can be transmitted via breast milk.8,9 The illness spectrum varies from mild febrile illness to major systemic disease with endocarditis, meningitis, arthritis, or osteomyelitis. The disease is sometimes localized to a single organ, such as the musculoskeletal, pulmonary, cardiovascular, or neurologic systems.1

Diagnosis

A definitive diagnosis of brucellosis is made when the agent is isolated from blood, bone marrow, or other fluid cultures. The serologic diagnosis is typically made using the serum agglutination test (SAT), which should demonstrate a 4-fold or greater rise in titer or be positive at dilutions of 1:160 or greater10 or less commonly by an enzyme immunoassay.11 In the United States, both tests use B abortus as the antigen, and the titers reported are based on cross-reactions. Of note is that these assays do not detect antibodies to B canis. Brucella titers tend to fall during treatment, and a persistently high IgG titer suggests continuing infection. The white cell count is typically normal but may be low in one third of the cases. Anemia and monocytosis are the most common hematological manifestations. The erythrocyte sedimentation rate is normal to mildly elevated, the C-reactive protein is often elevated as are the liver enzymes.2,12-14

The organisms are found intracellularly in polymorphonuclear and mononuclear phagocytes. During bacteremia, organisms distribute throughout the reticuloendothelial system, localizing in the spleen and liver, as well as in other organs where it manifests with noncaseating granulomas.

Treatment and Prevention

The commonly used treatment regimens consist of doxycycline for 45 days, in combination with gentamicin for 7 days; or doxycycline and rifampin for 45 days.16 Trimethoprim-sulfamethoxazole for 4 to 6 weeks in combination with rifampin is recommended for younger children.17,18 Monotherapy regimens are associated with a high failure rate. For more serious infections, or in the presence of complications, a 7- to 14-day course of gentamicin can be added to the traditional regimen of trimethoprim-sulfamethoxazole and rifampin. Relapse rates of around 3.5% to 20% are reported in children and require retreatment. Patients with persisting bacteremia or evidence of relapse may need special radiographic studies, such as bone scans or abdominal scans, to look for specific foci of infection requiring surgical drainage or more prolonged treatment. In endemic areas, household members of individuals with brucellosis should be screened; they may be asymptomatic even in the face of bacteremia, and B melitensis has been isolated from the blood of such individuals and, rarely, from breast milk.9,15 Of concern is the increasing rate of resistance of Brucella to trimethoprim-sulfamethoxazole increasing the risk of relapse.19 In endemic areas, household members of individuals with brucellosis should be screened; they may be asymptomatic even in the face of bacteremia, and B melitensis has been isolated from the blood of such individuals and, rarely, from breast milk.9,15

No human vaccine is available. Prevention is achieved by control of brucellosis in animals and pasteurization of milk. Individuals should avoid the ingestion of unpasteurized milk products and cheeses from Mexico or other endemic areas. Goat’s milk is most commonly involved in food source outbreaks of brucellosis, but exposure to infected cattle and swine, or their products, can also lead to disease. Laboratory-acquired brucellosis has been reported on many occasions. There is an attenuated vaccine that can be used to immunize animals, but this product is responsible for human disease and can be hazardous to animal handlers.