Mycobacteria ulcerans, a slow-growing acid-fast bacillus (AFB), arose from Mycobacteria marinum and acquired a virulence plasmid coding for mycolactone, a necrotizing, apoptotic, immunosuppressive toxin that mediates pathogenesis. BU is characterized clinically by indolent necrotizing skin, subcutaneous and sometimes bone lesions, often with severe residual scarring. It is an important public health issue.
The incidence of BU is highest in West Africa, particularly Benin, Ivory Coast, and Ghana. Far fewer cases have been reported in Australia, China, Japan, Mexico, Papua, and in some South American countries such as Colombia, French Guiana, Brazil, and Peru. In industrialized countries, the disease is occasionally imported. A history of travel to endemic regions, especially West Africa, is important. Geographically, multiple strains of M. ulcerans exhibit variable pathogenicity and immunogenicity.
In endemic regions, exposure to stagnant water, especially swampy areas, may be a predisposing factor. One plausible mode of transmission is minor skin trauma meditating inoculation of M. ulcerans, but other modes, and reservoirs, are under investigation. In Australia, BU is considered a zoonosis transmitted by mosquitoes from opossums to humans.
Somewhat similar to tuberculosis, exposure of cutaneous tissues to M. ulcerans may lead to one of three outcomes:
- Clearance of the infection,
- Clinical disease relatively soon after infection (primary BU), or
- Subclinical or asymptomatic infection (latent BU) that may subsequently reactivate and produce disease.
BU is most common in children less than 15 years in age. After inoculation of the skin, followed in general by a 2-3 month incubation period, the extracellular bacilli proliferate and release mycolactone, which causes apoptosis, necrosis, and local immunosuppression.
BU typically presents as one or more painless solitary lesions. In Africa, about 13% of patients develop bone disease (osteitis, osteomyelitis), either subjacent or distant to a skin lesion. Distant lesions are probably caused by lymphohematogenous spread of M. ulcerans.
Because M. ulcerans is an environmental organism, it is generally accepted that person-to-person spread is uncommon or does not occur. In limited disease, there are few systemic manifestations. Lymphadenopathy and fever are rare unless secondary bacterial infection develops. Small ulcers may self heal or progress to chronic, nonhealing lesions over a period of months.
Multi-disciplinary research is providing insight into M. ulcerans evolution, genotypic variants, and pathogenesis, prompting improved control and treatment strategies. Since 1998, the World Health Organization (WHO), working closely with endemic countries, nongovernmental organizations, and universities, has highlighted the growing problem of BU and developed improved treatment and control programs. However, questions remain in the areas of transmission, vectors, and how to improve diagnostic techniques and therapy.
The CDC provides useful information about BU, as does the WHO. A confirmed or highly suspected case in a new region should be reported to WHO.
A31.1 – Cutaneous mycobacterial infection
15845006 – Buruli ulcer