Genetic surveillance for monitoring the impact of drug use on Plasmodium falciparum populations

Abstract

The use of antimalarial drugs is an effective strategy in the fight against malaria. However, selection of drug resistant parasites is a constant threat to the continued use of this approach. Antimalarial drugs are used not only to treat infections but also as part of population-level strategies to reduce malaria transmission toward elimination. While there is strong evidence that the ongoing use of antimalarial drugs increases the risk of the emergence and spread of drug-resistant parasites, it is less clear how population-level use of drug-based interventions like seasonal malaria chemoprevention (SMC) or mass drug administration (MDA) may contribute to drug resistance or loss of drug efficacy. Critical to sustained use of drug-based strategies for reducing the burden of malaria is the surveillance of population-level signals related to transmission reduction and resistance selection. Here we focus on Plasmodium falciparum and discuss the genetic signatures of a parasite population that are correlated with changes in transmission and related to drug pressure and resistance as a result of drug use. We review the evidence for MDA and SMC contributing to malaria burden reduction and drug resistance selection and examine the use and impact of these interventions in Senegal. Throughout we consider best strategies for ongoing surveillance of both population and resistance signals in the context of different parasite population parameters. Finally, we propose a roadmap for ongoing surveillance during population-level drug-based interventions to reduce the global malaria burden.

Impact of different mutations on Kelch13 protein levels, ART resistance and fitness cost inPlasmodium falciparumparasites

“…Due to their lower fitness cost, they may be favored in high malaria incidence settings due to high inter-parasite competition (high rate of multiple infections) and lower treatment rates in the infected population 34–36 . Our findings therefore suggest that lowering malaria incidence through control measures may increase the risk for the development of higher level resistance, as previously proposed 27,35,43,51,52 . The presence of low-resistance mutations in Sub-Saharan Africa also shows that resistance can occur at high malaria incidence.…”

Low genetic diversity of Plasmodium falciparum merozoite surface protein 1 and 2 and multiplicity of infections in western Ethiopia following effective malaria interventions

“…Though high MOI and genetic diversity have been associated with higher malaria-endemicity, these indices as determined by msp1 and msp2 typing may not be sensitive enough at a lower overall transmission level as seen in Ethiopia [12,41,50,51]. However, the lack of differences with the relative variance in transmission intensities might be an indication that malaria control measures that reduce entomological inoculation rate [52,53], and deployment of artemisinin-combination therapy that reduce population diversity by removing the drug-sensitive parasites [54] have been effective in Ethiopia. It is also possible differences in human demography, ecology, and Anopheles mosquito vector might be shaping P. falciparum population structure in malaria-endemic sites [55][56][57].…”

Evolutionary genetics of malaria

“…Namely, more parasite genomics data is being generated, which has enough resolution to study genetic relatedness of parasites. Such data is appropriate for molecular surveillance of transmission routes ( Ndiaye et al, 2021 ). Formal population-genetic frameworks to describe the evolutionary genetics of malaria that consider relapses do not exist.…”