Ex Vivo Susceptibility of Plasmodium falciparum to antimalarial drugs in western, Northern, and Eastern Cambodia, 2011-2012: Association with molecular markers
In 2008, dihydroartemisinin (DHA)-piperaquine (PPQ) became the first-line treatment for uncomplicated Plasmodium falciparum malaria in western Cambodia. Recent reports of increased treatment failure rates after DHA-PPQ therapy in this region suggest that parasite resistance to DHA, PPQ, or both is n...
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th-mahidol.320982018-10-19T12:42:40Z Ex Vivo Susceptibility of Plasmodium falciparum to antimalarial drugs in western, Northern, and Eastern Cambodia, 2011-2012: Association with molecular markers Pharath Lim Dalin Dek Vorleak Try Richard T. Eastman Sophy Chy Sokunthea Sreng Seila Suon Sivanna Mao Chantha Sopha Baramey Sam Elizabeth A. Ashley Olivo Miotto Arjen M. Dondorp Nicholas J. White Xin Zhuan Su Meng Chuor Char Jennifer M. Anderson Chanaki Amaratunga Didier Menard Rick M. Fairhurst National Institute of Allergy and Infectious Diseases National Center for Parasitology, Entomology and Malaria Control Institut Pasteur du Cambodge Sampov Meas Referral Hospital Makara 16 Referral Hospital Ratanakiri Referral Hospital Mahidol University University of Oxford Medicine Pharmacology, Toxicology and Pharmaceutics In 2008, dihydroartemisinin (DHA)-piperaquine (PPQ) became the first-line treatment for uncomplicated Plasmodium falciparum malaria in western Cambodia. Recent reports of increased treatment failure rates after DHA-PPQ therapy in this region suggest that parasite resistance to DHA, PPQ, or both is now adversely affecting treatment. While artemisinin (ART) resistance is established in western Cambodia, there is no evidence of PPQ resistance. To monitor for resistance to PPQ and other antimalarials, we measured drug susceptibilities for parasites collected in 2011 and 2012 from Pursat, Preah Vihear, and Ratanakiri, in western, northern, and eastern Cambodia, respectively. Using a SYBR green I fluorescence assay, we calculated the ex vivo 50% inhibitory concentrations (IC50s) of 310 parasites to six antimalarials: chloroquine (CQ), mefloquine (MQ), quinine (QN), PPQ, artesunate (ATS), and DHA. Geometric mean IC50s (GMIC50s) for all drugs (except PPQ) were significantly higher in Pursat and Preah Vihear than in Ratanakiri (P ≤ 0.001). An increased copy number of P. falciparum mdr1 (pfmdr1), an MQ resistance marker, was more prevalent in Pursat and Preah Vihear than in Ratanakiri and was associated with higher GMIC50s for MQ, QN, ATS, and DHA. An increased copy number of a chromosome 5 region (X5r), a candidate PPQ resistance marker, was detected in Pursat but was not associated with reduced susceptibility to PPQ. The ex vivo IC50and pfmdr1 copy number are important tools in the surveillance of multidrug-resistant (MDR) parasites in Cambodia. While MDR P. falciparum is prevalent in western and northern Cambodia, there is no evidence for PPQ resistance, suggesting that DHA-PPQ treatment failures result mainly from ART resistance. Copyright © 2013, American Society for Microbiology. 2018-10-19T05:13:17Z 2018-10-19T05:13:17Z 2013-11-01 Article Antimicrobial Agents and Chemotherapy. Vol.57, No.11 (2013), 5277-5283 10.1128/AAC.00687-13 10986596 00664804 2-s2.0-84885941960 https://repository.li.mahidol.ac.th/handle/123456789/32098 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84885941960&origin=inward |
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Medicine Pharmacology, Toxicology and Pharmaceutics Pharath Lim Dalin Dek Vorleak Try Richard T. Eastman Sophy Chy Sokunthea Sreng Seila Suon Sivanna Mao Chantha Sopha Baramey Sam Elizabeth A. Ashley Olivo Miotto Arjen M. Dondorp Nicholas J. White Xin Zhuan Su Meng Chuor Char Jennifer M. Anderson Chanaki Amaratunga Didier Menard Rick M. Fairhurst Ex Vivo Susceptibility of Plasmodium falciparum to antimalarial drugs in western, Northern, and Eastern Cambodia, 2011-2012: Association with molecular markers |
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In 2008, dihydroartemisinin (DHA)-piperaquine (PPQ) became the first-line treatment for uncomplicated Plasmodium falciparum malaria in western Cambodia. Recent reports of increased treatment failure rates after DHA-PPQ therapy in this region suggest that parasite resistance to DHA, PPQ, or both is now adversely affecting treatment. While artemisinin (ART) resistance is established in western Cambodia, there is no evidence of PPQ resistance. To monitor for resistance to PPQ and other antimalarials, we measured drug susceptibilities for parasites collected in 2011 and 2012 from Pursat, Preah Vihear, and Ratanakiri, in western, northern, and eastern Cambodia, respectively. Using a SYBR green I fluorescence assay, we calculated the ex vivo 50% inhibitory concentrations (IC50s) of 310 parasites to six antimalarials: chloroquine (CQ), mefloquine (MQ), quinine (QN), PPQ, artesunate (ATS), and DHA. Geometric mean IC50s (GMIC50s) for all drugs (except PPQ) were significantly higher in Pursat and Preah Vihear than in Ratanakiri (P ≤ 0.001). An increased copy number of P. falciparum mdr1 (pfmdr1), an MQ resistance marker, was more prevalent in Pursat and Preah Vihear than in Ratanakiri and was associated with higher GMIC50s for MQ, QN, ATS, and DHA. An increased copy number of a chromosome 5 region (X5r), a candidate PPQ resistance marker, was detected in Pursat but was not associated with reduced susceptibility to PPQ. The ex vivo IC50and pfmdr1 copy number are important tools in the surveillance of multidrug-resistant (MDR) parasites in Cambodia. While MDR P. falciparum is prevalent in western and northern Cambodia, there is no evidence for PPQ resistance, suggesting that DHA-PPQ treatment failures result mainly from ART resistance. Copyright © 2013, American Society for Microbiology. |
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National Institute of Allergy and Infectious Diseases |
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National Institute of Allergy and Infectious Diseases Pharath Lim Dalin Dek Vorleak Try Richard T. Eastman Sophy Chy Sokunthea Sreng Seila Suon Sivanna Mao Chantha Sopha Baramey Sam Elizabeth A. Ashley Olivo Miotto Arjen M. Dondorp Nicholas J. White Xin Zhuan Su Meng Chuor Char Jennifer M. Anderson Chanaki Amaratunga Didier Menard Rick M. Fairhurst |
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Article |
author |
Pharath Lim Dalin Dek Vorleak Try Richard T. Eastman Sophy Chy Sokunthea Sreng Seila Suon Sivanna Mao Chantha Sopha Baramey Sam Elizabeth A. Ashley Olivo Miotto Arjen M. Dondorp Nicholas J. White Xin Zhuan Su Meng Chuor Char Jennifer M. Anderson Chanaki Amaratunga Didier Menard Rick M. Fairhurst |
author_sort |
Pharath Lim |
title |
Ex Vivo Susceptibility of Plasmodium falciparum to antimalarial drugs in western, Northern, and Eastern Cambodia, 2011-2012: Association with molecular markers |
title_short |
Ex Vivo Susceptibility of Plasmodium falciparum to antimalarial drugs in western, Northern, and Eastern Cambodia, 2011-2012: Association with molecular markers |
title_full |
Ex Vivo Susceptibility of Plasmodium falciparum to antimalarial drugs in western, Northern, and Eastern Cambodia, 2011-2012: Association with molecular markers |
title_fullStr |
Ex Vivo Susceptibility of Plasmodium falciparum to antimalarial drugs in western, Northern, and Eastern Cambodia, 2011-2012: Association with molecular markers |
title_full_unstemmed |
Ex Vivo Susceptibility of Plasmodium falciparum to antimalarial drugs in western, Northern, and Eastern Cambodia, 2011-2012: Association with molecular markers |
title_sort |
ex vivo susceptibility of plasmodium falciparum to antimalarial drugs in western, northern, and eastern cambodia, 2011-2012: association with molecular markers |
publishDate |
2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/32098 |
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1763491011359670272 |