Buruli Ulcer (Acha-ere): Pathogenesis and Manifestation

Abstract

Infection of subcutaneous tissue with Mycobacterium ulcerans can lead to chronic skin ulceration known as Buruli ulcer. It has been reported in over 33 countries around the world, the greatest burden of disease is in the tropical regions of West and Central Africa, Australia, and Japan. It primarily affects children aged 5-15 years. Buruli ulcers generally begin as a painless dermal papule or subcutaneous edematous nodule, which over a period of weeks to months, breaks down to form an extensive necrotic ulcer with undermined edges. The pathogenesis of this neglected tropical disease is dependent on a lipidlike toxin, mycolactone, which diffuses through tissue away from the infecting organisms and elucidate its cytotoxic and immunosuppressive properties. The underlying molecular targets for mycolactone are: First, it can target scaffolding proteins (such as Wiskott Aldrich Syndrome Protein), which control actin dynamics in adherent cells and therefore lead to detachment and cell death. Second, it prevents the co-translational translocation (and therefore production) of many proteins that pass through the endoplasmic reticulum for secretion or placement in cell membranes.  Treatment includes a prolonged course of antibiotics and surgical debridement. Early identification and treatment are key, as lesions heal with scarring that can be a significant source of morbidity.