Publication: Distribution and Temporal Dynamics of Plasmodium falciparum Chloroquine Resistance Transporter Mutations Associated with Piperaquine Resistance in Northern Cambodia
Issued Date
2021-09-15
Resource Type
ISSN
15376613
00221899
00221899
Other identifier(s)
2-s2.0-85111089379
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Infectious Diseases. Vol.224, No.6 (2021), 1077-1085
Suggested Citation
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. Journal of Infectious Diseases. Vol.224, No.6 (2021), 1077-1085. doi:10.1093/infdis/jiab055 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/77853
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Title
Distribution and Temporal Dynamics of Plasmodium falciparum Chloroquine Resistance Transporter Mutations Associated with Piperaquine Resistance in Northern Cambodia
Author(s)
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
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
Other Contributor(s)
Abstract
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.