Abstract
<title>Abstract</title> <p>Background: Malaria incidence has plateaued in recent years, with periodic increasesobserved in some settings. This trend is driven by multiple factors, including health systemdisruptions, vector and parasite resistance, and environmental changes. The emergence ofpartial resistance to artemisinin-based combination therapies (ACTs) has contributed todelayed parasite clearance and, in some regions, treatment failure. Methods: The systematic review and meta-analysis employed the population, intervention ortest, comparison, and outcome (PICO) and preferred reporting items for systematic reviewsand meta-analyses (PRISMA) guidelines to formulate the research questions and reportthe reviewed articles completely in both the studies in Nigeria and imported Plasmodiumfalciparum kelch-13 (Pfk13 ) studies from Nigeria reported in other countries. The reviewedarticles were generated from PubMed, Springer Nature, and Google Scholar using the litsearchrand metagear packages in R. Heterogeneity analyses for the articles and reported SNPs werecarried out. Furthermore, the ordinary least squares (OLS) network model was used to assessthe effect of distance on Pfk13 SNP occurrence, while the geostatistical model was used topredict the frequency of Pfk13 SNP in the country. Results: In Nigeria, about 124 different Pfk13 single nucleotide polymorphisms (SNPs) havebeen reported, which are predominantly non-synonymous mutants domiciled in the kelch-13propeller domain. The studies were heterogeneous in reporting SNPs occurrence (I2 = 95.3%,τ 2 = 0.0683, p < 0.0001), and no dominant SNP was reported from the pooled studies (I2= 36.0%, τ 2 < 0.0001, p < 0.0001). The network model showed no correlation between the spatial locations of the states and the similarity of their Pfk13 alleles (β = 0.00035, p =0.51), with high nucleotide diversity (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 thevarious reports, and the predicted Pfk13 mutation frequency showed a marginally higheroccurrence in the Southeast and South-South regions of the country and Lagos State. Conclusion: Highly diverse and independent emergence of Pfk13 SNPs together withthose that are responsible for artemisinin partial resistance has been reported in Nigeria.These patterns underscore the urgent need for sustained Pfk13 genomic surveillance andACT therapeutic efficacy studies to preempt and mitigate the establishment and spread ofartemisinin- and partner drug-resistant strains in the country.</p>