Skip to main content
Journal cover image

Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia.

Publication ,  Journal Article
Takala-Harrison, S; Clark, TG; Jacob, CG; Cummings, MP; Miotto, O; Dondorp, AM; Fukuda, MM; Nosten, F; Noedl, H; Imwong, M; Bethell, D; Se, Y ...
Published in: Proceedings of the National Academy of Sciences of the United States of America
January 2013

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.

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

January 2013

Volume

110

Issue

1

Start / End Page

240 / 245

Related Subject Headings

  • Selection, Genetic
  • Regression Analysis
  • Principal Component Analysis
  • Polymorphism, Single Nucleotide
  • Plasmodium falciparum
  • Oligonucleotide Array Sequence Analysis
  • Odds Ratio
  • Likelihood Functions
  • Genotype
  • Genetic Markers
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Takala-Harrison, S., Clark, T. G., Jacob, C. G., Cummings, M. P., Miotto, O., Dondorp, A. M., … Plowe, C. V. (2013). Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia. Proceedings of the National Academy of Sciences of the United States of America, 110(1), 240–245. https://doi.org/10.1073/pnas.1211205110
Takala-Harrison, Shannon, Taane G. Clark, Christopher G. Jacob, Michael P. Cummings, Olivo Miotto, Arjen M. Dondorp, Mark M. Fukuda, et al. “Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia.Proceedings of the National Academy of Sciences of the United States of America 110, no. 1 (January 2013): 240–45. https://doi.org/10.1073/pnas.1211205110.
Takala-Harrison S, Clark TG, Jacob CG, Cummings MP, Miotto O, Dondorp AM, et al. Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia. Proceedings of the National Academy of Sciences of the United States of America. 2013 Jan;110(1):240–5.
Takala-Harrison, Shannon, et al. “Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia.Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 1, Jan. 2013, pp. 240–45. Epmc, doi:10.1073/pnas.1211205110.
Takala-Harrison S, Clark TG, Jacob CG, Cummings MP, Miotto O, Dondorp AM, Fukuda MM, Nosten F, Noedl H, Imwong M, Bethell D, Se Y, Lon C, Tyner SD, Saunders DL, Socheat D, Ariey F, Phyo AP, Starzengruber P, Fuehrer H-P, Swoboda P, Stepniewska K, Flegg J, Arze C, Cerqueira GC, Silva JC, Ricklefs SM, Porcella SF, Stephens RM, Adams M, Kenefic LJ, Campino S, Auburn S, MacInnis B, Kwiatkowski DP, Su X-Z, White NJ, Ringwald P, Plowe CV. Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia. Proceedings of the National Academy of Sciences of the United States of America. 2013 Jan;110(1):240–245.
Journal cover image

Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

January 2013

Volume

110

Issue

1

Start / End Page

240 / 245

Related Subject Headings

  • Selection, Genetic
  • Regression Analysis
  • Principal Component Analysis
  • Polymorphism, Single Nucleotide
  • Plasmodium falciparum
  • Oligonucleotide Array Sequence Analysis
  • Odds Ratio
  • Likelihood Functions
  • Genotype
  • Genetic Markers