Understanding genetic variation in in vivo tolerance to artesunate: implications for treatment efficacy and resistance monitoring

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 ...青蒿素类药物是当前治疗人类疟疾感染的一线用药，但近期有报告显示感染清除速度放缓，这或预示着疟原虫正逐渐产生抗药性，引发学界担忧。由于目前尚未发现抗药性相关的分子标志物，当前监测药物疗效的手段均基于感染体内疟原虫的清除速率。然而，若要精准识别感染半衰期出现具有统计学意义的上升，需先掌握疟原虫易感性的固有遗传变异情况。本研究显示，5株此前未暴露于该类药物的啮齿类疟原虫查氏株（Plasmodium chabaudi）基因型，其体内对药物治疗的应答反应存在显著差异。清除速率较慢的疟原虫株并未与疟原虫的毒力或增殖速率存在关联，这与"药物治疗会推动该体系中毒力演化"的假说相悖。本研究仅针对少量基因型开展分析，所观测到的变异程度表明，现有具备"抗药性"的疟原虫可能存在于……