High prevalence of pfmdr1 and pfpm2 amplification and pfmdr1 haplotypes in Plasmodium falciparum isolates circulating in Ghana.
4 affiliations
- 1West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra, Ghana.
- 2Department of Biology, University of Virginia, Charlottesville, VA, USA.
- 3Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Accra, Ghana.
- 4West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra, Ghana. [email protected].
Abstract
Background
In Ghana, artemether-lumefantrine (AL), and artesunate-amodiaquine (AS-AQ) are the main first-line ACTs for uncomplicated malaria, with dihydroartemisinin-piperaquine (DHA-PPQ) as an alternative treatment regimen. Copy Number Polymorphisms (CNPs) in Plasmodium falciparum multidrug resistance 1 (pfmdr1) and plasmepsin 2 (pfpm2) genes, as well as specific pfmdr1 haplotypes have been implicated in resistance to AL and DHA-PPQ partner drugs.Methods
This study characterised pfmdr1 and pfpm2 CNPs and pfmdr1 haplotypes in 900 clinical malaria samples across three transmission zones in Ghana. Using a SYBR Green-based Quantitative real-time Polymerase Chain Reaction (qPCR) assay, followed by targeted amplicon sequencing.Results
Successful pfmdr1 and pfpm2 amplifications were detected in 32.0% (n = 288) and 27.8% (n = 250) isolates respectively. No significant difference in the prevalence of these gene amplifications was observed across the three eco-epidemiological zones (pfmdr1: p = 0.888; pfpm2: p = 0.081). Furthermore, a weak positive correlation was observed between pfmdr1 and pfpm2 copy numbers (ρ = 0.196), suggesting limited co-selection of these loci. Pfmdr1 haplotype analysis at codons N86Y, Y184F, and D1246Y revealed a high prevalence (55.6%) of the NFD haplotype linked to lumefantrine selection. Interestingly, this haplotype allele was equally prevalent among isolates carrying single or multiple gene copy numbers.Conclusion
Taken together, this study observed increased prevalence of pfmdr1 and pfpm2 gene amplification in Ghana. Also, a high frequency of the single mutant NFD pfmdr1 haplotype suggesting ongoing selection pressure potentially driven by widespread AL use in Ghana. In addition, pfpm2 CNP has been associated with piperaquine resistance. These findings provide a critical baseline for ongoing molecular surveillance as an early warning for ACT partner drug resistance in Ghana.
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BibTeX
@article{kassim2026high,
title = {{High prevalence of pfmdr1 and pfpm2 amplification and pfmdr1 haplotypes in Plasmodium falciparum isolates circulating in Ghana.}},
author = {Abdul Rashid Kassim and Priscilla Akuba Younge and Ignatus Nunana Dorvi and Samirah Saiid and Mona-Liza Ebiere Sakyi and Osumanu Ahmed and Albert Yao Kudakpo and Stephen Tetteh Addo and Silas Nkansah Yeboah and Charles Mensah and Isaiah Debrah and Collins Misita Morang'a and Dominic S Y Amuzu and Gordon A Awandare and Yaw Aniweh and Lucas Naam-Kayagre Amenga-Etego},
journal = {Malaria journal},
year = {2026},
month = aug,
doi = {10.1186/s12936-026-06075-9},
url = {https://europepmc.org/article/MED/42958349},
note = {CC BY},
}
RIS
TY - JOUR
TI - High prevalence of pfmdr1 and pfpm2 amplification and pfmdr1 haplotypes in Plasmodium falciparum isolates circulating in Ghana.
AU - Abdul Rashid Kassim
AU - Priscilla Akuba Younge
AU - Ignatus Nunana Dorvi
AU - Samirah Saiid
AU - Mona-Liza Ebiere Sakyi
AU - Osumanu Ahmed
AU - Albert Yao Kudakpo
AU - Stephen Tetteh Addo
AU - Silas Nkansah Yeboah
AU - Charles Mensah
AU - Isaiah Debrah
AU - Collins Misita Morang'a
AU - Dominic S Y Amuzu
AU - Gordon A Awandare
AU - Yaw Aniweh
AU - Lucas Naam-Kayagre Amenga-Etego
PY - 2026
DA - 2026/08/01
JO - Malaria journal
DO - 10.1186/s12936-026-06075-9
UR - https://europepmc.org/article/MED/42958349
AB - Background In Ghana, artemether-lumefantrine (AL), and artesunate-amodiaquine (AS-AQ) are the main first-line ACTs for uncomplicated malaria, with dihydroartemisinin-piperaquine (DHA-PPQ) as an alternative treatment regimen. Copy Number Polymorphisms (CNPs) in Plasmodium falciparum multidrug resistance 1 (pfmdr1) and plasmepsin 2 (pfpm2) genes, as well as specific pfmdr1 haplotypes have been implicated in resistance to AL and DHA-PPQ partner drugs.Methods This study characterised pfmdr1 and pfpm2 CNPs and pfmdr1 haplotypes in 900 clinical malaria samples across three transmission zones in Ghana. Using a SYBR Green-based Quantitative real-time Polymerase Chain Reaction (qPCR) assay, followed by targeted amplicon sequencing.Results Successful pfmdr1 and pfpm2 amplifications were detected in 32.0% (n = 288) and 27.8% (n = 250) isolates respectively. No significant difference in the prevalence of these gene amplifications was observed across the three eco-epidemiological zones (pfmdr1: p = 0.888; pfpm2: p = 0.081). Furthermore, a weak positive correlation was observed between pfmdr1 and pfpm2 copy numbers (ρ = 0.196), suggesting limited co-selection of these loci. Pfmdr1 haplotype analysis at codons N86Y, Y184F, and D1246Y revealed a high prevalence (55.6%) of the NFD haplotype linked to lumefantrine selection. Interestingly, this haplotype allele was equally prevalent among isolates carrying single or multiple gene copy numbers.Conclusion Taken together, this study observed increased prevalence of pfmdr1 and pfpm2 gene amplification in Ghana. Also, a high frequency of the single mutant NFD pfmdr1 haplotype suggesting ongoing selection pressure potentially driven by widespread AL use in Ghana. In addition, pfpm2 CNP has been associated with piperaquine resistance. These findings provide a critical baseline for ongoing molecular surveillance as an early warning for ACT partner drug resistance in Ghana.
SN - 1475-2875
ER -