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

Metronidazole Topically Immobilized Electrospun Nanofibrous Scaffold: Novel Secondary Intention Wound Healing Accelerator

The process of secondary intention wound healing includes long repair and healing time. Electrospun nanofibrous scaffolds have shown potential for wound dressing. Biopolymers have gained much attention due to their remarkable characteristics such as biodegradability, biocompatibility, non-immunogenicity and nontoxicity. This study anticipated to develop a new composite metronidazole (MTZ) immobilized nanofibrous scaffold based on poly (3-hydroxy butyrate) (PHB) and Gelatin (Gel) to be utilized as a novel secondary intention wound healing accelerator. Herein, PHB and Gel were mixed together at different weight ratios to prepare polymer solutions with final concentration of (7%), loaded with two different concentrations 5% (Z1) and 10% (Z2) of MTZ. Nanofibrous scaffolds were obtained by manipulating electrospinning technique. The properties of MTZ immobilized PHB/Gel nanofibrous scaffold were evaluated (SEM, FTIR, TGA, water uptake, contact angle, porosity, mechanical properties and antibacterial activity). Additionally, in vitro cytocompatibility of the obtained nanofibrous scaffolds were assessed by using the cell counting kit-8 (CCK-8 assay). Moreover, in vivo wound healing experiments revealed that the prepared nanofibrous scaffold highly augmented the transforming growth factor (TGF-β) signaling pathway, moderately suppressed the pro-inflammatory cytokine (IL-6). These results indicate that MTZ immobilized PHB/Gel nanofibrous scaffold significantly boost accelerating secondary intention wound healing

Can antibody conjugated nanomicelles alter the prospect of antibody targeted therapy against schistosomiasis mansoni?

BackgroundCLA (conjugated linoleic acid)-mediated activation of the schistosome tegument-associated sphingomyelinase and consequent disruption of the outer membrane might allow host antibodies to access the apical membrane antigens. Here, we investigated a novel approach to enhance specific antibody delivery to concealed surface membrane antigens of Schistosoma mansoni utilising antibody-conjugated-CLA nanomicelle technology.Methodology/principal findingsWe invented and characterised an amphiphilic CLA-loaded whey protein co-polymer (CLA-W) as an IV injectable protein nanocarrier. Rabbit anti-Schistosoma mansoni infection (anti-SmI) and anti-Schistosoma mansoni alkaline phosphatase specific IgG antibodies were purified from rabbit sera and conjugated to the surface of CLA-W co-polymer to form antibody-conjugated-CLA-W nanomicelles (Ab-CLA-W). We investigated the schistosomicidal effects of CLA-W and Ab-CLA-W in a mouse model of Schistosoma mansoni against early and late stages of infection. Results showed that conjugation of nanomicelles with antibodies, namely anti-SmI, significantly enhanced the micelles' schistosomicidal and anti-pathology activities at both the schistosomula and adult worm stages of the infection resulting in 64.6%-89.9% reductions in worm number; 72.5-94% and 66.4-85.2% reductions in hepatic eggs and granulomas, respectively. Treatment induced overall improvement in liver histopathology, reducing granuloma size and fibrosis and significantly affecting egg viability. Indirect immunofluorescence confirmed CLA-W-mediated antigen exposure on the worm surface. Electron microscopy revealed extensive ultrastructural damage in worm tegument induced by anti-SmI-CLA-W.Conclusion/significanceThe novel antibody-targeted nano-sized CLA delivery system offers great promise for treatment of Schistosoma mansoni infection and control of its transmission. Our in vivo observations confirm an immune-mediated enhanced effect of the schistosomicidal action of CLA and hints at the prospect of nanotechnology-based immunotherapy, not only for schistosomiasis, but also for other parasitic infections in which chemotherapy has been shown to be immune-dependent. The results propose that the immunodominant reactivity of the anti-SmI serum, Schistosoma mansoni fructose biphosphate aldolase, SmFBPA, merits serious attention as a therapeutic and vaccine candidate

Formulation and Antibacterial Activity Evaluation of Quaternized Aminochitosan Membrane for Wound Dressing Applications

Much attention has been paid to chitosan biopolymer for advanced wound dressing owing to its exceptional biological characteristics comprising biodegradability, biocompatibility and respectable antibacterial activity. This study intended to develop a new antibacterial membrane based on quaternized aminochitosan (QAMCS) derivative. Herein, aminochitosan (AMCS) derivative was quaternized by N-(2-Chloroethyl) dimethylamine hydrochloride with different ratios. The pre-fabricated membranes were characterized by several analysis tools. The results indicate that maximum surface potential of +42.2 mV was attained by QAMCS3 membrane compared with +33.6 mV for native AMCS membrane. Moreover, membranes displayed higher surface roughness (1.27 ± 0.24 μm) and higher water uptake value (237 ± 8%) for QAMCS3 compared with 0.81 ± 0.08 μm and 165 ± 6% for neat AMCS membranes. Furthermore, the antibacterial activities were evaluated against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus cereus. Superior antibacterial activities with maximum inhibition values of 80–98% were accomplished by QAMCS3 membranes compared with 57–72% for AMCS membrane. Minimum inhibition concentration (MIC) results denote that the antibacterial activities were significantly boosted with increasing of polymeric sample concentration from 25 to 250 µg/mL. Additionally, all membranes unveiled better biocompatibility and respectable biodegradability, suggesting their possible application for advanced wound dressing

Rosavin Ameliorates Hepatic Inflammation and Fibrosis in the NASH Rat Model via Targeting Hepatic Cell Death

Background: Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease that urgently needs effective therapy. Rosavin, a major constituent of the Rhodiola Rosea plant of the family Crassulaceae, is believed to exhibit multiple pharmacological effects on diverse diseases. However, its effect on non-alcoholic steatohepatitis (NASH), the progressive form of NAFLD, and the underlying mechanisms are not fully illustrated. Aim: Investigate the pharmacological activity and potential mechanism of rosavin treatment on NASH management via targeting hepatic cell death-related (HSPD1/TNF/MMP14/ITGB1) mRNAs and their upstream noncoding RNA regulators (miRNA-6881-5P and lnc-SPARCL1-1:2) in NASH rats. Results: High sucrose high fat (HSHF) diet-induced NASH rats were treated with different concentrations of rosavin (10, 20, and 30 mg/kg/day) for the last four weeks of dietary manipulation. The data revealed that rosavin had the ability to modulate the expression of the hepatic cell death-related RNA panel through the upregulation of both (HSPD1/TNF/MMP14/ITGB1) mRNAs and their epigenetic regulators (miRNA-6881-5P and lnc-SPARCL1-1:2). Moreover, rosavin ameliorated the deterioration in both liver functions and lipid profile, and thereby improved the hepatic inflammation, fibrosis, and apoptosis, as evidenced by the decreased protein levels of IL6, TNF-α, and caspase-3 in liver sections of treated animals compared to the untreated NASH rats. Conclusion: Rosavin has demonstrated a potential ability to attenuate disease progression and inhibit hepatic cell death in the NASH animal model. The produced effect was correlated with upregulation of the hepatic cell death-related (HSPD1, TNF, MMP14, and ITGB1) mRNAs—(miRNA-6881-5P—(lnc-SPARCL1-1:2) RNA panel