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A. Introduction navigator

  1. Caused by bacteria of genus Brucella
    1. Pleiomorphic gram negative coccobacilli
    2. B. abortus - cattle borne (most common in USA), buffalo, camals, yaks
    3. B. melitensis - borne by sheep, goats, camels
    4. Very uncommon: B. suis (swine borne) and B. canis (canine borne)
    5. Very uncommon: B. ovis (sheep borne) and B. neotomae (rodent borne)
  2. Belongs to alpha2 subdivision of Proteobacteria including rikettsia
  3. Risks for Brucella Infection
    1. Humans develop disease by contact, ingestion, or inhalation
    2. Mainly associated with interactions with farm animals
    3. B. canis associated with some dog bites particularly beagles [4]
    4. Increased risk of contracting with travel to Middle East [6]
    5. Handling raw meat and eating unpasteurized cheese increase risk
  4. Cases By Country (Table 1, Ref [1])
    1. <150 cases / year in USA
    2. Syria, Iran, Turkey have >14,000 cases per year
    3. Mexico and Algeria have ~3000 cases per year
  5. No documented person to person transmission
  6. Facultative macrophage intracellular parasites
  7. Previously called undulant fever

B. Symptoms and Signs [2]navigator

  1. Often asymptomatic
  2. Fever, anemia, nonspecific constitutional symptoms - large differential [3]
  3. Types of Disease
    1. Acute
    2. Localized
    3. Chronic / Progressive
    4. Usually homes to organs high in macrophages
    5. Includes spleen, liver, lungs, central nervous system, bone marrow
  4. Acute Disease
    1. Low grade fever without localization
    2. Systemic Symptoms: malaise, weakness, fatigue, sweats, weight loss
    3. Myalgia and backache may occur (± frank spondylitis)
    4. Hepatomegaly ~35%
    5. Splenomegaly and/or lymphadenopathy ~20% of patients
  5. Localized Disease
    1. Any location, especially osteomyelitis, splenic abscess, UTI, gastrointestinal tract
    2. Endocarditis uncommon, but may cause significant morbidity (mortality)
    3. Arthritis is uncommon, usually with knee involvement or spondylitis (sacro-ileitis)
    4. Pulmonary disease with pneumonia ± effusions may occur
    5. Brucellosis of the spine may occur and present as a mass (absecess) lesion
  6. Chronic (Progressive) Disease
    1. At least 1 year nonspecific symptoms
    2. May have relapsing course, especially with arthritis
    3. Veterinarians are at particular risk for hypersensitivity reaction

C. Diagnosisnavigator

  1. Culture (usually bone marrow) is definitive method (may require prolonged incubation)
  2. Polymerase Chain Reaction (PCR)
    1. Fast method applicable to any body tissue
    2. Results may be positive within 10 days of inoculation
    3. Real-time PCR is being developed and may require only 30 minutes for diagnosis
    4. Multiplex PCR is also being developed for multiple organism identification
  3. Brucella Agglutination Test
    1. Titer at least 1:160 is positive
    2. IgM Ab rise usually within 1 week with peak and 3 months
    3. IgG may disappear within 1 year but requires 1-2 months to increase
    4. Cholera vaccination may give false positive
    5. Some cross-reaction with Francisella tularensis and Yersinia enterocolitica
  4. May be mistaken for moraxella species, particularly M. phenylpurvica [6]
  5. Antinuclear antibody (ANA) may be elevated [3]
  6. Bone marrow with non-caseating granulomas

D. Treatment [1,5]navigator

  1. Mild Cases
    1. Doxycycline 100mg po or IV bid x 6 weeks in mild cases
    2. Ofloxacin 400mg bid or ciprofloxacin 500mg bid both for 6 weeks also for mild cases
    3. Rifampin 600mg per day may be added to either quinolone or doxycycline
    4. TMP/SMX (Bactrim®, Septra®) DS tid x 4-6wks po alternative (increased relapse rate)
  2. Moderate to Severe Cases
    1. Doxycycline + rifampin (600-900mg/d) as effective as doxycycline + streptomycin
    2. Tetracycline 7.5mg/kg q6° x 4-6wks + streptomycin 15mg/kg q12hr x 2 weeks
    3. For patients with spondylitis, doxycycline + streptomycin is preferred
    4. Gentamicin 1.5mg q8 hours can be substituted for streptomycin
    5. Ciprofloxacin + doxycycline or rifampin
  3. Consider prednisone 60mg/d with rapid 5-7d taper in patients with severe debilitation
  4. Symptomatic therapy for bachache and headache

References navigator

  1. Pappas G, Akritidis N, Bosilkovski M, Tsianos E. 2005. NEJM. 352(22):2325 abstract
  2. Dames S, Tonnerre C, Saint S, Jones SR. 2005. NEJM. 352922):2338 (Case Discussion) abstract
  3. Noble JT and Mark EJ. 2002. NEJM. 347(3):200 (Case Record) abstract
  4. Tan JS. 1997. Arch Intern Med. 157(17):1933 abstract
  5. Drugs and Vaccines Against Biological Weapons. 1999. Med Let. 41(1046):15 abstract
  6. Kontoyiannis DP and Versalovic J. 2001. NEJM. 344(26):2009 (Case Record)