Susceptibility to development of Mycobacterium ulcerans disease: review ofpossible risk factors

Mycobacterium ulcerans disease, also known as Buruli ulcer (BU), is a disea se of subcutaneous fat tissue. BU is prevalent in riverine and swamp areas of the tropical zone in Africa, Asia and South America, and a few scattered foci in Australia. The mode of transmission of M. ulcerans has not been fu lly elucidated, but inoculation into the subcutaneous tissues probably occu rs through penetrating skin trauma. BU has not been linked with HIV infecti on. Antimycobacterial drug treatment is ineffective, and treatment is surgi cal. Patients eventually develop scars and contractures, with resulting dis abilities, and the disease imposes a large burden on affected populations. The incidence of BU has dramatically increased in West African countries ov er the last decade. There is an urgent need for research into host and envi ronmental risk factors for BU in order to develop effective strategies to c ombat this disease. We review possible genetic host susceptibility factors for BU that are relevant in other mycobacterial diseases: natural resistanc e-associated macrophage protein-1 (NRAMP-1), HLA-DR, vitamin D-3 receptor, mannose binding protein, interferon-gamma (IFN-gamma) receptor, tumour necr osis factor alpha (TNF-alpha), interleukin (IL)-1 alpha, 1 beta and their r eceptor antagonists; and IL-12. Schistosoma haematobium infection is highly endemic in many BU foci in West Africa, with a striking increase in transm ission after river darns were constructed. This observation, and the observ ations from interaction of schistosomiasis and tuberculosis, have fuelled o ur hypothesis that schistosomiasis is a risk factor for BU by driving the h ost immune response towards a predominantly Th-2 pattern, away from a Th-1 preponderant protection against mycobacterial infection. If the latter hypo thesis is confirmed, enhanced schistosomiasis control should impact on BU.