High Heritability of Malaria Parasite Clearance Rate Indicates a Genetic Basis for Artemisinin Resistance in Western Cambodia

被引:104
作者
Anderson, Tim J. C. [1 ]
Nair, Shalini [1 ]
Nkhoma, Standwell [1 ]
Williams, Jeff T. [1 ]
Imwong, Mallika [2 ]
Yi, Poravuth [4 ]
Socheat, Duong [4 ]
Das, Debashish [4 ]
Chotivanich, Kesinee [2 ]
Day, Nicholas P. J. [2 ,3 ]
White, Nicholas J. [2 ,3 ]
Dondorp, Arjen M. [2 ]
机构
[1] SW Fdn Biomed Res, San Antonio, TX 78245 USA
[2] Mahidol Univ, Fac Trop Med, Bangkok, Thailand
[3] Churchill Hosp, Ctr Trop Med, Oxford OX3 7LJ, England
[4] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia
基金
英国惠康基金;
关键词
UNCOMPLICATED FALCIPARUM-MALARIA; PLASMODIUM-FALCIPARUM; MICROSATELLITE MARKERS; EFFICACY;
D O I
10.1086/651562
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In western Cambodia, malaria parasites clear slowly from the blood after treatment with artemisinin derivatives, but it is unclear whether this results from parasite, host, or other factors specific to this population. We measured heritability of clearance rate by evaluating patients infected with identical or nonidentical parasite genotypes, using methods analogous to human twin studies. A substantial proportion (56%-58%) of the variation in clearance rate is explained by parasite genetics. This has 2 important implications: (1) selection with artemisinin derivatives will tend to drive resistance spread and (2) because heritability is high, the genes underlying parasite clearance rate may be identified by genome-wide association.
引用
收藏
页码:1326 / 1330
页数:5
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