Impact of dhps mutations on sulfadoxine-pyrimethamine protective efficacy and implications for malaria chemoprevention

Sulfadoxine-pyrimethamine (SP) is recommended for perennial malaria chemoprevention in young children in high burden areas across Africa. Mutations in the dihydropteroate synthase (dhps) gene (437 G/540E/581 G) associated with sulfadoxine resistance vary regionally, but their effect on SP protective efficacy is unclear. We retrospectively analyse time to microscopy and PCR-confirmed re-infection in seven efficacy trials including 1639 participants in 12 sites across Africa. We estimate the duration of SP protection against parasites with different genotypes using a Bayesian mathematical model that accounts for variation in transmission intensity and genotype frequencies. The longest duration of SP protection is >42 days against dhps sulfadoxine-susceptible parasites and 30.3 days (95%Credible Interval (CrI):17.1-45.1) against the West-African genotype dhps GKA (437G-K540-A581). A shorter duration of protection is estimated against parasites with additional mutations in the dhps gene, with 16.5 days (95%CrI:11.2-37.4) protection against parasites with the east-African genotype dhps GEA (437G-540E-A581) and 11.7 days (95%CrI:8.0-21.9) against highly resistant parasites carrying the dhps GEG (437G-540E-581G) genotype. Using these estimates and modelled genotype frequencies we map SP protection across Africa. This approach and our estimated parameters can be directly applied to any setting using local genomic surveillance data to inform decision-making on where to scale-up SP-based chemoprevention or consider alternatives.

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Publication Details

Journal
Nature Communications
Published
2025-05-08
DOI
https://doi.org/10.1038/s41467-025-58326-z
Citations
6
Primary Topic
Malaria Research and Control
Type
article
Field-Weighted Citation Impact
11.27

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article

Impact of dhps mutations on sulfadoxine-pyrimethamine protective efficacy and implications for malaria chemoprevention

Ana Chopo-Pizarro, Andria Mousa, Karen I. Barnes, Umberto D’Alessandro et al.
6 citations
Nature Communications
Malaria Research and Control
11.27
article

Impact of dhps mutations on sulfadoxine-pyrimethamine protective efficacy and implications for malaria chemoprevention

Ana Chopo-Pizarro, Andria Mousa, Karen I. Barnes, Umberto D’Alessandro, Emma Filtenborg Hocke, Yong See Foo, Hayley A Thompson, Colin J. Sutherland, Roly Gosling, Jaishree Raman, Gina Cuomo-Dannenburg, Lucy Okell, Helle Smedegaard Hansson, Jennifer A. Flegg, Alain Nahum, Khalid B. Beshir, Cally Roper, R Matthew Chico, David Bell, Michael Alifrangis, Lesley Workmann
article en
6 citations

Abstract

Sulfadoxine-pyrimethamine (SP) is recommended for perennial malaria chemoprevention in young children in high burden areas across Africa. Mutations in the dihydropteroate synthase (dhps) gene (437 G/540E/581 G) associated with sulfadoxine resistance vary regionally, but their effect on SP protective efficacy is unclear. We retrospectively analyse time to microscopy and PCR-confirmed re-infection in seven efficacy trials including 1639 participants in 12 sites across Africa. We estimate the duration of SP protection against parasites with different genotypes using a Bayesian mathematical model that accounts for variation in transmission intensity and genotype frequencies. The longest duration of SP protection is >42 days against dhps sulfadoxine-susceptible parasites and 30.3 days (95%Credible Interval (CrI):17.1-45.1) against the West-African genotype dhps GKA (437G-K540-A581). A shorter duration of protection is estimated against parasites with additional mutations in the dhps gene, with 16.5 days (95%CrI:11.2-37.4) protection against parasites with the east-African genotype dhps GEA (437G-540E-A581) and 11.7 days (95%CrI:8.0-21.9) against highly resistant parasites carrying the dhps GEG (437G-540E-581G) genotype. Using these estimates and modelled genotype frequencies we map SP protection across Africa. This approach and our estimated parameters can be directly applied to any setting using local genomic surveillance data to inform decision-making on where to scale-up SP-based chemoprevention or consider alternatives.

Nature CommunicationsVol. 16(1)
National Health Laboratory Service (ZA), University of Copenhagen (DK), University of London (GB), Program for Appropriate Technology in Health (US), University of Cape Town (ZA), The University of Melbourne (AU), University of the Witwatersrand (ZA), NHS Greater Glasgow and Clyde (GB), Copenhagen University Hospital (DK), London School of Hygiene & Tropical Medicine (GB), Aidjan-Lagos Corridor Organization (BJ), MRC Unit the Gambia (GM), Centre National Hospitalier et Universitaire Hubert Koutoukou MAGA (BJ), Progamme National Contre le Tuberculose (BJ), Global Brain Health Institute (US), London Centre for Neglected Tropical Disease Research (GB), South African Institute for Medical Research (ZA), Imperial College London (GB)
Global Fund to Fight AIDS, Tuberculosis and Malaria, European Commission, Foreign, Commonwealth and Development Office, Medical Research Council, European and Developing Countries Clinical Trials Partnership
Good health and well-being
Openalex Percentile: Top 2%
Malaria Research and Control
11.27
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