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Referral and warning signs
When to refer
Refer suspected cases to HC4/Hospital for diagnosis confirmation (serology/culture) and initiation of appropriate prolonged antibiotic therapy. Refer cases with complications (spondylitis, endocarditis, neurobrucellosis) to specialist/RR.
Red flags
- Focal neurological signs.
- Signs of endocarditis (new murmur, heart failure).
- Severe back pain with neurological symptoms (spondylitis).
- Failure to respond to initial therapy / Relapse.
Signs and symptoms
- Intermittent / Undulating / Fluctuating fever (key feature).
- Generalized aches and pains (arthralgia, myalgia).
- Headache, fatigue, weakness.
- Sweating (often profuse, night sweats).
- Loss of appetite, weight loss.
- Hepatosplenomegaly.
- Lymphadenopathy.
- Orchitis (inflammation of testes).
- Sacroiliitis / Spondylitis (vertebral osteomyelitis) - uncommon but characteristic.
- Neurobrucellosis (meningitis, encephalitis - rare).
- Endocarditis (rare).
Risk factors
- Occupational exposure (farmers, veterinarians, abattoir workers, butchers, lab workers).
- Consumption of unpasteurized milk or dairy products.
- Consumption of undercooked contaminated meat (e.g., 'muchomo').
- Direct contact with infected animals or their secretions/tissues.
Diagnosis
Clinical assessment
Suspicion based on prolonged/undulant fever, arthralgia/myalgia, fatigue, sweats, and relevant exposure history (occupation, animal contact, food consumption).
Differential diagnosis
- Typhoid fever
- Malaria
- Tuberculosis (TB)
- Trypanosomiasis (Sleeping Sickness)
- Infective endocarditis
- Lymphoma
- Other causes of prolonged fever (PUO)
Investigations
- Serology: Agglutination tests (e.g., SAT - Standard Agglutination Test, Rose Bengal) or Complement Fixation Test (CFT) or ELISA. Interpretation challenging in endemic areas due to background positivity; titres >1:160 or rising titres more significant. Positive results can persist after recovery.
- Blood Culture: Definitive diagnosis if positive, but often low yield and requires prolonged incubation/special media.
- Bone Marrow Culture: Higher yield than blood culture.
- Culture from other tissues (lymph node, CSF, joint fluid) if involved.
Diagnostic criteria
Clinical suspicion + Supporting serology (interpret with caution) OR Definitive diagnosis by culture.
Management
Non-pharmacological management
- Supportive care (rest, analgesia).
Pharmacological treatment
- Requires prolonged combination antibiotic therapy (6 weeks minimum) to prevent relapse. (LOC: HC4)
- Preferred Regimen (Adult & Child >8 years):
- - Doxycycline 100 mg PO every 12 hours for 6 WEEKS
- (Child >8y: 2 mg/kg/dose BID)
- - PLUS Gentamicin 5-7 mg/kg IV/IM daily for 2 WEEKS
- (Child >8y: Dose as per adult)
- Alternative Parenteral agent (if Gentamicin unavailable/contraindicated):
- - Streptomycin 1g IM daily for 2-3 weeks (Specialist use, ototoxicity/nephrotoxicity monitoring needed)
- Regimen for Children <8 years:
- - Cotrimoxazole 24 mg/kg PO every 12 hours for 6 WEEKS
- - PLUS Gentamicin 5-7 mg/kg IV/IM daily (in 1-3 divided doses) for 2 WEEKS
- Alternative Regimen (e.g., if Doxy/Gentamicin C/I - specialist advice):
- - Doxycycline 100mg BID + Rifampicin 600-900mg daily for 6 weeks.
- - Cotrimoxazole + Rifampicin for 6 weeks.
- Note: Ciprofloxacin mentioned in UCG as alternative to Gentamicin BUT generally less preferred due to resistance/relapse risk, and contraindicated <12 years. Doxycycline/Gentamicin contraindicated in pregnancy.
Monitoring
Monitor clinical response. Adherence to full 6-week course is crucial. Monitor for relapse after treatment completion.
Complications
- Relapse (common if treatment inadequate/short).
- Osteoarticular complications (arthritis, sacroiliitis, spondylitis).
- Orchitis/Epididymitis.
- Neurobrucellosis.
- Endocarditis.
- Hepatic abscess.
Prevention
- Pasteurization of milk and dairy products.
- Thorough cooking of meat.
- Occupational safety (use of PPE - gloves, masks, eye protection) for those handling animals/carcasses.
- Vaccination of livestock.
- Careful handling of potentially infected animal tissues/secretions.
Patient education
- Explanation of the zoonotic source.
- Critical importance of completing the FULL 6-WEEK antibiotic course to prevent relapse.
- Potential side effects of medication.
- Prevention measures (pasteurized milk, cooked meat, occupational safety).
- Need for follow-up.
Uganda-specific notes
Present in Uganda, linked to livestock. Diagnosis challenging due to nonspecific symptoms and limitations of serology interpretation. Prolonged treatment essential. Doxycycline + Gentamicin often used.
References
- Uganda Clinical Guidelines (UCG) 2023
Chapter 2, Section 2.1.2