a. Clinical Syndrome.

(1) Characteristics. Brucellosis is a systemic zoonotic disease caused by one of four species of bacteria: Brucella melitensis, B. abortus, B. suis, and B. canis; virulence for humans decreases somewhat in the order given. These bacteria are small gram-negative, aerobic, non-motile coccobacilli that grow within monocytes and macrophages. They reside quiescently in tissue and bone-marrow, and are extremely difficult to eradicate even with antibiotic therapy. Their natural reservoir is domestic animals, such as goats, sheep, and camels (B. melitensis); cattle (B. abortus); and pigs (B. suis). Brucella canis is primarily a pathogen of dogs, and only occasionally causes disease in humans. Humans are infected when they inhale contaminated aerosols, ingest raw (unpasteurized) infected milk or meat, or have abraded skin or conjunctival surfaces that come in contact with the bacteria. Laboratory infections are quite common, but there appears to be no human-to-human transmission; isolation of infected patients is, therefore, not required. Brucella species long have been considered potential candidates for use in biological warfare. The organisms are readily lyophilized, perhaps enhancing their infectivity. Under selected environmental conditions (for example, darkness, cool temperatures, high C02), persistence for up to 2 years has been documented. When used as a biological warfare agent, Brucellae would most likely be delivered by the aerosol route; the resulting infection would be expected to mimic natural disease.

(2) Clinical Features. Brucellosis presents after an incubation period normally ranging from 3-4 weeks, but may be as short as 1 week or as long as several months. Clinical disease presents typically as an acute, non-specific febrile illness with chills, sweats, headache, fatigue, myalgias, arthralgias, and anorexia. Cough occurs in 15-25%, but the chest x-ray usually is normal. Complications include sacroiliitis, arthritis, vertebral osteomyelitis, epididymo-orchitis, and rarely endocarditis. Physical findings include Iymphadenopathy in 10-20% and splenomegaly in 20-30% of cases. Untreated disease can persist for months to years, often with relapses and remissions. Disability may be pronounced. Lethality may approach 6% following infection with B. melitensis, but the disease is rarely fatal (0.5% or less) after infection with other serotypes (usually after endocarditis develops).

b. Diagnosis.

(1) Routine Laboratory Findings. Noncontributory.

(2) Differential Diagnosis. The initial symptoms of brucellosis are usually nonspecific. The differential diagnosis is therefore very broad and includes bacterial, viral, and mycoplasmal infections. The systemic symptoms of viral and mycoplasmal illnesses, however, are usually present for only a few days, while they persist for prolonged periods in brucellosis. Brucellosis may be indistinguishable clinically from the typhoidal form of tularemia or from typhoid fever itself.

(3) Specific Laboratory Diagnosis. Serology by agglutination or enzyme-linked immunasorbant assay may suggest the diagnosis. A definitive diagnosis of brucellosis is established by culture of blood or bone marrow, which may be positive in up to 70% and 90% of cases, respectively.

c. Therapy. The recommended treatment is doxycycline (200 mg/day) plus rifampin (900 mg/day) for 6 weeks. Alternative effective treatment consists of doxycycline (200 mg/day) for 6 weeks plus streptomycin (1 gm/day) for 3 weeks. Trimethoprimsulfamethoxazole given for 4-6 weeks is less effective. In 5-10% of cases, there may be relapse or treatment failure. Laboratory infections with brucellosis are quite common, but there is no human-to-human transmission and isolation is not required.

d. Prophylaxis. Killed and live attenuated human vaccines have been available in many countries but are of unproven efficacy. There is no information on the use of antibiotics for prophylaxis against human brucellosis.

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