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Title: Exploring the contribution of candidate genes to artemisinin resistance in plasmodium falciparum
Authors: Mallika Imwong
Arjen M. Dondorp
Francois Nosten
Poravuth Yi
Mathirut Mungthin
Sarun Hanchana
Debashish Das
Aung Phae Phyo
Khin Maung Lwin
Sasithon Pukrittayakamee
Sue J. Lee
Suwannee Saisung
Kitti Koecharoen
Chea Nguon
Nicholas P J Day
Duong Socheat
Nicholas J. White
Mahidol University
Churchill Hospital
National Center for Parasitology, Entomology and Malaria Control
Phramongkutklao College of Medicine
Royal Institute
Bangkok Hospital Trat
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jan-2010
Citation: Antimicrobial Agents and Chemotherapy. Vol.54, No.7 (2010), 2886-2892
Abstract: The reduced in vivo sensitivity of Plasmodium falciparum has recently been confirmed in western Cambodia. Identifying molecular markers for artemisinin resistance is essential for monitoring the spread of the resistant phenotype and identifying the mechanisms of resistance. Four candidate genes, including the P. falciparum mdr1 (pfmdr1) gene, the P. falciparum ATPase6 (pfATPase6) gene, the 6-kb mitochondrial genome, and ubp-1, encoding a deubiquitinating enzyme, of artemisinin-resistant P. falciparum strains from western Cambodia were examined and compared to those of sensitive strains from northwestern Thailand, where the artemisinins are still very effective. The artemisinin-resistant phenotype did not correlate with pfmdr1 amplification or mutations (full-length sequencing), mutations in pfATPase6 (full-length sequencing) or the 6-kb mitochondrial genome (full-length sequencing), or ubp-1 mutations at positions 739 and 770. The P. falciparum CRT K76T mutation was present in all isolates from both study sites. The pfmdr1 copy numbers in western Cambodia were significantly lower in parasite samples obtained in 2007 than in those obtained in 2005, coinciding with a local change in drug policy replacing artesunate-mefloquine with dihydroartemisinin-piperaquine. Artemisinin resistance in western Cambodia is not linked to candidate genes, as was suggested by earlier studies. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
ISSN: 10986596
Appears in Collections:Scopus 2006-2010

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