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Background: The World Health Organization (WHO) advises treatment of Mycobacterium ulcerans disease, also called "Buruli ulcer" (BU), with a combination of the antibiotics rifampicin and streptomycin (R+S), whether followed by surgery or not. In endemic areas, a clinical case definition is recommended. We evaluated the effectiveness of this strategy in a series of patients with large ulcers of ≥10 cm in longest diameter in a rural health zone of the Democratic Republic of Congo (DRC). Methods: A cohort of 92 patients with large ulcerated lesions suspected to be BU was enrolled between October 2006 and September 2007 and treated according to WHO recommendations. The following microbiologic data were obtained: Ziehl-Neelsen (ZN) stained smear, culture and PCR. Histopathology was performed on a sub-sample. Directly observed treatment with R+S was administered daily for 12 weeks and surgery was performed after 4 weeks. Patients were followed up for two years after treatment. Findings: Out of 92 treated patients, 61 tested positive for M. ulcerans by PCR. PCR negative patients had better clinical improvement than PCR positive patients after 4 weeks of antibiotics (54.8% versus 14.8%). For PCR positive patients, the outcome after 4 weeks of antibiotic treatment was related to the ZN positivity at the start. Deterioration of the ulcers was observed in 87.8% (36/41) of the ZN positive and in 12.2% (5/41) of the ZN negative patients. Deterioration due to paradoxical reaction seemed unlikely. After surgery and an additional 8 weeks of antibiotics, 98.4% of PCR positive patients and 83.3% of PCR negative patients were considered cured. The overall recurrence rate was very low (1.1%). Interpretation: Positive predictive value of the WHO clinical case definition was low. Low relapse rate confirms the efficacy of antibiotics. However, the need for and the best time for surgery for large Buruli ulcers requires clarification. We recommend confirmation by ZN stain at the rural health centers, since surgical intervention without delay may be necessary on the ZN positive cases to avoid progression of the disease. PCR negative patients were most likely not BU cases. Correct diagnosis and specific management of these non-BU ulcers cases are urgently needed. Author Summary: Buruli ulcer (BU) disease, a neglected devastating infection caused by Mycobacterium ulcerans, has a huge impact because of the massive necrotizing, disfiguring ulcers that may result if not treated. Therapeutic options are surgery, antibiotics or combinations of both. Since 2004, the World Health Organization has recommended the use of antibiotics (rifampicin and streptomycin) for the management of the disease. The effectiveness of this antibiotic treatment on advanced lesions is, however, not well documented. We evaluated this strategy on large ulcers clinically suspected to be BU, in a rural zone of the Democratic Republic of Congo, and also assessed the outcome of treatment based only on clinical diagnosis. All patients were treated with antibiotics for 12 weeks and surgery was performed after 4 weeks. BU was confirmed by laboratory tests in 67% of the patients indicating that the clinical diagnosis of ulcerated forms of BU may be more difficult than usually reported. Although delayed surgery seemed detrimental in some confirmed cases, it was possible to treat 92% of patients successfully with low recurrence rates (1.1%) by combining antibiotic treatment with surgery in a rural zone. However, the need for and the best time for surgery for large Buruli ulcers requires clarification. [ABSTRACT FROM AUTHOR]

Objective To describe lay perceptions of the ulcerated forms of Mycobacterium ulcerans, commonly called Buruli ulcer (BU), and therapeutic itineraries of BU patients in a rural area of the Democratic Republic of Congo. Methods Qualitative research consisting of semi-structured interviews of 19 patients with clinical signs of BU and 12 in-depth interviews of confirmed cases allowing for a detailed reconstruction of the itineraries followed. Results The first symptoms of BU are perceived as mild. The perceived seriousness of the disease increases as the ulceration persists, increases in size or results in complications. Knowledge about the biomedical aetiology of the disease is scarce; it is commonly believed to be due to witches’ attacks or bad fate. Four therapeutic paths are taken: self-medication, traditional therapy, the church and the health centre. However lay perception, recourse to traditional treatments and self-medication only partially explain the long delays in diagnosis (on average 6 months); the main problem lies with health providers, particularly the lack of proper diagnostic capability. Conclusions Diagnostic capabilities at health centre level need to be strengthened through training and supervision. Engaging with the population and the traditional healers would render health promotion messages on BU more relevant and culturally acceptable. [ABSTRACT FROM AUTHOR]

Buruli ulcer is an indolent, slowly progressing necrotizing disease of the skin caused by infection with Mycobacterium ulcerans. In the present study, we applied a redesigned technique to a vast panel of M. ulcerans disease isolates and clinical samples originating from multiple African disease foci in order to (i) gain fundamental insights into the population structure and evolutionary history of the pathogen and (ii) disentangle the phylogeographic relationships within the genetically conserved cluster of African M. ulcerans. Our analyses identified 23 different African insertion sequence element single nucleotide polymorphism (ISE-SNP) types that dominate in different areas where Buruli ulcer is endemic. These ISE-SNP types appear to be the initial stages of clonal diversification from a common, possibly ancestral ISE-SNP type. ISE-SNP types were found unevenly distributed over the greater West African hydrological drainage basins. Our findings suggest that geographical barriers bordering the basins to some extent prevented bacterial gene flow between basins and that this resulted in independent focal transmission clusters associated with the hydrological drainage areas. Different phylogenetic methods yielded two well-supported sister clades within the African ISE-SNP types. The ISE-SNP types from the "pan-African clade" were found to be widespread throughout Africa, while the ISE-SNP types of the "Gabonese/Cameroonian clade" were much rarer and found in a more restricted area, which suggested that the latter clade evolved more recently. Additionally, the Gabonese/Cameroonian clade was found to form a strongly supported monophyletic group with Papua New Guinean ISE-SNP type 8, which is unrelated to other Southeast Asian ISE-SNP types. [ABSTRACT FROM AUTHOR]