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(Undulant, Malta, Mediterranean, or Gibraltar Fever)

by Larry M. Bush, MD, Maria T. Perez, MD

Brucellosis is caused by Brucella sp. Symptoms begin as an acute febrile illness with few or no localized signs and progress to a chronic stage with relapses of fever, weakness, sweats, and vague aches and pains. Diagnosis is by culture, usually from the blood. Optimal treatment usually requires 2 antibiotics—doxycycline or trimethoprim/sulfamethoxazole plus gentamicin, streptomycin, or rifampin.

The causative organisms of human brucellosis are B. abortus (from cattle), B. melitensis (from sheep and goats), and B. suis (from hogs). B. canis (from dogs) has caused sporadic infections. Generally, B. melitensis and B. suis are more pathogenic than other Brucella sp. The most common sources of infection are farm animals and raw dairy products. Deer, bison, horses, moose, caribou, hares, chickens, and desert rats may also be infected; humans can acquire the infection from these animals as well.

Brucellosis is acquired by direct contact with secretions and excretions of infected animals; by ingesting undercooked meat, raw milk, or milk products containing viable organisms; or by inhaling aerosolized infectious material. Brucellosis is rarely transmitted from person to person. Most prevalent in rural areas, brucellosis is an occupational disease of meatpackers, veterinarians, hunters, farmers, livestock producers, and microbiology laboratory technicians. Brucellosis is rare in the US, Europe, and Canada, but cases occur in the Middle East, Mediterranean regions, Mexico, and Central America. Because very few organisms (perhaps as few as 10 to 100) may cause infection via aerosol exposure, Brucella sp are potential agents of biological terrorism (see Biological Agents as Weapons).

Patients with acute, uncomplicated brucellosis usually recover in 2 to 3 wk, even without treatment. Some go on to subacute, intermittent, or chronic disease.


Complications are rare but include subacute bacterial endocarditis, meningitis, encephalitis, neuritis, orchitis, cholecystitis, hepatic suppuration, and osteomyelitis (particularly sacroiliac or vertebral).

Symptoms and Signs

The incubation period varies from 5 days to several months and averages 2 wk. Onset may be sudden, with chills and fever, severe headache, joint and low back pain, malaise, and occasionally diarrhea. Or onset may be insidious, with mild prodromal malaise, muscular pain, headache, and pain in the back of the neck, followed by a rise in evening temperature. As the disease progresses, temperature increases to 40 to 41° C, then subsides gradually to normal or near-normal with profuse sweating in the morning.

Typically, intermittent fever persists for 1 to 5 wk, followed by a 2- to 14-day remission when symptoms are greatly diminished or absent. In some patients, fever may be transient. In others, the febrile phase recurs once or repeatedly in waves (undulations) and remissions over months or years and may manifest as FUO.

After the initial febrile phase, anorexia, weight loss, abdominal and joint pain, headache, backache, weakness, irritability, insomnia, depression, and emotional instability may occur. Constipation is usually pronounced. Splenomegaly appears, and lymph nodes may be slightly or moderately enlarged. Up to 50% of patients have hepatomegaly.


  • Blood cultures

  • Acute and convalescent serologic testing

Blood cultures should be obtained; growth may take > 7 days, and subcultures using special media may need to be held for up to 3 to 4 wk, so the laboratory should be notified of the suspicion of brucellosis.

Acute and convalescent sera should be obtained 3 wk apart. A 4-fold increase or an acute titer of 1:160 or higher is considered diagnostic, particularly if a history of exposure and characteristic clinical findings are present. The WBC count is normal or reduced with relative or absolute lymphocytosis during the acute phase.


  • Doxycycline plus either rifampin, an aminoglycoside (streptomycin or gentamicin), or ciprofloxacin

Activity should be restricted in acute cases, with bed rest recommended during febrile episodes. Severe musculoskeletal pains, especially over the spine, may require analgesia. Brucella endocarditis often requires surgery in addition to antibiotic therapy.

If antibiotics are given, combination therapy is preferred. Doxycycline 100 mg po bid for 3 to 6 wk plus streptomycin 1 g IM q 12 to 24 h (or gentamicin 3 mg/kg IV once/day ) for 14 days lowers the rate of relapse. For uncomplicated cases, rifampin 600 to 900 mg po bid for 6 wk can be used instead of an aminoglycoside. Regimens using ciprofloxacin 500 mg po bid for 14 days instead of an aminoglycoside have been shown to be equally effective. In children < 8 yr, trimethoprim/sulfamethoxazole (TMP/SMX) and oral rifampin for 4 to 6 wk have been used.

Even with antibiotic treatment, about 5 to 15% of patients relapse, so all should be followed clinically and with repeat serologic titers for 1 yr.


Pasteurization of milk helps prevent brucellosis. Cheese that is made from unpasteurized milk and is aged < 3 mo may be contaminated. People handling animals or carcasses likely to be infected should wear goggles and rubber gloves and protect skin breaks from exposure. Programs to detect infection in animals, eliminate infected animals, and vaccinate young seronegative cattle and swine are required in the US and in several other countries. There is no human vaccine; use of the animal vaccine in humans can cause infection. Immunity after human infection is short-lived, lasting about 2 yr.

Postexposure antibiotic prophylaxis is recommended for high-risk patients (eg, those who have unprotected exposure to infected animals or laboratory samples or who received animal vaccine). Regimens include doxycycline 100 mg po bid for 6 mo plus rifampin 600 mg po once/day for 3 wk; rifampin is not used for exposure to the B. abortus (strain RB51) vaccine, which is resistant to rifampin.

Key Points

  • Brucellosis is acquired by direct contact with secretions and excretions of infected animals.

  • Infection typically causes fever and constitutional symptoms, but specific organs (eg, brain, meninges, heart, liver, bones) are rarely affected.

  • Most patients recover in 2 to 3 wk, even without treatment, but some develop subacute, intermittent, or chronic disease.

  • Diagnose using blood cultures and acute and convalescent serologic testing.

  • Treat most patients with 2 antibiotics, typically doxycycline plus either rifampin, an aminoglycoside, or ciprofloxacin; monitor patients up to 1 yr for relapse.

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