Brucella melitensis

Background

• Causes brucellosis, also called Malta fever

Microbiology

• Facultative intracellular, Gram-negative coccobacillus
• Catalase positive, oxidase positive, nitrate positive, and urease positive
• Non-motile
• Risk group 3 organism
• When suspected, plates should be sealed and it should not be set up for mass spectrometry

Epidemiology

• Zoonotic transmission transmitted by ingesting contaminated food (such as unpasteurized milk products), direct contact with an infected animal, or inhalation of aerosols

Clinical Manifestations

Brucellosis

• Exposure to unpasteurized milk products or animals
• A common cause of fever without a focus in endemic countries
• Incubation period is usually 2-4 weeks (range 5 days to 6 months)
• Undulating fever
• Headache, arthralgia, night sweats, fatigue, anorexia
• Arthritis, spondylitis (especially sacroiliac and other large lower-extremity joints), osteomyelitis
• Hepatomegaly, splenomegaly, and lymphadenopathy
• Orchitis and epididymitis, prostatitis, and tubo-ovarian abscess
• Foul-smelling sweat
• Can have mild pancytopenia

Relapsed Brucellosis

• Occurs within six months of completing treatment in about 10% of patients

Diagnosis

• Culture
  • May be isolated from blood culture, but only intermittent and is a fastidious organism
    • Sensitivity is 50-70%
    • Cultures should be held for 10 days
  • Grows slowly on blood and chocolate agar; better on Brucella agar
  • On gram stain, the small coccobacilli look like fine grains of sand
• Serology
  • Acute and convalescent serology showing a fourfold rise in titres
  • Serum agglutination test titres of 1:160 or greater in the right clinical context
    • Cross-reacts with Francisella tularensis and Vibrio cholerae

Management

• Uncomplicated infection
  • First-line: doxycycline 100 mg PO bid for 6+ weeks, plus streptomycin 1 g IM daily for 2 to 3 weeks
  • Alternative: doxycycline 100 mg Pp bid for 6+ weeks, plus gentamicin 5 mg/kg IM daily for 1 week
  • Alternative: doxycycline 100 mg PO bid plus rifampin 600 to 900 mg (15 mg/kg) PO daily for 6+ weeks
• Neurobrucellosis:
  • First-line: ceftriaxone 2 g IV q12h for 1+ month, plus doxycycline 100 gm PO bid and rifampin 600 to 900 mg (15 mg/kg) PO daily for 4-5 months
  • Alternative: TMP-SMX 160/800 mg PO bid, plus doxycycline 100 mg PO bid, plus rifampin 600 to 900 mg (15 mg/kg) PO daily for 5 to 6 months
• Pregnancy
  • Rifampin 900 mg PO daily for 6+ weeks, ± TMP-SMX between the 13th and 36th weeks of gestational

Prevention

Lab Safety

• Assess risk and provide prophylaxis and monitoring per CDC guidelines
• Assess risk
  • Minimal risk
    • Manipulating routine specimen or enriched material in BSL2 with PPE
    • Being present while someone manipulates a routine specimen in BSL2, or on an open bench without aerosol-generating procedures
    • Manipulating or being present while someone manipulates enriched material in BSL2
  • Low risk
    • Being present more than 5 feet from someone manipulating enriched material on an open bench, without aerosol-generating procedures
  • High risk
    • Manipulating a routine specimen resulting in contact with broken skin or mucous membranes
    • Being present less than 5 feet from someone manipulating enriched material outside of a BSL2
    • Manipulating enriched material within a BSL2 without PPE
    • Being present in the lab during an aerosol-generating procedure
• Aerosol-generating procedures include centrifuging without sealed carriers, vortexing, sonicating, spillage/splashes
• Enriched material includes positive blood cultures, and reproductive clinical specimens (amniotic fluid, placental products) should be treated similarly
• People with high-risk exposures should have post-exposure prophylaxis and follow-up
  • PEP with doxycycline 100 mg PO bid plus rifampin 600 mg PO daily for 21 days
    • Either can be replaced by TMP-SMX if contraindications exist, but should ensure two effect antibiotics are used
  • Follow-up
    • Daily fever checks and weekly symptom watch for 24 weeks after last known exposure
    • Serial serology at 0, 6, 12, 18, and 24 weeks after last known exposure