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Buruli ulcer is an indolent necrotizing disease of the skin, subcutaneous tissue, and bone that is caused by Mycobacterium ulcerans. Buruli ulcer is presently the third most common mycobacterial disease of humans, after tuberculosis and leprosy, and the least understood of the three. The disease remained largely ignored by many national public health programs, but more recently, it has been recognized as an emerging health problem, primarily due to its frequent disabling and stigmatizing complications. The contribution discusses various aspects of Buruli ulcer, including its geographic distribution, incidence, and prevalence; mode of transmission, pathogenesis, and immunity; clinical manifestations; laboratory diagnosis; differential clinical diagnosis; and treatment.

Buruli ulcer (BU) is a devastating, necrotizing, tropical skin disease caused by infections with Mycobacterium ulcerans. In contrast to other mycobacterioses, BU has been associated with minimal or absent inflammation. However, here we show that in the mouse M. ulcerans induces persistent inflammatory responses with virulence-dependent patterns. Mycolactone-positive, cytotoxic strains are virulent for mice and multiply progressively, inducing both early and persistent acute inflammatory responses. The cytotoxicity of these strains leads to progressive destruction of the inflammatory infiltrates by postapoptotic secondary necrosis, generating necrotic acellular areas with extracellular bacilli released by the lysis of infected phagocytes. The necrotic areas, always surrounded by acute inflammatory infiltrates, expand through the progressive invasion of healthy tissues around the initial necrotic lesions by bacteria and by newly recruited acute inflammatory cells. Our observations show that the lack of inflammatory infiltrates in the extensive areas of necrosis seen in advanced infections results from the destruction of continuously produced inflammatory infiltrates and not from M. ulcerans-induced local or systemic immunosuppression. Whether this is the mechanism behind the predominance of minimal or absent inflammatory responses in BU biopsies remains to be elucidated.Pathogenic mycobacteria are intracellular parasites that are responsible for several clinically important infections in humans and animals. The most frequent mycobacterial infections in humans are caused by Mycobacterium tuberculosis and M. leprae. However, a unique group of mycobacterioses has been emerging and comprises infections caused by M. marinum, M. hemophilum, and M. ulcerans (12). These are slow-growing mycobacteria with some genetic relatedness (71) and common peculiar characteristics. These mycobacteria have optimal growth temperatures of 28 to 33°C and infect primarily the cooler parts of the body, mainly the skin. They have cytotoxic activity (17,56,57) and, as a consequence, produce necrotizing lesions (3,7,12,72).Buruli ulcer (BU), caused by M. ulcerans, has become the third most prevalent mycobacteriosis throughout the world, after tuberculosis and leprosy, with higher incidence in the tropical regions of western and central Africa (11,74). BU is a devastating skin disease characterized by different clinical forms, including nonulcerative subcutaneous nodules, papules, edema, and plaques, that can eventually progress to ulcerative forms and often to extensive necrotic lesions (11, 74). Osteomyelitis has been described as a complication of M. ulcerans infection, particularly in some African regions (11,39).Genetic analyses showed that M. marinum and M. ulcerans are very closely related to M. tuberculosis (71), a mycobacterium that also exhibits some cytotoxicity (14,19,37,43), which contributes to the necrotic lesions seen in tuberculosis (43). Recently, genes in the extRD1 region have been implicated in the cytotoxic activity of M...

Hospital data show that Buruli ulcer is highly endemic in southern Benin.

Background Mycobacterium ulcerans disease, or Buruli ulcer (BU), is an indolent, necrotizing infection of skin, subcutaneous tissue and, occasionally, bones. It is the third most common human mycobacteriosis worldwide, after tuberculosis and leprosy. There is evidence that M. ulcerans is an environmental pathogen transmitted to humans from aquatic niches; however, well-characterized pure cultures of M. ulcerans from the environment have never been reported. Here we present details of the isolation and characterization of an M. ulcerans strain (00-1441) obtained from an aquatic Hemiptera (common name Water Strider, Gerris sp.) from Benin.Methodology/Principal FindingsOne culture from a homogenate of a Gerris sp. in BACTEC became positive for IS2404, an insertion sequence with more than 200 copies in M. ulcerans. A pure culture of M. ulcerans 00-1441 was obtained on Löwenstein-Jensen medium after inoculation of BACTEC culture in mouse footpads followed by two other mouse footpad passages. The phenotypic characteristics of 00-1441 were identical to those of African M. ulcerans, including production of mycolactone A/B. The nucleotide sequence of the 5′ end of 16S rRNA gene of 00-1441 was 100% identical to M. ulcerans and M. marinum, and the sequence of the 3′ end was identical to that of the African type except for a single nucleotide substitution at position 1317. This mutation in M. ulcerans was recently discovered in BU patients living in the same geographic area. Various genotyping methods confirmed that strain 00-1441 has a profile identical to that of the predominant African type. Strain 00-1441 produced severe progressive infection and disease in mouse footpads with involvement of bone.ConclusionStrain 00-1441 represents the first genetically and phenotypically identified strain of M. ulcerans isolated in pure culture from the environment. This isolation supports the concept that the agent of BU is a human pathogen with an environmental niche.