AI Insight
This systematic review and meta-analysis examined artemisinin resistance in East Africa from 2014-2024, analyzing 24 studies for non-synonymous Kelch13 gene mutations in Plasmodium falciparum. The overall pooled proportion of resistance-mediating mutations was 5.0%, with highest prevalence in Rwanda and Uganda (10.0% each), and R561H and A675V identified as the most common mutation types at 9.0% and 7.0% respectively. Patients with these mutations showed significantly higher treatment failure rates compared to those with wild-type parasites.
Why it matters
Artemisinin-based combination therapies are the frontline treatment for malaria globally, and East Africa has historically been a source of antimalarial drug resistance spread across the continent. The documented presence and spread of these resistance mutations threatens malaria control efforts and necessitates enhanced molecular surveillance and coordinated containment strategies to prevent wider dissemination.
Understand the Science
by Anthony Kapesa, Vito Baraka, Richard Mwaiswelo, Maria Zinga, Karol J. Marwa, Eliningaya J. Kweka, Erasmus Kamugisha
Background
Resistance to antimalarial drugs has posed a significant challenge to global efforts to control and eliminate malaria. Partial artemisinin resistance has been observed in East Africa, a region that has been a historical hotspot for antimalarial drug resistance across the continent. Consequently, this review assesses the extent of non-synonymous mutations mediating artemisinin resistance, the varieties of these mutations, and their effects on treatment outcomes in East Africa.
Methods
Studies reporting artemisinin resistance (samples collected between 2014 and 2024), particularly the Pf-Kelch13 mutation among malaria patients in East Africa, were searched through the Medline, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, and EMBASE online databases. The protocol for the review was registered at PROSPERO (Reference number: CRD42024602752). Two independent reviewers extracted data. Potential publication bias was assessed using a funnel plot. Pooled proportion estimates were calculated using a random-effects model, and heterogeneity was assessed using I2 statistics.
Results
Twenty-four (24) studies were deemed eligible for data extraction. The heterogeneity among the studies included in the meta-analysis was high (I2 > 95% and p < 0.01). The overall estimated pooled proportions of non-synonymous Pf-Kelch13 mutations, using the random effects model, were 5.0% (95% CI 3.0%–7.0%), with the pooled proportion estimates being higher in Rwanda and Uganda (10.0%, 95% CI 4.0%–16.0%) and (10.0%, 95% CI 6.0%–14.0%), respectively. Subgroup analysis (per mutation type) revealed that R561H and A675V were the most prevalent non-synonymous mutations (9.0%, 95% CI 5.0%–15.0% and 7.0%, 95% CI 4.0%–10.0%, respectively). Patients harbouring parasites with Pf-Kelch13 non-synonymous mutations were significantly more likely to experience treatment failure than those harbouring wild P. falciparum parasites (Log OR: −2.06, 95% CI, −2.71–1.41).
Conclusion
The prevalence of Pf-Kelch13 non-synonymous mutations known to be associated with artemisinin resistance was significant. The most common mutations identified were R561H and A675V. Continued molecular surveillance and coordinated efforts are essential to contain the partial artemisinin resistance in the East African region and prevent its spread across the continent.