Changes in the prevalence of antimalarial partner drug resistance markers and policy in six sub-Saharan African countries from 2000 to 2021: A systematic review

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 based on 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. Estimated prevalence of Pfcrt 76T declined following cessation of CQ, though at variable levels between 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. 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 time 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.