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Item The Impact of Plasmodium falciparum Adenosine Triphosphatase-6 Gene (PfATPase6) Mutations in Artemisinin Resistance(Journal of Pure and Applied Microbiology, 2025) Obafemi, Dorcas Yemisi; Atokolo, AustineThe World Health Organization (WHO) recorded an estimated 263 million malaria cases globally in 2023, leading to about 597,000 mortalities. Most of this burden occurred in the WHO African Region, which accounted for approximately 94% of cases and 95% of malaria-related deaths. Artemisininbased combination therapies (ACTs) remain the mainstay of malaria treatment globally; however, the emergence of Plasmodium falciparum resistance compromises their sustained efficacy. Although mutations in the Plasmodium falciparum Kelch 13 (Pfk13) propeller domain are largely proven to be markers of partial artemisinin resistance, greater focus has turned to Plasmodium falciparum Adenosine Triphosphatase 6 (PfATPase6) as a potential supplementary determinant. This review compiled evidence from published articles between 2015 and 2025, sourced from Google Scholar, PubMed, ProQuest, and ScienceDirect, with a focus on PfATPase6 polymorphisms, their distribution, functional role, detection techniques, and implications for malaria prevention. Notable nonsynonymous single-nucleotide polymorphisms (SNPs) such as E431K, S769N, A623E, S769M, and M699V have been reported spanning Asia, the Americas, and Africa. Several studies reveal a correlation with decreased in vitro susceptibility or enhanced artemether Half Maximal Inhibitory Concentration (IC50), although findings are inconsistent due to interrelated resistance markers, environmental differences, and deviations in methodology. Recent improvements in molecular monitoring techniques, like nextgeneration sequencing, high-resolution melting analysis, and advanced real-time polymerase chain reaction (PCR) techniques, have broadened the ability to detect uncommon variants and have reinforced surveillance systems. Despite inconsistency in findings, there is evidence that PfATPase6 reduces sensitivity to artemisinin; therefore, it should be taken into consideration in resistance surveillance schemes. It is recommended to incorporate PfATPase6 genotyping alongside Pfk13 surveillance and treatment efficacy studies to offer more insights into the emergence of resistance. These approaches are vital to expound the underexplored role of the PfATPase6 in resistance patterns and encourage the sustainability of antimalarial drugs.Item Impact of multi-active ingredient long-lasting insecticidal nets for malaria vector control in sub-Saharan Africa: a systematic review and meta-analysis(Discover Public Health 23(1), 2026) Ahuekwe, E. F.; Taiwo, D. I.Strong selective pressures on mosquitoes arise from an over-reliance on a narrow range of insecticides and the continuous increase in insecticide resistance. This increased resistance weakens the effectiveness of conventional single-ingredient vector control interventions, thus undermining the efforts to reduce malaria transmission. This study aimed to assess the comparative efficacy of multi-active ingredients interventions, which include pyrethroid combinations with pyriproxyfen, chlorfenapyr, and piperonyl butoxide (PBO), versus single-active ingredients approaches in reducing malaria prevalence and key entomological outcomes in malaria-endemic regions. A systematic review and meta-analysis were conducted in accordance with the PRISMA guidelines. Studies were selected based on specific inclusion criteria, including randomised controlled trials conducted in sub-Saharan Africa and interventions focused on multi-active ingredient (MAI) approaches. Data on malaria prevalence, vector density, sporozoite rate, and entomological inoculation rate (EIR) were extracted. Random- and fixed-effects models were applied to evaluate the pooled effects, and heterogeneity was assessed using a diagnostic plot. Publication bias was examined using funnel and forest plots. Four studies met the inclusion criteria, which comprise a total of 135,706 households for pyrethroid-only ITNs, 117,652 for pyrethroid-pyriproxyfen, 118,518 for pyrethroid-chlorfenapyr, and 63,331 for pyrethroid-PBO interventions. Chlorfenapyr-pyrethroid combinations showed the most substantial reduction in malaria prevalence (adjusted odds ratio (aOR) 0.53; 95% CI: 0.30–0.67) and entomological inoculation rate (aOR 0.13; 95% CI: 0.07–0.31). Although pyriproxyfen and PBO combinations also reduced vector density and sporozoite rates, chlorfenapyr exhibited the highest efficacy, especially in regions with established pyrethroid resistance. Publication bias was observed, resulting in a slight overestimation of the effectiveness of MAI-LLINs interventions. MAI-LLINs approaches, particularly chlorfenapyr-pyrethroid interventions, have demonstrated superior effectiveness compared to single-active-ingredient (SAI) LLIN interventions in reducing malaria transmission metrics in sub-Saharan Africa. While the results underline the potential of MAI-LLINs strategies, further research and collaborative studies are needed to optimise MAI-LLINs deployment, assess long-term impacts on resistance, and ensure cost-effectiveness in resource-limited settings.Item Inhibitors of Protein Targets of Plasmodium falciparum(Journal of Pure and Applied Microbiology, 2024-11-24) Oranusi, Solomon Uche; Mameh, Emmanuel Ojochegbe; Oyegbade, Samuel Adeniyi; Balogun, Daniel Oluwatobiloba; Aririguzoh, Victoria-Grace OnyekachiThe World Health Organization documented 247 million reported malaria cases worldwide resulting in 619,000 fatalities in 2021. More than 70% of these deaths are attributed to Children under five years of age and sub-Saharan Africa is the region in which the highest number of deaths occur. The Plasmodium falciparum parasite is the deadliest form of malaria, and treating falciparum infection is becoming more challenging due to the emergence of drug-resistant parasites, causing a decrease in the efficiency of antimalarial medications. Artemisinin combination therapy is now considered the gold standard for malaria treatment; however, this method is at risk due to parasites exhibiting delayed clearance to artemisinin and resistance to partner drugs such as lumefantrine, amodiaquine, mefloquine, piperaquine, and sulfadoxine/pyrimethamine. This review assessed drug targets in Plasmodium falciparum for the development of novel antimalarials. Over Eighty-five papers on malaria, Plasmodium falciparum protein targets, and protein inhibitors were gathered from Google Scholar, ProQuest, PubMed, and Science Direct, between 2012 and 2023. Only articles with comparable keywords on malaria drug targets concentrating on enzyme proteins, carrier molecules present in Plasmodium falciparum, and their inhibitors were retrieved for review, while articles within that range that did not provide definite data were excluded. Most recently, inhibitors of dihydroorotate dehydrogenase (DHODH), artefenomel (OZ439), and ferroquine have been reported and are being explored in combination with other partner medications to work against different stages of plasmodium parasite. In identifying target proteins for drug development, essentiality and vulnerability throughout the life cycle of the parasite, its druggability, and the availability of target-based assays are critical factors. The use of modern proteomics and cellular proteins from database search which assists in parasite proliferation delivers optimal information on the new generation of lead compounds. In addition, advances in in silico methods enable the identification of protein targets for drug development.Item Prevalence and insecticide resistance in Anopheles coluzzii in Ado-Ota, Nigeria(Preprints, 2025-02-13) Nwinyi, Obinna Chukwuemeka; Balogun, D. O.; Isibor, P. O.Item Targeting invasion-associated proteins PfSUB2 and PfTRAMP in Plasmodium falciparum: identification of potential inhibitors via molecular docking(BMC Infectious Diseases, 2025) Okafor, Esther. O.; Bella-Omunagbe, Mercy; Elugbadebo, Temitope; Dokunmu, Titilope M.; Adebiyi, EzekielPlasmodium falciparum subtilisin-like protease 2 (PfSUB2) is responsible for processing Plasmodium falciparum thrombospondin-related apical merozoite protein (PfTRAMP). These proteins are essential for asexual blood stage growth and RBC invasion and have, therefore, been identified as potential drug targets. This study predicted the three-dimensional structure of PfSUB2 and PfTRAMP and identified potential inhibitors using molecular docking methods. Five hundred nineteen compounds were docked against both proteins with AutoDock Vina in PyRx. Compounds 139,974,934 and 154,414,021 exhibited better binding affinities when compared to the standard inhibitors, PMSF, which highlights them as suitable inhibitors and potential antimalarials targeting PfTRAMP and PfSUB2. It also highlights 155,204,487 as a compound with dual antimalarial target potential, exhibiting a better binding affinity to PfTRAMP and PfSUB2. The study recommends 139,974,934, 154,414,021, and 155,204,487 as possible compounds for antimalarial drug development.Item Interleukin-6-Mediated Inflammation on Telomere Length Dynamics in Malaria Infection(NIPES-Journal of Science and Technology, Research Vol. 7, 2025) Afolabi, Israel Sunmola; Fiamitia, Carrin—Malaria, an infectious disease caused by Plasmodium species, remains a significant global health concern, contributing to millions of deaths annually, particularly in endemic regions. In 2023, approximately 263 million malaria cases were reported, according to the World Malaria Report. Malaria infection triggers an inflammatory response critical to its pathogenesis, with cytokines as potential biomarkers and therapeutic targets. Among these, interleukin-6 (IL-6) plays a crucial role in disease progression, immune regulation, and severity. Emerging evidence suggests that chronic inflammation induced by malaria infection may accelerate telomere attrition. Telomere length, a key biomarker of cellular aging, naturally declines with age; however, malaria-associated inflammation appears to expedite this process. Telomere shortening can be counteracted by Telomerase, an enzyme whose activity is tightly regulated by human Telomerase reverse transcriptase (hTERT). Telomerase and hTERT contribute to genomic stability and cellular longevity, with hTERT expression modulated by IL-6 through activation of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway. Despite this understanding, the relationship between telomerase activity, telomere length, IL-6 levels, hTERT expression, and malaria infection remains poorly understood. This review synthesizes current findings on IL-6-mediated inflammation and its potential impact on telomere length, telomerase activity, and hTERT expression. We examine studies exploring how persistent inflammation in malaria may drive cellular senescence, telomere dysfunction, and disease severity. Gaining knowledge of how IL-6 regulates Telomerase may help identify new biomarkers, therapeutic targets, and immune based interventions for malaria-induced immune dysregulation. Future research should focus on elucidating the precise molecular mechanisms linking inflammation to telomere dynamics and exploring strategies to mitigate immune cell senescence in malaria patients.Item 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 DissertationMalaria 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.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 EFFECTS OF INTERLEUKIN- 6 MEDIATED INFLAMMATION ON TELOMERASE EXPRESSION IN MALARIA PATIENTS(Covenant University Ota, 2025-09) FIAMITIA, Carrin; Covenant University DissertationMalaria 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 NigeriaItem EFFECTS OF INTERLEUKIN- 6 MEDIATED INFLAMMATION ON TELOMERASE EXPRESSION IN MALARIA PATIENTS(Covenant University Ota, 2025-09) FIAMITIA, Carrin; Covenant University DissertationMalaria 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.