Plasmodium falciparum Drug Resistance in Madagascar: Facing the Spread of Unusual pfdhfr and pfmdr-1 Haplotypes and the Decrease of Dihydroartemisinin Susceptibility

Plasmodium falciparum Drug Resistance in Madagascar: Facing the Spread of Unusual pfdhfr and pfmdr-1 Haplotypes and the Decrease of Dihydroartemisinin Susceptibility
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DOI:
10.1128/aac.00610-09
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发表时间:
2009-11-01
影响因子:
4.9
通讯作者:
Menard, Didier
Menard, Didier
中科院分区:
医学2区
文献类型:
--
作者:
Andriantsoanirina, Valerie;Ratsimbasoa, Arsene;Menard, Didier

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本研究的目的是提供马达加斯加不同地理区域恶性疟原虫耐药性的第一张综合时空图。还收集了有关科摩罗群岛邻近岛屿抗疟疾耐药性的其他数据。我们评估了2006年至2008年在26个卫生中心(马达加斯加20个,科摩罗群岛6个)收集的1596株恶性疟原虫分离株中pfcrt、pfmdr-1、pfdhfr和pfdhps突变的流行率和pfmdr-1基因拷贝数。测定了373种寄生虫分离株对一组药物的体外反应。结果显示:(1)马达加斯加对氯喹的敏感性不同寻常;(2)同时携带pfdhfr和pfdhps突变的寄生虫的频率迅速上升;(3)单一pfdhfr 164L基因型的出现令人震惊;(4)对青蒿素衍生物最敏感的分离株逐渐丧失。在执行新的国家防治疟疾政策的背景下,今后需要继续进行监测,以发现恶性疟原虫耐药性。
The aim of this study was to provide the first comprehensive spatiotemporal picture of Plasmodium falciparum resistance in various geographic areas in Madagascar. Additional data about the antimalarial resistance in the neighboring islands of the Comoros archipelago were also collected. We assessed the prevalence of pfcrt, pfmdr-1, pfdhfr, and pfdhps mutations and the pfmdr-1 gene copy number in 1,596 P. falciparum isolates collected in 26 health centers (20 in Madagascar and 6 in the Comoros Islands) from 2006 to 2008. The in vitro responses to a panel of drugs by 373 of the parasite isolates were determined. The results showed (i) unusual profiles of chloroquine susceptibility in Madagascar, (ii) a rapid rise in the frequency of parasites with both the pfdhfr and the pfdhps mutations, (iii) the alarming emergence of the single pfdhfr 164L genotype, and (iv) the progressive loss of the most susceptible isolates to artemisinin derivatives. In the context of the implementation of the new national policy for the fight against malaria, continued surveillance for the detection of P. falciparum resistance in the future is required.