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

Shannon Takala-Harrison; T Clark; Christopher Jacob; MP Cummings; Olivo Miotto; Arjen Dondorp; Mark Fukuda; FranÃ§ois Nosten; H Noedl; Mallika Imwong; Delia Bethell; Y Se; Chantap Lon; SD Tyner; David Saunders; Duong Socheat; F Ariey; Aung Pyae Phyo; P Starzengruber; H Fuehrer; P Swoboda; Kasia Stepniewska; J Flegg; C Arze; GC Cerqueira; Joana Silva; SM Ricklefs; S Porcella; RM Stephens; Matthew Adams; L Kenefic; Susana Campino; Sarah Auburn; Bronwyn MacInnes; Dominic Kwiatkowski; Xin-Zhuan Su; Nicholas J White; P RINGWALD; C Plowe

doi:10.1073/pnas.1211205110

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

Shannon Takala-Harrison, T Clark, Christopher Jacob, MP Cummings, Olivo Miotto, Arjen Dondorp, Mark Fukuda, FranÃ§ois Nosten, H Noedl, Mallika Imwong, Delia Bethell, Y Se, Chantap Lon, SD Tyner, David Saunders, Duong Socheat, F Ariey, Aung Pyae Phyo, P Starzengruber, H FuehrerP Swoboda, Kasia Stepniewska, J Flegg, C Arze, GC Cerqueira, Joana Silva, SM Ricklefs, S Porcella, RM Stephens, Matthew Adams, L Kenefic, Susana Campino, Sarah Auburn, Bronwyn MacInnes, Dominic Kwiatkowski, Xin-Zhuan Su, Nicholas J White, P RINGWALD, C Plowe

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	240-245
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	110
Issue number	1
DOIs	https://doi.org/10.1073/pnas.1211205110
Publication status	Published - 2013
Externally published	Yes

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Takala-Harrison, S., Clark, T., Jacob, C., Cummings, MP., Miotto, O., Dondorp, A., Fukuda, M., Nosten, F., Noedl, H., Imwong, M., Bethell, D., Se, Y., Lon, C., Tyner, SD., Saunders, D., Socheat, D., Ariey, F., Phyo, A. P., Starzengruber, P., ... Plowe, C. (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

@article{03dd6733ff974724b9f57e214e1e83ce,

title = "Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia",

abstract = "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.",

author = "Shannon Takala-Harrison and T Clark and Christopher Jacob and MP Cummings and Olivo Miotto and Arjen Dondorp and Mark Fukuda and Fran{\~A}§ois Nosten and H Noedl and Mallika Imwong and Delia Bethell and Y Se and Chantap Lon and SD Tyner and David Saunders and Duong Socheat and F Ariey and Phyo, {Aung Pyae} and P Starzengruber and H Fuehrer and P Swoboda and Kasia Stepniewska and J Flegg and C Arze and GC Cerqueira and Joana Silva and SM Ricklefs and S Porcella and RM Stephens and Matthew Adams and L Kenefic and Susana Campino and Sarah Auburn and Bronwyn MacInnes and Dominic Kwiatkowski and Xin-Zhuan Su and White, {Nicholas J} and P RINGWALD and C Plowe",

year = "2013",

doi = "10.1073/pnas.1211205110",

language = "English",

volume = "110",

pages = "240--245",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences (USA)",

number = "1",

}

Takala-Harrison, S, Clark, T, Jacob, C, Cummings, MP, Miotto, O, Dondorp, A, Fukuda, M, Nosten, F, Noedl, H, Imwong, M, Bethell, D, Se, Y, Lon, C, Tyner, SD, Saunders, D, Socheat, D, Ariey, F, Phyo, AP, Starzengruber, P, Fuehrer, H, Swoboda, P, Stepniewska, K, Flegg, J, Arze, C, Cerqueira, GC, Silva, J, Ricklefs, SM, Porcella, S, Stephens, RM, Adams, M, Kenefic, L, Campino, S, Auburn, S, MacInnes, B, Kwiatkowski, D, Su, X-Z, White, NJ, RINGWALD, P & Plowe, C 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, vol. 110, no. 1, pp. 240-245. https://doi.org/10.1073/pnas.1211205110

Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia. / Takala-Harrison, Shannon; Clark, T; Jacob, Christopher et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 1, 2013, p. 240-245.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia

AU - Takala-Harrison, Shannon

AU - Clark, T

AU - Jacob, Christopher

AU - Cummings, MP

AU - Miotto, Olivo

AU - Dondorp, Arjen

AU - Fukuda, Mark

AU - Nosten, FranÃ§ois

AU - Noedl, H

AU - Imwong, Mallika

AU - Bethell, Delia

AU - Se, Y

AU - Lon, Chantap

AU - Tyner, SD

AU - Saunders, David

AU - Socheat, Duong

AU - Ariey, F

AU - Phyo, Aung Pyae

AU - Starzengruber, P

AU - Fuehrer, H

AU - Swoboda, P

AU - Stepniewska, Kasia

AU - Flegg, J

AU - Arze, C

AU - Cerqueira, GC

AU - Silva, Joana

AU - Ricklefs, SM

AU - Porcella, S

AU - Stephens, RM

AU - Adams, Matthew

AU - Kenefic, L

AU - Campino, Susana

AU - Auburn, Sarah

AU - MacInnes, Bronwyn

AU - Kwiatkowski, Dominic

AU - Su, Xin-Zhuan

AU - White, Nicholas J

AU - RINGWALD, P

AU - Plowe, C

PY - 2013

Y1 - 2013

N2 - 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.

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.

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U2 - 10.1073/pnas.1211205110

DO - 10.1073/pnas.1211205110

M3 - Article

SN - 0027-8424

VL - 110

SP - 240

EP - 245

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

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

IS - 1

ER -

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

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