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用于监测药物使用对恶性疟原虫群体影响的基因监测。

Genetic surveillance for monitoring the impact of drug use on Plasmodium falciparum populations.

作者信息

Ndiaye Yaye Die, Hartl Daniel L, McGregor David, Badiane Aida, Fall Fatou Ba, Daniels Rachel F, Wirth Dyann F, Ndiaye Daouda, Volkman Sarah K

机构信息

Dantec Teaching and Research Hospital, Dakar, Senegal.

Harvard University, Cambridge, MA, USA.

出版信息

Int J Parasitol Drugs Drug Resist. 2021 Dec;17:12-22. doi: 10.1016/j.ijpddr.2021.07.004. Epub 2021 Jul 26.

Abstract

The use of antimalarial drugs is an effective strategy in the fight against malaria. However, selection of drug resistant parasites is a constant threat to the continued use of this approach. Antimalarial drugs are used not only to treat infections but also as part of population-level strategies to reduce malaria transmission toward elimination. While there is strong evidence that the ongoing use of antimalarial drugs increases the risk of the emergence and spread of drug-resistant parasites, it is less clear how population-level use of drug-based interventions like seasonal malaria chemoprevention (SMC) or mass drug administration (MDA) may contribute to drug resistance or loss of drug efficacy. Critical to sustained use of drug-based strategies for reducing the burden of malaria is the surveillance of population-level signals related to transmission reduction and resistance selection. Here we focus on Plasmodium falciparum and discuss the genetic signatures of a parasite population that are correlated with changes in transmission and related to drug pressure and resistance as a result of drug use. We review the evidence for MDA and SMC contributing to malaria burden reduction and drug resistance selection and examine the use and impact of these interventions in Senegal. Throughout we consider best strategies for ongoing surveillance of both population and resistance signals in the context of different parasite population parameters. Finally, we propose a roadmap for ongoing surveillance during population-level drug-based interventions to reduce the global malaria burden.

摘要

使用抗疟药物是抗击疟疾的一项有效策略。然而,耐药寄生虫的出现对持续采用这一方法构成了持续威胁。抗疟药物不仅用于治疗感染,还作为群体层面策略的一部分,以减少疟疾传播直至消除。虽然有充分证据表明持续使用抗疟药物会增加耐药寄生虫出现和传播的风险,但群体层面使用季节性疟疾化学预防(SMC)或大规模药物给药(MDA)等基于药物的干预措施如何导致耐药性或药物疗效丧失尚不清楚。持续采用基于药物的策略以减轻疟疾负担的关键在于监测与传播减少和耐药性选择相关的群体层面信号。在此,我们聚焦于恶性疟原虫,讨论寄生虫群体的基因特征,这些特征与传播变化相关,并因药物使用而与药物压力和耐药性有关。我们回顾了关于MDA和SMC有助于减轻疟疾负担及选择耐药性的证据,并考察了这些干预措施在塞内加尔的使用情况及影响。在整个过程中,我们考虑在不同寄生虫群体参数背景下持续监测群体和耐药性信号的最佳策略。最后,我们提出了在群体层面基于药物的干预措施期间进行持续监测以减轻全球疟疾负担的路线图。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5447/8342550/2f476deb4bae/ga1.jpg

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