The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

User Association Strategy for Energy Efficiency and Interference Mitigation of Heterogeneous Networks

The necessity of the use of several mobile services increases every day. This requires the consumption of energy rates. Hence, minimizing the energy and interferences of mobile users are major concerns of Heterogeneous Networks (HetNet). This paper aims to improve the energy of mobile users by minimizing a weighted function. To consider significant weights values, we have exploited the multicriteria AHP method. The cost function represents the cost of users toward available BS. It includes the essential criteria influencing energy consumption. Moreover, we introduce an optimal user association based on their minimal cost values. Simulation results prove that the optimal method has saved more energy and reduced network interferences

A combination of coenzyme Q10, feverfew and magnesium for migraine prophylaxis: a prospective observational study

Abstract Background Feverfew (Tanacetum parthenium L.), magnesium and coenzyme Q10 are frequently used for migraine prophylaxis. Supplementation with a fixed combination of these three agents (Antemig®, PiLeJe) was investigated in an observational study. Methods Adult patients suffering from migraine according to the criteria of the International Headache Society were enrolled by general practitioners (≥2 migraine attacks during previous month; exclusion of chronic migraine and medication overuse) and after a one-month baseline phase, supplemented with one tablet of 100 mg feverfew, 100 mg coenzyme Q10 and 112.5 mg magnesium per day for 3 months. Results Supplementation significantly reduced the number of days with migraine headache during third month of supplementation compared to baseline phase (1.3 days ±1.5 versus 4.9 days ±2.6, p < 0.0001; n = 68 intention to treat; primary criterion). The decrease was progressive over the period of supplementation and significant from first month (1st month: −2.5 days ±3.1, p < 0.0001; 2nd month: −3 days ±2.8, p < 0.0001). The proportion of patients with a reduction of at least 50% in the number of days with migraine headache was 75% (51/68) after 3 months, with a progressive increase over the period of supplementation (63.2% [43/68] after 1 month and 70.6% [48/68] after 2 months). The proportion of patients with anxiety and depressive symptoms (Hospital Anxiety and Depression Scale) decreased between baseline phase and third month of supplementation from 61.9% (39/63 patients with information available) to 35% (21/60) for depression and from 52.4% (33/63) to 30% (18/60) for anxiety. An improvement of quality of life (Qualité de Vie et Migraine questionnaire) was also observed. The combination was well tolerated. Conclusions Results suggest that the proprietary supplement containing feverfew, coenzyme Q10 and magnesium assessed could be beneficial and safe for the prevention of migraine in adult patients and merits further study. Trial registration ClinicalTrials.gov: NCT02901756 , retrospectively registered on August 24, 2016

Bioavailability of Melatonin after Administration of an Oral Prolonged-Release Tablet and an Immediate-Release Sublingual Spray in Healthy Male Volunteers

Abstract Background The benefit of exogenous melatonin is based on its bioavailability, which depends on the galenic form, the route of administration, the dosage, and the individual absorption and rate of hepatic metabolism. Objective The objective of this study is to investigate the bioavailability of melatonin after administration of an oral prolonged-release tablet (PR form) and an immediate-release sublingual spray (IR form). The main metabolite of melatonin, 6-sulfatoxymelatonin (6-SMT), was also measured, which has not been done in previous studies. Its determination is important as an index of the hepatic transformation of melatonin. Methods In this single-center, open-label, randomized, crossover study, 14 healthy male volunteers received one tablet of the PR form (1.9 mg melatonin) or two sprays of the IR form (1 mg melatonin) during two visits separated by a washout period. Blood samples were collected over 7 and 9 h for the IR and PR form, respectively, to determine the main pharmacokinetic parameters. Results The observed kinetics were consistent with those expected for immediate and prolonged-release forms. Pulverization of the spray resulted in an early, high plasma melatonin peak (C max: 2332 ± 950 pg/mL; T max: 23.3 ± 6.5 min), whereas tablet intake produced a lower peak (C max: 1151 ± 565 pg/mL; T max: 64.2 ± 44.2 min; p < 0.001 for comparison of C max and T max) followed by a plasma melatonin plateau and a more prolonged decay over time. Plasma melatonin/6-SMT AUC0–540/420 ratio was 0.09 for the PR form and 0.16 for the IR form. Both galenic forms were well tolerated. Conclusions The results suggest that the galenic forms containing melatonin assessed in this study are suitable for the treatment of certain sleep disorders such as sleep onset delay and transient nocturnal awakenings for the IR form and insomnia for the PR form. Trial Registry Registration number: NCT04574141

Effect of a multistrain probiotic on leaky gut in patients with diarrhea-predominant irritable bowel syndrome (IBS-D): a pilot study

Background: A probiotic mixture prevented epithelial barrier impairment in various experimental models. The objective was to evaluate its effects in patients suffering from IBS-D with confirmed leaky gut. Methods: IBS D patients with increased intestinal permeability measured by radionuclide tracers were enrolled in this pilot, open-label, prospective, interventional, single-center, Phase IV study. Patients received two capsules of a multistrain probiotic a day for 30 days and were evaluated by repeated intestinal permeability test, the Bristol Stool Scale, and patient-perceived quality of life and satisfaction. Results: Of the 30 enrolled patients (mean age: 42.1 [SD: 13.1] years; female: 60%), 27 completed the study (Full Analysis Set [FAS]), 18 had no major protocol violation (Per Protocol Set [PPS]). On D30, an improvement of intestinal permeability was observed in 81.5% of patients in FAS, normalization being observed in 37% of the participants (44% in PPS). Mean intestinal permeability was significantly decreased: baseline minus D30, 3.4 (95%CI: 1.7, 5.2); IBS-QOL Total score was significantly increased: D30 minus baseline, 8.0 (95%CI: 3.0, 12.9); stool consistency was significantly improved. On D15 and D30, 96.3% of patients claimed that their IBS symptoms had been satisfactory alleviated, and a significant improvement was reported for the following VAS-IBS items: Abdominal pain, Diarrhea, Impact of gastrointestinal problems in daily life. Compliance and tolerance were satisfactory. Conclusion: The multistrain probiotic tested may reduce intestinal permeability in a considerable proportion of patients and may improve abdominal pain, stool consistency, and quality of life. These results pave the way for larger, placebo-controlled clinical studies

Could the Microbiota Be a Predictive Factor for the Clinical Response to Probiotic Supplementation in IBS-D? A Cohort Study

Background: Increasing evidence suggests the beneficial effects of probiotics in irritable bowel syndrome (IBS), but little is known about how they can impact the gut microbiota. Our objective was to evaluate the effects of a multistrain probiotic on IBS symptoms, gut permeability and gut microbiota in patients with diarrhoea-predominant IBS (IBS-D). Methods: Adults with IBS-D were enrolled in an open-label trial to receive a multistrain probiotic for 4 weeks. Abdominal pain, stool frequency, quality of life, gut permeability, and the luminal and adherent microbiota from colonic biopsies were evaluated before and after supplementation. Results: Probiotics significantly improved symptoms and quality of life, despite having no impact on permeability in the global population. In the population stratified by the response, the diarrhoea responders displayed reduced colonic permeability after supplementation. The luminal and adherent microbiota were specifically altered depending on the patients’ clinical responses regarding pain and diarrhoea. Interestingly, we identified a microbial signature in IBS-D patients that could predict a response or lack of response to supplementation. Conclusions: The multistrain probiotic improved the symptoms of IBS-D patients and induced distinct effects on the gut microbiota according to the patient’s clinical response and initial microbiota composition. Our study further supports the need to develop individualised probiotic-based approaches regarding IBS