02680nas a2200313 4500000000100000008004100001260001300042653003200055653002100087653002300108653001300131653001100144653001000155653001200165653002600177653002700203653002500230653001600255653001400271653002600285100001100311700001700322245009900339856007300438300001400511490000700525520182000532022001402352 2010 d c2010 Jun10aBacterial Typing Techniques10aCluster Analysis10aDNA Fingerprinting10agenotype10aHumans10aIndia10aleprosy10aMinisatellite Repeats10aMolecular Epidemiology10aMycobacterium leprae10aPhilippines10aPhylogeny10aPolymorphism, Genetic1 aHall B1 aSalipante SJ00aMolecular epidemiology of Mycobacterium leprae as determined by structure-neighbor clustering. uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884520/pdf/0149-10.pdf a1997-20080 v483 a
It has proven challenging to investigate the molecular epidemiology of Mycobacterium leprae, the causative agent of leprosy, due to difficulties with culturing of the organism and a lack of genetic heterogeneity between strains. Recently, a cost-effective panel of variable-number tandem-repeat (VNTR) markers has been developed. Use of this panel allows some of those limitations to be overcome and has allowed the genotyping of 475 M. leprae strains from six different countries. In the present report, we provide a comprehensive analysis of the relationships among the strains in order to investigate the patterns of transmission and migration of M. leprae. We find phylogenetic analysis to be inadequate and have developed an alternative method, structure-neighbor clustering, which assigns isolates with the most similar genotypes to the same groups and, subsequently, subgroups, without inferring how the strains descended from a common ancestor. We validate the approach by using simulated data and detecting expected epidemiological relationships from experimental data. Our results suggest that most M. leprae strains from a given country cluster together and that the occasional isolates assigned to different clusters are a consequence of migration. We found three genetically distinguishable populations among isolates from the Philippines, as well as evidence for the significant influx of strains to that nation from India. We also report that reference strain TN originated from the Philippines and not from India, as was previously believed. Lastly, analysis of isolates from the same families and villages suggests that most community infections originate from a common source or person-to-person transmission but that infection from independent sources does occur with measurable frequency.
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