Changing Molecular Markers of Antimalarial Drug Sensitivity across Uganda
Changing Molecular Markers of Antimalarial Drug Sensitivity across Uganda
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DOI：
10.1128/aac.01818-18
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发表时间：
2019-03-01
影响因子：
4.9
通讯作者：
Rosenthal, Philip J.
中科院分区：
文献类型：
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作者：
Asua, Victor;Vinden, Joanna;Rosenthal, Philip J.
抗疟药物抗药性可能蔓延到非洲，特别是对青蒿素和主要伙伴药物的抗药性，这是一个重大关切。我们于2016年和2017年在代表乌干达一系列流行病学环境的10个地点以类似于6个月的间隔调查了3次与药物敏感性相关的恶性疟原虫遗传标记。对于假定的药物转运蛋白，我们发现继续向野生型序列与氯喹的敏感性增加。对于pfcrt K76 T，到2017年，野生型的患病率在所有位点>60%，在6个位点>90%。对于pfmdr1 N86 Y和D1246 Y等位基因，野生型患病率范围为80%至100%。我们发现K13螺旋桨结构域突变的患病率较低，这与亚洲的青蒿素耐药性有关，但先前在乌干达北方发现的一种突变675 V在2.0%的样本中发现，包括来自3个最北端地点的5.5%。pfmdr1和plasmepsin2基因的扩增分别与本芴醇和哌喹敏感性降低相关，
The potential spread of antimalarial drug resistance to Africa, in particular for artemisinins and key partner drugs, is a major concern. We surveyed Plasmodium falciparum genetic markers associated with drug sensitivity on 3 occasions at similar to 6-month intervals in 2016 and 2017 at 10 sites representing a range of epidemiological settings in Uganda. For putative drug transporters, we found continued evolution toward wild-type sequences associated with increased sensitivity to chloroquine. For pfcrt K76T, by 2017 the prevalence of the wild type was >60% at all sites and >90% at 6 sites. For the pfmdr1 N86Y and D1246Y alleles, wild type prevalence ranged from 80 to 100%. We found low prevalence of K13 propeller domain mutations, which are associated with artemisinin resistance in Asia, but one mutation previously identified in northern Uganda, 675V, was seen in 2.0% of samples, including 5.5% of those from the 3 northernmost sites. Amplification of the pfmdr1 and plasmepsin2 genes, associated elsewhere with decreased sensitivity to lumefantrine and piperaquine, respectively, was seen in