National Institute for Pharmaceutical Research and Development

BackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency, prevalent in malaria-endemic regions, has been associated with a reduced risk of severe malaria due to impaired parasite growth in deficient erythrocytes. The G6PD gene, located on the X chromosome, harbours various mutations associated with differing enzyme activity levels. This study investigates the prevalence of G6PD deficiency variants and their impact on parasite density and haemoglobin levels among malaria-positive patients in Awka, Anambra State, Nigeria.Materials and MethodsBlood samples were collected from 100 malaria positive participants; 64 participants with complete genotyping and clinical data were included in the analysis and screened for the A376G and G202A variants using PCR and Sanger sequencing.Results Molecular analysis indicated that the B variant (normal) was predominant, with 83% of the participants possessing this variant. None of the participants tested had the A- variant, associated with G6PD defciency, suggesting no evidence of the G202A (A−) variant in this hospital-based sample. The B variant and the A+ variant showed no significant impact on the haemoglobin and parasitaemia levels of the study participants. Conclusions The findings support the absence of the G202A (A−) variant in this cohort and show no detectable differences in parasitaemia or haemoglobin between A+ and B genotypes. Broader genotyping and/or G6PD enzyme activity testing in community representative samples is recommended before drawing population-level conclusions or informing treatment policy.

Vaccines are essential health interventions that have become a cost-effective tool for maintaining public health. Access to vaccines in Nigeria and other developing countries is, however, affected by various relevant issues, including insufficient supply, inequitable distribution, vaccine hesitancy, and a lack of local manufacturing capacity. This study, therefore, aimed to gain an in-depth understanding of the challenges impeding vaccine production in Nigeria, taking lessons from the COVID-19 pandemic. A qualitative study was undertaken using a purposive sampling strategy to recruit key stakeholders across Nigeria's vaccine value chain. Interviews were carried out using a semi-structured interview guide. Relevant stakeholders with varying levels of experience across the vaccine value chain were interviewed to ensure that robust and comprehensive data were obtained. The data collected were subjected to thematic analysis, following the interpretivist tradition. Throughout the study, trustworthiness was assured by adopting relevant processes such as data triangulation, reflexive and audit trails. Ethical approval was obtained from the National Institute for Pharmaceutical Research and Development Health Research Ethics Committee prior to the commencement of data collection. This study revealed eight thematic areas underpinning the gaps associated with local vaccine production in Nigeria. Challenges included limited capacity, inadequate research and development, infrastructure deficits, and a sub-optimal environment for vaccine development. Furthermore, the challenges associated with commercialisation and distribution were identified. Findings also revealed a lack of critical factors required for expediting vaccine manufacturing in Nigeria, including poor commitment to collaboration, an absence of sustainability policies and sub-optimal legislation. The study provides insight into systemic and structural barriers to local vaccine production in Nigeria. It identifies key areas requiring urgent intervention, which include funding, infrastructure, human capacity, and regulatory reform. Addressing these gaps through multi-level strategies is critical for improving vaccine self-sufficiency. Evidence from this study can help develop contextual strategies that will expedite vaccine production and Medicines' Security in Nigeria.

The COVID-19 pandemic posed a major public health challenge with varying devastating effects on the global community. Vaccination is the most effective measure in combating this pandemic. A major challenge, especially in resource-limited settings, was the shortage of the vaccines. However, evidence by WHO in the use of fractionated doses in combating yellow fever prompted the evaluation of the safety and immunogenicity of fractionated doses of COVID-19 vaccines (ChAd0x1, AD26.COV2.S, and BNT162B2) among Nigerian adults (18-65years). This is a multi-center, non-inferiority randomized, triple-blind trial involving 1812 COVID-19 vaccine naïve participants. Six hundred four eligible participants will be randomized into each of the three vaccine arms of ChAd0x1, AD26.COV2.S, and BNT162B2 COVID-19 vaccine. 151 participants will be randomized each into the 25% and 50% fractionated dose and 300 in the standard full dose arm for the ChAd0x1 and AD26.COV2.S group. In the BNT162B2 group, 201 participants will be randomized into the 50% fractionated dose and 403 into the standard dose arms. The efficacy (immunogenicity) will be evaluated by collecting blood samples at baseline (day 0) and day 28 after immunization to determine the geometric mean fold rise (GMFR) of ≥ 2.5 within the range of 20% non-inferiority to the standard dose of anti-SARS-CoV-2 S antibody response detected by ELISA termed as seroconversion. Safety and adverse events will be evaluated through active evaluation during the first 72h of vaccine administration and on days 14 and 28 of clinic visits. The trial will also assess secondary immunogenicity variables of 50% plaque plaalite reduction neutralization by antibodies against SARS-CoV-2 variants (α, δ, and κ) and cytokines production (IFNα, γ, and IL-2 producing CD4 and CD8 T lymphocytes). The proposed trial will allow for a comprehensive understanding of the immunologic responses and safety profile of fractional doses compared to full doses of COVID-19 vaccines among Nigerian adults. In addition, this will guide policy implementation for prompt vaccination of the population to maximize access to the limited vaccines available during the COVID-19 pandemic or future epidemics/pandemics. The study is registered at the Pan African Clinical Trials Registry (PACTR), a primary registry in the WHO International Clinical Trial Platforms. PACTR202206754734018. Registered on June 1, 2022, Accessible at: https://pactr.samrc.ac.za/ Trial Sponsor: Open Philanthropy.

This study aimed to examine the molecular docking studies of methanol seed fractions of Buchholzia coriacea GCMS identified compounds against target compound protein structure via experimental and computational models. This study identified the active sites, as well as the functional groups (Methane isocyanato, xylene) in the α-amylase and α-glucosidase enzymes which were competitively inhibited. The mode of inhibition of in vitro α-amylase and α-glucosidase activity on the carbohydrate metabolizing enzymes was established to be competitive inhibition. The result of the oxidative stress enzyme shows that, there was a significant decrease (p<0.05) in super oxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and a significant increase (p>0.05) in TBARS in diabetic rats when compared with normal and extract treated rats. A closer look at the results of the carbohydrate metabolizing enzymes shows that there was a significant increase (p>0.05) in Hexokinase, Phosphofructokinase (PFK), Glucose-6-phosphatase and Liver glycogen. When looking at the kidney function indices, the results reveal that there was a significant decrease (p<0.05) in Serum creatinine, Serum Urea and Serum Albumin, when compared with the diabetic control and extract treated Rats. Molecular docking of GC-MS-identified phyto-compounds from Buchholzia coriacea methanol seed fractions demonstrates strong binding potential to target proteins, supporting their therapeutic relevance. These findings, validated through experimental and computational models, highlight the plant’s promise for future drug development.

BackgroundDiabetes mellitus (DM) is a major cause of morbidity and mortality globally as it is associated with long-term health complications which affect the quality of life. Several plants are used in traditional medicine to manage diabetes, with claims of efficacy from traditional healers. One such plant is Balanites aegyptiaca (L.) Delile commonly called Desert Date. This systematic review examines the therapeutic effect of B.aegyptiaca on diabetes mellitus.MethodsThe protocol for the systematic review was registered with PROSPERO (CRD42024587444). Four databases were searched for articles from 1986 to 1st August 2024. Keywords related to “therapeutic effect”, “Balanites aegyptiaca” and “diabetes mellitus” were used. Studies included were all animal models. Each article was critically appraised by two independent reviewers for their methodological quality using the Joanna Briggs Institute Case Control Checklist. The Cochrane SYRICLE Risk of bias tool was used for risk of bias assessment in these animal intervention studies. The animal experiments were conducted mainly in Alloxan- and streptozotocin-induced rat/mice diabetes and a control of non-diabetes induced rats.ResultA total of 32 articles were included. All the studies were appraised for blood glucose levels, and a reduction in blood glucose was reported in all in vivo studies, regardless of the plant part used. Significant decrease in blood glucose level was recorded in Alloxan- and streptozotocin-induced rat/mice diabetes. All the studies reported reduced blood glucose, reduced levels of lipids, reduced weight and increased insulin production. B. aegyptiaca mitigated hyperglycaemia irrespective of the presentation form, which includes extract and meal supplementation in rodents, oral capsule intake, and tea or fruit consumption in humans. Various mechanisms, including modulation of glucose metabolizing enzymes, were reported to underlie the B. aegyptiaca antidiabetic effect.ConclusionsRepeated administration of different parts of B. aegyptiaca in different presentation forms controlled hyperglycaemia in animal-models. A full-phase clinical trial is needed to determine the therapeutic effects of B. aegyptiaca in humans.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024587444.

e23059 Background: The STAMPEDE2 trial builds on the foundational STAMPEDE trial, which introduced innovative multi-arm treatment protocols for metastatic prostate cancer. This survey assessed Nigeria’s readiness for the STAMPEDE2 trial by evaluating current clinical practices, radiotherapy infrastructure, systemic therapy usage, and imaging capabilities across its six geopolitical zones. Methods: We mapped the radiotherapy centres and machines currently available (commissioned) and in the pipeline in Nigeria. A structured questionnaire comprising 31 questions in six sections was disseminated to clinical oncologists via Google Forms. The survey ran from July to September 2024, gathering data on radiotherapy availability, systemic therapies, advanced imaging, and readiness for clinical trial participation. Descriptive statistical analysis was conducted using Microsoft Excel. Responses were aggregated from 14 cancer centres across Nigeria, encompassing public and private facilities. Results: The survey identified 23 operational radiotherapy machines distributed across 12 centres, with 19 additional facilities in the pipeline. These centres were predominantly located in urban areas such as Lagos and Abuja. Prostate cancer treatment modalities are available; however, access to novel agents such as abiraterone and enzalutamide was reported in 73% of centres. There is one operational PET/CT facility in Nigeria. Clinicians expressed strong interest in participating in trials, though some gaps in infrastructure, particularly in rural areas, and limited access to advanced treatments like 177Lu-PSMA-617 were noted. Conclusions: The findings underscore Nigeria’s potential readiness for the STAMPEDE2 trial, as well as other clinical trials and collaborative research, bolstered by an expanding radiotherapy infrastructure and clinician enthusiasm for advanced therapeutic approaches. Initiatives like the Cancer Health Fund (CHF) and the National Cancer Access Partnership (NCAP) represent significant steps towards equitable cancer care.

Background: Aspirin is widely utilized for cardiovascular event prevention and fever management, making it one of the most frequently prescribed medications. It boasts a singular mechanism of action, specifically targeting thromboxane A2 production to prevent platelet activation, unmatched by other antiplatelet agents. The majority of commercial aspirin products are plagued by gastrointestinal sideeffects and inconsistent absorption, ultimately reducing their bioavailability and therapeutic potential. These observations underscore the critical need for aspirin formulation that exhibit optimal absorption and minimized variability. The liquisolid process is an age-long approach for improving oral drug solubility and absorption. Methods: Herein, we formulated different aspirin liquisolid tablets (ALS1-ALS15) and exposed them to pre and post-compression studies to identify the optimized formulation, after which we compared and investigated the predicted plasma concentration-time profiles of aspirin prototype drug from in vitro dissolution results using a mathematical convolution approach for In vitro-in vivo correlation (IVIVC) study. Results: All formulations had near-excellent flowability. The differential scanning calorimetry and Fourier transform infra-red spectral showed no major interactions between aspirin crystals and the excipients used in this study. Formulation ALS5 exhibited preferred physicochemical properties and was therefore chosen as the optimal formula. The time to attain peak plasma concentration was similar for both the test and the reference product (0.5 h). In contrast, their maximum plasma concentration deviates by 1.23 and 21.75 percent from the authentic reference values derived from the literature. Conclusion: The percentage of predicted errors achieved revealed that the convolution technique could predict plasma drug levels of aspirin liquisolid tablets as per FDA guidelines.

Lack of access to effective contraception methods can lead to an increased prevalence of unintended pregnancies, as well as possible deleterious health consequences. Community pharmacies represent the most accessible gateway for population medicines' and healthcare needs. Regarding contraceptives, they have also been identified as a platform for the provision of additional services, such as complementary counselling. This study aimed at assessing the knowledge, attitudes, and practices of community pharmacy staff towards contraception. A cross-sectional study was undertaken in the Federal Capital Territory, Nigeria. Data were collected from 315 community pharmacy staff using self-administered questionnaires. The participants' knowledge and attitude scores were categorised using Bloom's cut-off point. Analyses were undertaken using Statistical Package for Social Sciences. The data were analysed using frequency distribution, chi-square, and linear regression at a 5% level of significance. Male participants in the study (165/315, 52.4%) were slightly higher than the female respondents (150/315, 47.6%), and about two-thirds of the study cohort were pharmacists (200/315, 63.5%). The majority of the participants (183/315, 58.1%) had poor knowledge of contraceptive use. A quarter of them (81/315, 25.7%) reported moderate attitudes. Almost all the participants (279/298, 93.6%) indicated recommending contraceptives for married adults, and a significant proportion of them (136/292, 45.5%) were opposed to recommending contraceptives for unmarried adolescents. Study respondents' professional role was also identified as a significant influence on their knowledge of contraceptives and contraception (p < 0.001). Findings from this study revealed poor knowledge and negative attitudes of community pharmacy staff towards contraception. Government and relevant stakeholders can build on these novel findings to reform pertinent contextual policies and practices. This can significantly improve access to contraceptives amongst the populace, and consequently reduce unintended pregnancies alongside possible health and societal implications.

Abstract: Human immunodeficiency virus (HIV), the primary cause of Acquired Immunodeficiency Syndrome (AIDS), is responsible for millions of deaths worldwide. As of 2022, Nigeria has a prevalence rate of 1.4%, with approximately 1.9 million individuals infected, contributing to about two-thirds of the deaths attributable to this illness in sub-Saharan Africa. Micronutrient deficiency is a common issue among individuals living with HIV, exacerbating immune suppression, negatively impacting prognosis, and accelerating the progression of the infection. Therefore, this research aimed to investigate the effects of various doses of selenium and zinc supplements on the weight and immune function of HIV-infected individuals through weight and CD4 monitoring, with the goal of providing a solution for improved management of HIV. A total of 30 subjects (25 HIV-infected individuals and 5 healthy controls) were selected and divided into six groups, with five individuals per group; groups 1 and 6 served as negative and positive controls, respectively. Different doses of selenium and zinc, or combinations thereof, were administered to the groups for 12 weeks while assessing the outcomes through weight measurements and CD4 count analysis at 28-day intervals. The generated data were analyzed using two-way ANOVA. The results demonstrated a significant difference in mean weight and CD4 counts across the different groups (p-value &lt; 0.05). This indicates that selenium and zinc supplements are viable options for enhancing antiretroviral therapy (ART) in the treatment of HIV..