PDF(Pubmed)
Abstract：
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.
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.
摘要：
抗疟药耐药性正在东南亚部分地区迅速蔓延，双氢青蒿素-哌喹被用作恶性疟原虫疟疾的一线治疗方法。2013年，柬埔寨西部首次发布了有关抗疟药耐药性的报告。这里,我们分析了这些报告之前6年柬埔寨西部恶性疟原虫种群的遗传变化。
我们分析了来自东南亚11个地点的1492个恶性疟原虫样本的基因组序列数据，包括2007年至2013年在柬埔寨西部收集的464个样本。通过对kelch13青蒿素抗性基因座和plasmepsin2-3哌喹抗性基因座的单倍型分析，确定了抗性的不同流行病学起源。
我们确定了30多个独立的青蒿素抗性来源，其中KEL1谱系占对双氢青蒿素-哌喹耐药的154种寄生虫中的140种（91％）。2008年，KEL1与PLA1结合，这是与哌喹抗性相关的主要谱系。到2013年，KEL1/PLA1共同谱系在柬埔寨西部达到63％（24/38）的频率，并已扩散到柬埔寨北部。
KEL1/PLA1共同谱系出现在同年，双氢青蒿素-哌喹成为柬埔寨西部的一线抗疟药，此后迅速传播，取代其他抗青蒿素的寄生虫谱系。这些发现对于管理与当前东南亚多药耐药疟疾爆发相关的全球健康风险具有重要意义。
惠康信托基金,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的校内研究计划。
我们分析了来自东南亚11个地点的1492个恶性疟原虫样本的基因组序列数据，包括2007年至2013年在柬埔寨西部收集的464个样本。通过对kelch13青蒿素抗性基因座和plasmepsin2-3哌喹抗性基因座的单倍型分析，确定了抗性的不同流行病学起源。
我们确定了30多个独立的青蒿素抗性来源，其中KEL1谱系占对双氢青蒿素-哌喹耐药的154种寄生虫中的140种（91％）。2008年，KEL1与PLA1结合，这是与哌喹抗性相关的主要谱系。到2013年，KEL1/PLA1共同谱系在柬埔寨西部达到63％（24/38）的频率，并已扩散到柬埔寨北部。
KEL1/PLA1共同谱系出现在同年，双氢青蒿素-哌喹成为柬埔寨西部的一线抗疟药，此后迅速传播，取代其他抗青蒿素的寄生虫谱系。这些发现对于管理与当前东南亚多药耐药疟疾爆发相关的全球健康风险具有重要意义。
惠康信托基金,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的校内研究计划。
