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抗疟药物对 2003-2015 年肯尼亚西部耐药标志物的影响。

Impacts of Antimalarial Drugs on Drug Resistance Markers, Western Kenya, 2003-2015.

机构信息

Program in Public Health, University of California, Irvine, California.

Department of Biological Sciences, University of North Carolina, Charlotte, North Carolina.

出版信息

Am J Trop Med Hyg. 2018 Mar;98(3):692-699. doi: 10.4269/ajtmh.17-0763. Epub 2018 Jan 18.

Abstract

Antimalarial drug resistance has threatened global malaria control since chloroquine (CQ)-resistant emerged in Asia in the 1950s. Understanding the impacts of changing antimalarial drug policy on resistance is critical for resistance management. isolates were collected from 2003 to 2015 in western Kenya and analyzed for genetic markers associated with resistance to CQ (), sulfadoxine-pyrimethamine (SP) (/), and artemether-lumefantrine (AL) (/) antimalarials. In addition, household antimalarial drug use surveys were administered. 76T prevalence decreased from 76% to 6% from 2003 to 2015. / quintuple mutants decreased from 70% in 2003 to 14% in 2008, but increased to near fixation by 2015. SP "super resistant" alleles 581G and 613S/T were not detected in the 2015 samples that were assessed. The N86-184F-D1246 haplotype associated with decreased lumefantrine susceptibility increased significantly from 4% in 2005 to 51% in 2015. No mutations that have been previously associated with artemisinin resistance were detected in the study populations. The increase in / quintuple mutants that associates with SP resistance may have resulted from the increased usage of SP for intermittent preventative therapy in pregnancy (IPTp) and for malaria treatment in the community. Prevalent / mutations call for careful monitoring of SP resistance and effectiveness of the current IPTp program in Kenya. In addition, the commonly occurring N86-184F-D1246 haplotype associated with increased lumefantrine tolerance calls for surveillance of AL efficacy in Kenya, as well as consideration for a rotating artemisinin-combination therapy regimen.

摘要

自上世纪 50 年代亚洲出现抗氯喹疟疾以来,抗疟药物耐药性一直威胁着全球疟疾控制。了解不断变化的抗疟药物政策对耐药性的影响,对于耐药性管理至关重要。本研究从 2003 年至 2015 年在肯尼亚西部采集了疟原虫分离株,并分析了与氯喹(CQ)()、磺胺多辛-乙胺嘧啶(SP)(/)和青蒿琥酯-甲氟喹(AL)(/)抗疟药物耐药相关的遗传标记。此外,还进行了家庭抗疟药物使用调查。76T 阳性率从 2003 年的 76%降至 2015 年的 6%。2003 年 581G 和 613S/T 这两种 SP“超级耐药”等位基因在 2015 年的样本中并未检出,/五倍突变体从 2003 年的 70%减少到 2008 年的 14%,但到 2015 年已接近固定。与青蒿琥酯敏感性降低相关的 N86-184F-D1246 单倍型从 2005 年的 4%显著增加到 2015 年的 51%。在研究人群中未检测到与青蒿素耐药性相关的其他突变。与 SP 耐药性相关的 /五倍突变体的增加可能是由于 SP 在妊娠期间间歇性预防治疗(IPTp)和社区疟疾治疗中的使用增加所致。目前在肯尼亚,SP 耐药性监测和当前 IPTp 项目的有效性受到流行的 /突变的影响。此外,普遍存在的与青蒿琥酯耐受性增加相关的 N86-184F-D1246 单倍型需要监测肯尼亚青蒿琥酯的疗效,并考虑使用轮换青蒿素联合疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67dd/5930917/f4feb07f36b7/tpmd170763f1.jpg

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