title: Molecular, ethno-spatial epidemiology of leprosy in China: novel insights for tracing leprosy in endemic and non endemic provinces.
abstract: Leprosy continues to be detected at near stable rates in China even with established control programs, necessitating new knowledge and alternative methods to interrupt transmission. A molecular epidemiology investigation of 190 patients was undertaken to define Mycobacterium leprae strain types and discern genetic relationships and clusters in endemic and non-endemic regions spanning seventeen provinces and two autonomous regions. The findings support multiple locus variable number of tandem repeat (VNTR) analysis as a useful tool in uncovering characteristic patterns across the multiethnic and divergent geographic landscape of China. Several scenarios of clustering of leprosy from township to provincial to regional levels were recognized, while recent occupational or remote migration showed geographical separation of certain strains. First, prior studies indicated that of the four major M. leprae subtypes defined by single nucleotide polymorphisms (SNPs), only type 3 was present in China, purportedly entering from Europe/West/Central Asia via the Silk Road. However, this study revealed VNTR linked strains that are of type 1 in Guangdong, Fujian and Guangxi in southern China. Second, a subset of VNTR distinguishable strains of type 3, co-exist in these provinces. Third, type 3 strains with rpoT VNTR allele of 4, detected in Japan and Korea were discovered in Jiangsu and Anhui in the east and in western Sichuan bordering Tibet. Fourth, considering the overall genetic diversity, strains of endemic counties of Qiubei, Yunnan; Xing Yi, Guizhou; and across Sichuan in southwest were related. However, closer inspection showed distinct local strains and clusters. Altogether, these insights, primarily derived from VNTR typing, reveal multiple and overlooked paths for spread of leprosy into, within and out of China and invoke attention to historic maritime routes in the South and East China Sea. More importantly, new concepts and approaches for prospective case finding and tracking of leprosy from county to national level have been introduced.
authors.affiliation: Beijing Friendship Hospital - Affiliate of Capital University of Medical Sciences, Beijing Tropical Medicine Research Institute, 95 Yang An Road, Beijing 100050, China.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Weng
authors.forename: Yan
authors.initials: Y
authors.lastname: Xing
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Ning
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wu
authors.forename: Lianhua
authors.initials: L
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Jason
authors.initials: J
authors.lastname: Vander Heiden
authors.forename: Varalakshmi
authors.initials: V
authors.lastname: Vissa
mesh_terms: D002681:China / Q000453:epidemiology; D016000:Cluster Analysis; D004269:DNA, Bacterial / Q000235:genetics; D062306:Geography, Medical; D006801:Humans; D007918:Leprosy / Q000453:epidemiology* / Q000635:transmission; D018598:Minisatellite Repeats / Q000235:genetics; D058889:Molecular Typing; D009166:Mycobacterium leprae / Q000145:classification / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D004269:DNA, Bacterial