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 M. 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.

The genome sequence of a SNP type 3K strain of Mycobacterium leprae isolated from a seventh‐century Hungarian case of lepromatous leprosy

“…The presence of only three copies of GACATC in the rpoT tandem repeat distinguishes KD271, as well as S9 and S10, all of which have earlier branch points, from the modern isolates from Japan, Korea, and parts of China that result from an apparently recent radiation of 3K0 strains, and all contain four copies of the hexanucleotide (Kai et al, ; Weng et al, ).…”

“…The presence of 3K0 strains in seventh‐century Hungarian remains and of a 3K strain from the 10th centrury is consistent with two contrasting scenarios for the origins of geographical distibution of 3K M. leprae strains. The global distribution of 3K0 and 3K1 strains is today restricted to regions of the Western Pacific such as Japan (except Okinawa), Korea, China, The Philippines, New Caledonia and Indonesia, among others (Avanzi et al, ; Honap et al, ; Kai et al, ; Monot et al, ; Weng et al, ). This could indicate that the 3K lineage originated in Northern or Eastern Asia.…”

Perfil epidemiológico da hanseníase em um município do nordeste brasileiro: Uma análise retrospectiva Epidemiological profile of leprosy in a municipality in the Brazilian Northeast: a retrospective analysis

“…Case detection rates and delay in diagnosis are dependent on several factors, such as age, occupation, nationality, endemicity, type of leprosy and method of detection. 8 When analyzing the general detection coefficient of leprosy in the study period, there was a decline in the detection rate of new cases infection, from 56.5 to 35.6 cases per 100,000 inhabitants, with increasing oscillations. It is conjectured that these oscillations in the detection rate occurred due to the campaigns operated by the health services of the municipality, in order to develop actions to control the disease.…”

Metagenomics of Imported Multidrug-Resistant Mycobacterium leprae, Saudi Arabia, 2017

“…The predominant genotypes of M. leprae strains in the Middle East are subtypes 2 and 3 (7). Most 3K cases are found in countries of East Asia, such as China (8), Japan (9), Korea (2), and the Philippines (8). In addition, >37% of the leprosy cases in Saudi Arabia occur in persons from other countries (1).…”