Genomic Characterization of Recrudescent Plasmodium malariae after Treatment with Artemether/Lumefantrine

Genomic Characterization of Recrudescent Plasmodium malariae after Treatment with Artemether/Lumefantrine
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DOI:
10.3201/eid2308.161582
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发表时间:
2017-08-01
影响因子:
11.8
通讯作者:
Price, Ric N.
Price, Ric N.
中科院分区:
医学2区
文献类型:
--
作者:
Rutledge, Gavin G.;Marr, Ian;Price, Ric N.

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三日疟原虫是唯一一种红细胞内周期为72小时并能够在宿主体内终生存在的人类疟疾寄生虫。我们提出了一个病例的三日疟原虫感染与临床复发后,直接观察管理蒿甲醚/苯芴醇。通过使用全基因组测序,我们表明,初始感染是多克隆的,复发分离物是一个单一的克隆,在初始感染中以低密度存在。在初始感染的克隆的单倍型分析表明,它们都是密切相关的,并推测是重组后代来自同一感染性蚊子叮咬。我们回顾了三日疟原虫治疗失败的可能解释,并得出结论,为期3天的蒿甲醚/苯芴醇方案是次优的,因为它的无性生命周期长。
Plasmodium malariae is the only human malaria parasite species with a 72-hour intraerythrocytic cycle and the ability to persist in the host for life. We present a case of a P. malariae infection with clinical recrudescence after directly observed administration of artemether/lumefantrine. By using whole-genome sequencing, we show that the initial infection was polyclonal and the recrudescent isolate was a single clone present at low density in the initial infection. Haplotypic analysis of the clones in the initial infection revealed that they were all closely related and were presumably recombinant progeny originating from the same infective mosquito bite. We review possible explanations for the P. malariae treatment failure and conclude that a 3-day artemether/lumefantrine regimen is suboptimal for this species because of its long asexual life cycle.