Abstract
BACKGROUND: Prompt malaria case management is a cornerstone for malaria control and elimination. However, this strategy is threatened by the development of antimalarial drug resistance. Resistance is mediated through spontaneous genetic changes such as mutations, but drug pressure is the main driver of resistance spread. Molecular markers of resistance may provide insight into spatiotemporal dynamics of drug resistance and how drug policy changes may affect the spread of resistance. METHODS: We conducted a systematic review to assess the dynamics of Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps mutations from 2000 to 2021. Six countries from sub-Saharan Africa were selected by availability of molecular data and varying antimalarial drug policies: Kenya, Malawi, and Uganda in East Africa and Burkina Faso, Côte d'Ivoire, and Nigeria in West Africa. Medline, Embase, Cochrane, and Elsevier databases were searched for relevant literature, and identified records were screened for prevalence data and extracted. RESULTS: Overall, 138 studies were included. The estimated prevalence of Pfcrt 76T declined following cessation of chloroquine, though at variable levels among countries. All countries saw an increase in Pfmdr1 N86/D1246 prevalence, with faster increases in East Africa, while Pfmdr1 184F prevalence increased, except in Burkina Faso. The prevalence of Pfdhfr (51I/59R/108N) and Pfdhps (436A/437G/540E) mutations reached fixation levels in most countries; however, the 164L and 581G mutations increased during the period only in Kenya and Uganda. CONCLUSIONS: Our study provides compelling evidence on the impact of antimalarial drug policy change on molecular markers of resistance and their potential use to monitor drug resistance spread.