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Author: search.filters.author.Covenant University DissertationSubject: search.filters.subject.Malaria

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    EXPRESSION PROFILES OF CYTOCHROME P450 GENES ASSOCIATED WITH PERMETHRIN RESISTANCE IN Anopheles gambiae s.l. IN ADO-ODO OTA, OGUN STATE
    (Covenant University Ota, 2025-10) AINA, Motunrayo Oluwabunmi; Covenant University Dissertation
    Malaria remains a significant tropical public health threat, where resistance to insecticides constitutes a severe hindrance to the efficacy of its primary vector control methods. Routinely applied pyrethroid insecticides are increasingly facing resistance associated with the overexpression of cytochrome P450 genes in the Anopheles gambiae sensu lato, underscoring the urgent search into these associated genes. This study assessed the expression profile of cytochrome P450 genes associated with permethrin resistance in Anopheles gambiae sensu lato collected from three localities in Ado-Odo, Ota. Ethical approval was obtained from the Covenant Health Research Ethics Committee (CHREC). Based on the WHO standard, female adult An. gambiae larvae (n=300) were collected using the dipping method and reared into adults in the Insectary Laboratory. These laboratory-reared mosquitoes were phenotypically identified using microscopy and genotypically characterised using polymerase chain reaction (PCR) based on species-specific primers. Thereafter, a WHO susceptibility bioassay was conducted in vivo for mosquitocidal activity against these adult mosquitoes in four replicates at a 0.75% permethrin concentration each on day 3 post-adult emergence. The relative expression of the cytochrome P450 genes (CYP6M2 and CYP6P3) was carried out using the quantitative real-time PCR (qRT-PCR). Higher occurrence rate of An. gambiae sensu lato. was recorded in Nestle (80%)), Chelsea (78%)) compared Gasline (30%) localities of Ado-Odo. In vivo insecticide susceptibility testing revealed consistently low mortality rates across all the replicates, ranging from 20% to 32% indicating increased resistance to permethrin. Results of relative expression of cytochrome P450 genes showed higher fold changes in CYP6M2 ranging from 0.63 to 122.4 than in CYP6P3 0.63 to 34.39 across the tested mosquito replicates. Thus, this study has further emphasized the prevalence of An. gambiae sensu lato members in Ado-Odo, Ota. Additionally, the results of higher permethrin resistant and upregulation of CYP6M2 and CYP6P3 genes inform the imminent need for integrated resistance surveillance with newer vector management for improved malaria control.
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    EVALUATION OF SYNTHETIC FLAVONOID BASED COMPOUNDS AS INHIBITORS OF Plasmodium falciparum TRANSKETOLASE
    (Covenant University Ota, 2025-09) OROGUN, Yetunde Grace; Covenant University Dissertation
    Malaria, 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.
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    EFFECTS OF INTERLEUKIN- 6 MEDIATED INFLAMMATION ON TELOMERASE EXPRESSION IN MALARIA PATIENTS
    (Covenant University Ota, 2025-09) FIAMITIA, Carrin; Covenant University Dissertation
    Malaria remains a major global health burden that mostly affects young children in the African region, which has been associated with cellular aging and immune system exhaustion that is potentially mediated through telomere shortening and altered telomerase activity. The influence of malaria on the catalytic subunit hTERT, and how it modulates telomerase expression, in relation to the proinflammatory cytokines such as interleukin-6 (IL-6) and interferon-gamma (IFN-γ) is yet to be established. This study, therefore, aimed to explore the relationship between IL-6, IFN-γ levels, and hTERT gene expression in individuals with malaria infection. Ethical approval was obtained from the Covenant Health Research Ethics Committee (CHREC) before commencement of the study. A total of 50 malaria-infected samples were collected from ACE-Medicare and Covenant University Medical Center. Plasma generated from venous blood samples (5 ml) was separated by centrifugation, collected, and stored at –80 °C for subsequent cytokine analysis. Total RNA was extracted for cDNA synthesis and RT-qPCR-based quantification of hTERT expression. RNA concentration, integrity, and purity were analyzed using a Nanodrop spectrophotometer. A portion of the plasma (100 μl) was used for cytokine analysis using human IL-6 and IFN-γ using ELISA technique. Interleukin-6 levels (17.47 ± 25.11 pg/ml) were significantly higher (p<0.05) in the case compared to the control group (0.54 ± 0.46 pg/ml). The interferon gamma levels (117.74 ± 51.62 pg/ml) in the case group showed no significant difference (p>0.05) compared to the control group (104.50 ± 55.23 pg/ml). The Ct values of the hTERT gene expression were 33.38±4.48 in malaria patients in Nigeria, which is a possible standard range. For the first time, this study reports hTERT gene expression levels in Nigerian malaria patients and IL-6 as potential biomarkers for monitoring malaria progression, thereby providing a valuable tool for precision malaria treatment in Nigeria
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    EFFECTS OF INTERLEUKIN- 6 MEDIATED INFLAMMATION ON TELOMERASE EXPRESSION IN MALARIA PATIENTS
    (Covenant University Ota, 2025-09) FIAMITIA, Carrin; Covenant University Dissertation
    Malaria remains a major global health burden that mostly affects young children in the African region, which has been associated with cellular aging and immune system exhaustion that is potentially mediated through telomere shortening and altered telomerase activity. The influence of malaria on the catalytic subunit hTERT, and how it modulates telomerase expression, in relation to the proinflammatory cytokines such as interleukin-6 (IL-6) and interferon-gamma (IFN-γ) is yet to be established. This study, therefore, aimed to explore the relationship between IL-6, IFN-γ levels, and hTERT gene expression in individuals with malaria infection. Ethical approval was obtained from the Covenant Health Research Ethics Committee (CHREC) before commencement of the study. A total of 50 malaria-infected samples were collected from ACE-Medicare and Covenant University Medical Center. Plasma generated from venous blood samples (5 ml) was separated by centrifugation, collected, and stored at –80 °C for subsequent cytokine analysis. Total RNA was extracted for cDNA synthesis and RT-qPCR-based quantification of hTERT expression. RNA concentration, integrity, and purity were analyzed using a Nanodrop spectrophotometer. A portion of the plasma (100 μl) was used for cytokine analysis using human IL-6 and IFN-γ using ELISA technique. Interleukin-6 levels (17.47 ± 25.11 pg/ml) were significantly higher (p<0.05) in the case compared to the control group (0.54 ± 0.46 pg/ml). The interferon gamma levels (117.74 ± 51.62 pg/ml) in the case group showed no significant difference (p>0.05) compared to the control group (104.50 ± 55.23 pg/ml). The Ct values of the hTERT gene expression were 33.38±4.48 in malaria patients in Nigeria, which is a possible standard range. For the first time, this study reports hTERT gene expression levels in Nigerian malaria patients and IL-6 as potential biomarkers for monitoring malaria progression, thereby providing a valuable tool for precision malaria treatment in Nigeria.