Monitoring Plasmodium vivax resistance to antimalarials: Persisting challenges and future directions.
Monitoring Plasmodium vivax resistance to antimalarials: Persisting challenges and future directions.
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DOI：
10.1016/j.ijpddr.2020.12.001
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Gil JP
中科院分区：
文献类型：
--
作者：
Ferreira MU;Nobrega de Sousa T;Rangel GW;Johansen IC;Corder RM;Ladeia-Andrade S;Gil JP
新出现的抗疟药物耐药性可能会破坏目前控制和消除间日疟原虫的努力，间日疟原虫是地理上分布最广但被忽视的人类疟疾寄生虫。疟疾流行国家应定期评估所用抗疟药物的疗效，以调整其疟疾治疗政策，但往往缺乏适当的资金和训练有素的人力资源，无法进行相对复杂和昂贵的临床研究，最好辅之以体外抗药性测定。在这里，我们审查的挑战，在体内评估间日疟原虫反应常用的抗疟药，特别是氯喹和伯氨喹，在存在混杂因素，如可变的药物吸收，代谢和相互作用，并成功根治后的新感染的风险。我们介绍了一个简单的建模方法，以量化的相对贡献复发和新的感染，以经常性的寄生虫血症在临床研究的杀催眠虫剂。最后，我们研究了最近的方法学进展，可能使离体检测更实用，并广泛用于确认间日疟原虫耐药表型在地方性环境中，并审查目前的方法来开发强大的遗传标记监测氯喹耐药性间日疟原虫种群。间日疟原虫对氯喹的抗药性可能破坏消灭疟疾的努力。间日疟原虫对杀疟原虫剂的耐药性主要在疗效研究中监测。确定伯氨喹抗复发疗效的体内研究在设计和执行方面具有挑战性。测定间日疟原虫对杀疟原虫剂抗性的离体测定仍然限于研究环境。目前缺乏监测间日疟原虫耐药性的强有力的分子标记。
Emerging antimalarial drug resistance may undermine current efforts to control and eliminate Plasmodium vivax, the most geographically widespread yet neglected human malaria parasite. Endemic countries are expected to assess regularly the therapeutic efficacy of antimalarial drugs in use in order to adjust their malaria treatment policies, but proper funding and trained human resources are often lacking to execute relatively complex and expensive clinical studies, ideally complemented by ex vivo assays of drug resistance. Here we review the challenges for assessing in vivo P. vivax responses to commonly used antimalarials, especially chloroquine and primaquine, in the presence of confounding factors such as variable drug absorption, metabolism and interaction, and the risk of new infections following successful radical cure. We introduce a simple modeling approach to quantify the relative contribution of relapses and new infections to recurring parasitemias in clinical studies of hypnozoitocides. Finally, we examine recent methodological advances that may render ex vivo assays more practical and widely used to confirm P. vivax drug resistance phenotypes in endemic settings and review current approaches to the development of robust genetic markers for monitoring chloroquine resistance in P. vivax populations. Plasmodium vivax resistance to chloroquine may undermine malaria elimination efforts. Plasmodium vivax resistance to schizontocides has been mostly monitored in therapeutic efficacy studies. In vivo studies to determine the anti-relapse efficacy of primaquine are challenging to design and execute. Ex vivo assays to determine Plasmodium vivax resistance to schizontocides remain limited to research settings. Robust molecular markers to monitor Plasmodium vivax drug resistance are currently lacking.
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