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Buruli ulcer (BU) is a slowly progressive necrotizing infection of the skin and soft tissue caused by Mycobacterium ulcerans.1,2 It is the third most common mycobacterial infection in otherwise healthy humans worldwide, after tuberculosis and leprosy. BU is prevalent in defined endemic regions across 33 countries, and is 1 of 19 neglected tropical diseases identified by WHO based on its morbidity and socioeconomic burden in developing countries.3
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Sir Albert Cook, a medical missionary in Uganda, had described large ulcers with undermined edges of unknown cause on the African continent as early as 1897. The first case series of six Australian patients was published in 1948 by MacCallum et al., who identified the pathogen as a strongly acid fast mycobacterium which could only be cultured at temperatures below 37ºC, and thus represented a separate entity from Mycobacterium tuberculosis.4 The name BU originated from the region of Uganda where the disease was endemic in the 1960s, but is now no longer prevalent.5 In the 1980s, the main foci of infection on the African continent shifted to Western Africa, where the majority of cases are still seen today.
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From recent genetic studies, it is evident that M. ulcerans has evolved from a Mycobacterium marinum progenitor. However, the acquisition of the virulence plasmid pMUM distinguishes M. ulcerans from closely related M. marinum. pMUM encodes an enzyme which produces the toxin mycolactone, which mediates surrounding tissue necrosis and inhibits the host immune response,6 by inhibiting molecular translocation in the host cell’s endoplasmic reticulum and the subsequent the production of inflammatory cytokines including TNF, IL-6, and Cox-2.7
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The ancestral lineage causes sporadic disease in Asia and the Americas whereas the classical lineage causes focal pockets of endemic high-burden disease in Africa and Australia. Isolates of classical lineage are closely related but can be distinguished by a small group of single nucleotide polymorphisms (SNPs). These SNPs have allowed microbial geneticists to track the historical spread of the classical lineage of M. ulcerans. It has been hypothesized that the M. ulcerans originally arrived on the Australian continent relatively recently from Papua New Guinea.8 The genetic trail leads in a series of steps down the Australian east coast all the way to temperate Victoria, which is now experiencing major new outbreaks of human BU. The pattern or isolate relatedness now being uncovered through whole genome sequencing suggest that M. ulcerans appears to be introduced by some chance event and expands rapidly rather than being widely dispersed and subsequently amplified.
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M. ulcerans is a slowly replicating mycobacterium that grows optimally at 30–32°C, which may lead it to prefer cooler parts of the body, such as the distal limbs. Alternatively, lesion distribution may reflect environmental contact; although lesions can occur anywhere on the body, they are most common on exposed skin.9,10 The key ...