TY - JOUR T1 - Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia JF - Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America Y1 - 2013 A1 - Takala-Harrison, Shannon A1 - Clark, Taane G. A1 - Jacob, Christopher G. A1 - Michael P. Cummings A1 - Miotto, Olivo A1 - Dondorp, Arjen M. A1 - Fukuda, Mark M. A1 - Nosten, Francois A1 - Noedl, Harald A1 - Imwong, Mallika A1 - Bethell, Delia A1 - Se, Youry A1 - Lon, Chanthap A1 - Tyner, Stuart D. A1 - Saunders, David L. A1 - Socheat, Duong A1 - Ariey, Frederic A1 - Phyo, Aung Pyae A1 - Starzengruber, Peter A1 - Fuehrer, Hans-Peter A1 - Swoboda, Paul A1 - Stepniewska, Kasia A1 - Flegg, Jennifer A1 - Arze, Cesar A1 - Cerqueira, Gustavo C. A1 - Silva, Joana C. A1 - Ricklefs, Stacy M. A1 - Porcella, Stephen F. A1 - Stephens, Robert M. A1 - Adams, Matthew A1 - Kenefic, Leo J. A1 - Campino, Susana A1 - Auburn, Sarah A1 - Macinnis, Bronwyn A1 - Kwiatkowski, Dominic P. A1 - Su, Xin-Zhuan A1 - White, Nicholas J. A1 - Ringwald, Pascal A1 - Plowe, Christopher V. AB - The recent emergence of artemisinin-resistant Plasmodium falciparum malaria in western Cambodia could threaten prospects for malaria elimination. Identification of the genetic basis of resistance would provide tools for molecular surveillance, aiding efforts to contain resistance. Clinical trials of artesunate efficacy were conducted in Bangladesh, in northwestern Thailand near the Myanmar border, and at two sites in western Cambodia. Parasites collected from trial participants were genotyped at 8,079 single nucleotide polymorphisms (SNPs) using a P. falciparum-specific SNP array. Parasite genotypes were examined for signatures of recent positive selection and association with parasite clearance phenotypes to identify regions of the genome associated with artemisinin resistance. Four SNPs on chromosomes 10 (one), 13 (two), and 14 (one) were significantly associated with delayed parasite clearance. The two SNPs on chromosome 13 are in a region of the genome that appears to be under strong recent positive selection in Cambodia. The SNPs on chromosomes 10 and 13 lie in or near genes involved in postreplication repair, a DNA damage-tolerance pathway. Replication and validation studies are needed to refine the location of loci responsible for artemisinin resistance and to understand the mechanism behind it; however, two SNPs on chromosomes 10 and 13 may be useful markers of delayed parasite clearance in surveillance for artemisinin resistance in Southeast Asia. VL - 110 ER -