Selection and spread of artemisinin-resistant alleles in Thailand prior to the global artemisinin resistance containment campaign.
Selection and spread of artemisinin-resistant alleles in Thailand prior to the global artemisinin resistance containment campaign.
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DOI：
10.1371/journal.ppat.1004789
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发表时间：
2015-04
期刊：
影响因子：
6.7
通讯作者：
Udhayakumar V
中科院分区：
文献类型：
--
作者：
Talundzic E;Okoth SA;Congpuong K;Plucinski MM;Morton L;Goldman IF;Kachur PS;Wongsrichanalai C;Satimai W;Barnwell JW;Udhayakumar V
最近大湄公河次区域出现的青蒿素耐药性对全球控制疟疾的努力构成了重大威胁。追踪青蒿素抗药性寄生虫的传播和进化对于帮助遏制抗药性的传播至关重要。 2007 年泰国十个府的疟疾监测研究期间收集的总共 417 名患者样本，被用于青蒿素耐药性候选恶性疟原虫分子标记 K13 的基因分型。检查寄生虫基因型是否与青蒿素抗性相关的 K13 螺旋桨突变、正选择的特征，以及青蒿素抗性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。最常见的青蒿素耐药性相关 K13 突变 C580Y 携带两种不同的单倍型特征，这两种单倍型特征根据地理分布（沿泰国-柬埔寨和泰国-缅甸边境）分开。看来这两种单倍型可能具有独立的进化起源。总之，在该地区实施青蒿素抗药性遏制项目之前，与青蒿素抗药性相关的具有 K13 螺旋桨突变的寄生虫在泰国-柬埔寨和泰缅边境广泛存在。引起疟疾的恶性疟原虫正在对我们最有效、最有效的抗疟疾药物青蒿素产生耐药性。目前，柬埔寨、泰国、缅甸、越南等大湄公河次区域多个国家正在出现青蒿素耐药性。从历史上看，泰国和柬埔寨边境地区一直是多种抗疟疾药物耐药的中心。为了防止青蒿素抗性寄生虫从大湄公河次区域传播，全球青蒿素抗性项目于2009年启动。在这里，我们发现早在2007年，青蒿素抗性相关的K13基因突变就在泰国各地广泛存在，主要是泰国-柬埔寨和泰缅边境地区。基于微卫星标记的附加数据表明，最常见的 K13 C580Y 等位基因可能有两个最近独立的起源于泰国，位于柬埔寨和缅甸边境。
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. The Plasmodium falciparum parasites that cause malaria are evolving resistance to our most effective and potent anti-malarial drugs available, called artemisinins. Currently, artemisinin resistance is emerging in a number of countries in the Greater Mekong Subregion, including Cambodia, Thailand, Myanmar, and Vietnam. Historically, the Thai-Cambodia border region has been an epicenter of resistance to several anti-malarial drugs. To prevent the spread of artemisinin resistant parasites from the Greater Mekong Subregion, a global artemisinin resistance project was initiated in 2009. Here, we show that artemisinin resistance associated mutation in the K13 gene were widely present throughout Thailand, as early as 2007, primarily along the Thai-Cambodia and Thai-Myanmar border regions. Additional data based on microsatellite markers suggests that the most commonly found K13 C580Y allele may have two recent independent origins in Thailand, on the borders of Cambodia and Myanmar.
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影响因子：
15.8
作者：
Carrara VI;Lwin KM;Phyo AP;Ashley E;Wiladphaingern J;Sriprawat K;Rijken M;Boel M;McGready R;Proux S;Chu C;Singhasivanon P;White N;Nosten F
通讯作者：
Nosten F
影响因子：
3
作者：
Pumpaibool T;Arnathau C;Durand P;Kanchanakhan N;Siripoon N;Suegorn A;Sitthi-Amorn C;Renaud F;Harnyuttanakorn P
通讯作者：
Harnyuttanakorn P
影响因子：
6.4
作者：
Alam, Md Tauqeer;de Souza, Dziedzom K.;Koram, Kwadwo A.
通讯作者：
Koram, Kwadwo A.
DOI：
10.4269/ajtmh.2007.76.641
发表时间：
2007-04-01
影响因子：
3.3
作者：
Alker, Alisa P.;Lim, Pharath;Meshnick, Steven R.
通讯作者：
Meshnick, Steven R.
影响因子：
4.9
作者：
Alam, Md Tauqeer;Vinayak, Sumiti;Udhayakumar, Venkatachalam
通讯作者：
Udhayakumar, Venkatachalam