Abstract
Abstract
Background
The emergence and subsequent spread of antimalarial drug resistance represent a significant threat to the efficacy of artemisinin-based combination therapies (ACTs) in sub-Saharan Africa. Multiple molecular markers have been implicated in resistance to artemisinin and its partner drugs. We conducted a systematic review and meta-analysis of studies published between 2010 and 2024 in sub-Saharan Africa.
Methods
The protocol was registered in PROSPERO (CRD42023432718). Studies were identified through PubMed/MEDLINE, Web of Science, Scopus, Embase, and African Journal Online. Study selection, data extraction, and risk-of-bias assessment were performed independently by two reviewers in accordance with the PRISMA 2020 guidelines. Prevalence data for mutations in
PfKelch13
,
Pfcrt
,
Pfmdr1
, and
Pfdhfr/Pfdhps
were extracted and analysed using random-effects models, with pooled prevalence estimates generated using a generalized linear mixed model (GLMM) with logit transformation. Between-study heterogeneity was assessed using Cochran’s Q and I
2
statistics.
Results
A total of 172 studies on
PfKelch13
, 182 on
Pfcrt
, 196 on
Pfmdr1
, and 176 on
Pfdhfr/Pfdhps
were included. From 2014 to 2023, validated
PfKelch13
mutations exhibited marked spatial and temporal heterogeneity, with R622I, R561H, and A675V expanding primarily in East Africa, reaching prevalences of 10–25% in Rwanda, Uganda, and Tanzania. In Central Africa, emergence was observed in 2021 at low levels (below 5%), while West Africa reported only sporadic low-prevalence (below 1%) detections. In contrast, resistance to some partner drugs declined substantially across Africa, with
Pfcrt
K76T decreasing from 76% (95% CI: 49% − 91%;
I
2
= 97.9%) in 2010 to 9% (95% CI: 8.7% − 9.5%;
I
2
= 96.8%) in 2023 and
Pfmdr1
N86Y falling from 34% (95% CI: 26% − 43%;
I
2
= 93.5%) to zero (95% CI: 0% − 11%;
I
2
= 97.1%), with persistent regional heterogeneity. Certain markers of sulfadoxine–pyrimethamine (SP) resistance (
Pfdhfr
N51I, C59R, S108N and
Pfdhps
A437G) remained near fixation, whereas
Pfdhfr
I164L,
Pfdhps
K540E, and
Pfdhps
A581G showed pronounced spatial clustering, with the highest prevalence reported in East and parts of Central Africa.
Conclusion
Overall, the temporal and regional patterns of antimalarial drug resistance molecular markers across sub-Saharan Africa underscore the need for sustained molecular surveillance tailored to local epidemiological trends of resistance markers.
Registration
Protocol registered in the International Prospective Register of Systematic Reviews (PROSPERO; registration number CRD42023432718).