Mapping Plasmodium falciparum mutations in Africa: A critical review of emerging drug resistance and implications for malaria control

Abstract

Malaria remains a significant public health concern in Africa, with the efficacy of artemisinin-based combination therapies being threatened by the emergence of Plasmodium falciparum (Pf) kelch13 mutations. The current genetic diversity of Pf and associated contributing factors reported in Africa between 2019 and 2024 were reviewed. It was shown that validated kelch13 mutations are mainly distributed in east African regions, particularly, in Eritrea (R622I, 68%) and Uganda (R561H, 52%). Emerging Pf mutations have been documented in Rwanda (C469F, 36%), Uganda (C469F, 59% and P441L, 69%), and Tanzania (P441L, 20%). Resistance markers for partner drugs, including Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps, were prevalent in eastern (30-38%) and western African regions (44-55%). The key factors contributing to the development of Pf mutations were identified as drug pressure (23-35%), misuse of antimalarial drugs (10-12.5%), and cross-border population movements (10%). This review posits a critical need to refine malaria control programs, crucially reinforcing drug regulations, enhancing community awareness on appropriate treatment practices, and integrating molecular epidemiologic surveillance systems.

Keywords: Africa; Artemisinin; Mutations; Plasmodium falciparum; Resistance.

Figure 1

(a, b, and c) Distribution of candidate and validated mutations in African regions.

Figure 2

(a, b, c, and d) Frequency of reported candidate and validated mutations in African regions.