气候变化领域集成服务门户(CCPortal): Mapping partner drug resistance to guide antimalarial combination therapy policies in sub-Saharan Africa

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DOI	10.1073/pnas.2100685118
	Mapping partner drug resistance to guide antimalarial combination therapy policies in sub-Saharan Africa
	Ehrlich H.Y.; Bei A.K.; Weinberger D.M.; Warren J.L.; Parikh S.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:29
英文摘要	Resistance to artemisinin-based combination therapies (ACTs) threatens the global control of Plasmodium falciparum malaria. ACTs combine artemisinin-derived compounds with partner drugs to enable multiple mechanisms of clearance. Although ACTs remain widely effective in sub-Saharan Africa, long-standing circulation of parasite alleles associated with reduced partner drug susceptibility may contribute to the development of clinical resistance. We fitted a hierarchical Bayesian spatial model to data from over 500 molecular surveys to predict the prevalence and frequency of four key markers in transporter genes (pfcrt 76T and pfmdr1 86Y, 184F, and 1246Y) in first-level administrative divisions in sub-Saharan Africa from the uptake of ACTs (2004 to 2009) to their widespread usage (2010 to 2018). Our models estimated that the pfcrt 76T mutation decreased in prevalence in 90% of regions; the pfmdr1 N86 and D1246 wild-type genotypes increased in prevalence in 96% and 82% of regions, respectively; and there was no significant directional selection at the pfmdr1 Y184F locus. Rainfall seasonality was the strongest predictor of the prevalence of wild-type genotypes, with other covariates, including first-line drug policy and transmission intensity more weakly associated. We lastly identified regions of high priority for enhanced surveillance that could signify decreased susceptibility to the local first-line ACT. Our results can be used to infer the degree of molecular resistance and magnitude of wild-type reversion in regions without survey data to inform therapeutic policy decisions. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Malaria \| drug resistance \| surveillance
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238860
作者单位	Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, CT 06510, United States; Public Health Modeling Unit, Yale School of Public Health, Yale University, New Haven, CT 06510, United States; Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, CT 06510, United States
推荐引用方式 GB/T 7714	Ehrlich H.Y.,Bei A.K.,Weinberger D.M.,et al. Mapping partner drug resistance to guide antimalarial combination therapy policies in sub-Saharan Africa[J],2021,118(29).
APA	Ehrlich H.Y.,Bei A.K.,Weinberger D.M.,Warren J.L.,&Parikh S..(2021).Mapping partner drug resistance to guide antimalarial combination therapy policies in sub-Saharan Africa.Proceedings of the National Academy of Sciences of the United States of America,118(29).
MLA	Ehrlich H.Y.,et al."Mapping partner drug resistance to guide antimalarial combination therapy policies in sub-Saharan Africa".Proceedings of the National Academy of Sciences of the United States of America 118.29(2021).