Drug treatment for Buruli ulcer

PhD ceremony: Ms. W.A. Nienhuis, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Drug treatment for Buruli ulcer

Promotor(s): prof. T.S. van der Werf

Faculty: Medical Sciences

Buruli ulcer (BU) is a tropical ulcerating skin disease caused by Mycobacterium ulcerans. In its Plan to combat Neglected Tropical Diseases (2008-2015), The World Health Organization denotes BU tool-deficient, as it lacks cost-effective control methods. For long, surgery was believed to be the only available option to cure the disease. The disadvantages of surgery are high risks of recurrent disease and the extra tissue damage induced by the large excisions. This thesis focused on the effectiveness and safety of drug treatment to control infection. In Ghana, West Africa, 151 patients with early, limited (<10 cm) disease were treated with a combination of antimicrobials. Two different schedules were compared. From the study it was concluded that daily treatment with two antibiotics during 8 weeks (streptomycin injections and rifampicin tablets) was highly effective. More than 90% of patients was cured and had no recurrent disease in the subsequent year. When injection therapy was replaced by tablets during the second 4 weeks of treatment (claritromycin tablets instead of streptomycin injections), effectiveness was similar. Analysis of serial surface area measurements of affected tissue revealed that in the majority of patients, an increase in surface area preceded healing. Besides progressive ulceration, new ulceration was also seen in patients who eventually healed on treatment. This paradoxical response to antimicrobials has probably been one of the most important reasons that the effectiveness of antibiotics for the treatment of BU has not been recognized earlier.