Secondary bacterial infections of buruli ulcer lesions before and after chemotherapy with streptomycin and rifampicin

Buruli ulcer (BU), caused by Mycobacterium ulcerans is a chronic necrotizing skin disease. It usually starts with a subcutaneous nodule or plaque containing large clusters of extracellular acid-fast bacilli. Surrounding tissue is destroyed by the cytotoxic macrolide toxin mycolactone produced by microcolonies of M. ulcerans. Skin covering the destroyed subcutaneous fat and soft tissue may eventually break down leading to the formation of large ulcers that progress, if untreated, over months and years. Here we have analyzed the bacterial flora of BU lesions of three different groups of patients before, during and after daily treatment with streptomycin and rifampicin for eight weeks (SR8) and determined drug resistance of the bacteria isolated from the lesions. Before SR8 treatment, more than 60% of the examined BU lesions were infected with other bacteria, with Staphylococcus aureus and Pseudomonas aeruginosa being the most prominent ones. During treatment, 65% of all lesions were still infected, mainly with P. aeruginosa. After completion of SR8 treatment, still more than 75% of lesions clinically suspected to be infected were microbiologically confirmed as infected, mainly with P. aeruginosa or Proteus miriabilis. Drug susceptibility tests revealed especially for S. aureus a high frequency of resistance to the first line drugs used in Ghana. Our results show that secondary infection of BU lesions is common. This could lead to delayed healing and should therefore be further investigated

Sero-Epidemiology as a Tool to Screen Populations for Exposure to Mycobacterium ulcerans

Sero-epidemiological analyses revealed that a higher proportion of sera from individuals living in the Buruli ulcer (BU) endemic Densu River Valley of Ghana contain Mycobacterium ulcerans 18 kDa small heat shock protein (shsp)-specific IgG than sera from inhabitants of the Volta Region, which was regarded so far as BU non-endemic. However, follow-up studies in the Volta Region showed that the individual with the highest anti-18 kDa shsp-specific serum IgG titer of all participants from the Volta Region had a BU lesion. Identification of more BU patients in the Volta Region by subsequent active case search demonstrated that sero-epidemiology can help identify low endemicity areas. Endemic and non-endemic communities along the Densu River Valley differed neither in sero-prevalence nor in positivity of environmental samples in PCR targeting M. ulcerans genomic and plasmid DNA sequences. A lower risk of developing M. ulcerans disease in the non-endemic communities may either be related to host factors or a lower virulence of local M. ulcerans strains