🎙️ Episode 19: Genotype-Specific Chemoprevention with Sulfadoxine-Pyrimethamine

🧬 In this episode of Base by Base, we examine a comprehensive analysis by Mousa et al. (2025) in Nature Communications that quantifies how mutations in the Plasmodium falciparum dihydropteroate synthase (dhps) gene affect the duration of protection conferred by sulfadoxine-pyrimethamine (SP) chemoprevention across Africa. A Bayesian multi-strain model was applied to reinfection data from seven therapeutic efficacy studies involving 1,639 participants across twelve African sites, enabling simultaneous estimation of genotype-specific protective durations and mapping of SP efficacy in diverse resistance settings .

🔍 Main highlights: Protection against dhps sulfadoxine-susceptible parasites extends beyond 42 days, while protection against the West African dhps GKA genotype lasts a median of 30.3 days (95% Credible Interval: 17.1–45.1). The East African dhps GEA and highly resistant dhps GEG genotypes reduce median protection to 16.5 days (95% CrI: 11.2–37.4) and 11.7 days (95% CrI: 8.0–21.9), respectively; model validation against intermittent preventive treatment in infants (IPTi) trials from Mozambique and Tanzania demonstrated strong agreement between predicted and observed reinfection patterns. Continent-wide predictions based on genotype frequency maps revealed 30-day protective efficacy ranging from 59.3% to 91.5% and median protection durations from 17.2 to 37.2 days, guiding targeted SP deployment strategies. Comparative analyses with SP–amodiaquine (SPAQ) and SP–chloroquine (SPCQ) combinations highlight enhanced protection against resistant genotypes where amodiaquine efficacy remains high .

🧠 Conclusion: By providing robust genotype-specific estimates of SP protective efficacy and developing an interactive prediction tool for local genomic surveillance integration, this study equips malaria control programs with actionable insights to tailor chemoprevention strategies and optimize SP-based interventions across varying transmission and resistance landscapes .

📖 Reference:
Mousa, A., Cuomo-Dannenburg, G., Thompson, H. A., et al. (2025). Impact of dhps mutations on sulfadoxine-pyrimethamine protective efficacy and implications for malaria chemoprevention. Nature Communications, 16, 4268. https://doi.org/10.1038/s41467-025-58326-z

📜 License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International license (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/