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Brucellosis

(Undulant Fever; Malta Fever; Mediterranean Fever; Gibraltar Fever)

By

Larry M. Bush

, MD, FACP, Charles E. Schmidt College of Medicine, Florida Atlantic University;


Maria T. Vazquez-Pertejo

, MD, FCAP, Wellington Regional Medical Center

Last full review/revision Feb 2020| Content last modified Feb 2020
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NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version

Brucellosis is caused by Brucella species, which are gram-negative bacteria. Symptoms begin as an acute febrile illness with few or no localized signs and may 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 species.

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

  • Ingesting undercooked meat, raw milk, or milk products containing viable organisms

  • Inhaling aerosolized infectious material

  • Rarely, person-to-person transmission

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 species are potential agents of biological terrorism.

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

Complications

Complications of brucellosis are rare but include subacute bacterial endocarditis, neurobrucellosis (which includes acute and chronic meningitis, encephalitis, and neuritis), orchitis, cholecystitis, hepatic suppuration, and osteomyelitis (particularly sacroiliac or vertebral).

Symptoms and Signs

The incubation period for brucellosis varies from 5 days to several months and averages 2 weeks.

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, muscle 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 weeks, 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 fever of unknown origin.

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.

Brucellosis is fatal in < 5% of patients, usually as a result of endocarditis or severe central nervous system complications.

Diagnosis

  • Blood, bone marrow, and cerebrospinal fluid (CSF) cultures

  • Acute and convalescent serologic testing (not reliable for B. canis) and polymerase chain reaction (PCR) assay

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 weeks, so the laboratory should be notified of the suspicion of brucellosis.

Samples of bone marrow and CSF may also be cultured.

Acute and convalescent sera should be obtained 3 weeks 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. Serologic testing is not reliable for B. canis.

PCR assay can be done on blood or any body tissue and can be positive as early as 10 days after inoculation.

Treatment

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

Activity should be restricted in acute cases of brucellosis, 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 because relapse rates with monotherapy are high. Oral doxycycline 100 mg 2 times a day for 6 weeks plus streptomycin 1 g IM every 12 to 24 hours (or gentamicin 3 mg/kg IV once a day) for 14 days lowers the rate of relapse. For uncomplicated cases, oral rifampin 600 to 900 mg 2 times a day for 6 weeks can be used instead of an aminoglycoside. Regimens using oral ciprofloxacin 500 mg 2 times a day for 14 to 42 days plus rifampin or doxycycline instead of an aminoglycoside have been shown to be equally effective.

In children < 8 years, trimethoprim/sulfamethoxazole (TMP/SMX) and oral rifampin for 4 to 6 weeks have been used.

Neurobrucellosis and endocarditis require prolonged treatment.

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

Prevention

Pasteurization of milk helps prevent brucellosis. Cheese that is made from unpasteurized milk and is aged < 3 months 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 (a live-attenuated preparation) in humans can cause infection. Immunity after human infection is short-lived, lasting about 2 years.

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 orally 2 times a day plus rifampin 600 mg orally once a day for 3 weeks; rifampin is not used for exposure to the vaccine with B. abortus (strain RB51), which is resistant to rifampin.

Key Points

  • Brucellosis is acquired by direct contact with secretions and excretions of infected animals or by ingestion of contaminated food or dairy products.

  • 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 weeks, even without treatment, but some develop subacute, intermittent, or chronic disease.

  • Diagnose using cultures of blood, bone marrow, or cerebrospinal fluid 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 year for relapse.

Drugs Mentioned In This Article

Drug Name Select Trade
CILOXAN, CIPRO
No US brand name
PERIOSTAT, VIBRAMYCIN
GENOPTIC
RIFADIN, RIMACTANE
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NOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer Version
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