SELECTIVE SWEEP AND PHYLOGENETIC MODELS FOR THE EMERGENCE AND SPREAD OF SULFADOXINE-RESISTANCE MUTATION IN PLASMODIUM FALCIPARUM MALARIA WITHIN THE TRIBAL AREAS OF KHYBER PAKHTUNKHWA PAKISTAN
Main Article Content
Keywords
Malaria, plasmodium falciparum, DHPS gene, haplotypes, sulfadoxine-resistance, selective sweep model
Abstract
Background: Malaria remains a significant global health challenge, particularly affecting populations in tropical and subtropical regions. In Pakistan, malaria is highly prevalent and pose a substantial burden on public health especially in the Tribal Areas of Khyber Pakhtunkhwa province, which shares borders with Afghanistan. However, due to political instability and challenges in implementing malaria control initiatives, resistance to sulfadoxine has emerged in this region, subsequently spreading to other parts of the country. Here, we present for the first time evidence of emergence and spread of signal nucleosides polymorphisms (SNPs) of dihydropteroate synthetase (DHPS) gene in plasmodium falciparum (P.f) in tribal areas of Khyber Pakhtunkhwa (KP) province, Pakistan.
Methodology: After the microscopic and rapid diagnostic test, DNA of P. falciparum was extracted from infected patients blood samples and a 711-base pair segment of the DHPS gene having polymorphic codons, using nested PCR. The PCR products were then subjected to Sanger sequencing and sequences were further verified using Bioedit software to confirm peak patterns, and a phylogenetic tree was constructed using MEGA12 software. Selective sweep models were employed to examine the soft and hard selective sweep model for sulfadoxine resistance gene in nine localities with in each tribal area of Khyber Pakhtunkhwa. Pakistan.
Results: Sixteen mutations were identified in the DHPS gene of plasmodium falciparum. Notably, E556K and K582K mutations were observed in all the samples, while R610K were occurred in 82.35%, M538R in 76.47%, and R608K in 64.71% of the samples respectively. Conversely, H536L and H630L mutations exhibited the lowest occurrence at 5.88%. Phylogenetic analysis revealed 16 unique haplotypes, with FATA regions of Dera Ismail Khan and Kohat each displaying a single haplotype. Bajaur Agency exhibited a higher degree of similarity with a specific haplotype.
Conclusion: This study sheds light on the dynamics of sulfadoxine resistance emergence and spread in P. falciparum DHPS gene within tribal areas of Khyber Pakhtunkwa, highlighting the importance of continued molecular surveillance in guiding malaria control strategies. The findings underscore the urgent need for targeted interventions to mitigate the spread of sulfadoxine-resistant strains and preserve the efficacy of antimalarial treatments in these high-risk areas.
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Abdul Wahab
Department of Microbiology, Kohat University of Science and Technology, Kohat, Pakistan,
Mubbashir Hussain
Department of Microbiology, Kohat University of Science and Technology, Kohat, Pakistan
Taj Ali Khan
Department of Medicine, University of Florida, USA
Umer Chaudry
Department of Comparative Biomedical Sciences, School of Veterinary Medicine, University of Surrey, Guildford GU2 7AL, United Kingdom
Mohammad Haroon Khan
City University of Science and Information Technology Peshawar, Pakistan
Fozia Fozia
Department of Biochemistry, KMU Institute of Dental Sciences, Kohat,26000, KP, Pakistan
Ijaz Ahmad
Department of Chemistry, Kohat University of Sciences & Technology, Kohat, Pakistan
Noor Ul Akbar
Department of Zoology, Kohat University of Science and Technology, Kohat, Pakistan,