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

• Published in: The Journal of infectious diseases Vol. 201; no. 9; pp. 1326 - 1330
• Main Authors: Anderson, Tim J. C., Nair, Shalini, Nkhoma, Standwell, Williams, Jeff T., Imwong, Mallika, Yi, Poravuth, Socheat, Duong, Das, Debashish, Chotivanich, Kesinee, Day, Nicholas P. J., White, Nicholas J., Dondorp, Arjen M.
• Format: Journal Article
• Language: English
• Published: United States The University of Chicago Press 01-05-2010; University of Chicago Press
• Subjects: Antimalarials - therapeutic use; Artemisinins; Artemisinins - therapeutic use; Cambodia; Drug Resistance - genetics; Genetic Variation - genetics; Genotype; Genotypes; Grants; Heritability; Humans; Identical twins; Malaria; Malaria, Falciparum - drug therapy; Malaria, Falciparum - genetics; Malaria, Falciparum - parasitology; Medical genetics; Microsatellite Repeats - genetics; Parasite hosts; Parasites; Phenotypic traits; Plasmodium falciparum - drug effects; Plasmodium falciparum - genetics; Quantitative Trait, Heritable; Cambodia
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/651562

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. Trial Registration. ClinicalTrials.gov identifier: NCT00493363; Current Controlled Trials identifier: ISRCTN15351875.