Improving antimicrobial therapy for Buruli ulcer : Pre-clinical studies towards highly efficient, short-course therapy

Buruli ulcer is an infectious disease that is caused by a bacterium called Mycobacterium ulcerans. The disease mainly occurs in West Africa but also in Australia. In West Africa, mainly poor and rural communities are affected. It is unclear how the disease is transmitted to humans. However, we know that the bacterium occurs in the environment. It has been found in water, plants and insects. Buruli ulcer is a disease of the skin and the underlying tissue. It causes a nodule or an open wound, an ulcer. For a long time, Buruli ulcer was treated with surgery. The affected skin was cut out, or limbs were amputated. Since a few years, Buruli ulcer is treated with antibiotics efficiently. The antibiotic treatment takes 2 months. This is a long duration and better and more modern antibiotics are available now. This thesis first described the epidemiology and current treatment of Buruli ulcer. The main part then focused on laboratory research to find more efficient and shorter antibiotic options to treat Buruli ulcer. In our experiments we found that higher doses of rifampin are very efficient and can shorten the treatment of Buruli ulcer to only one month instead of two months. Based on these findings, a clinical trial is discussed that could use high-dose rifampin in combination with another drug to shorten the treatment of Buruli ulcer.