BACKGROUND Innovative approaches are needed to limit antimalarial resistance evolution. Understanding the role of intermittent preventive treatment in pregnancy (IPTp) on the selection for resistance and the impact such selection has on pregnancy outcomes can guide future interventions. METHODS Plasmodium falciparum isolates (n = 914) from 2 randomized clinical trials were screened for pfmdr1 copy number variation and pfcrt, pfmdr1, pfdhfr, and pfdhps resistance markers. The trials were conducted between 2010 and 2013 in Benin, Gabon, Kenya, and Mozambique to establish the efficacy of IPTp-mefloquine (MQ) compared with IPTp-sulphadoxine-pyrimethamine (SP) in human immunodeficiency virus (HIV)-uninfected and to IPTp-placebo in HIV-infected women. RESULTS In HIV-uninfected women, the prevalence of pfcrt mutants, pfdhfr/pfdhps quintuple mutants, and pfmdr1 copy number was similar between women receiving IPT-SP and IPTp-MQ. However, prevalence of pfmdr1 polymorphism 86Y was lower in the IPTp-MQ group than in the IPTp-SP group, and within the IPTp-MQ group it was lower at delivery compared with recruitment. No effect of IPTp-MQ on resistance markers was observed among HIV-infected women. The carriage of resistance markers was not associated with pregnancy outcomes. CONCLUSIONS Selection of wild-type pfmdr1 polymorphism N86 by IPTp-MQ highlights the strong selective pressure IPTp can exert and the opportunity for using negative cross-resistance in drug choice for clinical treatment and IPTp.

中文翻译：

---

在妊娠中通过间歇性预防治疗来反选择抗疟疾耐药性多态性。

背景技术需要创新的方法来限制抗疟药耐药性的发展。了解妊娠间歇性预防治疗（IPTp）在抵抗力选择上的作用以及这种选择对妊娠结局的影响可以指导未来的干预措施。方法筛选2项随机临床试验中的恶性疟原虫分离株（n = 914）的pfmdr1拷贝数变异和pfcrt，pfmdr1，pfdhfr和pfdhps抗性标记。该试验于2010年至2013年之间在贝宁，加蓬，肯尼亚和莫桑比克进行，旨在确定IPTp-甲氧喹（MQ）与IPTp-磺胺多辛-乙胺嘧啶（SP）在未感染人免疫缺陷病毒（HIV）和IPTp中的功效艾滋病毒感染妇女使用安慰剂。结果在未感染HIV的妇女中，pfcrt突变体，pfdhfr / pfdhps五元组突变体的流行率很高，接受IPT-SP和IPTp-MQ的女性之间的pfmdr1拷贝数相似。但是，在IPTp-MQ组中pfmdr1多态性86Y的患病率比在IPTp-SP组中低，而在IPTp-MQ组中，与募集相比，其分娩时更低。在HIV感染的妇女中未观察到IPTp-MQ对耐药标记的影响。抗性标记物的携带与妊娠结局无关。结论IPTp-MQ选择野生型pfmdr1多态性N86突出了IPTp可以发挥的强大选择性压力，以及在临床治疗和IPTp的药物选择中使用负交叉耐药性的机会。在IPTp-MQ组中，其交付率比招聘时要低。在HIV感染的妇女中未观察到IPTp-MQ对耐药标记的影响。抗性标记物的携带与妊娠结局无关。结论IPTp-MQ选择野生型pfmdr1多态性N86突出了IPTp可以发挥的强大选择性压力，以及在临床治疗和IPTp的药物选择中使用负交叉耐药性的机会。在IPTp-MQ组中，其交付率比招聘时要低。在HIV感染的妇女中未观察到IPTp-MQ对耐药标记的影响。抗性标记物的携带与妊娠结局无关。结论IPTp-MQ选择野生型pfmdr1多态性N86突出了IPTp可以发挥的强大选择性压力，以及在临床治疗和IPTp的药物选择中使用负交叉耐药性的机会。