Potential policy interventions for slowing the spread of artemisinin-resistant pfkelch R561H mutations in Rwanda

Artemisinin combination therapies (ACTs) are highly effective at treating uncomplicated Plasmodium falciparum malaria. However, the emergence of a novel pfkelch13 R561H mutation in Rwanda, with associated delayed parasite clearance, suggests that drug policy interventions are needed to delay the fixation and slow the spread of this mutation. Using a spatial, stochastic, individual-based model calibrated and validated for the Rwanda's malaria epidemiology, we evaluate seventeen strategies aimed at minimizing treatment failures and delaying the spread of R561H. The primary measures evaluated are projected treatment failures and R561H allele frequency over three, five, and ten years. Lengthening courses of treatment, deploying multiple first-line therapies, and custom rotation strategies all provide a benefit when compared to the status quo. The best intervention options, five years into the future, result in slower spread of R561H (0.16 allele frequency difference) and absolute treatment failure counts that are 44% lower than projected under the status quo.