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Abstract：
The emergence of antimalarial drug resistance is an impediment to malaria control and elimination in Africa. Analysis of temporal trends in molecular markers of resistance is critical to inform policy makers and guide malaria treatment guidelines. In a low and seasonal transmission region of southern Zambia, we successfully genotyped 85.5% (389/455) of Plasmodium falciparum samples collected between 2013-2018 from 8 spatially clustered health centres using molecular inversion probes (MIPs) targeting key drug resistance genes. Aside from one sample carrying K13 R622I, none of the isolates carried other World Health Organization-validated or candidate artemisinin partial resistance (ART-R) mutations in K13. However, 13% (CI, 9.6-17.2) of isolates had the AP2MU S160N mutation, which has been associated with delayed clearance following artemisinin combination therapy in Africa. This mutation increased in prevalence between 2015-2018 and bears a genomic signature of selection. During this time period, there was an increase in the MDR1 NFD haplotype that is associated with reduced susceptibility to lumefantrine. Sulfadoxine-pyrimethamine polymorphisms were near fixation. While validated ART-R mutations are rare, a mutation associated with slow parasite clearance in Africa appears to be under selection in southern Zambia.
摘要：
抗疟疾药物耐药性的出现是非洲疟疾控制和消除的障碍。分析耐药性分子标记的时间趋势对于告知政策制定者和指导疟疾治疗指南至关重要。在赞比亚南部的低季节性传播地区，我们使用靶向关键耐药基因的分子倒置探针(MIPs),成功对2013-2018年间从8个空间聚集的健康中心收集的85.5%(389/455)的恶性疟原虫样本进行基因分型.除了一个携带K13R622I的样品，在K13中，没有一个分离株携带其他世界卫生组织验证的或候选的青蒿素部分耐药（ART-R）突变。然而,13%（CI，9.6-17.2）的分离株具有AP2MUS160N突变，这与非洲青蒿素联合治疗后的清除延迟有关。这种突变在2015-2018年间患病率增加，并具有选择的基因组特征。在此期间,MDR1NFD单倍型增加,与本特林易感性降低相关.磺胺多辛-乙胺嘧啶多态性接近固定。虽然经过验证的ART-R突变很少见，与非洲寄生虫清除缓慢相关的突变在赞比亚南部似乎正在选择中。
