What is the recommended investigation and treatment for a Buruli ulcer?

Diagnosis and Treatment of Buruli Ulcer Disease

The recommended diagnostic approach for Buruli ulcer disease is PCR targeting IS2404 as the gold standard, with treatment consisting of an 8-week course of rifampicin and streptomycin combined with surgical management for extensive lesions.

Diagnostic Approach

Buruli ulcer disease (BUD) is a necrotizing cutaneous infection caused by Mycobacterium ulcerans. Early diagnosis is crucial to prevent morbidity and inappropriate treatment. The main laboratory methods for diagnosis include:

Primary Diagnostic Tests

• PCR targeting IS2404: Gold standard for laboratory confirmation with highest sensitivity (85%) 1
  • For non-ulcerative lesions: 3-mm punch biopsy tissue specimens (94% sensitivity)
  • For ulcerative lesions: Swab samples (90% sensitivity) 2

Secondary Diagnostic Tests

• Microscopy: 57% sensitivity, used routinely for diagnosis 1, 2
• Culture: 51% sensitivity, only method that detects viable bacilli; useful for diagnosing relapse and monitoring drug resistance 1, 3
• Histopathology: Helps confirm diagnosis and assess tissue response to treatment 2

Stepwise Diagnostic Approach

A cost-effective approach to diagnosis in resource-limited settings:

1. For pre-ulcerative lesions: Tissue microscopy followed by tissue PCR (confirms 65% of cases)
2. For ulcerative lesions: Swab smear microscopy followed by swab PCR (confirms 70% of cases) 4

Important: One positive diagnostic test may be sufficient for laboratory confirmation of BUD due to the high specificity of microscopy (96.6%) and PCR (100%) 4

Treatment Recommendations

Antimicrobial Therapy

• First-line treatment: 8-week course of rifampicin and streptomycin (R/S) 5, 6
  • This combination induces rapid local cellular immune responses
  • Promotes phagocytosis of extracellular M. ulcerans
  • Leads to declining levels of mycolactone toxin in tissues 6

Surgical Management

• Pre-ulcerative lesions: Can be treated effectively by:

  • Excision and primary closure
  • Rifampicin monotherapy
  • Heat therapy 5

• Large established ulcers:

  • Medical treatment alone is often disappointing
  • Surgical debridement combined with skin grafting is usually the treatment of choice 5
  • Post-surgical antimycobacterial treatment may prevent relapse or metastasis 5

Treatment Response Monitoring

• PCR is not suitable for monitoring treatment success due to extended presence of mycobacterial DNA during treatment
• Culture remains the only valid confirmatory test for detecting viable bacilli during treatment monitoring 3

Clinical Considerations

Clinical Presentation

• Indolent, progressive necrotic skin lesions with indeterminate scalloped edges
• Lesions occur most commonly in children and young adults
• Can result in severe scarring and deformities of extremities 5

Transmission

• Infection occurs through abraded or compromised skin after contact with contaminated water or soil 5

Treatment Challenges

• Previous antimycobacterial treatment significantly decreases the sensitivity of PCR and culture, complicating diagnosis in previously treated patients 2
• Duration of disease does not significantly influence test sensitivity 2

Prevention of Complications

• Early diagnosis and treatment are essential to prevent morbidity
• Clarithromycin and rifampicin may be the best choice for controlling complications of established ulcers 5
• Regular follow-up is necessary to monitor treatment response and detect potential relapse

The combination of accurate laboratory diagnosis and appropriate antimicrobial therapy with surgical intervention when needed provides the best outcomes for patients with Buruli ulcer disease.