Genetic diversity, population structure, and drug resistance of Plasmodium falciparum in Kenya: a systematic review and meta-analysis

A systematic review and meta-analysis of studies carried out in Kenya to assess Plasmodium falciparum genetic diversity and drug resistance was conducted with the aim of tracking parasite dynamics over time and space. In Kenya, malaria has declined in certain regions making it an ideal setting to investigate the impact of control interventions on the parasite population. A systematic electronic search yielded a total of 737 articles from PUBMED (392), google scholar (105) science direct (16) and Web of Science (224). Of these, 58 articles published in Kenya between 2002 and 2023 were eligible and included 21 articles on P. falciparum genetic diversity and 37 articles on drug resistance. Two independent reviewers performed screening, quality and risk of bias assessment and data extraction. Non-parametric tests were used to assess temporal trends. Heterogeneity across studies was assessed using I² statistic and visualized using forest and funnel plots. p-values less than 0.05 were considered significant. To determine parasite diversity, MOI and drug resistance, microsatellites, antigenic targets (Pfmsp1, Pfmsp2, Pfcsp, Pfglurp, Pfs47), SNPs, Pfdhfr/Pfdhps, Pfcrt, and Pfmdr1 genes were genotyped using PCR, sequencing, restriction fragment length polymorphism and Mass array.Expected heterozygosity (He) was high: 0.79 (95% CI 0.77-0.81), 0.80 (95%CI 0.78-0.81) and 0.96 (95% CI 0.96-0.97) in the Lake Basin, Highlands and Coastal region respectively. Heterogeneity was low in the Lake Basin (I² = 32.9%), moderate in the Highlands (I² = 57.6%), and high at the Coast (I² = 92%). Infections were multiclonal (34% to 80%) with a high mean MOI (2-4.8) and lacked spatial or temporal trends. Genetic differentiation varied over time and between regions. Pfcrt haplotype CVIET reduced from 96% in 1999 to 1% in 2017, whereas the CVMNK haplotype increased from 6.8% in 1998 to 98.8% in 2017. A temporal increase in frequency of Pfdhfr-51I, Pfdhfr-59R, Pfdhps-437G and Pfdhps-540E (Mann-Kendall test p < 0.05) was reported. Pfk13 mutations (R539T, N458Y, R561H, A675V and V568G) were reported in the Lake Basin and Highland regions (2018-2024). Pfmdr1 NFD and NYD haplotypes, increased between 2012 and 2017. This review highlights P. falciparum diversity, multiclonal infections, temporal shifts in drug resistance mutations and low to moderate genetic differentiation in parasites from different regions suggesting ongoing transmission and potential connectivity between parasite populations.