Breaking the cycle of malaria treatment failure.
Breaking the cycle of malaria treatment failure.
复制标题
DOI：
10.3389/fepid.2022.1041896
复制
发表时间：
2022-01-01
期刊：
影响因子：
--
通讯作者：
Boni, Maciej F
中科院分区：
文献类型：
--
作者：
Boni, Maciej F
第二次世界大战后，症状性疟疾的治疗成为临床和公共卫生应对疟疾的常规组成部分。然而，所有用于治疗疟疾的抗疟药物最终都产生了足够的耐药性，不得不停止使用。氯喹、磺胺嘧啶-乙胺嘧啶和甲氟喹都是众所周知的抗疟药，它们过去和现在都已经产生耐药性。青蒿素联合疗法目前面临着同样的挑战，因为青蒿素耐药性在东南亚广泛存在，并在非洲出现。在这里，我回顾了疟疾耐药性管理的一些方面，这些方面影响了对耐药疟原虫的选择性压力的强度，以及我们将来可以采取的方法，以避免重复部署新药并等待耐药性和治疗失败的常见错误。耐药性管理的一个理想目标是减少选择压力，而不减少接受治疗的患者的总体百分比。这可以通过在人群中同时分发多种一线疗法来实现，以治疗无并发症的恶性疟疾，从而保持高水平的治疗，但每种疗法施加的总体选择压力较低。我回顾的主要原因，使MFT的首选耐药管理选项，在许多疟疾流行的设置，我描述了两个例外，谨慎和额外的分析，可能需要部署MFT之前。MFT已被证明在许多地方性环境中是可行的。疟疾基因组监测的持续改进和覆盖面的扩大可能使各国能够根据其目前的耐药性概况实施定制的MFT战略。
Treatment of symptomatic malaria became a routine component of the clinical and public health response to malaria after the second world war. However, all antimalarial drugs deployed against malaria eventually generated enough drug resistance that they had to be removed from use. Chloroquine, sulfadoxine-pyrimethamine, and mefloquine are well known examples of antimalarial drugs to which resistance did and still does ready evolve. Artemisinin-based combination therapies (ACTs) are currently facing the same challenge as artemisinin resistance is widespread in Southeast Asia and emerging in Africa. Here, I review some aspects of drug-resistance management in malaria that influence the strength of selective pressure on drug-resistant malaria parasites, as well as an approach we can take in the future to avoid repeating the common mistake of deploying a new drug and waiting for drug resistance and treatment failure to arrive. A desirable goal of drug-resistance management is to reduce selection pressure without reducing the overall percentage of patients that are treated. This can be achieved by distributing multiple first-line therapies (MFT) simultaneously in the population for the treatment of uncomplicated falciparum malaria, thereby keeping treatment levels high but the overall selection pressure exerted by each individual therapy low. I review the primary reasons that make MFT a preferred resistance management option in many malaria-endemic settings, and I describe two exceptions where caution and additional analyses may be warranted before deploying MFT. MFT has shown to be feasible in practice in many endemic settings. The continual improvement and increased coverage of genomic surveillance in malaria may allow countries to implement custom MFT strategies based on their current drug-resistance profiles.