Buruli Ulcer: History and Disease Burden

Excerpt

Buruli ulcer (BU) is a neglected, debilitating skin disease caused by infection with Mycobacterium ulcerans. After the first definite description in 1948, M. ulcerans infections have been reported from 34 countries, mainly with tropical and subtropical climates. Following a peak of 5954 reported BU cases globally in 2004 the number of new recorded cases has been decreasing over the past years. In 2016, a total of 1952 BU cases were reported to the World Health Organization (WHO) from twelve different countries. Underreporting is considered likely, as BU mostly affects populations in remote areas with limited access to the formal health sector. Although transmission pathways of M. ulcerans are still unclear, infection foci are closely associated with wetlands. Considering that M. ulcerans has evolved from the fish pathogen M. marinum, involvement of an environmental niche is strongly suggestive. The key event for the emergence of M. ulcerans as a species highly pathogenic for humans appears to be the acquisition of a plasmid, bearing genes encoding polyketide synthases and polyketide-modifying enzymes involved in the biosynthesis of a unique macrolide toxin, named mycolactone. The cytotoxic and immunosuppressive properties of mycolactone account for much of the pathology of BU, which is characterized by the formation of chronic, necrotizing, ulcerative skin lesions. In the further course of its reductive evolution, M. ulcerans has diverged into at least two principal niche-adapted lineages connected with different patterns of BU case distribution. Strains of the classical lineage are responsible for BU foci in Africa and Australia that are typically characterized by high local prevalence. In contrast, scattered, sporadic BU cases recorded in Asia and the Americas are caused by strains of the ancestral lineage, which also comprises globally distributed fish and frog pathogens. Adaptation of these divergent mycolactone-producing mycobacterial lineages to different ecological habitats seems likely. Limited knowledge on definite reservoirs and potential vectors as well as the lack of a vaccine hamper the control of BU. Therefore, early identification and adequate treatment of patients are currently the most important measures to prevent the debilitating consequences of the disease.