Journal article
Disparate co-evolution and prevalence of sulfadoxine and pyrimethamine resistance alleles and haplotypes at dhfr and dhps genes across Africa
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 3.1MB, Terms of use)
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- Publisher copy:
- 10.1038/s41598-025-98035-7
Authors
+ Gates Foundation
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- Funder identifier:
- https://ror.org/0456r8d26
- Grant:
- OPP1204628
- Publisher:
- Springer Nature
- Journal:
- Scientific Reports More from this journal
- Volume:
- 15
- Issue:
- 1
- Article number:
- 13222
- Place of publication:
- England
- Publication date:
- 2025-04-17
- Acceptance date:
- 2025-04-09
- DOI:
- EISSN:
-
2045-2322
- Pmid:
-
40247054
- Language:
-
English
- Keywords:
- Pubs id:
-
2120561
- Local pid:
-
pubs:2120561
- Deposit date:
-
2025-08-15
- ARK identifier:
Terms of use
- Copyright holder:
- White et al
- Copyright date:
- 2025
- Rights statement:
- © 2025 The Authors. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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