Search

We earlier reported the protective effect of Solanum dasyphyllum against cyanide neurotoxicity. In furtherance to this, we investigated the protective effect of S. dasyphyllum against rotenone, a chemical toxin that causes brain-related diseases. Mitochondria fraction obtained from the brain of male Wistar rats was incubated with various solvents (hexane, dichloromethane, ethylacetate, and methanol) extracts of S. dasyphyllum before rotenone exposure. Mitochondria respiratory enzymes (MRE) were evaluated along with markers of oxidative stress. The inhibition of MRE by rotenone was reversed by treatment with various fractions of S. dasyphyllum. The oxidative stress induced by rotenone was also reversed by fractions of S. dasyphyllum. In addition, the ethylacetate fraction of S. dasyphyllum was most potent against rotenone-induced neurotoxicity. In conclusion, S. dasyphyllum is rich in active phytochemicals that can prevent some neurotoxic effects of rotenone exposure. Further study can be done in an in vivo model to substantiate our results.

A 32-year-old woman presented with low pressure headache 3 days after delivery of her baby. An assessment of postdural puncture headache was made. This was initially treated with analgesia, caffeine, and fluids for the presumed cerebrospinal fluid (CSF) leak. The woman was readmitted two days after her hospital discharge with generalised seizures. A brain scan showed features of intracranial hypotension, and she was treated for CSF leak using an epidural blood patch. Her symptoms worsened and three days later, she developed a left homonymous quadrantanopia. An MRI scan confirmed a right parietal haematoma with evidence of isolated cortical vein thrombosis (ICVT).

Objectives: Evidence indicates that people living with HIV (PLHIV) are more impacted by COVID-19. The burden of SARS-CoV-2 infection among PLHIV is unknown in Nigeria., Methods: We conducted repeated cross-sectional SARS-CoV-2 serosurveys in 14 states and the Federal Capital Territory in Nigeria among PLHIV who had an HIV viral load (VL) test during April 2022-January 2023. Evidence of SARS-CoV-2 immunoglobulin G (IgG) antibodies was assessed using a multiplex bead assay (MBA) to measure IgG to spike (S), receptor binding domain (RBD), and nucleocapsid (N) proteins to identify potential infection and/or vaccination status., Results: Between April 2022 and January 2023, 47,614 remnant VL samples were included and tested for SARS-CoV-2 antibodies. Seroprevalence of SARS-CoV-2 infection, defined as IgG antibodies to spike and RBD591 [S+] and nucleocapsid [N+], (S+N+), ranged between 21·1% (95% CI: 11·4-31·8) in Ekiti State in January 2023 to 71·4% (95% CI 71·9-81·9) in Gombe State in November 2022, with overall steady trends within and between states over time, across age and sex., Conclusions: High rates of SARS-CoV-2 antibody seroprevalence among PLHIV in Nigeria were observed. This underscores the need to understand the association between HIV and SARS-CoV-2 to inform strategies to reduce the threat posed by COVID-19., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Ligand binding hotspots are regions of protein surfaces that form particularly favourable interactions with small molecule pharmacophores. Targeting interactions with these hotspots maximises the efficiency of ligand binding. Existing methods are capable of identifying hotspots but often lack assays to quantify ligand binding and direct elaboration at these sites. Herein, we describe a fragment-based competitive 19 F Ligand Based NMR (LB-NMR) screening platform that enables routine, quantitative ligand profiling focused at ligand-binding hotspots. As a proof of concept, the method was applied to 4'-phosphopantetheine adenylyltransferase (PPAT) from Mycobacterium abscessus (Mabs). X-ray crystallographic characterisation of the hits from a 960-member fragment screen identified three ligand-binding hotspots across the PPAT active site. From the fragment hits a collection of 19 F reporter candidates were designed and synthesised. By rigorous prioritisation and use of optimisation workflows, a single 19 F reporter molecule was generated for each hotspot. Profiling the binding of a set of structurally characterised ligands by competitive 19 F LB-NMR with this suite of 19 F reporters recapitulated the binding affinity and site ID assignments made by ITC and X-ray crystallography. This quantitative mapping of ligand binding events at hotspot level resolution establishes the utility of the fragment-based competitive 19 F LB-NMR screening platform for hotspot-directed ligand profiling., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Malaria remains a major health priority in Nigeria. Among children with fever who seek care, less than a quarter gets tested for malaria, leading to inappropriate use of the recommended treatment for malaria; Artemisinin-based Combination Therapy (ACT). Here we test an innovative strategy to target ACT subsidies to clients seeking care in Nigeria's private retail health sector who have a confirmed malaria diagnosis. We supported point-of-care malaria testing (mRDTs) in 48 Private Medicine Retailers (PMRs) in the city of Lagos, Nigeria and randomized them to two study arms; a control arm offering subsidized mRDT testing for USD $0.66, and an intervention arm where, in addition to access to subsidized testing as in the control arm, clients who received a positive mRDT at the PMR were eligible for a free (fully subsidized) first-line ACT and PMRs received USD $0.2 for every mRDT performed. Our primary outcome was the proportion of ACTs dispensed to individuals with a positive diagnostic test. Secondary outcomes included proportion of clients who were tested at the PMR and adherence to diagnostic test results. Overall, 23% of clients chose to test at the PMR. Test results seemed to inform treatment decisions and resulted in enhanced targeting of ACTs to confirmed malaria cases with only 26% of test-negative clients purchasing an ACT compared to 58% of untested clients. However, the intervention did not offer further improvements, compared to the control arm, in testing rates or dispensing of ACTs to test-positive clients. We found that ACT subsidies were not passed on to clients testing positive in the intervention arm. We conclude that mRDTs could reduce ACT overconsumption in Nigeria's private retail health sector, but PMR-oriented incentive structures are difficult to implement and may need to be complemented with interventions targeting clients of PMRs to increase test uptake and adherence. Trials registration: Clinical Trials Registration Number: NCT04428307. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816435/ Correction: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476591/., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Visser et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: An estimated 50% of suspected malaria cases in sub-Saharan Africa first seek care in the private sector, especially in private medicine retail outlets. Quality of care in these outlets is generally unknown but considered poor with many patients not receiving a confirmatory diagnosis or the recommended first-line artemisinin-based combination therapy (ACT). In 2010, a subsidy pilot scheme, the Affordable Medicines Facility malaria, was introduced to crowd out the use of monotherapies in favour of WHO-pre-qualified artemisinin-based combinations (WHO-PQ-ACTs) in the private health sector. The scheme improved the availability, market share, and cost of WHO-PQ-ACTs in countries like Nigeria and Uganda, but in 2018, the subsidies were halted in Nigeria and significantly reduced in Uganda. This paper presents findings from six retail audit surveys conducted from 2014 to 2021 in Nigeria and Uganda to assess whether the impact of subsidies on the price, availability, and market share of artemisinin-based combinations has been sustained after the subsidies were reduced or discontinued., Methods: Six independent retail audits were conducted in private medicine retail outlets, including pharmacies, drug shops, and clinics in Nigeria (2016, 2018, 2021), and Uganda (2014, 2019, 2020) to assess the availability, price, and market share of anti-malarials, including WHO-PQ-ACTs and non-WHO-PQ-ACTs, and malaria rapid diagnostic tests (RDTs)., Results: Between 2016 and 2021, there was a 57% decrease in WHO-PQ-ACT availability in Nigeria and a 9% decrease in Uganda. During the same period, non-WHO-PQ-ACT availability increased in Nigeria by 41% and by 34% in Uganda. The price of WHO-PQ-ACTs increased by 42% in Nigeria to $0.68 and increased in Uganda by 24% to $0.95. The price of non-WHO-PQ-ACTs decreased in Nigeria by 26% to $1.08 and decreased in Uganda by 64% to $1.23. There was a 76% decrease in the market share of WHO-PQ-ACTs in Nigeria and a 17% decrease in Uganda. Malaria RDT availability remained low throughout., Conclusion: With the reduction or termination of subsidies for WHO-PQ-ACTs in Uganda and Nigeria, retail prices have increased, and retail prices of non-WHO-PQ-ACTs decreased, likely contributing to a shift of higher availability and increased use of non-WHO-PQ-ACTs., (© 2024. The Author(s).)

Serological surveys provide an objective biological measure of population immunity, and tetanus serological surveys can also assess vaccination coverage. We undertook a national assessment of immunity to tetanus and diphtheria among Nigerian children aged <15 years using stored specimens collected during the 2018 Nigeria HIV/AIDS Indicator and Impact Survey, a national cross-sectional household-based survey. We used a validated multiplex bead assay to test for tetanus and diphtheria toxoid-antibodies. In total, 31,456 specimens were tested. Overall, 70.9% and 84.3% of children aged <15 years had at least minimal seroprotection (≥0.01 IU/mL) against tetanus and diphtheria, respectively. Seroprotection was lowest in the north west and north east zones. Factors associated with increased tetanus seroprotection included living in the southern geopolitical zones, urban residence, and higher wealth quintiles ( p < 0.001). Full seroprotection (≥0.1 IU/mL) was the same for tetanus (42.2%) and diphtheria (41.7%), while long-term seroprotection (≥1 IU/mL) was 15.1% for tetanus and 6.0% for diphtheria. Full- and long-term seroprotection were higher in boys compared to girls ( p < 0.001). Achieving high infant vaccination coverage by targeting specific geographic areas and socio-economic groups and introducing tetanus and diphtheria booster doses in childhood and adolescence are needed to achieve lifelong protection against tetanus and diphtheria and prevent maternal and neonatal tetanus.

Objectives: Determining an accurate estimate of SARS-CoV-2 seroprevalence has been challenging in African countries where malaria and other pathogens are endemic. We compared the performance of one single-antigen assay and three multi-antigen SARS-CoV-2 IgG assays in a Nigerian population endemic for malaria., Methods: De-identified plasma specimens from SARS-CoV-2 RT-PCR positive, dried blood spot (DBS) SARS-CoV-2 RT-PCR positive, and pre-pandemic negatives were used to evaluate the performance of the four SARS-CoV-2 assays (Tetracore, SARS2MBA, RightSign, xMAP)., Results: Results showed higher sensitivity with the multi-antigen (81% (Tetracore), 96% (SARS2MBA), 85% (xMAP)) versus the single-antigen (RightSign (64%)) SARS-CoV-2 assay. The overall specificities were 98% (Tetracore), 100% (SARS2MBA and RightSign), and 99% (xMAP). When stratified based on <15 days to ≥15 days post-RT-PCR confirmation, the sensitivities increased from 75% to 88.2% for Tetracore; from 93% to 100% for the SARS2MBA; from 58% to 73% for RightSign; and from 83% to 88% for xMAP. With DBS, there was no positive increase after 15-28 days for the three assays (Tetracore, SARS2MBA, and xMAP)., Conclusion: Multi-antigen assays performed well in Nigeria, even with samples with known malaria reactivity, and might provide more accurate measures of COVID-19 seroprevalence and vaccine efficacy., Competing Interests: The authors have no conflicts of interest to declare.

Fake COVID-19 tweets are dangerous since they are misinformative, completely inaccurate, as threatening the efforts for flattening the pandemic curve. Thus, aside the COVID-19 pandemic, dealing with fake news and myths about the virus constitute an infodemic issue, which must be tackled by ensuring only valid information. In this context, this study proposed the Synthetic Minority Over-Sampling Technique (SMOTE) and the classifier vote ensemble (SCLAVOEM) method as a fake news classifier and a hyper parameter optimization approach for predictive modelling of COVID-19 infodemic tweets. Hyper parameter optimization variables were deployed across specific points of the proposed model and a minority oversampling of training sets was applied within imbalanced class representations. Experimental applications by the SCLAVOEM for COVID-19 infodemic prediction returned 0.999 and 1.000 weighted averages for F-measure and area under curve (AUC), respectively. Thanks to the SMOTE, the performance increases of 3.74 and 1.11%; 5.05 and 0.29%; 4.59 and 8.05% was seen in three different data sets. Eventually, the SCLAVOEM provided a framework for predictive detecting 'fake tweets' and three classifiers: 'positive', 'negative' and 'click-trap' (piège à clics). It is thought that the model will automatically flag fake information on Twitter, hence protecting the public from inaccurate and information overload., Competing Interests: Conflict of interestThe authors have no conflicts of interest to declare that are relevant to the content of this article., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022.)

Arsenic compromises the gastrointestinal integrity and function via the body's anti-oxidative system breakdown.  Hence, this study aimed to investigate the effects of tocopherol on redox imbalance and histoarchitectural alterations in rats' gastrointestinal tract exposed to sodium arsenite. Sodium arsenite and graded doses of tocopherol were administered orally into experimental rats assigned to different groups for four weeks concurrently. Redox status assay was done in homogenized samples by spectrophotometry. Parietal cell mass and mucous cell density (stomach), villus height and crypt depth (ileum), goblet cells count, and crypt depth (colon) were evaluated by histomorphometry. Inflammatory cells infiltration was also assessed using a semi-quantitative procedure. Sodium arsenite caused a significant increase in Malondialdehyde and Myeloperoxidase but, decreased Superoxide dismutase, Catalase, Nitric oxide, Glutathione peroxidase, Glutathione, and Glutathione-S-Transferase. Tocopherol treatment reversed the changes (p<0.05) though not largely dose-dependent. Furthermore, tocopherol annulled sodium arsenite-induced increase in parietal cell mass and decrease in mucous cell density in the stomach, decrease in villus height and villus height/crypt depth ratio in the ileum, and decrease in goblets cells and increase in crypt depth in the colon. Moreover, activated inflammatory cell infiltration by sodium arsenite was mitigated by tocopherol. Sodium arsenite provokes not only marked inflammatory cellular infiltration but a focal loss of glands, hyperplasia of crypts, atrophic villi, and hypertrophy of Peyer's patches in the intestines, which are all lessened with tocopherol treatment.  These findings underscore the anti-oxidative properties of tocopherol as a potent dietary factor against sodium arsenite toxicity in the gastrointestinal tract. Keywords: Tocopherol, arsenic, stomach, ileum, colon.

Serosurveillance can provide estimates of population-level exposure to infectious pathogens and has been used extensively during the COVID-19 pandemic. Simultaneous, serological testing for multiple pathogens can be done using bead-based immunoassays to add value to disease-specific serosurveys. We conducted a validation of four SARS-CoV-2 antigens-full-length spike protein, two receptor binding domain proteins, and the nucleocapsid protein-on our existing multiplex bead assay (MBA) for enteric diseases, malaria, and vaccine preventable diseases. After determining the optimal conditions for coupling the antigens to microsphere beads, the sensitivity and specificity of the assay were determined on two instruments (Luminex-200 and MAGPIX) when testing singly (monoplex) versus combined (multiplex). Sensitivity was assessed using plasma from 87 real-time reverse transcription polymerase chain reaction (rRT-PCR) positive persons collected in March-May of 2020 and ranged from 94.3% to 96.6% for the different testing conditions. Specificity was assessed using 98 plasma specimens collected prior to December 2019 and plasma from 19 rRT-PCR negative persons and ranged from 97.4% to 100%. The positive percent agreement was 93.8% to 97.9% using 48 specimens collected > 21 days post-symptom onset, while the negative percent agreement was ≥ 99% for all antigens. Test performance was similar using monoplex or multiplex testing. Integrating SARS-CoV-2 serology with other diseases of public health interest could add significant value to public health programs that have suffered severe programmatic setbacks during the COVID-19 pandemic.

Objective: There is a need for reliable serological assays to determine accurate estimates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence. Most single target antigen assays have shown some limitations in Africa. To assess the performance of a multi-antigen assay, we evaluated a commercially available SARS-CoV-2 Multi-Antigen IgG assay for human coronavirus disease 2019 (COVID-19) in Nigeria., Methods: Validation of the xMAP SARS-CoV-2 Multi-Antigen IgG assay was carried out using well-characterized SARS-CoV-2 reverse transcription polymerase chain reactive positive (97) and pre-COVID-19 pandemic (86) plasma panels. Cross-reactivity was assessed using pre-COVID-19 pandemic plasma specimens (213) from the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS)., Results: The overall sensitivity of the xMAP SARS-CoV-2 Multi-Antigen IgG assay was 75.3% [95% CI: 65.8%- 82.8%] and specificity was 99.0% [95% CI: 96.8%- 99.7%]. The sensitivity estimate increased to 83.3% [95% CI: 70.4%- 91.3%] for specimens >14 days post-confirmation of diagnosis. However, using the NAIIS pre-pandemic specimens, the false positivity rate was 1.4% (3/213)., Conclusions: Our results showed overall lower sensitivity and a comparable specificity with the manufacturer's validation. There appears to be less cross-reactivity with NAIIS pre-pandemic COVID-19 specimens using the xMAP SARS-CoV-2 Multi-Antigen IgG assay. In-country SARS-CoV-2 serology assay validation can help guide the best choice of assays in Africa., Competing Interests: The authors have declared that no competing interests exist.

Accurate SARS-CoV-2 serological assays are critical for COVID-19 serosurveillance. However, previous studies have indicated possible cross-reactivity of these assays, including in areas where malaria is endemic. We tested 213 well-characterized prepandemic samples from Nigeria using two SARS-CoV-2 serological assays, Abbott Architect IgG and Euroimmun NCP IgG assay, both targeting SARS-CoV-2 nucleocapsid protein. To assess antibody binding strength, an avidity assay was performed on these samples and on plasma from SARS-CoV-2 PCR-positive persons. Thirteen (6.1%) of 212 samples run on the Abbott assay and 38 (17.8%) of 213 run on the Euroimmun assay were positive. Anti- Plasmodium IgG levels were significantly higher among false positives for both Abbott and Euroimmun; no association was found with active Plasmodium falciparum infection. An avidity assay using various concentrations of urea wash in the Euroimmun assay reduced loosely bound IgG: of 37 positive/borderline prepandemic samples, 46%, 86%, 89%, and 97% became negative using 2 M, 4 M, 5 M, and 8 M urea washes, respectively. The wash slightly reduced avidity of antibodies from SARS-CoV-2 patients within 28 days of PCR confirmation; thereafter, avidity increased for all urea concentrations except 8 M. This validation found moderate to substantial cross-reactivity on two SARS-CoV-2 serological assays using samples from a setting where malaria is endemic. A simple urea wash appeared to alleviate issues of cross-reactivity.

Background: A large proportion of artemisinin-combination therapy (ACT) anti-malarial medicines is consumed by individuals that do not have malaria. The over-consumption of ACTs is largely driven by retail sales in high malaria-endemic countries to clients who have not received a confirmatory diagnosis. This study aims to target ACT sales to clients receiving a confirmatory diagnosis using malaria rapid diagnostic tests (mRDTs) at retail outlets in Kenya and Nigeria., Methods: This study comprises two linked four-arm 2 × 2 factorial cluster randomized controlled trials focused on malaria diagnostic testing and conditional ACT subsidies with the goal to evaluate provider-directed and client-directed interventions. The linked trials will be conducted at two contrasting study sites: a rural region around Webuye in western Kenya and the urban center of Lagos, Nigeria. Clusters are 41 and 48 participating retail outlets in Kenya and Nigeria, respectively. Clients seeking care at participating outlets across all arms will be given the option of paying for a mRDT-at a study-recommended price-to be conducted at the outlet. In the provider-directed intervention arm, the outlet owner receives a small monetary incentive to perform the mRDT. In the client-directed intervention arm, the client receives a free ACT if they purchase an mRDT and receive a positive test result. Finally, the fourth study arm combines both the provider- and client-directed interventions. The diagnosis and treatment choices made during each transaction will be captured using a mobile phone app. Study outcomes will be collected through exit interviews with clients, who sought care for febrile illness, at each of the enrolled retail outlets., Results: The primary outcome measure is the proportion of all ACTs that are sold to malaria test-positive clients in each study arm. For all secondary outcomes, we will evaluate the degree to which the interventions affect purchasing behavior among people seeking care for a febrile illness at the retail outlet., Conclusions: If our study demonstrates that malaria case management can be improved in the retail sector, it could reduce overconsumption of ACTs and enhance targeting of publicly funded treatment reimbursements, lowering the economic barrier to appropriate diagnosis and treatment for patients with malaria., Trial Registration: ClinicalTrials.gov NCT04428307 , registered June 9, 2020, and NCT04428385 , registered June 9, 2020.

Introduction: Hypoxemia is a life-threatening condition and is commonly seen in children with severe pneumonia. A government-led, NGO-supported, multifaceted oxygen improvement program was implemented to increase access to oxygen therapy in 29 hospitals in Kaduna, Kano, and Niger states. The program installed pulse oximeters and oxygen concentrators, trained health care workers, and biomedical engineers (BMEs), and provided regular feedback to health care staff through quality improvement teams., Objective: The aim of this study is to evaluate whether the program increased screening for hypoxemia with pulse oximetry and prescription of oxygen for patients with hypoxemia., Methodology: The study is an uncontrolled before-after interventional study implemented at the hospital level. Medical charts of patients under 5 admitted for pneumonia between January 2017 and August 2018 were reviewed and information on patient care was extracted using a standardized form. The preintervention period of this study was defined as 1 January to 31 October 2017 and the postintervention period as 1 February to 31 August 2018. The primary outcomes of the study were whether blood-oxygen saturation measurements (SpO 2 ) were documented and whether children with hypoxemia were prescribed oxygen., Results: A total of 3418 patient charts were reviewed (1601 during the preintervention period and 1817 during the postintervention period). There was a significant increase in the proportion of patients with SpO 2 measurements after the interventions were conducted (adjusted odds ratio [aOR] 5.0; 4.3-5.7, P < .001). Before the interventions, only 13.7% (95% confidence interval [CI]: 12.2-15.3) of patients had SpO 2 measurements and after the interventions, 82.4% (95% CI: 80.7-84.1) had SpO 2 measurements. Oxygen administration for patients with clinical signs of hypoxemia also increased significantly (aOR 5.0; 4.2-5.9, P < .001)-from 22.8% (95% CI: 18.8-27.2) to 77.9% (95% CI: 73.9-81.5)., Conclusion: Increasing pulse oximetry and oxygen therapy access and utilization in a low-resourced environment is achievable through a multifaceted program focused on strengthening government-owned systems., (© 2020 Wiley Periodicals, Inc.)

Background: Histopathology is basically the microscopic differentiation of normal from abnormal cells and tissues hence normal cells must not be made to look abnormal or vice versa during preparations. Some laboratories do not follow the adequate procedures that can pass Quality Assurance Test thereby giving false impression on slides and subsequently false reports., Objective: This paper attempts to demonstrate the intricacies of histological procedures and techniques highlighting reasons why it is inevitable to follow the various precautionary measures in the production of valuable sections that will give the required results., Method: The bulk of this report is made up of personal laboratory experiences (its successes and failures), also wide and extensive research from secondary data (text books and manuals)., Result: Carelessly made sections will give false reports that will mislead the pathologist. It will not present the tissue as it was in vivo as required., Conclusion: Precisely made sections that show trivial details are the only ones that can give authentic and reliable reports expected for patient's diagnosis, research work or teaching purposes.