Adebanjo Jonathan Adegbola

Despite decades of investment in global health, Africa remains underrepresented in the generation of scientific knowledge needed to address its own health challenges [1–3]. This persistent imbalanc...

Lumefantrine is a key partner drug in artemether-lumefantrine therapy, yet data describing its pharmacokinetics among women with efavirenz-based antiretroviral therapy remains limited. This study aimed to characterise the population pharmacokinetics of lumefantrine in pregnant and non-pregnant Nigerians living with HIV, evaluate the influence of pregnancy and CYP3A5 genotype, and assess the adequacy of current and alternative dosing regimens with respect to day-7 plasma concentration targets. Plasma lumefantrine concentrations were analysed using nonlinear mixed-effects modelling in Pumas. Structural models comprising one to three compartments, along with alternative absorption models, were evaluated. Pregnancy status and CYP3A5 expressor status, among other candidate covariates, were tested using a stepwise covariate modelling procedure. Model robustness was assessed using nonparametric bootstrap resampling and simulation-based diagnostics. Monte Carlo simulations were then performed to compare the probability of achieving a day-7 lumefantrine concentration of at least 0.2 µg/mL under current versus alternative dosing regimens. Lumefantrine pharmacokinetics were adequately described by a two-compartment model with transit absorption. Pregnancy status and functionally relevant CYP3A5 genotype were not identified as significant covariates on lumefantrine pharmacokinetic parameters among the study population. At the currently recommended twice-daily dosing for 3 days, approximately 65% of simulated patients achieved the day-7 concentration target. Extending dosing to twice daily for 5 days increased target attainment to approximately 96%, while alternative intensified regimens also improved exposure. No statistically significant effect of pregnancy on lumefantrine pharmacokinetics was identified in this EFV-treated population. However, the standard 3-day dosing regimen may result in suboptimal exposure in a substantial proportion of patients. Simulation results suggest that extended dosing regimens could markedly improve day-7 target attainment, supporting further evaluation of alternative dosing strategies to optimise the efficacy of artemether-lumefantrine among people with concurrent EFV-based ART.

Introduction: Hypertension is one of the most common non-communicable diseases, and reports indicate that its prevalence is escalating globally due to several factors. Studies in different countries have shown an upsurge in the use of Herbal Medicinal Products (HMPs), including herbal antihypertensive medicines taken by people with hypertension, and 20-80 % of hypertensive patients concurrently use these herbal medicines and conventional antihypertensive medicines or other drugs. The safety and efficacy of the concurrent use of herbal and orthodox medicines are of great concern because of the high possibility of herb-drug interactions. Methods: An extensive literature search was undertaken, and the information obtained was subjected to critical analysis. This review aimed to update the available data on HMPs with reproducible evidence-based antihypertensive efficacies. Additionally, the major phytochemical and bioactive constituents of these HMPs were identified along with a discussion of their potential to modulate activities of drug-metabolizing enzymes and drug transport systems, especially Pglycoprotein. Results: More than 50 commonly used medicinal plants from different regions of the world have been documented for their anti-hypertensive activity. Most of these studies used animal models to authenticate the antihypertensive activities of the herbs. In contrast, a few studies on extracts of Hibiscus sabdariffa, Allium sativum, Apium graveolens, Nigella sativa, Linum usitatissimum, and Camellia sinensis involved clinical trials. Potentials for herb-drug interactions varied among the clinically effective HMPs due to the wide variability in their phytochemical constituents. Conclusion: Safety issues in using these HMPs were highlighted by the identification of beneficial or adverse, clinically significant herb-drug interactions.

Background: Malaria in pregnancy is a major public health issue, particularly among vulnerable populations in malaria-endemic sub-Saharan African countries. To mitigate its risks, WHO recommends sulphadoxine-pyrimethamine (SP) for chemoprevention and artemisinin-based combination therapy (ACT) to treat uncomplicated Plasmodium falciparum malaria. These interventions have helped to alleviate the risk associated with malaria in pregnancy; however, in the context of the emergence of SP- and ACT-resistant P. falciparum, maintained efficacy is under threat. Molecular surveillance is a reliable tool to monitor the emergence of resistance where molecular markers are known. Thus, the objective of the study was to use a multiplexed amplicon Oxford Nanopore sequencing approach to assess the molecular markers for antimalarial resistance among pregnant women in Nigeria.Methods: Dried blood spots (DBS) were collected from pregnant women who received IPTp-SP at the enrollment and follow-up visits. P. falciparum genomic DNA was extracted by the Chelex^® method and Pf18S qPCR was used to detect parasite DNA in each sample. With nested PCR assays, fragments of Pfdhps, Pfdhfr, Pfmdr1, Pfcrt, Pfk13 and Pfama1 genes were amplified and multiplexed amplicon-based sequencing was conducted on the minION Oxford Nanopore Technology.Result: In total, 251 pregnant women were enrolled in the study and 457 DBS samples were collected. P. falciparum genomic DNA was detected in 12% (56/457) of the samples, 31 at baseline and the remaining during the follow-up visits. Pfama1, pfk13, Pfdhps, Pfdhfr, Pfmdr1 and Pfcrt were successfully sequenced in a single run. Notably, k13 artemisinin resistance mutations were absent, the frequencies of Pfdhfr and Pfdhps SP resistance haplotypes, IRN for pyrimethamine resistance and ISGKA/IAGKA associated with sulphadoxine resistance were 82% (36/44) and 64% (27/42), respectively, and the Pfcrt CVIET resistant haplotype was at approximately 22% (7/32).Conclusion and recommendations: Here a multiplexed amplicon-based ONT assay established that triple mutant Pfdfhr-IRN, double mutant Pfdhps-SG haplotypes and the chloroquine sensitive strain were prevalent among pregnant women in Nigeria.

Background: About 32 million pregnant women are at the risk of malaria infection yearly in malaria-endemic sub-Saharan Africa. To mitigate the risks associated with malaria in pregnancy, the WHO recommends ≥3 doses of intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP), covering from the second trimester of pregnancy until delivery. Methods: This cross-sectional study assessed the uptake and extent of adherence with IPTp-SP among pregnant women in Osun State, Nigeria, from October 2020 to March 2021. Assessment of the uptake was done by extracting information from the validated case report forms. Venous blood samples were obtained to assess the levels of sulphadoxine in plasma through HPLC-UV. Results: In total, 49.24%, 38.17% and 12.58% of the study participants obtained 1, 2 and ≥3 doses of IPTp-SP, respectively. In assessing the extent of adherence, 46.67% obtained their last dose within 28 d before sample collection. Uptake of IPTp-SP is not associated with gravidity (p=0.603), but is weakly associated with the age of the study participants (p=0.04). The median (IQR) plasma sulphadoxine concentration was 10.6248 (2.8124–27.1242) ug/mL. Conclusions: Utilisation of the intervention is still very low and adherence appears to be inadequate among the study population, suggesting that more advocacy on the IPTp-SP strategy and the implementation of directly observed therapy is necessary.

Background: Herb-drug interactions are of growing concern due to the widespread use of herbal supplements alongside medications. These interactions can affect therapeutic outcomes. Understanding and identifying specific interactions is crucial for ensuring safe and effective medication use. Objective: This study investigated the impact of Garcinia kola, a common food supplement, on the dissolution of atorvastatin tablets.Methods: The dissolution profiles of atorvastatin tablets were investigated alone and in the presence of varying concentrations of G. Kola by mixing 1, 2, or 4g of G. Kola powder respectively with the dissolution medium. Samplings were performed at predetermined time points (10, 20, 30, 45 and 60 minutes) and the amount of atorvastatin dissolved was measured using a validated HPLC method. Statistical analyses were conducted to assess the significance of the observed differences.Results: The percentages of atorvastatin released in dissolution medium without G. kola were 31.38±11.81,46.02±8.73, 72.23±33.30, 63.55±27.10, 82.54±31.12% across the sampling time points. Whereas the percentage of drug released were 17.01±7.33, 27.02±8.42, 34.70±13.90, 39.74±13.53, 28.47±11.78% in the presence of 1g G. kola; 12.44±5.89, 11.87±1.51, 23.33±5.18, 27.33±8.50, 52.49±11.66% in the presence of 2g G. kola and 2.28±3.53, 4.94±7.21, 7.26±9.01, 4.68±7.37, 6.86±8.70% in the presence of 4g G. kola. There was a statistically significant difference in the amount of drug dissolved in conditions studied.Conclusion: There was a significant change in the dissolution profile of atorvastatin with increasing concentrations of G. kola. This suggests a need to establish the impact of G. kola on the disposition of atorvastatin in vivo.

Hydroquinone, Mercury (Hg), and Arsenic (As) are hazardous to health upon long-term exposure. Hydroquinone, Hg, and As were analysed in skin-lightening cosmetics randomly purchased from different cosmetic outlets within the Ilorin metropolis, Nigeria. The amount of hydroquinone in the samples was determined using a UV-spectrophotometry method at 290 nm. Hg and As were quantified using atomic absorption spectrophotometry (AAS). UV-spectrophotometry method validation showed excellent linearity (r² = 0.9993), with limits of detection (0.75 µg/mL), limits of quantification (2.28 µg/mL), relative standard deviation (0.01–0.35%), and recovery (95.85–103.56%) in the concentration range of 5–50 µg/mL. Similarly, r², LOD, and LOQ for Hg and As were 0.9983 and 0.9991, (0.5 and 1.0 µg/L) and 1.65 and 3.3 µg/L) respectively. All the samples contained hydroquinone, Hg and As in varying amounts. The amounts of hydroquinone, Hg and As present were in the ranges of 1.9–3.3%, 0.08–2.52 µg/g and 0.07–5.30 µg/g respectively. Only three of the analysed samples contained hydroquinone within the permissible limit of 2.0% w/w in cosmetic products. All the samples analysed contained mercury and arsenic in varying amounts. The need to periodically monitor the levels of hydroquinone, mercury, and arsenic in skin-lightening cosmetics marketed in Nigeria is recommended.

Background: As per current treatment guidelines, artemether-lumefantrine and efavirenz-based antiretroviral therapy are recommended drugs for falciparum malaria and human immunodeficiency virus (HIV) infections, respectively. A liquid chromatography-ultraviolet detection method for simultaneous quantification of lumefantrine and efavirenz was developed and validated for efficacy and pharmacokinetic clinical studies. Lumefantrine and efavirenz were separated using a 100 × 4.6 mm × 3 µm Fortis C₁₈ chromatographic column, and a multistep gradient mobile phase. Calibration curves were obtained with a series of standard solutions containing known concentrations of the chemical reference of both analytes prepared concomitantly in drug-free plasma. The assay was validated within the calibration ranges of 78.125–20,000 ng/mL for lumefantrine and 187.15–24,000 ng/mL for efavirenz. Stability assessment was carried out with or without heating the quality control sample to 58 °C for 45 min. The method was employed to measure the plasma concentrations of lumefantrine and efavirenz in a study conducted among malaria-HIV co-infected patients. Result: Lumefantrine and efavirenz were well separated from each other and from the biological matrix. The method demonstrated a good recovery of 72.64% for lumefantrine and 117.17% for efavirenz. The intra- and inter-day accuracy presented as 95.36–105.14% for lumefantrine and 104.11–115% for efavirenz and precision ranged from 1.15 to 6.45% for lumefantrine and 0.43 to 13.12 for efavirenz, were within ± 15% at the three quality control levels. The analytes from both quality control lots and samples collected from HIV-malaria co-infected individuals were found to be stable post-deactivation of infectious virus by heating to 58 °C for 45 min. Conclusion: The assay is accurate, precise and shown to simultaneously measure the lumefantrine and EFV in human plasma.

Background: Malaria is a major public health issue with substantial risks among vulnerable populations. Currently, the World Health Organization (WHO) recommends SP-IPTp in the second and third trimesters. However, the efficacy of SP-IPTp is threatened by the emergence of sulfadoxine-pyrimethamine resistant malaria parasites due to single nucleotide polymorphisms in the Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthetase genes. This study aimed to assess the current prevalence of Pfdhfr/Pfdhps mutations in P. falciparum isolates collected from individuals residing in Ile-Ife, Nigeria, and also present maps of the prevalence of Pfdhps 431V and 581G within Nigeria and surrounding countries. Methods: Between October 2020 and April 2021, samples were collected as dried blood spots among 188 participants who showed malaria positivity with a histidine-rich-protein-based rapid diagnostic test (RDT). Nested PCR assays were used to confirm falciparum in the samples with RDT positivity, and to amplify fragments of the Pfdhfr/Pfdhps genes followed by targeted amplicon sequencing. Published data since 2007 on the prevalence of the Pfdhps genotypes in Nigeria and the neighbouring countries were used to produce maps to show the distribution of the mutant genotypes. Results: Only 74 and 61 samples were successfully amplified for the Pfdhfr and Pfdhps genes, respectively. At codons resulting in N51I, C59R, and S108N, Pfdhfr carried mutant alleles of 97.3% (72/74), 97.3% (72/74) and 98.6% (73/74), respectively. The Pfdhps gene carried mutations at codons resulting in amino acid changes at 431–436-437–540-581–613; I431V [45.9%, (28/61)], A581G [31.1% (19/61)] and A613S [49.2% (30/61)]. Constructed haplotypes were mainly the triple Pfdhfr mutant 51I-59R-108N (95.9%), and the most common haplotypes observed for the Pfdhps gene were the ISGKAA (32.8%), ISGKGS (8.2%), VAGKAA (14.8%), VAGKAS (9.8%) and VAGKGS (14.8%). In the context of the previously published data, a high prevalence of 431V/581G mutations was found in the study population. It seems quite evident that the Pfdhps 431V, 581G and 613S often co-occur as Pfdhps-VAGKGS haplotype. Conclusion: This study showed that the prevalence of VAGKGS haplotype seems to be increasing in prevalence. If this is similar in effect to the emergence of 581G in East Africa, the efficacy of SP-IPTp in the presence of these novel Pfdhps mutants should be re-assessed.

Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) constitutes a source of great concern to health authorities worldwide. Herbal medicinal products are used as a significant treatment option for highly active antiretroviral therapies, the efficacies of which are negatively impacted by the emergence of multidrug-resistant strains to the recommended treatment guidelines. This review provides an updated synopsis of available documents on herbal medicinal products with anti-HIV activities. Concurrent consumption of herbal products with conventional drugs, which is often necessitated by co-morbidity of HIV with other diseases, can potentially alter the pharmacokinetics of the co-administered orthodox drugs. Phytochemical constituents of the herbal medicinal products with antiretroviral activities were identified, and their potential to mediate pharmacokinetic changes through modulation of drug-metabolizing enzymes and P-glycoprotein was reported. Herb-drug interactions (HDIs) that can result in significant adverse effects were also discussed with documenting the information for the therapeutic utility of these clinically effective antiretroviral herbal medicinal products with potential for development into newer anti-HIV drugs.