The spread of artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion: a molecular epidemiology observational study.
The spread of artemisinin-resistant Plasmodium falciparum in the Greater Mekong subregion: a molecular epidemiology observational study.
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DOI：
10.1016/s1473-3099(17)30048-8
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发表时间：
2017-05
期刊：
影响因子：
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通讯作者：
Dondorp AM
中科院分区：
文献类型：
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作者：
Imwong M;Suwannasin K;Kunasol C;Sutawong K;Mayxay M;Rekol H;Smithuis FM;Hlaing TM;Tun KM;van der Pluijm RW;Tripura R;Miotto O;Menard D;Dhorda M;Day NPJ;White NJ;Dondorp AM
有证据表明，在恶性疟疾中赋予青蒿素耐药性的PfKelch 13突变在大湄公河次区域有多个独立的起源，这促使制定了区域消除疟疾议程。我们的目的是使用分子基因分型来评估抗疟药物耐药性的选择和传播在大湄公河次区域。在这项观察性研究中，我们检测了来自缅甸、泰国东北部、老挝南部和柬埔寨西部的恶性疟原虫分离株的PfKelch 13突变和Pfplasmepsin 2基因扩增（表明哌喹耐药性）。我们收集了经显微镜或快速检测证实为无并发症的恶性疟患者的血斑。我们使用微卫星基因分型来评估遗传相关性。作为2008年1月1日至2015年12月31日期间青蒿素耐药疟疾流行病学研究的一部分，我们收集了434个分离株。在2014-15年，一个单一的长PfKelch 13 C580 Y单倍型（−50至+31 statis 5 kb）谱系，2008年出现在柬埔寨西部，在泰国东北部的88个分离株中有65个，老挝南部的111个分离株中有86个，柬埔寨西部的14个分离株中有14个，这意味着一个硬跨国选择性扫描。Pfplasmepsin 2扩增仅发生在该谱系内，到2015年，这些密切相关的寄生虫在柬埔寨的14个分离株中的10个和泰国东北部的15个分离株中发现。来自缅甸的C580 Y突变寄生虫具有不同的遗传起源。我们的研究结果表明，占主导地位的青蒿素耐药恶性疟原虫C580 Y谱系可能出现在柬埔寨西部，然后蔓延到泰国和老挝，竞争其他寄生虫和获得哌喹耐药性。合适的青蒿素耐药性恶性疟原虫谱系的出现和传播，然后在大湄公河次区域获得伙伴抗药性，威胁到区域疟疾控制和消除目标。在现有的抗疟药物仍然有效的情况下，应加速在该区域消灭恶性疟疾。威康信托基金会和比尔及梅林达·盖茨基金会。
Evidence suggests that the PfKelch13 mutations that confer artemisinin resistance in falciparum malaria have multiple independent origins across the Greater Mekong subregion, which has motivated a regional malaria elimination agenda. We aimed to use molecular genotyping to assess antimalarial drug resistance selection and spread in the Greater Mekong subregion. In this observational study, we tested Plasmodium falciparum isolates from Myanmar, northeastern Thailand, southern Laos, and western Cambodia for PfKelch13 mutations and for Pfplasmepsin2 gene amplification (indicating piperaquine resistance). We collected blood spots from patients with microscopy or rapid test confirmed uncomplicated falciparum malaria. We used microsatellite genotyping to assess genetic relatedness. As part of studies on the epidemiology of artemisinin-resistant malaria between Jan 1, 2008, and Dec 31, 2015, we collected 434 isolates. In 2014–15, a single long PfKelch13 C580Y haplotype (−50 to +31·5 kb) lineage, which emerged in western Cambodia in 2008, was detected in 65 of 88 isolates from northeastern Thailand, 86 of 111 isolates from southern Laos, and 14 of 14 isolates from western Cambodia, signifying a hard transnational selective sweep. Pfplasmepsin2 amplification occurred only within this lineage, and by 2015 these closely related parasites were found in ten of the 14 isolates from Cambodia and 15 of 15 isolates from northeastern Thailand. C580Y mutated parasites from Myanmar had a different genetic origin. Our results suggest that the dominant artemisinin-resistant P falciparum C580Y lineage probably arose in western Cambodia and then spread to Thailand and Laos, outcompeting other parasites and acquiring piperaquine resistance. The emergence and spread of fit artemisinin-resistant P falciparum parasite lineages, which then acquire partner drug resistance across the Greater Mekong subregion, threatens regional malaria control and elimination goals. Elimination of falciparum malaria from this region should be accelerated while available antimalarial drugs still remain effective. The Wellcome Trust and the Bill and Melinda Gates Foundation.