Brucella Species - Brucellosis

Brucellosis (also called undulant fever, Malta fever, Mediterranean fever) is a major bacterial zoonosis involving many mammals, including domestic cows (Brucella abortus), pigs (B. suis), goats/sheep (B. melitensis), and dogs (B. canis). The disease is also found in wild ruminant mammals such as deer, elk, and moose.

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • High level of suspicion based on occupation, activities, or travel history

Laboratory Testing

  • CDC Brucellosis testing and diagnosis information
  • Initial testing
    • CBC – white blood cell (WBC) usually normal to low
      • Pancytopenia can occur
    • C-reactive protein (CRP)
    • Liver function testing – minor elevations are common
  • Specific testing
    • Serology – primary method used for diagnosis
      • Agglutination testing – detects IgG, IgM, IgA antibodies
        • 4-fold rise in titer considered diagnostic
      • IgG and IgM by ELISA – not preferred; less sensitive than agglutination
      • Febrile antibodies (febrile agglutinins) testing – not specific for Brucella
    • Gold standard – culture of tissue, blood, bone marrow, or fluids
      • Variable yield
        • Higher yield in acute cases; much lower yield in chronic cases
        • Bone marrow culture has higher yield than blood, especially in chronic cases
      • May require several weeks because organism is very slow growing and difficult to culture
    • Cerebrospinal fluid (CSF) analysis for central nervous system (CNS) disease
      • Elevated protein levels
      • Pleocytosis of 10-200 WBC (mononuclear predominance)
      • Hypoglycorrhachia
      • Adenosine deaminase elevated – similar to tuberculosis (TB) meningitis

Differential Diagnosis


  • Incidence – 1/100,000 in U.S.
    • Most common zoonosis worldwide but relatively rare in North America and western Europe
    • Endemic in the Mediterranean, Middle East, Mongolia, Russia, Mexico, and Latin America
  • Transmission
    • Most commonly from eating or drinking infected, unpasteurized dairy products (eg, soft cheeses)
    • Inhalation (primarily from occupational exposure)
    • Via skin wounds and abrasions
    • Vertical transmission via breast feeding


  • Brucella spp (gram-negative coccobacilli)
  • Facultative intracellular pathogens
  • Human infections are caused most frequently by B. melitensis, B. suis, and B. abortus; rare infections are caused by B. canis
    • Sheep and goats are the most common reservoir

Risk Factors

  • Occupational or recreational exposure to animals
    • >70% of reported cases occur in the meat-processing and livestock industries
    • Brucella spp are able to penetrate imperceptible cuts or abrasions in the skin, leading to infections from handling infected animals
    • Brucella presents a higher risk of infection than other organisms among laboratory workers preparing cultures for bacterial agents

Clinical Presentation

  • Brucellosis in humans has variable incubation time, insidious or abrupt onset, and no pathognomonic symptoms or signs
  • Flu-like symptoms usually appear 1-3 weeks after exposure; organism resides in the lymph nodes during incubation (2-8 weeks)
    • Constitutional (most cases) – fever, chills, headache, weakness
    • Osteoarticular – sacroiliitis, spondylitis, osteomyelitis
    • Gastrointestinal – hepatomegaly (granulomatous hepatitis), splenomegaly, pancreatitis, ileitis
    • Genitourinary – orchiepididymitis, glomerulonephritis, renal abscesses
    • Neurologic – peripheral neuropathy, chorea, meningitis/encephalitis, radiculitis, myelitis
    • Dermatologic – purpura, maculopapular rashes, Stevens-Johnson syndrome, ulcers
    • Pulmonary – pneumonia, pleural effusions, bronchitis, empyema
    • Cardiovascular – endocarditis (aortic valve most common), myocarditis, pericarditis, endarteritis
    • ​Ocular – uveitis, keratoconjunctivitis, optic neuritis
  • Relapse – usually occurs in small percent within the first 6 months following treatment
  • Untreated, the disease tends to become chronic and persist for years
    • Chronic symptoms may also occur up to 1 year from onset of illness and include recurrent fever, arthritis, and fatigue
    • Rarely fatal but can be severely debilitating
    • Mortality low (<1%) and almost exclusively from cardiac complications
    • Generalized infection – spondylitis, osteomyelitis, tissue abscesses
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Hepatic Function Panel 0020416
Method: Quantitative Enzymatic/Quantitative Spectrophotometry

Brucella Antibody (Total) by Agglutination 0050135
Method: Semi-Quantitative Agglutination


Cross-reactions may occur between Brucella and Francisella tularensis antigens and antisera; parallel tests should be run with these antigens

Brucella Culture 0060159
Method: Culture/Identification


Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Nov 2017]

General References

Araj GF. Update on laboratory diagnosis of human brucellosis. Int J Antimicrob Agents. 2010; 36 Suppl 1: S12-7. PubMed

Franco MP, Mulder M, Gilman RH, Smits HL. Human brucellosis. Lancet Infect Dis. 2007; 7(12): 775-86. PubMed

Mantur BG, Amarnath SK, Shinde RS. Review of clinical and laboratory features of human brucellosis. Indian J Med Microbiol. 2007; 25(3): 188-202. PubMed

Shen MW. Diagnostic and therapeutic challenges of childhood brucellosis in a nonendemic country. Pediatrics. 2008; 121(5): e1178-83. PubMed

Medical Reviewers

Last Update: November 2017