Distribution and Temporal Dynamics of Plasmodium falciparum Chloroquine Resistance Transporter Mutations Associated with Piperaquine Resistance in Northern Cambodia
Background: Newly emerged mutations within the Plasmodium falciparum chloroquine resistance transporter (PfCRT) can confer piperaquine resistance in the absence of amplified plasmepsin II (pfpm2). In this study, we estimated the prevalence of co-circulating piperaquine resistance mutations in P. fal...
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th-mahidol.778532022-08-04T16:12:26Z Distribution and Temporal Dynamics of Plasmodium falciparum Chloroquine Resistance Transporter Mutations Associated with Piperaquine Resistance in Northern Cambodia Biraj Shrestha Zalak Shah Andrew P. Morgan Piyaporn Saingam Chaiyaporn Chaisatit Suwanna Chaorattanakawee Chantida Praditpol Nonlawat Boonyalai Paphavee Lertsethtakarn Mariusz Wojnarski Molly Deutsch-Feldman Matthew Adams Darapiseth Sea Soklyda Chann Stuart D. Tyner Charlotte A. Lanteri Michele D. Spring David L. Saunders Philip L. Smith Chanthap Lon Panita Gosi Somethy Sok Prom Satharath Huy Rekol Dysoley Lek Brian A. Vesely Jessica T. Lin Norman C. Waters Shannon Takala-Harrison The University of North Carolina at Chapel Hill Armed Forces Research Institute of Medical Sciences, Thailand University of Maryland School of Medicine Mahidol University U.S. Army Medical Research Institute of Infectious Diseases Village Trapangsvay Royal Cambodian Armed Forces Medicine Background: Newly emerged mutations within the Plasmodium falciparum chloroquine resistance transporter (PfCRT) can confer piperaquine resistance in the absence of amplified plasmepsin II (pfpm2). In this study, we estimated the prevalence of co-circulating piperaquine resistance mutations in P. falciparum isolates collected in northern Cambodia from 2009 to 2017. Methods: The sequence of pfcrt was determined for 410 P. falciparum isolates using PacBio amplicon sequencing or whole genome sequencing. Quantitative polymerase chain reaction was used to estimate pfpm2 and pfmdr1 copy number. Results: Newly emerged PfCRT mutations increased in prevalence after the change to dihydroartemisinin-piperaquine in 2010, with >98% of parasites harboring these mutations by 2017. After 2014, the prevalence of PfCRT F145I declined, being outcompeted by parasites with less resistant, but more fit PfCRT alleles. After the change to artesunate-mefloquine, the prevalence of parasites with amplified pfpm2 decreased, with nearly half of piperaquine-resistant PfCRT mutants having single-copy pfpm2. Conclusions: The large proportion of PfCRT mutants that lack pfpm2 amplification emphasizes the importance of including PfCRT mutations as part of molecular surveillance for piperaquine resistance in this region. Likewise, it is critical to monitor for amplified pfmdr1 in these PfCRT mutants, as increased mefloquine pressure could lead to mutants resistant to both drugs. 2022-08-04T09:12:26Z 2022-08-04T09:12:26Z 2021-09-15 Article Journal of Infectious Diseases. Vol.224, No.6 (2021), 1077-1085 10.1093/infdis/jiab055 15376613 00221899 2-s2.0-85111089379 https://repository.li.mahidol.ac.th/handle/123456789/77853 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85111089379&origin=inward |
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Medicine Biraj Shrestha Zalak Shah Andrew P. Morgan Piyaporn Saingam Chaiyaporn Chaisatit Suwanna Chaorattanakawee Chantida Praditpol Nonlawat Boonyalai Paphavee Lertsethtakarn Mariusz Wojnarski Molly Deutsch-Feldman Matthew Adams Darapiseth Sea Soklyda Chann Stuart D. Tyner Charlotte A. Lanteri Michele D. Spring David L. Saunders Philip L. Smith Chanthap Lon Panita Gosi Somethy Sok Prom Satharath Huy Rekol Dysoley Lek Brian A. Vesely Jessica T. Lin Norman C. Waters Shannon Takala-Harrison Distribution and Temporal Dynamics of Plasmodium falciparum Chloroquine Resistance Transporter Mutations Associated with Piperaquine Resistance in Northern Cambodia |
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Background: Newly emerged mutations within the Plasmodium falciparum chloroquine resistance transporter (PfCRT) can confer piperaquine resistance in the absence of amplified plasmepsin II (pfpm2). In this study, we estimated the prevalence of co-circulating piperaquine resistance mutations in P. falciparum isolates collected in northern Cambodia from 2009 to 2017. Methods: The sequence of pfcrt was determined for 410 P. falciparum isolates using PacBio amplicon sequencing or whole genome sequencing. Quantitative polymerase chain reaction was used to estimate pfpm2 and pfmdr1 copy number. Results: Newly emerged PfCRT mutations increased in prevalence after the change to dihydroartemisinin-piperaquine in 2010, with >98% of parasites harboring these mutations by 2017. After 2014, the prevalence of PfCRT F145I declined, being outcompeted by parasites with less resistant, but more fit PfCRT alleles. After the change to artesunate-mefloquine, the prevalence of parasites with amplified pfpm2 decreased, with nearly half of piperaquine-resistant PfCRT mutants having single-copy pfpm2. Conclusions: The large proportion of PfCRT mutants that lack pfpm2 amplification emphasizes the importance of including PfCRT mutations as part of molecular surveillance for piperaquine resistance in this region. Likewise, it is critical to monitor for amplified pfmdr1 in these PfCRT mutants, as increased mefloquine pressure could lead to mutants resistant to both drugs. |
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The University of North Carolina at Chapel Hill |
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The University of North Carolina at Chapel Hill Biraj Shrestha Zalak Shah Andrew P. Morgan Piyaporn Saingam Chaiyaporn Chaisatit Suwanna Chaorattanakawee Chantida Praditpol Nonlawat Boonyalai Paphavee Lertsethtakarn Mariusz Wojnarski Molly Deutsch-Feldman Matthew Adams Darapiseth Sea Soklyda Chann Stuart D. Tyner Charlotte A. Lanteri Michele D. Spring David L. Saunders Philip L. Smith Chanthap Lon Panita Gosi Somethy Sok Prom Satharath Huy Rekol Dysoley Lek Brian A. Vesely Jessica T. Lin Norman C. Waters Shannon Takala-Harrison |
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Article |
author |
Biraj Shrestha Zalak Shah Andrew P. Morgan Piyaporn Saingam Chaiyaporn Chaisatit Suwanna Chaorattanakawee Chantida Praditpol Nonlawat Boonyalai Paphavee Lertsethtakarn Mariusz Wojnarski Molly Deutsch-Feldman Matthew Adams Darapiseth Sea Soklyda Chann Stuart D. Tyner Charlotte A. Lanteri Michele D. Spring David L. Saunders Philip L. Smith Chanthap Lon Panita Gosi Somethy Sok Prom Satharath Huy Rekol Dysoley Lek Brian A. Vesely Jessica T. Lin Norman C. Waters Shannon Takala-Harrison |
author_sort |
Biraj Shrestha |
title |
Distribution and Temporal Dynamics of Plasmodium falciparum Chloroquine Resistance Transporter Mutations Associated with Piperaquine Resistance in Northern Cambodia |
title_short |
Distribution and Temporal Dynamics of Plasmodium falciparum Chloroquine Resistance Transporter Mutations Associated with Piperaquine Resistance in Northern Cambodia |
title_full |
Distribution and Temporal Dynamics of Plasmodium falciparum Chloroquine Resistance Transporter Mutations Associated with Piperaquine Resistance in Northern Cambodia |
title_fullStr |
Distribution and Temporal Dynamics of Plasmodium falciparum Chloroquine Resistance Transporter Mutations Associated with Piperaquine Resistance in Northern Cambodia |
title_full_unstemmed |
Distribution and Temporal Dynamics of Plasmodium falciparum Chloroquine Resistance Transporter Mutations Associated with Piperaquine Resistance in Northern Cambodia |
title_sort |
distribution and temporal dynamics of plasmodium falciparum chloroquine resistance transporter mutations associated with piperaquine resistance in northern cambodia |
publishDate |
2022 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/77853 |
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1763488379614265344 |