Treating Mycobacterium ulcerans disease (Buruli ulcer): from surgery to antibiotics, is the pill mightier than the knife?

Abstract

Until 2004, the skin disease known as Buruli ulcer, caused by Mycobacterium ulcerans, could only be treated by surgery and skin grafting. Although this worked reasonably well on early lesions typically found in patients in Australia, the strategy was usually impractical on large lesions resulting from diagnostic delay in patients in rural West Africa. Based on promising preclinical studies, treatment trials in West Africa have shown that a combination of rifampin and streptomycin administered daily for 8 weeks can kill M. ulcerans bacilli, arrest the disease, and promote healing without relapse or reduce the extent of surgical excision. Improved treatment options are the focus of research that has increased tremendously since the WHO began its Global Buruli Ulcer Initiative in 1998.

Figure 1. Growth in scientific publications concerning Mycobacterium ulcerans has accelerated since the late 1990s

For the first 22 years after the discovery of the causative organism of what is now called Buruli ulcer, publications were rare (approximately two per year) but outlined much of the research that has answered important questions about pathogenesis, epidemiology and treatment. There was a slight increase in publication frequency (nearly six per year) following publication of the Ugandan studies in the 1970s. However, with increased involvement from the WHO and definitive characterization of the mycolactone toxin, there have been over 38 publications per year since 1998. ^†Based on a search of PubMed using Mycobacterium ulcerans and publication year. Avg.: Average.

Figure 2. The mouse footpad model of Mycobacterium ulcerans disease

Grade 1 swelling of the footpad is easily distinguished from the normal footpad 4–8 weeks after infection. Swelling progresses to the grade 2 stage with increasing inflammation. At grade 3, inflammation is apparent further up the leg. If mice are not sacrificed, there can be manifestations of ulceration with cage bedding sticking to the foot. See also Box 1 discussing the model.

Figure 3. Clinical manifestations of Mycobacterium ulcerans infection

The earliest manifestations of Buruli ulcer range from small nodules to firm plaques to edematous lesions. These may prompt patients to seek medical attention before the occurrence of ulceration as in both the Category I and Category II patients shown here. Before treatment could be administered the small nodule ulcerated on the lower leg of the girl. The Category III patient had first noticed her symptoms 2 weeks before coming to hospital. For the WHO’s classification system see reference [202].