Genetic Insights into Plasmodium falciparum Resistance to Sulfadoxine-Pyrimethamine through a Study of the 540-dihydropteroate synthetase gene Mutations in Jos, Nigeria

Abstract

<title>Abstract</title> <bold>Aims:</bold> To investigate mutations in the 540-dihydropteroate synthetase ( <italic>540dhps)</italic> gene, specifically at codon 540, that may confer resistance to sulfadoxine-pyrimethamine treatment by <italic>Plasmodium falciparum</italic> in Jos. <bold>Study design:</bold> This cross-sectional study. <bold>Place and Duration of Study:</bold> The samples for this study were gathered in Jos, Plateau State, Nigeria, between October 2019 and January 2021. <bold>Methodology:</bold> One hundred malaria cases were assessed, and parasite DNA was extracted from whole blood samples using Zymo extraction kits. PCR and gel electrophoresis identified the <italic>Plasmodium</italic> genus and <italic>Plasmodium falciparum</italic> , along with the 540-dihydropteroate synthetase gene. Sanger sequencing and bioinformatics analyses (nucleotide blast, blastx, and query-anchored alignment view with dot of the NCBI tool) were employed. <bold>Results:</bold> Results revealed that 50% of the tested samples were positive for the Plasmodium genus, with 96% identified as <italic>Plasmodium falciparum</italic> . Point mutations were found in the <italic>540dhps</italic> gene at codon K540E in 16.67% of the samples. Interestingly, while a nucleotide mutation occurred in the DNA's coding region, it did not translate into amino acid changes, indicating no likely impact on the protein's functionality. <bold>Conclusion:</bold> This study highlights the prevailing presence of <italic>Plasmodium falciparum</italic> in Jos, with a significant 96% prevalence among malaria patients. Contrary to the previously reported mutations at codon K540E on 540dhps, the mutation observed in the nucleotide sequence in our findings did not affect the amino acid sequence, suggesting that this mutation may not be associated with the literature previously reported on resistance to sulfadoxine-pyrimethamine drug