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Item SINGLE NUCLEOTIDE POLYMORPHISMS OF Pfdhfr RESISTANCE GENE AMONG SYMPTOMATIC PATIENTS’ ISOLATES FROM SELECTED HOSPITALS IN IFO LGA, OGUN STATE(Covenant University Ota, 2025-10) SULE, Queen Elizabeth; Covenant University DissertationMalaria remains a primary universal health concern, particularly in endemic areas where drug resistance poses a serious threat to the effectiveness of key treatment and prevention strategies. Sulfadoxine-pyrimethamine (SP), commonly used for malaria prophylaxis, is increasingly compromised by resistance associated with mutations in the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) gene. This study aimed to assess the prevalence of P. falciparum infection and identify the single-nucleotide polymorphisms (SNPs) in the Pfdhfr resistance gene among symptomatic patients in Ifo Local Government Area, Ogun State, Nigeria. Five hundred patients with severe P. falciparum infection were recruited, and demographic data were recorded. Blood samples were analysed for P. falciparum stages and parasitemia levels using microscopy. DNA was extracted from samples with high parasitemia and genotyped for Pfdhfr mutations using PCR, followed by visualisation on 1% agarose gel electrophoresis. Microscopy confirmed P. falciparum malaria in 300 patients (60%). A significantly higher prevalence (71.05%) was recorded in the 0–4 years’ age group, while males accounted for 64.31% of cases (p < 0.05). Parasitemia levels (greater than 200 parasites/100 μL) were more pronounced in males than in females, and were highest among individuals aged 0–4 years. Among the 10.67% Pfdhfr genotypes identified, males exhibited a higher frequency (6.0%) than females. The overall prevalence of pfdhfr SNPs in N51I, C59R, S108, and I64L was (96%), (96%), (100%), and (0%), respectively. tripple mutant halotype (N51I+ C59R+S108), prevance was 92%. Males have a higher mutation rate (60%) than females (40%). The overall prevalence of pfdhfr SNPs in N51I, C59R, S108, and I164L was (96%), (96%), (100%), and (0%), respectively. tripple mutant halotype (N51I+ C59R+S108), prevance was 92%. Males have a higher mutation rate (60%) than females (40%). Also, individuals aged 0-4 years (20%) and 15-20 years (20%) show higher SNPs than the other age groups. The study highlights a high prevalence of P. falciparum and emerging Pfdhfr resistance mutations, emphasising the need for continuous surveillance and targeted interventions in malaria-endemic regions, such as Ifo LGA, Nigeria.Item EVALUATION OF SYNTHETIC FLAVONOID BASED COMPOUNDS AS INHIBITORS OF Plasmodium falciparum TRANSKETOLASE(Covenant University Ota, 2025-09) OROGUN, Yetunde Grace; Covenant University DissertationMalaria, primarily attributed to Plasmodium falciparum, remains a significant contributor to global mortality, with Africa experiencing the greatest burden, particularly in countries such as Nigeria, the Democratic Republic of Congo, and Mozambique. The rise in resistance to present therapies, including Artemisinin-based Combination Therapies (ACTs), underscores the urgent need for novel drug targets. Transketolase, a thiamine-dependent enzyme in the non-oxidative arm of the pentose phosphate pathway, is vital for parasite metabolism and structurally distinct from the human enzyme, making it a promising selective target. Twenty synthetic flavonoid-based compounds were evaluated as potential inhibitors of P. falciparum transketolase (PfTk). Molecular docking revealed strong binding affinities, while ADMET profiling showed that most compounds complied with Lipinski’s rule. Notably, Compounds 6, 7, 11, and 13 were predicted to be orally bioavailable with favorable pharmacokinetic and drug-likeness properties. The compounds were further tested in vitro against PfTk and human transketolase (hTk), with oxythiamine as the positive control, and cytotoxicity was assessed using hemolysis assays on human red blood cells. The results demonstrated that several compounds exhibited high potency and selective inhibition of PfTk with minimal activity on hTk. Among them, Compounds 6, 7, and 10 emerged as the most promising leads, combining high selectivity, oral bioavailability, and favorable safety margins. Additionally, Compounds 11 and 13, analogues of Compound 10, showed good drug-likeness and oral bioavailability, indicating potential for structural optimization. Hemolysis assays confirmed minimal red blood cell lysis across all compounds, supporting their safety. In conclusion, this study validates PfTk as a viable drug target and identifies Compounds 6, 7, and 10 as strong lead candidates, with Compounds 11 and 13 as promising analogues for further optimization and development of safe, effective antimalarial agents.Item DEVELOPMENT OF A MULTI-LABEL CLASSIFIER FOR PREDICTING GENETIC MARKERS ASSOCIATED WITH MULTI-DRUG RESISTANCE IN Plasmodium falciparum STRAINS(Covenant University Ota, 2025-08) OGUNDIMU, Temitayo Ayomikun; Covenant University DissertationMalaria is an infectious disease of global health importance caused by Plasmodium falciparum. It is highly complicated by parasite’s ability to gain resistance to multiple antimalarial drugs simultaneously, a phenomenon known as multidrug resistance (MDR). Single-label models only predict resistance to one drug at a time and as such would not capture these complex resistance patterns, limiting their utility for real-world surveillance. To bridge this gap, this study developed and evaluated four advanced multi-label classification models: Random Forest with Binary Relevance (RFDTBR), Ensemble of Classifier Chains (ECCJ48), Ensemble of Binary Relevance (EBRJ48), and a Backpropagation Neural Network (BPNN), using genomic and phenotypic data for five key antimalarials. Notably, RFDTBR and EBRJ48 outperformed others in predicting exact MDR profiles, while BPNN performed faster compared to the other models. Sulfadoxine-Pyrimethamine had the lowest performance across the models. Specific genomic features consistently emerged as key predictive factors across all models. These findings demonstrate the value of multi-label learning for comprehensive MDR prediction. Also, effective models and genomic regions were identified, warranting further investigation, thereby paving the way for improved resistance surveillanceItem GENOME-WIDE IDENTIFICATION OF SHORT TANDEM REPEATS ASSOCIATED WITH MULTI-DRUG RESISTANCE IN Plasmodium falciparum STRAINS(Covenant University Ota, 2025-08) EMMANUELLA EKURI MAMTUMAMBOH; Covenant University DissertationAntimalarial drug resistance in Plasmodium falciparum threatens global malaria control, and while single nucleotide polymorphisms (SNPs) are well-studied, the role of short tandem repeats (STRs) remains underexplored. This study investigates the contribution of pathogenic STRs to drug resistance using STR genotypes from HipSTR, phenotypic resistance data, and machine learning models. Allele frequency analysis revealed consistently lower alternative allele frequencies in resistant strains across all 14 chromosomes, with strong selective signals on chromosomes 2, 3, 4, 8, and 13. Population differentiation analyses (PCA, FST) identified key resistance loci near PfKelch13 and plasmepsin 2/3, along with potential novel resistance regions. A logistic regression model trained on STR alleles achieved perfect classification (AUC = 1.00), demonstrating the strong predictive power of STRs in distinguishing resistant from sensitive parasites. Top STRs showed both known and novel associations with resistance, reinforcing the polygenic nature of antimalarial resistance. These findings establish STRs as important genetic markers for resistance surveillance and highlight their potential utility in guiding malaria treatment strategies.