Origins of the current outbreak of multidrug-resistant malaria in southeast Asia: a retrospective genetic study.
Origins of the current outbreak of multidrug-resistant malaria in southeast Asia: a retrospective genetic study.
复制标题
DOI：
10.1016/s1473-3099(18)30068-9
复制
发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Kwiatkowski DP
中科院分区：
文献类型：
--
作者：
Amato R;Pearson RD;Almagro-Garcia J;Amaratunga C;Lim P;Suon S;Sreng S;Drury E;Stalker J;Miotto O;Fairhurst RM;Kwiatkowski DP
抗疟药耐药性正在东南亚部分地区迅速蔓延，在这些地区，双氢青蒿素-哌喹被用作恶性疟原虫疟疾的一线治疗药物。2013年，第一批关于抗疟药物耐药性的报告来自柬埔寨西部。在这里，我们分析了在这些报告之前的6年，在柬埔寨西部的恶性疟原虫人口的遗传变化。我们分析了来自东南亚11个地点的1492份恶性疟原虫样本的基因组序列数据，其中包括2007年至2013年在柬埔寨西部收集的464份样本。通过kelch 13青蒿素抗性位点和plasmepsin 2-3哌喹抗性位点的单倍型分析，鉴定了不同的流行病学抗性起源。我们确定了30多个独立的青蒿素耐药起源，其中KEL 1谱系占154个对双氢青蒿素-哌喹耐药的寄生虫中的140个（91%）。2008年，KEL 1与PLA 1结合，PLA 1是与哌喹耐药性相关的主要谱系。到2013年，KEL 1/PLA 1共谱系在柬埔寨西部的频率达到63%（24/38），并已传播到柬埔寨北方。KEL 1/PLA 1共谱系出现的同一年，双氢青蒿素-哌喹成为柬埔寨西部的一线抗疟药物，此后迅速传播，取代了其他青蒿素耐药寄生虫谱系。这些发现对管理与东南亚目前爆发的耐多药疟疾相关的全球健康风险具有重要意义。惠康信托基金会、比尔和梅林达盖茨基金会、医学研究理事会、英国国际发展部和国家过敏和传染病研究所校内研究计划。
Antimalarial resistance is rapidly spreading across parts of southeast Asia where dihydroartemisinin–piperaquine is used as first-line treatment for Plasmodium falciparum malaria. The first published reports about resistance to antimalarial drugs came from western Cambodia in 2013. Here, we analyse genetic changes in the P falciparum population of western Cambodia in the 6 years before those reports. We analysed genome sequence data on 1492 P falciparum samples from 11 locations across southeast Asia, including 464 samples collected in western Cambodia between 2007 and 2013. Different epidemiological origins of resistance were identified by haplotypic analysis of the kelch13 artemisinin resistance locus and the plasmepsin 2–3 piperaquine resistance locus. We identified more than 30 independent origins of artemisinin resistance, of which the KEL1 lineage accounted for 140 (91%) of 154 parasites resistant to dihydroartemisinin–piperaquine. In 2008, KEL1 combined with PLA1, the major lineage associated with piperaquine resistance. By 2013, the KEL1/PLA1 co-lineage had reached a frequency of 63% (24/38) in western Cambodia and had spread to northern Cambodia. The KEL1/PLA1 co-lineage emerged in the same year that dihydroartemisinin–piperaquine became the first-line antimalarial drug in western Cambodia and spread rapidly thereafter, displacing other artemisinin-resistant parasite lineages. These findings have important implications for management of the global health risk associated with the current outbreak of multidrug-resistant malaria in southeast Asia. Wellcome Trust, Bill & Melinda Gates Foundation, Medical Research Council, UK Department for International Development, and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases.