World Health Organization. World Malaria Report 2023. (Geneva, 2023).
World Health Organization. WHO Guidelines for Malaria. (Geneva, 2022).
Esu, E. B., Oringanje, C. & Meremikwu, M. M. Intermittent preventive treatment for malaria in infants. Cochrane Database Syst. Rev. 7, Cd011525 (2021).
Okell, L. C., Griffin, J. T. & Roper, C. Mapping sulphadoxine-pyrimethamine-resistant Plasmodium falciparum malaria in infected humans and in parasite populations in Africa. Sci. Rep. 7, 7389 (2017).
Plowe, C. V. Malaria chemoprevention and drug resistance: a review of the literature and policy implications. Malar. J. 21, 104 (2022).
Amimo, F. et al. Plasmodium falciparum resistance to sulfadoxine-pyrimethamine in Africa: a systematic analysis of national trends. BMJ Glob. Health 5, e003217 (2020).
Picot, S. et al. A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria. Malar. J. 8, 89 (2009).
Gregson, A. & Plowe, C. V. Mechanisms of resistance of malaria parasites to antifolates. Pharm. Rev. 57, 117–145 (2005).
Infectious Diseases Data Observatory (IDDO). SP Molecular Surveyor. Infectious Diseases Data Observatory. (InteractiveResource). https://www.wwarn.org/tracking-resistance/sp-molecular-surveyor (2015).
Naidoo, I. & Roper, C. Mapping ‘partially resistant’, ‘fully resistant’, and ‘super resistant’ malaria. Trends Parasitol. 29, 505–515 (2013).
Flegg, J. A. et al. Spatiotemporal spread of Plasmodium falciparum mutations for resistance to sulfadoxine-pyrimethamine across Africa, 1990-2020. PLoS Comput. Biol. 18, e1010317 (2022).
Gosling, R. D. et al. Protective efficacy and safety of three antimalarial regimens for intermittent preventive treatment for malaria in infants: a randomised, double-blind, placebo-controlled trial. Lancet 374, 1521–1532 (2009).
Gesase, S. et al. High resistance of Plasmodium falciparum to sulphadoxine/pyrimethamine in northern Tanzania and the emergence of dhps resistance mutation at Codon 581. PLoS ONE 4, e4569 (2009).
Griffin, J. T. et al. Protective efficacy of intermittent preventive treatment of malaria in infants (IPTi) using sulfadoxine-pyrimethamine and parasite resistance. PLoS ONE 5, e12618 (2010).
Cairns, M. et al. Duration of protection against clinical malaria provided by three regimens of intermittent preventive treatment in tanzanian infants. PLoS ONE 5, e9467 (2010).
Gutman, J. et al. The A581G mutation in the gene encoding plasmodium falciparum dihydropteroate synthetase reduces the effectiveness of sulfadoxine-pyrimethamine preventive therapy in Malawian pregnant women. J. Infect. Dis. 211, 1997–2005 (2015).
Chico, R. M. et al. Influence of malaria transmission intensity and the 581G mutation on the efficacy of intermittent preventive treatment in pregnancy: systematic review and meta-analysis. Trop. Med. Int. Health 20, 1621–1633 (2015).
Hansson, H. et al. Reduced birth weight caused by sextuple drug-resistant Plasmodium falciparum Infection in early second trimester. J. Infect. Dis. 224, 1605–1613 (2021).
Sandison, T. G. et al. Protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children in rural Uganda: a randomised clinical trial. Br. Med. J. 342, d1617 (2011).
Macete, E. et al. Intermittent preventive treatment for malaria control administered at the time of routine vaccinations in Mozambican infants: a randomized, placebo-controlled trial. J. Infect. Dis. 194, 276–285 (2006).
Mayor, A. et al. Molecular markers of resistance to sulfadoxine-pyrimethamine during intermittent preventive treatment for malaria in Mozambican infants. J. Infect. Dis. 197, 1737–1742 (2008).
Chandramohan, D. et al. Cluster randomised trial of intermittent preventive treatment for malaria in infants in area of high, seasonal transmission in Ghana. Br. Med. J. 331, 727–733 (2005).
Cairns, M. et al. Duration of protection against malaria and anaemia provided by intermittent preventive treatment in infants in Navrongo, Ghana. PLoS ONE 3, e2227 (2008).
Bell, D. J. et al. Sulfadoxine-pyrimethamine-based combinations for malaria: a randomised blinded trial to compare efficacy, safety and selection of resistance in Malawi. PLoS ONE 3, e1578 (2008).
Nahum, A. et al. Extended high efficacy of the combination sulphadoxine-pyrimethamine with artesunate in children with uncomplicated falciparum malaria on the Benin coast, West Africa. Malar. J. 8, 37 (2009).
Barnes, K. I. et al. Sulfadoxine-pyrimethamine pharmacokinetics in malaria: pediatric dosing implications. Clin. Pharmacol. Therap. 80, 582–596 (2006).
Mabuza, A. et al. Therapeutic efficacy of sulfadoxine-pyrimethamine for Plasmodium falciparum malaria. S. Afr. Med. J. 95, 346–349 (2005).
Barnes, K. I. et al. Increased gametocytemia after treatment: an early parasitological indicator of emerging sulfadoxine-pyrimethamine resistance in falciparum malaria. J. Infect. Dis. 197, 1605–1613 (2008).
Bredenkamp, B. L. F., Sharp, B. L. & Barnes, K. I. Failure of sulphadoxine-pyrimethamine in treating Plasmodium falciparum malaria in KwaZulu-Natal. SAMJ 91, 970–972 (2001).
Allen, E. N. et al. Efficacy of sulphadoxine-pyrimethamine with or without artesunate for the treatment of uncomplicated Plasmodium falciparum malaria in southern Mozambique: a randomized controlled trial. Malar. J. 8, 141 (2009).
Mousa, A. et al. Measuring protective efficacy and quantifying the impact of drug resistance: a novel malaria chemoprevention trial design and methodology. PLoS Med. 21, e1004376 (2024).
Morris, C. A. et al. Review of the clinical pharmacokinetics of artesunate and its active metabolite dihydroartemisinin following intravenous, intramuscular, oral or rectal administration. Malar. J. 10, 263 (2011).
Bell, D. J. et al. Measurement of adherence, drug concentrations and the effectiveness of artemether-lumefantrine, chlorproguanil-dapsone or sulphadoxine-pyrimethamine in the treatment of uncomplicated malaria in Malawi. Malar. J. 8, 204 (2009).
Foo, Y. S. & Flegg, J. A. A spatio-temporal model of multi-marker antimalarial resistance. J. R. Soc. Interface 21, 20230570 (2024).
Watkins, W. M., Mberu, E. K., Winstanley, P. A. & Plowe, C. V. The efficacy of antifolate antimalarial combinations in Africa: a predictive model based on pharmacodynamic and pharmacokinetic analyses. Parasitol. Today 13, 459–464 (1997).
Cissé, B. et al. Seasonal intermittent preventive treatment with artesunate and sulfadoxine-pyrimethamine for prevention of malaria in Senegalese children: a randomised, placebo-controlled, double-blind trial. Lancet 367, 659–667 (2006).
Sokhna, C. et al. A trial of the efficacy, safety and impact on drug resistance of four drug regimens for seasonal intermittent preventive treatment for malaria in Senegalese children. PLoS ONE 3, e1471 (2008).
Nuwa, A. et al. A non-randomized controlled trial to assess the protective effect of SMC in the context of high parasite resistance in Uganda. Malar. J. 22, 63 (2023).
Juliano, J. J., Gadalla, N., Sutherland, C. J. & Meshnick, S. R. The perils of PCR: can we accurately ‘correct’ antimalarial trials? Trends Parasitol. 26, 119–124 (2010).
Barnes, K. I., Watkins, W. M. & White, N. J. Antimalarial dosing regimens and drug resistance. Trends Parasitol. 24, 127–134 (2008).
Adegbola, A. J. et al. A snapshot of the prevalence of dihydropteroate synthase-431V mutation and other sulfadoxine-pyrimethamine resistance markers in Plasmodium falciparum isolates in Nigeria. Malar. J. 22, 71 (2023).
Lynch, C. et al. Emergence of a dhfr mutation conferring high-level drug resistance in Plasmodium falciparum populations from southwest Uganda. J. Infect. Dis. 197, 1598–1604 (2008).
Takata, J. et al. The World Wide Antimalarial Resistance Network Clinical Trials Publication Library: a live, open-access database of plasmodium treatment efficacy trials. Am. J. Trop. Med. Hyg. 103, 359–368 (2020).
Okell, L. C. et al. Contrasting benefits of different artemisinin combination therapies as first-line malaria treatments using model-based cost-effectiveness analysis. Nat. Commun. 5, 5606 (2014).
Bretscher, M. T. et al. The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data. BMC Med. 18, 47 (2020).
Stan Development Team RStan: the R interface to Stan. https://mc-stan.org/ (2024).
Griffin, J. T. et al. Reducing Plasmodium falciparum malaria transmission in Africa: a model-based evaluation of intervention strategies. PLOS Med. 7, e1000324 (2010).
Griffin, J. T., Ferguson, N. M. & Ghani, A. C. Estimates of the changing age-burden of Plasmodium falciparum malaria disease in sub-Saharan Africa. Nat. Commun. 5, 3136 (2014).
Weiss, D. J. et al. Mapping the global prevalence, incidence, and mortality of Plasmodium falciparum, 2000-17: a spatial and temporal modelling study. Lancet 394, 322–331 (2019).
Pfeffer, D. A. et al. malariaAtlas: an R interface to global malariometric data hosted by the Malaria Atlas Project. Malar. J. 17, 352 (2018).
Vehtari, A., Gelman, A., Simpson, D., Carpenter, B. & Bürkner, P.-C. Rank-normalization, folding, and localization: an improved R ̂ for assessing convergence of MCMC (with discussion). Bayesian Anal. 16, 667–718 (2021).
Tatem, A. J. WorldPop, open data for spatial demography. Sci. Data 4, 170004 (2017).
Mousa, A. SP-resistance-protective-efficacy-code. https://doi.org/10.5281/zenodo.14988819 (2025).
Roper, C. et al. Antifolate antimalarial resistance in southeast Africa: a population-based analysis. Lancet 361, 1174–1181 (2003).
Svigel, S. S. et al. Low prevalence of highly sulfadoxine‐resistant dihydropteroate synthase alleles in Plasmodium falciparum isolates in Benin. Malar. J. 20, 72 (2021).
Guémas, E. et al. Evolution and spread of Plasmodium falciparum mutations associated with resistance to sulfadoxine-pyrimethamine in central Africa: a cross-sectional study. Lancet Microbe 4, e983–e993 (2023).
da Silva, C. et al. Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique. Commun. Biol. 6, 619 (2023).
