Osazuwa John Patrick, Olukemi Kehinde Amodu, Adewale Allen Sokan-Adeaga, Micheal Ayodeji Sokan-Adeaga, Yasuhiro Kotera
The emergence and spread of the Plasmodium falciparum multidrug-resistant 1 (Pfmdr1) allele pose a significant setback to global efforts to control and eradicate malaria infection by diminishing the efficacy of commonly prescribed antimalarial drugs, particularly in Sub-Saharan Africa, where malaria remains endemic. The Pfmdr1 D1246Y mutation is of specific importance due to its potential role in modulating parasite susceptibility to antimalarial medicines and treatment outcomes. This study aimed to determine the presence and prevalence of the wild-type and mutant D1246Y alleles of Pfmdr1 among children in Ibadan, Southwest Nigeria. A total of 133 archived DNA samples collected between March 2016 and June 2021 from children aged 6 to 132 months with varying malaria phenotypes (asymptomatic infection, uncomplicated, and severe malaria) were analyzed. The Pfmdr1 D1246Y allele was amplified via nested PCR, and the mutation was detected using the restriction enzyme EcoRV. The digested nested PCR products were resolved on a 2% agarose gel and visualized under ultraviolet light. All statistical analyses were performed using SPSS version 25, and statistical significance was set at p ≤ 0.05. Among the 133 samples, 97 (72.9%) were successfully genotyped. Of these, 50 (51.55%) carried the wild-type allele, while 47 (48.45%) had the mutant allele. Notably, the Pfmdr1-1246Y mutation was detected in all severe malaria cases (41/41, 100%), whereas its prevalence was significantly lower in asymptomatic (3/36, 8.3%) and uncomplicated malaria cases (3/20, 15%). The difference in mutation prevalence across the malaria phenotypes was statistically significant (p < 0.05). The study provided valuable insight into the coexistence of wild-type and mutant Pfmdr1 D1246Y alleles within the population. It revealed a significantly higher mutation rate in all severe malaria cases, while the wild-type allele remained more prevalent overall. These findings contribute to a deeper understanding of the possible role of the wild-type and mutant D1246Y alleles in the various clinical manifestations of malaria.
Multidrug Resistance-Associated Proteins
Antimalarials
Mdr1 protein, Plasmodium falciparum
