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.

新出现的抗疟药物耐药性可能会破坏当前控制和消灭间日疟原虫的努力，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。预计流行国家将定期评估正在使用的抗疟药物的治疗效果，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来执行相对复杂和昂贵的临床研究，理想情况下辅以体外检测耐药性。在这里，我们回顾了评估体内间日疟原虫的挑战在存在混杂因素（如药物吸收、代谢和相互作用以及成功根治后新感染的风险）的情况下，对常用抗疟药（尤其是氯喹和伯氨喹）的反应。我们引入了一种简单的建模方法来量化复发和新感染对催眠药临床研究中复发性寄生虫血症的相对贡献。最后，我们研究了最近的方法学进展，这些进展可能使离体检测更实用，并被广泛用于确认流行环境中的间日疟原虫耐药表型，并审查目前开发用于监测间日疟原虫种群氯喹耐药性的稳健遗传标记的方法。