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.

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: Coadministration of artemether–lumefantrine and efavirenz has been shown to result in significant interactions. The influence of functional genetic polymorphisms in selected CYPs on the magnitude of this interaction was investigated in pregnant and nonpregnant adults. Method: A standard 3-day regimen of artemether–lumefantrine was administered to each patient on steady-state efavirenz-based antiretroviral therapy (ART). Pharmacokinetic parameters were obtained from intensive plasma concentration–time data. Genotyping data were tested for compliance with Hardy–Weinberg equilibrium by Chi-square test. Linear regressions, Mann–Whitney U-test or Kruskal–Wallis tests were conducted to examine the association of lumefantrine plasma level with CYP2B6 c.516G>T, NR1I3 152c-1089T>C, CYP2B6 c.983T>C, CYP3A5*3 and CYP3A4*22. Results: Among a total of 69 malaria–HIV coinfected patients (34 nonpregnant and 35 pregnant), median (interquartile range) age was 33 (27–36.5) years and body weight was 59.5 (50–67.5) kg. In nonpregnant group, CYP2B6 c.516G>T was significantly associated with lower log C _{day 7} of lumefantrine using multivariate linear regressions (β = −0.239; P = 0.013). In 59% of women with CYP2B6 c.516T, C _{day 7} of lumefantrine was below the target of 280 ng/mL compared to 47% in the noncarriers. CYP2B6 c.983T>C significantly associated with higher log C _{day 7} of desbutyl lumefantrine in both pregnant (β = 0.383; P = 0.033) and nonpregnant (β = 0.395; P = 0.023) groups. Composite genotypes for both CYP2B6 Single-nucleotide polymorphisms strongly associated with lumefantrine plasma concentration. An associative trend between lumefantrine pharmacokinetics and NR1I3 152c-1089T>C genotypes indicated that 70% of the C _{day 7} of lumefantrine in those with NR1I3 152c-1089TT genotype was below 280 ng/mL compared to 53% in those with NR1I3 152c-1089CC or CT genotype. Conclusion: The findings revealed that the efavirenz–lumefantrine interaction was accentuated in the group with CYP2B6 c.516T, c.983C and NR1I3 152c-1089T alleles. This warrants further investigations of other drug–drug interactions for optimising dosing in genetically defined subgroups, particularly during drug development.

Aim: We aimed to assess the effect of a functional polymorphism of CYP3A5 on lumefantrine pharmacokinetics. Patients & methods: Sixty-nine women diagnosed with malaria received standard doses of ar...

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.

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.