Understanding genetic variation in in vivo tolerance to artesunate: implications for treatment efficacy and resistance monitoring.
Understanding genetic variation in in vivo tolerance to artesunate: implications for treatment efficacy and resistance monitoring.
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DOI：
10.1111/eva.12194
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发表时间：
2015-03
影响因子：
4.1
通讯作者：
Read AF
中科院分区：
文献类型：
--
作者：
Pollitt LC;Sim D;Salathé R;Read AF
以青蒿素为基础的药物是治疗人类疟疾病例的一线武器，但人们担心，最近关于感染缓慢清除的报告可能表明对治疗产生了抗药性。在缺乏耐药性分子标记的情况下，目前监测药物疗效的努力是基于寄生虫从感染中清除的速度。然而，需要对寄生虫易感性的长期变化有一些了解，才能确定感染半衰期有意义的增加。在这里，我们展示了五种以前未接触过的啮齿动物疟疾寄生虫查鲍迪疟原虫的基因类型在体内对治疗的反应有很大的不同。较慢的清除率与寄生虫的毒力或生长速度无关，这与药物治疗将推动该系统中的毒力进化的说法背道而驰。这里观察到的在相对较少的基因类型中观察到的变异水平表明，种群中可能存在现有的“抗药性”寄生虫，因此，寄生虫清除率的增加可能代表对先前存在的变异的选择，而不是从头开始的抗药性事件。这对耐药性监测有影响，因为敏感性可能取决于与药物暴露无关的进化特征。
Artemisinin-based drugs are the front-line weapon in the treatment of human malaria cases, but there is concern that recent reports of slow clearing infections may signal developing resistance to treatment. In the absence of molecular markers for resistance, current efforts to monitor drug efficacy are based on the rate at which parasites are cleared from infections. However, some knowledge of the standing variation in parasite susceptibility is needed to identify a meaningful increase in infection half-life. Here, we show that five previously unexposed genotypes of the rodent malaria parasite Plasmodium chabaudi differ substantially in their in vivo response to treatment. Slower clearance rates were not linked to parasite virulence or growth rate, going against the suggestion that drug treatment will drive the evolution of virulence in this system. The level of variation observed here in a relatively small number of genotypes suggests existing ‘resistant’ parasites could be present in the population and therefore, increased parasite clearance rates could represent selection on pre-existing variation rather than de novo resistance events. This has implications for resistance monitoring as susceptibility may depend on evolved traits unrelated to drug exposure.
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影响因子：
2.4
作者：
CARTER, R
通讯作者：
CARTER, R
影响因子：
15.8
作者：
Carrara VI;Lwin KM;Phyo AP;Ashley E;Wiladphaingern J;Sriprawat K;Rijken M;Boel M;McGready R;Proux S;Chu C;Singhasivanon P;White N;Nosten F
通讯作者：
Nosten F
DOI：
10.1073/pnas.0500078102
发表时间：
2005-05-24
影响因子：
11.1
作者：
de Roode, JC;Pansini, R;Read, AF
通讯作者：
Read, AF
影响因子：
2.1
作者：
Huijben, S.;Sim, D. G.;Read, A. F.
通讯作者：
Read, A. F.
影响因子：
2.9
作者：
Mideo, Nicole;Barclay, Victoria C.;Day, Troy
通讯作者：
Day, Troy