Seasonal malaria chemoprevention and the spread of Plasmodium falciparum quintuple mutant parasites resistant to sulfadoxine-pyrimethamine: a modelling study

BackgroundSeasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ) prevents millions of clinical malaria cases in children under five in Africas Sahel region. However, parasites partially resistant to SP (with "quintuple" mutations) potentially threaten SMC protective effectiveness. We evaluated its spread and clinical consequences. MethodsAn individual-based malaria transmission model with explicit parasite dynamics and drug pharmacological models, was used to identify and quantify the influence of factors driving quintuple mutant spread and predict the time needed for the mutant to spread from 1% to 50% of inoculations for several SMC deployment strategies. We estimated the impact of this spread on SMC effectiveness against clinical malaria. FindingsHigher transmission intensity, SMC coverage, and expanded age range of chemoprevention promoted mutant spread. SMC implementation in a high transmission setting (40% parasite prevalence in children aged 2-10 years) with four monthly cycles to children aged three months to five years (with 95% initial coverage declining each cycle), the mutant requires 53{middle dot}1 years (95% CI 50{middle dot}5-56{middle dot}0) to spread from 1% to 50% of inoculations. This time increased in lower transmission settings and reduced by half when SMC was extended to children under ten, or reduced by 10-13 years when an additional monthly cycle of SMC was deployed. For the same setting, the effective reduction in clinical cases in children receiving SMC was 79{middle dot}0% (95% CI 77{middle dot}8-80{middle dot}8) and 60{middle dot}4% (95% CI 58{middle dot}6-62{middle dot}3) during the months of SMC implementation when the mutant was absent or fixed in the population, respectively. InterpretationSMC with SP+AQ leads to a relatively slow spread of SP-resistant quintuple mutants and remains effective at preventing clinical malaria despite the mutant spread. SMC with SP+AQ should be considered in seasonal settings where this mutant is already prevalent. FundingSwiss National Science Foundation and Marie Curie Individual Fellowship.