Clinical and bacteriological efficacy of rifampin-streptomycin combination for two weeks followed by rifampin and clarithromycin for six weeks for treatment of Mycobacterium ulcerans disease.

Buruli ulcer, an ulcerating skin disease caused by Mycobacterium ulcerans infection, is common in tropical areas of western Africa. We determined the clinical and microbiological responses to administration of rifampin and streptomycin for 2 weeks followed by administration of rifampin and clarithromycin for 6 weeks in 43 patients with small laboratory-confirmed Buruli lesions and monitored for recurrence-free healing. Bacterial load in tissue samples before and after treatment for 6 and 12 weeks was monitored by semiquantitative culture. The success rate was 93%, and there was no recurrence after a 12-month follow-up. Eight percent had a positive culture 4 weeks after antibiotic treatment, but their lesions went on to heal. The findings indicate that rifampin and clarithromycin can replace rifampin and streptomycin for the continuation phase after rifampin and streptomycin administration for 2 weeks without any apparent loss of efficacy.

Combined inflammatory and metabolic defects reflected by reduced serum protein levels in patients with Buruli ulcer disease.

Buruli ulcer is a skin disease caused by Mycobacterium ulcerans that is spreading in tropical countries, with major public health and economic implications in West Africa. Multi-analyte profiling of serum proteins in patients and endemic controls revealed that Buruli ulcer disease down-regulates the circulating levels of a large array of inflammatory mediators, without impacting on the leukocyte composition of peripheral blood. Notably, several proteins contributing to acute phase reaction, lipid metabolism, coagulation and tissue remodelling were also impacted. Their down-regulation was selective and persisted after the elimination of bacteria with antibiotic therapy. It involved proteins with various functions and origins, suggesting that M. ulcerans infection causes global and chronic defects in the host's protein metabolism. Accordingly, patients had reduced levels of total serum proteins and blood urea, in the absence of signs of malnutrition, or functional failure of liver or kidney. Interestingly, slow healers had deeper metabolic and coagulation defects at the start of antibiotic therapy. In addition to providing novel insight into Buruli ulcer pathogenesis, our study therefore identifies a unique proteomic signature for this disease.