Efforts to control the spread of Buruli ulcer – an emerging ulcerative skin infection caused by Mycobacterium ulcerans - have been hampered by our poor understanding of reservoirs and transmission. To help address this issue, we compared whole genomes from 18 clinical M. ulcerans isolates from a 30km2 region within the Asante Akim North District, Ashanti region, Ghana, with 15 other M. ulcerans isolates from elsewhere in Ghana and the surrounding countries of Ivory Coast, Togo, Benin and Nigeria. Contrary to our expectations of finding minor DNA sequence variations among isolates representing a single M. ulcerans circulating genotype, we found instead two distinct genotypes. One genotype was closely related to isolates from neighbouring regions of Amansie West and Densu, consistent with the predicted local endemic clone, but the second genotype (separated by 138 single nucleotide polymorphisms [SNPs] from other Ghanaian strains) most closely matched M. ulcerans from Nigeria, suggesting another introduction of M. ulcerans to Ghana, perhaps from that country. Both the exotic genotype and the local Ghanaian genotype displayed highly restricted intra-strain genetic variation, with less than 50 SNP differences across a 5.2Mbp core genome within each genotype. Interestingly, there was no discernible spatial clustering of genotypes at the local village scale. Interviews revealed no obvious epidemiological links among BU patients who had been infected with identical M. ulcerans genotypes but lived in geographically separate villages. We conclude that M. ulcerans is spread widely across the region, with multiple genotypes present in any one area. These data give us new perspectives on the behaviour of possible reservoirs and subsequent transmission mechanisms of M. ulcerans. These observations also show for the first time that M. ulcerans can be mobilized, introduced to a new area and then spread within a population. Potential reservoirs of M. ulcerans thus might include humans, or perhaps M. ulcerans-infected animals such as livestock that move regularly between countries.

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Whole genome comparisons suggest random distribution of Mycobacterium ulcerans genotypes in a Buruli ulcer endemic region of Ghana.

Efforts to control the spread of Buruli ulcer – an emerging ulcerative skin infection caused byMycobacterium ulcerans have been hampered by our poor understanding of reservoirs and transmission. To help address this issue, we compared whole genomes from 18 clinical M. ulcerans isolates from a 30km region within the Asante Akim North District, Ashanti region, Ghana, with 15 otherM. ulcerans isolates from elsewhere in Ghana and the surrounding countries of Ivory Coast, Togo, Benin and Nigeria. Contrary to our expectations of finding minor DNA sequence variations among isolates representing a singleM. ulcerans circulating genotype, we found instead two distinct genotypes. One genotype was closely related to isolates from neighbouring regions of Amansie West and Densu, consistent with the predicted local endemic clone, but the second genotype (separated by 138 single nucleotide polymorphisms [SNPs] from other Ghanaian strains) most closely matchedM. ulcerans from Nigeria, suggesting another introduction ofM. ulcerans to Ghana, perhaps from that country. Both the exotic genotype and the local Ghanaian genotype displayed highly restricted intra-strain genetic variation, with less than 50 SNP differences across a 5.2Mbp core genome within each genotype. Interestingly, there was no discernible spatial clustering of genotypes at the local village scale. Interviews revealed no obvious epidemiological links among BU patients who had been infected with identicalM. ulcerans genotypes but lived in geographically separate villages. We conclude thatM. ulcerans is spread widely across the region, with multiple genotypes present in any one area. These data give us new perspectives on the behaviour of possible reservoirs and subsequent transmission mechanisms of M. ulcerans. These observations also show for the first time thatM. ulcerans can be mobilized, introduced to a new area and then spread within a population. Potential reservoirs of PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd.0003681 March 31, 2015 1 / 14 a11111

/pdf/correction-to-whole-genome-comparisons-suggest-random-3inej9d72r.pdf

Correction to: Whole Genome Comparisons Suggest Random Distribution of Mycobacterium ulcerans Genotypes in a Buruli Ulcer Endemic Region of Ghana (PLoS Negl Trop Dis, 9, 5)

Buruli ulcer is an endemic severe human skin disease caused by Mycobacterium ulcerans, which prevails in western Africa in swampy areas and primarily hits children. Its gravity comes from the extent of tissue destruction, created by the toxin mycolactone. We describe here how the Centre Pasteur of Cameroon, with the help of the ministry of Health, gathered a network of multidisciplinary partners to fight against Buruli ulcer starting in the years 2000. The Centre Pasteur develops three missions : patient care, training of health care workers and research on the insect vector. Ten years of efforts resulted in significant medical advances such as the design of an early diagnostic test using PCR, or the observation that bed net use significantly decreased the risk of Buruli ulcer, offering useful prevention ; on the research side, entomological studies on aquatic bugs, coupled with epidemiological data, point to the role of these insects in the transmission of the disease. This study examplifies how an efficient network can contribute to the prevention and treatment of debilitating infectious diseases.

/pdf/l-ulcere-de-buruli-un-modele-de-recherche-transversale-3n88hrie82.pdf

Sara Eyangoh

Papers

L’ulcère de Buruli – Un modèle de recherche transversale dynamique au sein du réseau des Instituts Pasteur