Brucellosis: Clinical Presentation, Diagnostic Testing, and Therapeutic Options
Clinical Presentation
Brucellosis typically presents with non-specific symptoms including fever with characteristic afternoon temperature swings accompanied by profuse sweating, malaise, myalgia, arthralgia, loss of appetite, weight loss, and hepatosplenomegaly. 1, 2, 3
Key Clinical Features to Identify:
- Fever pattern: Remittent fever with profuse sweating, particularly in the afternoon hours 1
- Musculoskeletal symptoms: Arthralgia and myalgia are prominent, with osteoarticular involvement being the most common complication (prevalence 2-77%) 3
- Hepatosplenomegaly: Present in approximately 50% of patients 3
- Gastrointestinal symptoms: Abdominal pain, nausea, vomiting 3
- Constitutional symptoms: Weight loss, malaise, prolonged fever 2, 4
System-Specific Complications:
- Osteoarticular (most common): Spondylitis, sacroiliac arthritis, peripheral arthritis 5, 3
- Genitourinary: Unilateral epididymal-orchitis in 2-20% of male cases 3
- Cardiovascular: Endocarditis (incidence <2% but accounts for >80% of brucellosis deaths) 3
- Neurological: Neurobrucellosis occurs in 0.5-25% of cases, mainly as meningitis 6, 3
- Hematologic: Anemia in 20-53% of children during acute phase 3
- Respiratory: Less common but includes pneumonia, pleurisy, pleural effusion 3
Diagnostic Pitfalls:
- Diagnosis is frequently delayed (average 2-4 months) because back/neck pain and fever are extremely common symptoms 5
- Fever is only present in up to 45% of patients with bacterial vertebral osteomyelitis from Brucella 5
- Clinical presentation mimics other febrile illnesses including malaria, tuberculosis, typhoid fever, and tularemia 7
Diagnostic Testing
Blood Cultures:
- Obtain 2 sets of aerobic and anaerobic blood cultures in all suspected cases 5
- Blood cultures yield Brucella species but are time-consuming and not always reliable 7, 4
- Positive blood cultures obviate the need for tissue biopsy in patients with suspected vertebral osteomyelitis 5
Serologic Testing:
In endemic areas, serologic testing with serum agglutination titers ≥1:160 is highly sensitive for brucellosis and strongly positive serology (≥1:160) eliminates the need for invasive biopsy. 5
- Serum agglutination test and Coombs test: Cutoff point ≥1:160 5
- False-negative serologic tests are unusual in brucellar vertebral osteomyelitis; all patients in one study had titers ≥1:160 5
- In non-endemic areas (like the United States), ELISA screening is performed first, followed by confirmatory agglutination test 5
- False-positive tests are more likely in low-endemicity countries, potentially warranting tissue biopsy confirmation 5
Baseline Laboratory Studies:
- ESR and CRP should be obtained in all suspected cases 5
Imaging Studies:
MRI is the first-line imaging modality for suspected vertebral involvement, with 97% sensitivity, 93% specificity, and 94% accuracy. 5
- MRI findings in brucellar spondylitis: T1-weighted sequences are more sensitive than T2-weighted for demonstrating inflammatory processes 5
- When MRI is contraindicated (implantable devices, claustrophobia), use combination gallium/Tc99 bone scan, CT, or PET scan 5
Tissue Biopsy:
- Image-guided aspiration biopsy is NOT recommended when Brucella bloodstream infection is documented or when strongly positive serology (≥1:160) exists in endemic settings 5
- Biopsy IS indicated when blood cultures are negative and serology is equivocal, particularly in non-endemic areas 5
- Specimens should be sent for bacterial, mycobacterial, brucellar, and fungal cultures 5
Molecular Testing:
- PCR and restriction fragment length polymorphism are needed to differentiate Brucella species and strains 7
Therapeutic Options
First-Line Regimens for Uncomplicated Brucellosis:
The optimal treatment is doxycycline 100 mg twice daily for 6 weeks combined with either streptomycin 15 mg/kg daily IM for 2-3 weeks (lowest relapse rate) or rifampicin 600-900 mg daily for 6 weeks. 5, 8
Preferred Regimen #1:
- Doxycycline 100 mg PO twice daily for 6 weeks 8
- PLUS Streptomycin 15 mg/kg IM daily for 2-3 weeks 8, 9
- This combination has the lowest relapse rate 8
Preferred Regimen #2:
- Doxycycline 100 mg PO twice daily for 6 weeks 8
- PLUS Rifampicin 600-900 mg PO daily (single morning dose) for 6 weeks 8
Alternative First-Line Regimen:
- Doxycycline 100 mg PO twice daily for 6 weeks 8
- PLUS Gentamicin 5 mg/kg IV/IM daily (single dose) for 7 days 8
- Gentamicin offers comparable efficacy to streptomycin with wider availability and shorter parenteral therapy duration 8
- Do NOT use fixed 500 mg gentamicin dosing; weight-based dosing (5 mg/kg) is mandatory 8
Second-Line Regimens:
- Trimethoprim-sulfamethoxazole 800/160 mg PO twice daily for 6 weeks: Cost-effective alternative in resource-limited settings 8
- Quinolone-containing regimens (ofloxacin, ciprofloxacin): Reserved as second or third agents in combination therapy due to higher cost and antimicrobial resistance concerns 8
Treatment Duration and Expected Outcomes:
- Standard duration is 6 weeks for most regimens 5, 8
- Relapse rates are 5-15% even with appropriate treatment 5
- Relapses are usually mild and respond to the same regimens 5
- Full symptom resolution may take several weeks despite appropriate therapy 1
- Fever and chills typically represent ongoing inflammatory response rather than treatment failure during the first 7-14 days 1
Monitoring Treatment Response:
- Clinical assessment of symptom progression; improvement expected within 7-14 days 1
- Serologic testing is not helpful for early treatment response assessment 1
- Consider switching regimens if symptoms persist or worsen after 2 weeks of therapy 1
Special Considerations:
Neurobrucellosis:
- Doxycycline plus rifampicin for at least 6 weeks (often longer duration required) 6
- MRI should be performed when spinal involvement is suspected 6
Brucellar Vertebral Osteomyelitis:
- Same antibiotic regimens as uncomplicated brucellosis but typically require longer duration 5
- Consultation with infectious disease specialist and spine surgeon is advised 5
Critical Public Health Warning:
In regions where brucellosis and tuberculosis coexist, the use of rifampicin for brucellosis poses significant risk for promoting mycobacterial resistance to this critical tuberculosis drug—the public health impact may exceed the cumulative brucellosis morbidity. 5
Supportive Care During Treatment:
- Antipyretics (acetaminophen) for fever and discomfort 1
- Adequate hydration during sweating episodes 1
- Rest during symptomatic periods with gradual return to activities 1