Artemisinin Resistance-Associated K13 Polymorphisms of Plasmodium falciparum in Southern Rwanda, 2010-2015

Artemisinin Resistance-Associated K13 Polymorphisms of Plasmodium falciparum in Southern Rwanda, 2010-2015
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DOI:
10.4269/ajtmh.16-0483
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发表时间:
2016-11-01
影响因子:
3.3
通讯作者:
Mockenhaupt, Frank P.
Mockenhaupt, Frank P.
中科院分区:
医学4区
文献类型:
--
作者:
Tacoli, Costanza;Gai, Prabhanjan P.;Mockenhaupt, Frank P.

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新出现的青蒿素耐药性对全球疟疾控制构成威胁。恶性疟原虫Kelch 13(K13)推进器结构域的突变赋予青蒿素抗性,并构成其检测和监测的分子标记。我们对2010年、2014年和2015年从卢旺达南部Huye区社区儿童中获得的222株恶性疟原虫分离株进行了测序,以调查K13多态性的存在。在2010年没有观察到多态性,但在2014年和2015年分别有2.5%和4.5%。2015年,两个分离株显示出候选K13耐药突变(P574L和A675V),这在东南亚很常见,与寄生虫清除延迟有关。K13多态性在卢旺达南部并不常见,但包括与青蒿素耐药性相关的变异。除了进一步监测研究区域的K13多态性外,还需要建立与局部治疗反应和体外耐药测定的相关性。
Emerging artemisinin resistance is a threat to global malaria control. Mutations in the Plasmodium falciparum Kelch 13 (K13) propeller domain confer artemisinin resistance and constitute molecular markers for its detection and monitoring. We sequenced 222 P. falciparum isolates obtained from community children in the Huye District of southern Rwanda in 2010, 2014, and 2015 to investigate the presence of K13 polymorphisms. No polymorphisms were observed in 2010 but they were present in 2.5% and 4.5% in 2014 and 2015, respectively. In 2015, two isolates showed candidate K13 resistance mutations (P574L and A675V), which are common in southeast Asia and associated with delayed parasite clearance. K13 polymorphisms in southern Rwanda are infrequent but include variants associated with artemisinin resistance. Establishing correlations with local treatment response and in vitro resistance assays are needed in addition to further monitoring K13 polymorphisms in the study area.