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

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

Background

Epidemiology

  • 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

Organisms

  • 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

ARUP Lab Tests

Primary Tests

Order to differentiate bacterial from viral etiology

Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)

Initial screening for hepatobiliary inflammation

Panel includes albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin direct, protein total, bilirubin total

Recommended serology test to detect recent infection from Brucella in the context of a clinically compatible illness and exposure history

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

Gold standard for detection of Brucella in blood (optimum), cerebrospinal fluid (CSF), body fluids, and abscesses

Related Tests

Nonspecific test used to detect inflammation associated with infections, cancers, and autoimmune diseases

Reference method for identification of most bacterial species

Identify aerobic bacterial isolates

For suspected agents of bioterrorism, notify state department of health and refer isolates to state laboratory for identification

Susceptibilities on agents of bioterrorism are not performed at ARUP

For identification by 16s rDNA sequencing only, refer to organism identification by 16s rDNA sequencing; for identification AND susceptibility testing, refer to aerobic organism identification with reflex to susceptibility

Confirm presence of disease; not recommended for initial testing

Panel includes Brucella antibody (total) by agglutination; Rickettsia rickettsii antibody, IgM; Rickettsia rickettsii antibody, IgG; Rickettsia typhi antibody, IgG by IFA; Rickettsia typhi antibody, IgM by IFA, and Salmonella typhi and paratyphi antibodies

Medical Experts

Contributor

Couturier

Marc Roger Couturier, PhD, D(ABMM)
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Parasitology/Fecal Testing, Infectious Disease Antigen Testing, Bacteriology, and Molecular Amplified Detection, ARUP Laboratories
Contributor

Fisher

Mark A. Fisher, PhD, D(ABMM)
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Bacteriology, Special Microbiology, and Antimicrobial Susceptibility Testing, ARUP Laboratories
Contributor

Genzen

Jonathan R. Genzen, MD, PhD
Associate Professor of Clinical Pathology, University of Utah
Chief Operations Officer, Medical Director of Automated Core Laboratory and Farmington Health Center Clinical Laboratory, ARUP Laboratories
Contributor

Lehman

Christopher M. Lehman, MD
Associate Professor of Clinical Pathology, University of Utah
Medical Director, University of Utah Health Hospital Clinical Laboratory, ARUP Laboratories

References

Additional Resources