Regional variation in sulfadoxine-pyrimethamine resistance genotypes and haplotypes of Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase genes in Western Kenya.

ABSTRACT:

Background

Surveillance of molecular markers associated with antimalarial resistance in Plasmodium falciparum is critical for tracking the emergence, evolution, and spread of resistant malaria parasites in the population for timely and effective interventions. As shifting use of sulfadoxine-pyrimethamine (SP) in Kenya constitutes a differential selection pressure, this study compared resistance genotypes and haplotypes in P. falciparum isolates from endemic and epidemic regions of western Kenya.

Methods

A cross-sectional design was employed to collect blood samples from febrile patients residing in Ahero in Kisumu County, an endemic region, and Marani in Kisii County, an epidemic region. Molecular markers for antifolate resistance, dihydrofolate reductase (Pfdhfr) and dihydrofolate synthetase (Pfdhps), were genotyped for selected samples (N = 112) from Kisumu (n = 60) and Kisii (n = 52). Subsequent analysis was conducted for sequence polymorphisms, mutation frequency and haplotype prevalence.

Results

Genotyping of SP resistance markers identified 436H (28.8%), 437G (99%), and 540E (97.1%) in Pfdhps and 51I (100%), 59R (97.3%), and 108N (100%) in Pfdhfr as mutations that presented high frequency, with low multiplicity of infection (MOI) in both Kisumu (0.3196) and Kisii (0.2738). The double mutant SGEAA (70.18% in Kisumu vs. 51.06% in Kisii) and triple mutant HGEAA (26.31% vs. 44.68%) in Pfdhps, along with the triple mutant IRNI (86.67% vs. 98.08%) in Pfdhfr, exhibited significant regional differences in prevalence (p < 0.05). The Pfdhps-Pfdhfr haplotype analysis revealed a high prevalence of the quintuple mutant SGEAA-IRNI (57.89% in Kisumu vs. 48.94% in Kisii; p > 0.05) and a significantly higher prevalence of the sextuple mutant HGEAA-IRNI in Kisii compared to Kisumu (44.68% vs. 16.31%; p < 0.05). Comparatively, given that Pfdhps-516F and Pfdhfr-164L were the dominant alleles in Kisumu, while the Pfdhps-436H allele was dominant in Kisii, along with HGEAA and HGEAA-IRNI haplotypes (p < 0.05), they highlight regional variation in SP resistance genotypes and haplotypes.

Conclusions

This study demonstrates that the fully resistant double Pfdhps-SGEAA and triple Pfdhfr-IRNI haplotypes have approached fixation in both endemic and epidemic regions, while the dominance of the 164L allele in the endemic region signals the emergence of super-resistance. These findings suggest a review of the therapeutic efficacy of SP and continuous surveillance of resistance due to the presence of fully resistant haplotype (SGEAA-IRNI) and super-resistant haplotype (F/HGEAA-IRNL) in the population of P. falciparum strains in western Kenya.

SUBMITTER: Bungei J 

PROVIDER: S-EPMC12486705 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature