Neglected Diseases
Buruli ulcer, also known as Bairnsdale ulcer, is a chronic necrotizing skin disease caused by Mycobacterium ulcerans. In developing countries, children under the age of 15 are at greatest risk. While the exact transmission mode is unknown, living around marshy areas with stagnant or slow-moving water can be a risk factor in endemic regions.
Buruli ulcer usually appears as a painless lump or nodule that can later develop into an ulcer, usually on the arms or legs. M. ulcerans produces a toxin known as mycolactone, which causes tissue damage and can depress the immune response. As a result, coinfection with HIV can make Buruli ulcer more complex to address. Early case detection and antibiotic treatment remain the cornerstones of the control strategy for Buruli ulcer to reduce morbidity, treatment costs and prevent long-term disabilities. If left undiagnosed or untreated, infection with M. ulcerans can lead to skin, tissue or bone damage, with surgery or amputation sometimes required.
Adoption of IS2404 PCR by national Buruli ulcer (BU) programs has dramatically improved diagnostic and epidemiological accuracy in endemic countries. However, there remains a need for simpler diagnostic tools allowing prompt and accurate diagnosis at the community level. BU-MYCOLAC, the first RDT designed to detect mycolactone, still needs clinical evaluation in endemic settings, while other point-of-care molecular methods like BUD-LAMP require field evaluation. Treatment of BU remains cumbersome – often complicated by paradoxical reactions – and lengthy, making development of new drugs a key priority. Τelacebec, Clofazamine and TB47 are stand-alone or combination pipeline candidates – all still in preclinical or early clinical phases, highlighting the need for acceleration and diversification of drug R&D. Tools for immunization against BU remain underdeveloped. All vaccine candidates are in early preclinical stages, while the widely available repurposed TB vaccine, BCG vaccine, provides only short-term protection and is no substitute for a targeted BU vaccine.
There are just three products each in the Buruli ulcer therapeutic and prophylactic pipelines, which remains mainly at an early stage of development. Only two (repurposed) drugs have reached the clinical stage of development – one in Phase I and the other in Phase II. The remaining candidates, including all potential vaccines, are in the preclinical or discovery stage. Repurposing of tuberculosis drugs is the most promising avenue for alternative Buruli ulcer treatments: several antitubercular agents, including investigational compounds, have been tested in animal models for treating Buruli ulcer. One such compound, telacebec (Q203), a cytochrome bc1 complex inhibitor, has shown promising results in a mouse model of Buruli ulcer.