Epidemiology and management of Buruli ulcer

Abstract

Buruli ulcer (Mycobacterium ulcerans infection) is a neglected tropical disease of skin and subcutaneous tissue that can result in long-term cosmetic and functional disability. It is a geographically restricted infection but transmission has been reported in endemic areas in more than 30 countries worldwide. The heaviest burden of disease lies in West and Sub-Saharan Africa where it affects children and adults in subsistence agricultural communities. Mycobacterium ulcerans infection is probably acquired via inoculation of the skin either directly from the environment or indirectly via insect bites. The environmental reservoir and exact route of transmission are not completely understood. It may be that the mode of acquisition varies in different parts of the world. Because of this uncertainty it has been nicknamed the ‘mysterious disease’. The therapeutic approach has evolved in the past decade from aggressive surgical resection alone, to a greater focus on antibiotic therapy combined with adjunctive surgery.

Keywords::

• Buruli ulcer
• clarithromycin
• fluroquinolones
• Insertion sequence IS2404
• Mycobacterium ulcerans
• mycolactone
• paradoxical reaction
• rifampicin
• streptomycin
• WHO neglected tropical disease

Acknowledgements

The authors acknowledge Dr. Martin W Bratschi and Professor Gerd Pluschke, Swiss Tropical and Public Health Institute, Basel, Switzerland for the use of their high quality figures from their research in Bankim, Cameroon.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Buruli ulcer (Mycobacterium ulcerans infection) is the third most common mycobacterial infection of otherwise health humans with the greatest burden of disease in West and Sub-Saharan Africa.

• Buruli ulcer results in progressive necrotizing lesions of skin and soft tissue and is a significant cause of disability, particularly in Africa where patients often present late and have limited access to surgery and rehabilitation.

• Buruli ulcer lesions are associated with a notable lack of inflammatory response on histology, and patients often remain systemically well. Pathogenesis is mediated by an immunosuppressive cytotoxin mycolactone, which diffuses into the surrounding tissues, inhibits local immune responses and causes direct destruction of subcutaneous structures via apoptosis and necrosis.

• Within endemic countries, the disease occurs in environmentally discrete regions, often in proximity to water sources.

• The exact environmental reservoir and mode of acquisition are yet to be clearly elucidated; however there is circumstantial evidence that biting insects including mosquitoes may play a role in some regions.

• The treatment paradigm has shifted in the last decade from aggressive surgical resection alone to antibiotic therapy, combined with adjunctive surgery in some cases, to achieve an optimal result.

• Antibiotic options include 8 weeks of rifampicin + streptomycin or rifampicin + clarithromycin. Antibiotics are often combined with adjuvant surgery.

• Paradoxical reactions are a common occurrence with apparent clinical worsening of lesions after commencement of therapy with a peak timing of reactions occurring at 8 weeks. Steroid therapy may have a role in severe cases.

Notes