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

Author

Listed:
  • Andria Mousa

    (London School of Hygiene and Tropical Medicine
    Imperial College London)

  • Gina Cuomo-Dannenburg

    (Imperial College London)

  • Hayley A. Thompson

    (PATH)

  • David J. Bell

    (NHS Greater Glasgow and Clyde)

  • Umberto D’Alessandro

    (MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine)

  • Roly Gosling

    (London School of Hygiene and Tropical Medicine
    University of California San Francisco)

  • Alain Nahum

    (Centre de recherche entomologique de Cotonou)

  • Karen I. Barnes

    (University of Cape Town)

  • Jaishree Raman

    (South African National Institute for Communicable Diseases
    University of Witwatersrand)

  • Lesley Workmann

    (University of Cape Town)

  • Yong See Foo

    (The University of Melbourne)

  • Jennifer A. Flegg

    (The University of Melbourne)

  • Emma Filtenborg Hocke

    (University of Copenhagen
    Copenhagen University Hospital)

  • Helle Hansson

    (University of Copenhagen
    Copenhagen University Hospital)

  • Ana Chopo-Pizarro

    (London School of Hygiene and Tropical Medicine)

  • Khalid B. Beshir

    (London School of Hygiene and Tropical Medicine)

  • Michael Alifrangis

    (University of Copenhagen
    Copenhagen University Hospital)

  • R. Matthew Chico

    (London School of Hygiene and Tropical Medicine)

  • Colin J. Sutherland

    (London School of Hygiene and Tropical Medicine)

  • Lucy C. Okell

    (Imperial College London)

  • Cally Roper

    (London School of Hygiene and Tropical Medicine)

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.

Suggested Citation

  • Andria Mousa & Gina Cuomo-Dannenburg & Hayley A. Thompson & David J. Bell & Umberto D’Alessandro & Roly Gosling & Alain Nahum & Karen I. Barnes & Jaishree Raman & Lesley Workmann & Yong See Foo & Jenn, 2025. "Impact of dhps mutations on sulfadoxine-pyrimethamine protective efficacy and implications for malaria chemoprevention," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58326-z
    DOI: 10.1038/s41467-025-58326-z
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    References listed on IDEAS

    as
    1. Jamie T. Griffin & Neil M. Ferguson & Azra C. Ghani, 2014. "Estimates of the changing age-burden of Plasmodium falciparum malaria disease in sub-Saharan Africa," Nature Communications, Nature, vol. 5(1), pages 1-10, May.
    2. repec:plo:pone00:0001471 is not listed on IDEAS
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