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. 2013 Mar:14:361-8.
doi: 10.1016/j.meegid.201212009. Epub 2013 Jan 4.

Molecular, ethno-spatial epidemiology of leprosy in China: novel insights for tracing leprosy in endemic and non endemic provinces

Affiliations

Molecular, ethno-spatial epidemiology of leprosy in China: novel insights for tracing leprosy in endemic and non endemic provinces

Xiaoman Weng et al. Infect Genet Evol. 2013 Mar.

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.

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Figures

Figure 1
Figure 1. The geographical origins of the leprosy patients in the molecular epidemiology investigations
A: An outline map of the provinces of China. Only the provinces where patients were identified for the study are labeled. Each patient is represented by a circle except in Yunnan and Guizhou where the single large circle represents all the patients. B: The geographical region, province names, abbreviations and number of patients are listed (Refer to Figure 5 for more detailed maps of Sichuan, Yunnan and Guizhou)
Figure 2
Figure 2. M. leprae strain type variation in China
A: A principal component analysis plot derived from VNTR mapping at 17 loci shows associations between geography and genotypes. The VNTR profiles of strains from different provinces separate into at least three subpopulations which are depicted within dotted lined circles (denoted as Ch1, Ch2 and Ch3) and a smaller group (Ch4) straddling Ch1 and Ch3. B: Association between VNTR derived population structure and SNP types. The same VNTR based PCA plot shown in panel A is labeled according to the SNP types of the individuals.
Figure 3
Figure 3. VNTR Allele distribution in M. leprae strains from different provinces
A: The principal component analysis score loading plot of the variation in M. leprae strain types shown in Figure 2A. Panels B–I show the same plot and individuals except that the color coding indicates different alleles per the legend shown at each of eight loci that contribute to the population structure. B: 18-8, C: 12-5, D: (GGT)5, E: (AC)9, F: (AC)8a, G: (AC)8b, H: (TA)10 and I: 6-3a (rpoT)
Figure 4
Figure 4. A maximum parsimony tree based on multilocus VNTR M. leprae strain typing
The individuals are labeled (per Supplementary Table 1). The SNP type 1 individuals were used as the outgroup. The individuals shown within dotted circles represent groupings and transmission clusters with known epidemiological links (also see Figure 2A). Empty and filled arrows show patients enrolled in Guangdong clinics whose M. leprae genotypes differ from the majority of Guangdong patients. The filled arrows represent patients with known migration history from other provinces while no information is available for patients represented by empty arrows. GD500 is a migrant from Jiangxi; the M. leprae genotype falls within Ch4 where other Jiangxi patients cluster.
Figure 5
Figure 5. The spatial distribution of the Sichuan, Yunnan and Guizhou patients
Prefecture and county level location are represented in panels A–C. A: Sichuan, B: Yunnan, C: Guizhou. The western counties of Garze and Ngawa have been designated by as ‘Sichuan-Tibet’in this report. The web sources for the maps and legend for the prefectures are

  1. http://en.wikipedia.org/wiki/File:Sichuan_prfc_map.png

  2. http://en.wikipedia.org/wiki/File:Yunnan_prfc_map.png

  3. http://en.wikipedia.org/wiki/File:Guizhou_prfc_map.png

The relative size of the provinces is approximately to scale. Numbers embedded in the maps refer to specific prefectures per the key in the above referenced maps. D: A township level localization of Guizhou patients (the ID numbers per Supplementary Table 1) is shown in a map created with Google Maps application ((https://maps.google.com/maps?hl=en.). The placemarks were centered according to the latitude and longitude of the township. The superscripts placed after some of the individuals indicate distinct shared VNTR patterns. The geographical proximities of patients (within a range of 10–15 miles or less) with shared M. leprae VNTR genotypes (see Supplementary Table 1) suggests the presence of previously unknown transmission clusters. The arrow points to the town of BaJieZhen.

References

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WEB REFERENCES

Leprosy statistics:
    1. http://www.who.int/lep/situation/new_cases/en/index.html.

    1. http://www.who.int/wer/2011/wer8636.pdf: Weekly epidemiological record. 2011.

      Leprosy update, 36, 2011, 86, 389–400.

Maps:
    1. http://en.wikipedia.org/wiki/File:Sichuan_prfc_map.png.
    1. http://en.wikipedia.org/wiki/File:Yunnan_prfc_map.png.
    1. http://en.wikipedia.org/wiki/File:Guizhou_prfc_map.png.
    1. http://www.china.org.cn/english/features/zhenhe/132334.htm.

    1. http://en.wikipedia.org/wiki/File:Transasia_trade_routes_1stC_CE_gr2.png

      This map linked to http://en.wikipedia.org/wiki/Silk_Road is entitled ‘The Silk Road in the 1st century’. The file history for the map has the following comment: The map depicts trading routes used around the 1st century CE centred on the Silk Road. The routes remain largely valid for the period 500 BCE to 500 CE. Geographical labels for regions are adapted from the Geography of Ptolemy (c. 150 CE), some trading centre names date from later (c. 400 CE). Relying on Ptolemy's names is wrong but neutral.

      The map has also been used here: https://wiki.eee.uci.edu/index.php/History_134C_%28Spring_2010%29

Maritime Silk Route:

    1. http://www.harrassowitz-verlag.de/dzo/artikel/201/003/3771_201.pdf?t=1272014903: Aspects of the Maritime Silk Road: From the Persian Gulf to the East China Sea Edited by Ralph Kauz

    1. http://www.npr.org/templates/story/story.php?storyId=128113397: The 'Other' Silk Road: China Peers Into Maritime Past by Anthony Kuhn:

    1. http://english.ningbo.gov.cn/col/col55/index.html: Information on Ningbo port, China

    1. http://english.ningbo.gov.cn.

    1. Homepage →Discovering Ningbo→About the City→Overview

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