Intermittent preventive treatment in pregnancy (IPTp) with monthly sulfadoxine-pyrimethamine (SP) is recommended for malaria-endemic parts of Africa, but efficacy is compromised by resistance, and, in recent trials, dihydroartemisinin-piperaquine (DP) has shown better antimalarial protective efficacy. We utilized blood samples from a recent trial to evaluate selection by IPTp with DP or SP of Plasmodium falciparum genetic polymorphisms that alter susceptibility to these drugs. The prevalence of known genetic polymorphisms associated with altered drug susceptibility was determined in parasitemic samples, including 375 collected before IPTp drugs were administered, 125 randomly selected from those receiving SP, and 80 from those receiving DP. For women receiving DP, the prevalence of mixed/mutant sequences was greater in samples collected during IPTp than that in samples collected prior to the intervention for PfMDR1 N86Y (20.3% versus 3.9%; P < 0.001), PfMDR1 Y184F (73.0% versus 53.0%; P < 0.001), and PfCRT K76T (46.4% versus 24.0%; P < 0.001). Considering SP, prior to IPTp, the prevalence of all 5 common antifolate mutations was over 92%, and this prevalence increased following exposure to SP, although none of these changes were statistically significant. For two additional mutations associated with high-level SP resistance, the prevalence of PfDHFR 164L (13.7% versus 4.0%; P = 0.004), but not PfDHPS 581G (1.9% versus 3.0%; P = 0.74), was greater in samples collected during IPTp compared to those collected before the intervention. Use of IPTp in Uganda selected for parasites with mutations associated with decreased susceptibility to IPTp regimens. Thus, a potential drawback of IPTp is selection of parasites with decreased drug susceptibility.

中文翻译：

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乌干达孕妇疟疾预防方案与恶性疟原虫耐药性介导多态性之间的关联

建议在非洲疟疾流行地区使用每月一次的磺胺多辛-乙胺嘧啶 (SP) 进行妊娠期间歇性预防性治疗 (IPTp)，但耐药性会影响疗效，并且在最近的试验中，双氢青蒿素-哌喹 (DP) 显示出更好的抗疟疾保护作用功效。我们利用最近一项试验的血液样本来评估 IPTp 与恶性疟原虫的 DP 或 SP 的选择改变对这些药物的敏感性的遗传多态性。在寄生虫样本中确定了与药物敏感性改变相关的已知基因多态性的流行，包括在 IPTp 药物给药前收集的 375 个，从接受 SP 的那些中随机选择 125 个，从接受 DP 的那些中随机选择 80 个。对于接受 DP 的女性，在 IPTp 期间收集的样本中混合/突变序列的流行率高于干预前收集的样本中 PfMDR1 N86Y（20.3% 对 3.9%；P < 0.001）、PfMDR1 Y184F（73.0% 对 53.0 %；P < 0.001）和 PfCRT K76T（46.4% 对 24.0%；P< 0.001)。考虑到 SP，在 IPTp 之前，所有 5 种常见抗叶酸突变的患病率均超过 92%，并且这种患病率在暴露于 SP 后增加，尽管这些变化均无统计学意义。对于与高水平 SP 抗性相关的另外两个突变，在收集的样本中，PfDHFR 164L（13.7% 对 4.0%；P = 0.004）而不是 PfDHPS 581G（1.9% 对 3.0%；P = 0.74）的患病率更高IPTp 期间与干预前收集的数据相比。在乌干达选择使用 IPTp 来筛选具有与 IPTp 方案敏感性降低相关的突变的寄生虫。因此，IPTp 的一个潜在缺点是选择药物敏感性降低的寄生虫。