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