Genetic loci associated with delayed clearance of plasmodium falciparum following artemisinin
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...
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th-mahidol.328342018-10-19T12:51:11Z Genetic loci associated with delayed clearance of plasmodium falciparum following artemisinin Shannon Takala-Harrison Taane G. Clark Christopher G. Jacob Michael P. Cummings Olivo Miotto Arjen M. Dondorpe Mark M. Fukuda Francois Nosten Harald Noedl Mallika Imwong Delia Bethell Youry Se Chanthap Lon Stuart D. Tyner David L. Saunders Duong Socheat Frederic Ariey Aung Pyae Phyo Peter Starzengruber Hans Peter Fuehrer Paul Swoboda Kasia Stepniewska Jennifer Flegg Cesar Arze Gustavo C. Cerqueira Joana C. Silva Stacy M. Ricklefs Stephen F. Porcella Robert M. Stephens Matthew Adams Leo J. Kenefic Susana Campino Sarah Auburn Bronwyn MacInnis Dominic P. Kwiatkowskid Xin Zhuan Su Nicholas J. White Pascal Ringwald Christopher V. Plowe University of Maryland School of Medicine London School of Tropical Medicine University of Maryland University of Oxford Mahidol University Armed Forces Research Institute of Medical Sciences, Thailand Shoklo Malaria Research Unit Medizinische Universitat Wien Armed Forces Research Institute of Medical Sciences University of Health Sciences Institut Pasteur, Paris University of Maryland, Baltimore National Institutes of Health, Bethesda Advanced Biomedical Computing Center Wellcome Trust Sanger Institute National Institute of Allergy and Infectious Diseases Organisation Mondiale de la Sante Multidisciplinary 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. 2018-10-19T05:51:11Z 2018-10-19T05:51:11Z 2013-01-02 Article Proceedings of the National Academy of Sciences of the United States of America. Vol.110, No.1 (2013), 240-245 10.1073/pnas.1211205110 10916490 00278424 2-s2.0-84871944250 https://repository.li.mahidol.ac.th/handle/123456789/32834 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84871944250&origin=inward |
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Multidisciplinary Shannon Takala-Harrison Taane G. Clark Christopher G. Jacob Michael P. Cummings Olivo Miotto Arjen M. Dondorpe Mark M. Fukuda Francois Nosten Harald Noedl Mallika Imwong Delia Bethell Youry Se Chanthap Lon Stuart D. Tyner David L. Saunders Duong Socheat Frederic Ariey Aung Pyae Phyo Peter Starzengruber Hans Peter Fuehrer Paul Swoboda Kasia Stepniewska Jennifer Flegg Cesar Arze Gustavo C. Cerqueira Joana C. Silva Stacy M. Ricklefs Stephen F. Porcella Robert M. Stephens Matthew Adams Leo J. Kenefic Susana Campino Sarah Auburn Bronwyn MacInnis Dominic P. Kwiatkowskid Xin Zhuan Su Nicholas J. White Pascal Ringwald Christopher V. Plowe Genetic loci associated with delayed clearance of plasmodium falciparum following artemisinin |
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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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University of Maryland School of Medicine |
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University of Maryland School of Medicine Shannon Takala-Harrison Taane G. Clark Christopher G. Jacob Michael P. Cummings Olivo Miotto Arjen M. Dondorpe Mark M. Fukuda Francois Nosten Harald Noedl Mallika Imwong Delia Bethell Youry Se Chanthap Lon Stuart D. Tyner David L. Saunders Duong Socheat Frederic Ariey Aung Pyae Phyo Peter Starzengruber Hans Peter Fuehrer Paul Swoboda Kasia Stepniewska Jennifer Flegg Cesar Arze Gustavo C. Cerqueira Joana C. Silva Stacy M. Ricklefs Stephen F. Porcella Robert M. Stephens Matthew Adams Leo J. Kenefic Susana Campino Sarah Auburn Bronwyn MacInnis Dominic P. Kwiatkowskid Xin Zhuan Su Nicholas J. White Pascal Ringwald Christopher V. Plowe |
format |
Article |
author |
Shannon Takala-Harrison Taane G. Clark Christopher G. Jacob Michael P. Cummings Olivo Miotto Arjen M. Dondorpe Mark M. Fukuda Francois Nosten Harald Noedl Mallika Imwong Delia Bethell Youry Se Chanthap Lon Stuart D. Tyner David L. Saunders Duong Socheat Frederic Ariey Aung Pyae Phyo Peter Starzengruber Hans Peter Fuehrer Paul Swoboda Kasia Stepniewska Jennifer Flegg Cesar Arze Gustavo C. Cerqueira Joana C. Silva Stacy M. Ricklefs Stephen F. Porcella Robert M. Stephens Matthew Adams Leo J. Kenefic Susana Campino Sarah Auburn Bronwyn MacInnis Dominic P. Kwiatkowskid Xin Zhuan Su Nicholas J. White Pascal Ringwald Christopher V. Plowe |
author_sort |
Shannon Takala-Harrison |
title |
Genetic loci associated with delayed clearance of plasmodium falciparum following artemisinin |
title_short |
Genetic loci associated with delayed clearance of plasmodium falciparum following artemisinin |
title_full |
Genetic loci associated with delayed clearance of plasmodium falciparum following artemisinin |
title_fullStr |
Genetic loci associated with delayed clearance of plasmodium falciparum following artemisinin |
title_full_unstemmed |
Genetic loci associated with delayed clearance of plasmodium falciparum following artemisinin |
title_sort |
genetic loci associated with delayed clearance of plasmodium falciparum following artemisinin |
publishDate |
2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/32834 |
_version_ |
1763497678525693952 |