Accelerated Detection of Mycolactone Production and Response to Antibiotic Treatment in a Mouse Model of Mycobacterium ulcerans Disease

Overview

The diagnosis of Buruli ulcer, caused by infection with Mycobacterium ulcerans, is complicated by its resemblance to other diseases that may also cause ulcers in the skin. Clinical diagnosis can be supported by microscopic detection of acid-fast bacilli in the skin, by prolonged culture of at least 8 weeks, in a dedicated incubator set at 32°C, or by the polymerase chain reaction in a well-equipped laboratory usually far from the clinic where the patient comes for treatment.

The treatment involves taking two drugs, one requiring injections, every day for two months, a burden for patients and their families. Since all drugs may have side effects, it is important that the treatment be appropriate for the patient's disease. We describe a new technique to rapidly and inexpensively detect the presence of the unique toxin produced by M. ulcerans in the mouse footpad model of Buruli ulcer.

We show that the toxin can be detected in footpads before the development of signs of the disease, that more toxin is produced as the disease progresses, and that toxin levels decline in mice treated with either the current standard regimen of rifampin and streptomycin or a proposed all-oral drug regimen of rifampin and clarithromycin.