Brucellosis: causes, symptoms, diagnosis, treatment, and prevention

Brucellosis, also known as undulant fever, Malta fever, or Mediterranean fever, is an acute febrile infectious disease caused by Brucella. Acute fulminant or chronic onset can be present. The clinical manifestations are mainly fever and hepatosplenomegaly. Few patients may have rashes.


Causes

Brucella is a Gram-negative aerobic bacterium that spreads widely in cattle, sheep, goats, and swine and can cause abortion in female animals. According to the biochemical reaction and serum test, the bacterium can be divided into Brucella melitensis, Brucella abortus, Brucella suis, Brucella ovis, Brucella neotomae, Brucella canis, Brucella ceti, Brucella pinnipedialis, and Brucella microti. The highly pathogenic bacterium in humans is Brucella melitensis, followed by Brucella suis and Brucella abortus. It has recently been reported that Brucella canis is associated with infection in pet owners and veterinarians. Direct contact with infected animals or livestock carrying the bacteria, ingestion of milk and dairy products contaminated by infected animals, or ingestion of infected meat that is not thoroughly cooked may cause infection.

Brucella is an intracellular parasitic pathogen. The bacteria enter the human body from the skin or digestive tract, usually colonize in the phagocytes of the mononuclear phagocytic system through blood circulation, and reproduce mainly in the liver, spleen, bone marrow, and lymph nodes, forming granulomatous reaction.


Signs and Symptoms

Systemic brucellosis is with an incubation period of 5 - 30 days or longer. Patients present with headache, back pain, general malaise, undulant fever, chills, hyperhidrosis, muscle and joint pain, testitis in males, and oophoritis in females, as well as gastrointestinal disturbances, nervous system symptoms, and involvement of heart and kidney. Some patients present with low fever or irregular fever. About 50% of patients develop swollen lymph nodes, 25% of patients develop hepatomegaly. Skin lesions occur in about 10% of patients, without specificity. Skin lesions are mostly morbilliform or scarlatinoid eruption, or roseola, merely papules, vesicles, and hemorrhagic rashes. Polymorphous erythematoid nodules of the lower extremities are reported. In chronic cases, infections of bones, gallbladder, or other organs may be present. The disease usually lasts for 3 to 4 months, and recurrence is more common.

Contact Brucellosis, also known as Brucella dermatitis, is more common in veterinarians and those who are often in contact with infected animals. Patients are highly sensitive to Brucella antigen. After exposure to the secretion of the infected animal, pruritus, erythema, and wheals occur in the contact site within a short period of time, follicular papules occur within 48 hours, some progress into vesicles or pustules, and the skin lesions subside in 10 to 14 days, leaving small scars. There may be polymorphous erythematoid eruptions at sites away from the contact site, and painless ulcers may occur if the abrasion wounds are infected with Brucella.

Clinical stage can be divided into acute stage with duration less than 3 months, subacute stage with duration of 3 - 6 months, and chronic stage with duration more than 6 months.


Diagnosis

Before onset, if there are close contact with livestock and animal products with suspected Brucella infection, ingestion of raw milk and meat products, residence in the epidemic area of brucellosis, or occupation in culture and test of Brucella or Brucella vaccine production and use, on the basis of clinical findings such as fever for several days to weeks, hyperhidrosis, malaise, muscle and joint pain, as well as hepatosplenomegaly, lymphadenopathy, testitis in males, oophoritis in females, and various skin lesions and jaundice in few patients, brucellosis should be suspected.

Diagnostic considerations include:

  • Positive result in rose bengal plate agglutination test
  • Positive result in gold immunochromatography assay
  • Positive result in enzyme linked immunosorbent assay
  • Suspected Brucella found in the smear in Gram stain
  • Brucella isolated from cultures of any pathological material such as blood, bone marrow, body fluids, and discharges
  • Titer of 1:100 and above in serum agglutination test, or duration more than one year and presence of clinical symptoms and titer of 1:50 and above
  • Titer 1:10 and above in complement fixation test
  • Titer of 1:400 and above in antiglobulin test (Coombs test)

Clinical diagnosis can be provided based on any one of the diagnostic considerations.

Definitive diagnosis requires any one of the last 4 diagnostic considerations in suspected or clinically diagnosed patients.


Treatment

In the acute stage, movement should be restricted, and bed rest is appropriate during the febrile period. Severe musculoskeletal pain, especially spinal pain, may require painkillers. Brucella endocarditis usually requires surgery in addition to antibiotics.

If antibiotics are used, combination treatment is necessary, because high recurrence rate in monotherapy is present. A combination of doxycycline 100mg orally twice daily for 6 weeks plus streptomycin 1g intramuscularly once every 12 - 24 hours or gentamicin 3mg/kg intravenously once a day for 14 days can reduce the recurrence rate. For patients without complications, rifampicin 600 - 900mg twice daily for 6 weeks can be an alternative to one of aminoglycosides. Ciprofloxacin 500mg orally twice daily for 14 - 42 days in combination with rifampicin or doxycycline has been proved to be effective in place of an aminoglycoside. It has been reported that in children aged < 8 years, cotrimoxazole combined with oral rifampicin can be used for 4 to 6 weeks.

Even with antibiotics, relapses are present in about 5 - 15% patients. Therefore, one year of clinical follow-up and repeated serum antibody titer tests in all patients should be performed.


Prevention

Milk pasteurization helps prevent brucellosis. Cheese made from unpasteurized milk with a shelf life < 3 months may be contaminated.

Persons disposing animals or corpses with brucellosis need to wear goggles and rubber gloves to protect the skin from exposure. It is required to systematically monitor and dispose infected animals and vaccinate seronegative calves and swine.

No vaccine is currently available for humans. Short-term immunity can be obtained after infection, usually lasting for two years.

Antibiotic post-exposure prophylaxis is recommended for high risk persons. The regimen is doxycycline 100mg orally twice daily combined with rifampicin 600mg once daily for 3 weeks. Rifampicin cannot be used for post-exposure prophylaxis of Brucella abortus due to resistance.