Brucella Species

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, ESR, liver function
• Serology – primary method of diagnosis
  • IgG and IgM by ELISA – high sensitivity and specificity
    • Better accuracy in acute cases; false negatives in chronic cases
    • Fourfold rise in titer considered diagnostic
    • False positives due to nonspecific cross-reaction of unrelated antibodies (eg, Francisella tularensis)
    • IgG and IgM may be positive for years, even after successful treatment
  • Agglutination testing – detects IgG, IgM, IgA antibodies
    • Fourfold rise in titer considered diagnostic
  • Febrile antibodies (febrile agglutinins) testing is not specific for Brucella and is less useful than ELISA
• Gold standard – culture of tissue, blood, or fluids
  • Variable yield
    • 40-90% in acute cases
    • 5-20% in chronic cases
  • May require several weeks because organism is very slow growing and difficult to culture

Differential Diagnosis

• Acute disease
  • F. tularensis (tularemia)
  • Bartonella spp
  • Coxiella burnetii (Q-fever)
  • Treponema pallidum (syphilis)
  • Encephalitis/meningitis
  • Sepsis
  • Mycobacterium tuberculosis
  • Epstein-Barr virus
  • Yeast infection
    • Histoplasma capsulatum
    • Cryptococcus neoformans
  • Rickettsia rickettsii
  • Babesia microti
  • Leptospira spp
• Chronic disease
  • Lymphoma
    • B-cell, T/NK-cell
  • Malignant histiocytosis
  • Endocarditis from other bacterial agent
  • Chronic fatigue syndrome

Clinical Background

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.

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 common route is from eating or drinking infected, unpasteurized dairy products (eg, soft cheeses)
  • Inhalation (primarily from occupational exposure) and 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
  • Among laboratory workers preparing cultures for bacterial agents, Brucella presents a higher risk of infection than other organisms

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; during incubation (2-8 weeks), organism resides in the lymph nodes
  • Constitutional (~75% of cases) – fever, chills, headache, weakness
  • Osteoarticular (~22% of cases) – sacroiliitis, spondylitis, osteomyelitis
  • Gastrointestinal (30% of cases) – hepatomegaly (granulomatous hepatitis), splenomegaly
  • Genitourinary (5% of cases)– orchiepididymitis, glomerulonephritis, renal abscesses
  • Neurologic (6% of cases) – peripheral neuropathy, chorea, meningitis/encephalitis
  • Mucocutaneous – purpura, maculopapular lesions, Stevens-Johnson syndrome
  • Pulmonary – pneumonia, pleural effusions
  • Cardiovascular (2% of cases)– endocarditis; aortic valve most common
• 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

Prevention

• Control of disease in domestic livestock
• Avoidance of unpasteurized dairy products, including soft cheeses (especially goat cheese)

Indications for Laboratory Testing

• 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

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Organism Identification by 16S rDNA Sequencing 0060720 Method: 16S rDNA Sequencing
Aerobic Organism Identification 0060115 Method: Identification. Methods may include biochemical, mass spectrometry, or sequencing.	Include warning if organism suspected to be dangerous pathogen (eg, Salmonella, Shigella, Neisseria meningitides) 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
Febrile Antibodies Panel 2001789 Method: Semi-Quantitative Agglutination/Semi-Quantitative Indirect Fluorescent Antibody/Qualitative Immunoblot