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在全球青蒿素抗药遏制行动之前泰国青蒿素抗药等位基因的选择与传播。

Selection and spread of artemisinin-resistant alleles in Thailand prior to the global artemisinin resistance containment campaign.

作者信息

Talundzic Eldin, Okoth Sheila Akinyi, Congpuong Kanungnit, Plucinski Mateusz M, Morton Lindsay, Goldman Ira F, Kachur Patrick S, Wongsrichanalai Chansuda, Satimai Wichai, Barnwell John W, Udhayakumar Venkatachalam

机构信息

Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America; Atlanta Research and Education Foundation, Atlanta VA Medical Center, Atlanta, Georgia, United States of America.

Atlanta Research and Education Foundation, Atlanta VA Medical Center, Atlanta, Georgia, United States of America.

出版信息

PLoS Pathog. 2015 Apr 2;11(4):e1004789. doi: 10.1371/journal.ppat.1004789. eCollection 2015 Apr.

DOI:10.1371/journal.ppat.1004789
PMID:25836766
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4383523/
Abstract

The recent emergence of artemisinin resistance in the Greater Mekong Subregion poses a major threat to the global effort to control malaria. Tracking the spread and evolution of artemisinin-resistant parasites is critical in aiding efforts to contain the spread of resistance. A total of 417 patient samples from the year 2007, collected during malaria surveillance studies across ten provinces in Thailand, were genotyped for the candidate Plasmodium falciparum molecular marker of artemisinin resistance K13. Parasite genotypes were examined for K13 propeller mutations associated with artemisinin resistance, signatures of positive selection, and for evidence of whether artemisinin-resistant alleles arose independently across Thailand. A total of seven K13 mutant alleles were found (N458Y, R539T, E556D, P574L, R575K, C580Y, S621F). Notably, the R575K and S621F mutations have previously not been reported in Thailand. The most prevalent artemisinin resistance-associated K13 mutation, C580Y, carried two distinct haplotype profiles that were separated based on geography, along the Thai-Cambodia and Thai-Myanmar borders. It appears these two haplotypes may have independent evolutionary origins. In summary, parasites with K13 propeller mutations associated with artemisinin resistance were widely present along the Thai-Cambodia and Thai-Myanmar borders prior to the implementation of the artemisinin resistance containment project in the region.

摘要

近期在大湄公河次区域出现的青蒿素耐药性对全球疟疾防控工作构成了重大威胁。追踪青蒿素耐药寄生虫的传播和演变对于遏制耐药性传播的努力至关重要。2007年在泰国十个省份进行疟疾监测研究期间收集的417份患者样本,针对青蒿素耐药性的候选恶性疟原虫分子标记K13进行了基因分型。检查寄生虫基因型中与青蒿素耐药性相关的K13螺旋桨突变、正选择特征,以及青蒿素耐药等位基因是否在泰国各地独立出现的证据。总共发现了七个K13突变等位基因(N458Y、R539T、E556D、P574L、R575K、C580Y、S621F)。值得注意的是,R575K和S621F突变此前在泰国尚未有报道。最常见的与青蒿素耐药性相关的K13突变C580Y,携带两种不同的单倍型谱,根据地理位置在泰国与柬埔寨和泰国与缅甸边境沿线分开。看来这两种单倍型可能有独立的进化起源。总之,在该地区实施青蒿素耐药性遏制项目之前,与青蒿素耐药性相关的K13螺旋桨突变寄生虫在泰国与柬埔寨和泰国与缅甸边境广泛存在。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/873e/4383523/2461b4ed392d/ppat.1004789.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/873e/4383523/6dc14657ebf9/ppat.1004789.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/873e/4383523/7a5f60467841/ppat.1004789.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/873e/4383523/09e7f8507d94/ppat.1004789.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/873e/4383523/c6d951976d83/ppat.1004789.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/873e/4383523/2461b4ed392d/ppat.1004789.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/873e/4383523/6dc14657ebf9/ppat.1004789.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/873e/4383523/7a5f60467841/ppat.1004789.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/873e/4383523/09e7f8507d94/ppat.1004789.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/873e/4383523/c6d951976d83/ppat.1004789.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/873e/4383523/2461b4ed392d/ppat.1004789.g005.jpg

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