Evolving genetic landscapes of Plasmodium falciparum Kelch13 polymorphisms in Nigeria: a systematic review and meta-analysis

Abstract Background Malaria incidence has plateaued in recent years, with periodic increases observed in some settings. This trend is driven by multiple factors, including health system disruptions, vector and parasite resistance, and environmental changes. The emergence of partial resistance to artemisinin-based combination therapies (ACTs) has contributed to delayed parasite clearance and, in some regions, treatment failure. Hence, the need to study the polymorphisms in the Plasmodium falciparum Kelch13 gene from studies conducted in Nigeria and imported malaria cases from Nigeria reported in other countries. Methods The systematic review and meta-analysis employed the population, intervention or test, comparison, and outcome (PICO) and preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines to formulate the research questions and report the reviewed articles completely in both the studies in Nigeria and imported Plasmodium falciparum kelch-13 ( Pfk13 ) studies from Nigeria reported in other countries. The review included studies that contained any kind of mutation in the Pfk13 gene from P. falciparum and excluded reports for mutations of other antimalarial resistance. The reviewed articles were generated from PubMed, Springer Nature, and Google Scholar using the litsearchr and metagear packages in R. Heterogeneity analyses for the articles and reported SNPs were carried out. Furthermore, the ordinary least squares (OLS) network model was used to assess the effect of distance on Pfk13 SNP occurrence, while the geostatistical model was used to predict the frequency of Pfk13 SNP in the country. Results In Nigeria, about 124 different Pfk13 single nucleotide polymorphisms (SNPs) have been reported, which are predominantly non-synonymous mutants domiciled in the kelch-13 propeller domain. The studies were heterogeneous in reporting SNPs occurrence ( $$I^2$$ I 2 = 95.3%, $$\\tau ^2$$ τ 2 = 0.0683, $$p<$$ p < 0.0001), and no dominant SNP was reported from the pooled studies ( $$I^2$$ I 2 = 36.0%, $$\\tau ^2<$$ τ 2 < 0.0001, $$p<$$ p < 0.0001). The network model showed no correlation between the spatial locations of the states and the similarity of their Pfk13 alleles ( $$\\beta$$ β = 0.00035, p = 0.51), with high nucleotide diversity ( $$\\pi$$ π = 2.31) of the Pfk13 SNPs. A total of three validated (C580Y, F446I, and A675V) and one candidate (R515K) Pfk13 SNPs were present from the various reports, and the predicted Pfk13 mutation frequency showed a marginally higher occurrence in the Southeast and South-South regions of the country and Lagos State. Conclusion Highly diverse and independent emergence of Pfk13 SNPs together with those that are responsible for artemisinin partial resistance has been reported in Nigeria. These patterns underscore the urgent need for sustained Pfk13 genomic surveillance and ACT therapeutic efficacy studies to preempt and mitigate the establishment and spread of artemisinin- and partner drug-resistant strains in the country.