Summary
Brucellosis is a zoonotic infection caused by the gram-negative coccobacillus Brucella. In countries where brucellosis is endemic, the most common vectors are cattle, sheep, goats, and pigs. Transmission occurs through ingestion of contaminated animal products, contact with infected animals, or inhalation of Brucella. In the US, where livestock are routinely vaccinated, elk and bison are vectors, and locally acquired brucellosis is rare. Brucellosis typically manifests with flu-like symptoms. Other possible symptoms include hepatomegaly, splenomegaly, lymphadenopathy, and, rarely, focal organ infection (e.g., osteomyelitis, endocarditis, spondylitis). Diagnosis is based on positive cultures and/or serology. Treatment involves a combination antibiotic regimen based on disease severity. Prevention strategies include avoiding consumption of contaminated food, especially undercooked meat and unpasteurized dairy products, and contact with the tissues and fluids of infected animals; postexposure prophylaxis (PEP) with antibiotics may be recommended for individuals who have been exposed to Brucella.
Etiology
-
Pathogen: Brucella spp. are facultative intracellular, gram-negative, aerobic, coccobacilli. [1]
- Brucella melitensis: mainly affects sheep, goats, and camels → Malta fever
- Brucella abortus: mainly affects cattle, but also bison, deer, and elk → Bang disease
- Rare causes of disease in humans
-
Transmission: zoonotic [1]
- Contaminated food, esp. raw meat, unpasteurized dairy products
- Contact with infected animals
- Exposure to aerosolized particles [2]
- Risk factors: occupational or recreational exposure to infected animals and animal products (e.g., farmers, veterinarians, hunters, slaughterhouse workers, laboratory personnel)
- Pathophysiology: Brucella spp. survive and replicate within macrophages of the reticuloendothelial system → formation of noncaseating granulomas
Clinical features
- Incubation period: commonly 2–4 weeks (ranges from 5 days to 6 months) [1]
-
General [2]
- Flu-like symptoms
- Night sweats
- High, potentially undulant fever
- Painful lymphadenopathy
- Hepatomegaly
- Splenomegaly [2]
-
Localized infection
- Arthralgias, low back pain → osteoarticular infection (e.g., osteomyelitis, spondylitis)
- Epididymal and testicular tenderness, flank pain → genitourinary infection ; (e.g., epididymo-orchitis, pyelonephritis)
- Murmurs, friction rubs, tachycardia → cardiac infection (e.g., endocarditis, myocarditis)
- Additional symptoms may be present as Brucella can infect any organ.
Brucellosis in pregnancy can cause spontaneous abortion, preterm labor, and stillbirth. [3]
Brucellosis manifests as UNdulant fever and the causative pathogen is transmitted by UNpasteurized dairy products.
Diagnosis
Suspect brucellosis in adults and children with relevant exposure history, especially if common causes of symptoms have been ruled out and symptoms persist (e.g., in culture-negative endocarditis, CNS involvement). [1][3]
General principles
- Obtain confirmatory studies (e.g., blood cultures, serology) in all patients with suspected brucellosis.
- Consider additional directed studies (e.g., tissue biopsy, CSF culture) in patients with localized infection.
- Isolation of Brucella from a culture or a rise in antibody titers over 2 weeks confirms the diagnosis.
Diagnosing brucellosis can be challenging due to nonspecific symptoms and potential to impact any organ.
When submitting cultures, inform laboratory personnel of suspected Brucella, as additional protective equipment and precautions are required when handling Brucella specimens. [1]
Routine laboratory studies [2][4][5]
Findings are nonspecific but may support the diagnosis.
- CBC
- BMP: elevated creatinine (uncommon) [6]
- Liver enzymes: mildly elevated transaminases
- CPK: may be elevated [6]
Confirmatory studies [1][2][3]
-
Serology [1][7]
-
Methods
- Agglutination tests, e.g., serum agglutination test, Brucella microagglutination test, Rose Bengal test
- ELISA
- Confirmatory findings: fourfold rise in titers from samples taken ≥ 2 weeks apart [2][8]
-
Methods
-
Direct detection
- Blood culture (false negatives often occur): should be incubated for ≥ 10–14 days [1]
-
Tissue biopsy with histopathology and culture
- Specimen
- Bone marrow (gold standard) [2]
- Other affected areas, e.g., lymph node, CSF
- Histopathology: noncaseating granulomas [9]
- Culture medium for isolation, e.g., charcoal yeast extract agar (cysteine and iron buffered) [10]
- Specimen
- NAAT (e.g., PCR): detection of Brucella DNA in tissue or serum sample [8]
Brucella cultures require prolonged incubation. [1][3]
Treatment
Approach
- Consult infectious diseases (ID) to help guide antibiotic therapy.
- Notify the local health department.
- Use appropriate PPE (see “Prevention of brucellosis”).
- Arrange PEP for brucellosis contacts as needed.
- Refer to surgery for deep tissue infections and complicated infections (e.g., abscess, spinal instability). [1][11]
- For infections in children and pregnant individuals, see “Special patient groups.”
Brucellosis is a nationally notifiable disease in the US. Notify your local health department if a case is confirmed.
Antibiotic therapy [1][12]
Uncomplicated infection
- Doxycycline for 6 weeks [8][12]
-
PLUS one of the following: ; [1][12]
-
Aminoglycoside [2][11];
- Streptomycin for 2–3 weeks
- OR gentamicin (off-label) for 1–2 weeks [12]
- OR rifampin (off-label) for 6 weeks [8][12]
-
Aminoglycoside [2][11];
Complicated infection [8][11][12]
Complicated brucellosis infection refers to deep-seated or focal infection, e.g.:
-
Neurobrucellosis [13]
- Ceftriaxone (off-label) [11]
- PLUS doxycycline
- PLUS rifampin (off-label) [8]
-
Endocarditis
- Aminoglycoside: streptomycin OR gentamicin (off-label) [12]
- PLUS doxycycline
- PLUS rifampin (off-label) [8]
-
Spondylitis
- Doxycycline
- PLUS an aminoglycoside: e.g., streptomycin
Complicated infections often require three-drug therapy and/or a long treatment duration (e.g., 4–6 months). [11]
Prevention
Primary prevention of brucellosis
- There is no human vaccine for Brucella. [3]
- Avoid risky exposures, especially in endemic areas. [1][8][12]
- Consumption of improperly prepared animal products [1][8]
- Contact with livestock or wild animals [1]
- Handling raw meat
- Prevent healthcare infections by:
- Informing all personnel, including laboratory staff, of suspected Brucella
- Using appropriate protective equipment and taking precautions if there is potential for exposure [8]
- Contact precautions for handling wounds
- N95 masks during aerosol-generating procedures
Management of exposed Brucella contacts [8]
Discuss all Brucella and Brucella livestock vaccine contacts with ID for consideration of: [3]
- Symptom monitoring
- PEP, usually doxycycline and rifampin, for high-risk exposures [8]
Special patient groups
Brucellosis in children [3]
- Clinical features are similar in children and adults, although children are more likely to have abdominal pain and arthritis. [3]
- Diagnostics are the same in children and adults.
- Refer all patients with suspected or confirmed brucellosis to specialists for management, e.g.: [1][12]
- ID for antibiotic therapy
- Choice of antibiotic combination depends on age and type of infection.
- Treatment courses are usually at least 6 weeks.
- Surgery for interventions (e.g., for deep tissue infections, mycotic aneurysms, joint effusion) [3]
- ID for antibiotic therapy
Life-threatening infections require prolonged treatment (e.g., 4–6 months) with three antibiotics. [3]
Brucellosis in pregnancy and lactation [3]
- Brucellosis in pregnancy can cause miscarriage, preterm delivery, and stillbirth. [3]
- Vertical transmission can cause neonatal infection. [8]
- Refer all patients to ID and obstetrics for multidisciplinary care. [8]
- Patients with brucellosis should avoid breastfeeding until the infection has cleared. [3]
- Advise the following for infection prevention:
- Follow dietary restrictions during pregnancy.
- Seek immediate medical care for consideration of PEP in the case of Brucella contact. [8]