In Vitro Sensitivities of Plasmodium falciparum Isolates from the China-Myanmar Border to Piperaquine and Association with Polymorphisms in Candidate Genes
In Vitro Sensitivities of Plasmodium falciparum Isolates from the China-Myanmar Border to Piperaquine and Association with Polymorphisms in Candidate Genes
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中缅边境恶性疟原虫对哌喹的体外敏感性及其与候选基因多态性的关联
DOI：
10.1128/aac.02306-12
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发表时间：
2013-04-01
影响因子：
4.9
通讯作者：
Cui, Liwang
中科院分区：
文献类型：
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作者：
Hao, Mingming;Jia, Dandan;Cui, Liwang
近年来恶性疟原虫对青蒿素衍生物及其伙伴药物产生耐药性的报道，需要深入研究，以了解耐药性的分子机制。本研究对采自中缅边境地区的63株恶性疟原虫进行了体外药敏试验。寄生虫分离株对CQ保持高度耐药，几何平均50%抑制浓度（IC 50）为252.7 nM，范围为51.9至1，052.0 nM。相比之下，这些寄生虫对PPQ的几何平均IC 50为28.4 nM，范围相当宽，为5.3 - 132.0 nM，表明某些寄生虫分离株对PPQ表现出相对较高的耐药性。有趣的是，在4年的研究中，寄生虫表现出对CQ和PPQ的敏感性持续下降，并且对CQ和PPQ的反应之间存在显著相关性（Pearson相关系数= 0.79，P < 0.0001）。与CQ耐药表型一致，所有寄生虫均携带pfcrt K76 T突变，大多数寄生虫具有东南亚流行的CVIET型。相比之下，pfmdr 1突变相对罕见，没有检测到基因扩增。只有pfmdr 1 N1042 D突变与CQ耐药相关。对于pfmrp 1基因，4个替换达到> 22%的相对高的流行率，并且I876 V突变与对CQ的敏感性降低相关。然而，我们不能建立PPQ反应和喹啉耐药相关的三个基因的多态性之间的联系。
The recent reports of resistance in Plasmodium falciparum to artemisinin derivatives and their partner drugs demand intensive studies toward understanding the molecular mechanisms of resistance. In this study, we examined the in vitro susceptibility of 63 P. falciparum field isolates collected from the China-Myanmar border area to chloroquine (CQ) and piperaquine (PPQ). Parasite isolates remained highly resistant to CQ, with the geometric mean 50% inhibitory concentration (IC50) of 252.7 nM and a range of 51.9 to 1,052.0 nM. In comparison, these parasites had a geometric mean IC50 of 28.4 nM for PPQ, with a fairly wide range of 5.3 to 132.0 nM, suggesting that certain parasite isolates displayed relatively high levels of resistance to PPQ. Interestingly, within the 4 years of study, the parasites exhibited a continuous decline in susceptibilities to both CQ and PPQ, and there was a significant correlation between responses to CQ and PPQ (Pearson correlation coefficient = 0.79, P < 0.0001). Consistent with the CQ-resistant phenotype, all parasites carried the pfcrt K76T mutation, and most parasites had the CVIET type that is prevalent in Southeast Asia. In contrast, pfmdr1 mutations were relatively rare, and no gene amplification was detected. Only the pfmdr1 N1042D mutation was associated with resistance to CQ. For the pfmrp1 gene, four substitutions reached relatively high prevalence of >22%, and the I876V mutation was associated with reduced sensitivity to CQ. However, we could not establish a link between PPQ responses and the polymorphisms in the three genes associated with quinoline drug resistance.