Disparate co-evolution and prevalence of sulfadoxine and pyrimethamine resistance alleles and haplotypes at dhfr and dhps genes across Africa

Nina FD White ; Georgia Whitton ; Varanya Wasakul ; Lucas Amenga-Etego ; Antoine Dara ; Voahangy Andrianaranjaka ; Milijaona Randrianarivelojosia ; Olivo Miotto ; Umberto D’Alessandro ; Abdoulaye Djimdé ; +3 more... Cristina V Ariani ; Richard D Pearson ; Alfred Amambua-Ngwa ORCID logo ; (2025) Disparate co-evolution and prevalence of sulfadoxine and pyrimethamine resistance alleles and haplotypes at dhfr and dhps genes across Africa. Scientific reports, 15 (1). p. 13222. ISSN 2045-2322 DOI: 10.1038/s41598-025-98035-7
Copy

Abstract:

Sulfadoxine-pyrimethamine (SP), despite emergence of mutations in dhfr and dhps genes associated with lower treatment efficacy, is still recommended for preventive malaria treatment. Therefore, it is important to understand the evolution of P. falciparum dhfr and dhps genes. We used the MalariaGEN Pf7 dataset to describe haplotype frequencies across 22 African countries, including changes over time in The Gambia, Mali, Ghana, and Kenya. We show that the triple mutant of dhfr, N51I/C59R/S108N, has remained the dominant haplotype across the continent with limited evidence of additional mutations. There is greater variation for dhps in terms of haplotype diversity and spatial heterogeneity of haplotypes found across Africa. Although samples from Madagascar have low genetic differentiation from samples from mainland East Africa at the whole genome level, we show that dhps K540E is highly differentiated between the two populations, being at very low frequency in Madagascar (4%). Whole genome data reveal 12 SNPs which are also highly differentiated between Madagascar and East Africa, including aat1 and a possible novel drug resistance locus approximately 20 kb 3’ of mdr1. We highlight the value of longitudinal sampling and whole genome sequence data for understanding the heterogeneity and ongoing changes in anti-malarial drug resistance genetic markers.


picture_as_pdf
White-etal-2025-disparate-co-evolution-and-prevalence-of-sulfadocine-and-pyrimethamine-resistance-alleles-and-haplotypes-at-dfr-and-dhps-genes-across-africa.pdf
subject
Published Version
Available under Creative Commons: Attribution 4.0

View Download

Atom BibTeX OpenURL ContextObject in Span Multiline CSV OpenURL ContextObject Dublin Core Dublin Core MPEG-21 DIDL Data Cite XML EndNote HTML Citation JSON MARC (ASCII) MARC (ISO 2709) METS MODS RDF+N3 RDF+N-Triples RDF+XML RIOXX2 XML Reference Manager Refer Simple Metadata ASCII Citation EP3 XML
Export

Downloads