Antimalarial resistance is an inevitable feature of control efforts and a key threat to achieving malaria elimination. Plasmodium falciparum, the deadliest of several species causing human malaria, has developed resistance to essentially all antimalarials. This study sought to investigate the prevalence of molecular markers associated with resistance to sulfadoxine-pyrimethamine (SP) and artemether-lumefantrine (AL) in Southern and Western provinces in Zambia. SP is used primarily for intermittent preventive treatment during pregnancy, while AL is the first-line antimalarial for uncomplicated malaria in Zambia. Blood samples were collected from household members of all ages in a cross-sectional survey conducted during peak malaria transmission, April to May of 2017, and amplified by polymerase chain reaction (PCR). Amplicons were then analysed by high-resolution melt following PCR to identify mutations associated with SP resistance in the P. falciparum dihydrofolate reductase (Pfdhfr) and P. falciparum dihydropteroate synthase (Pfdhps) genes and lumefantrine resistance in the P. falciparum multi-drug resistance 1 (Pfmdr1) gene. Finally, artemether resistance was assessed in the P. falciparum Kelch 13 (PfK13) gene using nested PCR followed by amplicon sequencing. The results showed a high frequency of genotypic-resistant Pfdhps A437G (93.2%) and Pfdhfr C59R (86.7%), N51I (80.9%), and S108N (80.8%) of which a high proportion (82.4%) were quadruple mutants (Pfdhfr N51I, C59R, S108N +Pfdhps A437G). Pfmrd1 N86Y, Y186F, and D1246Y - NFD mutant haplotypes were observed in 41.9% of isolates. The high prevalence of quadruple dhps/dhfr mutants indicates strong antifolate drug pressure from SP or other drugs (e.g., co-trimoxazole). Three samples contained PfK13 mutations, two synonymous (T478 and V666) and one non-synonymous (A578S), none of which have been associated with delayed clearance. This suggests that artemisinin remains efficacious in Zambia, however, the moderately high prevalence of approximately 40% Pfmdr1 NFD mutations calls for close monitoring of AL.

抗疟疾抵抗是控制努力的必然特征，也是实现消除疟疾的主要威胁。恶性疟原虫是导致人类疟疾的几种物种中最致命的一种，已经对所有抗疟药产生了抗药性。这项研究旨在调查在赞比亚南部和西部各省与对磺胺多辛-乙胺嘧啶（SP）和蒿甲醚-萤石碱（AL）的耐药性相关的分子标记物的流行情况。SP主要用于怀孕期间的间歇性预防性治疗，而AL是赞比亚单纯性疟疾的一线抗疟药。在2017年4月至5月疟疾高峰传播期间进行的横断面调查中，从各个年龄段的家庭成员中采集血液样本，并通过聚合酶链反应（PCR）进行扩增。然后在PCR之后通过高分辨率熔解对扩增子进行分析，以鉴定与恶性疟原虫二氢叶酸还原酶（Pfdhfr）和恶性疟原虫二氢蝶呤合酶（Pfdhps）基因中的SP抗性相关的突变以及恶性疟原虫多药耐药性中的lumantantrine耐药性1（Pfmdr1）基因。最后，使用巢式PCR，然后进行扩增子测序，评估恶性疟原虫Kelch 13（PfK13）基因中的蒿甲醚抗性。结果显示，耐基因型的Pfdhps A437G（93.2％）和Pfdhfr C59R（86.7％），N51I（80.9％）和S108N（80.8％）的频率很高，其中高比例（82.4％）是四重突变体（Pfdhfr N51I，C59R，S108N + Pfdhps A437G）。在41.9％的分离物中观察到Pfmrd1 N86Y，Y186F和D1246Y-NFD突变单倍型。四个dhps / dhfr突变体的高流行率表明来自SP或其他药物（例如，co-trimoxazole）的强大的抗叶酸药物压力。三个样品包含PfK13突变，两个同义（T478和V666）和一个非同义（A578S），这些都与延迟清除无关。这表明青蒿素在赞比亚仍然有效，但是，大约40％Pfmdr1 NFD突变的中等高流行率要求密切监测AL。