Université de Paris, Paris, France
Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
Antimicrob Agents Chemother. 2020 May 21;64(6). doi: 10.1128/AAC.02029-19.
The continuous spread of antimalarial drug resistance is a threat to current chemotherapy efficacy. Therefore, characterizing the genetic diversity of drug resistance markers is needed to follow treatment effectiveness and further update control strategies. Here, we genotyped resistance gene markers associated with sulfadoxine-pyrimethamine (SP) and artemisinin-based combination therapy (ACT) in isolates from pregnant women in Ghana. The prevalence of the septuple I- K / haplotypes, including the A581G and A613S/T mutations, was high at delivery among post-SP treatment isolates (18.2%) compared to those of first antenatal care (before initiation of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine [IPTp-SP]; 6.1%; 0.03). Regarding the marker gene, two nonsynonymous mutations (N458D and A481C) were detected at positions previously related to artemisinin resistance in isolates from Southeast Asia. These mutations were predicted to alter the stability of the propeller-encoding domain. Overall, these findings highlight the need for intensified monitoring and surveillance of additional mutations associated with increased SP resistance as well as emergence of resistance against artemisinin derivatives.
抗疟药物耐药性的持续传播对当前的化疗效果构成威胁。因此，需要对耐药标志物的遗传多样性进行特征描述，以跟踪治疗效果并进一步更新控制策略。在这里，我们对加纳孕妇分离株中的磺胺多辛-乙胺嘧啶（SP）和基于青蒿素的联合疗法（ACT）相关耐药基因标志物进行了基因分型。与首次产前护理（在妊娠期间间歇性预防用磺胺多辛-乙胺嘧啶[IPTp-SP]开始之前）相比，在 SP 治疗后分离株中，包含 A581G 和 A613S/T 突变的七重 I-K/单倍型的流行率较高（18.2%；6.1%；0.03）。关于标记基因，在来自东南亚的分离株中，检测到了两个非同义突变（N458D 和 A481C），它们位于先前与青蒿素耐药性相关的位置。这些突变被预测会改变螺旋桨编码结构域的稳定性。总体而言，这些发现强调需要加强监测和监测与 SP 耐药性增加相关的其他突变以及青蒿素衍生物耐药性的出现。
