Atorvastatin prevents Plasmodium falciparum cytoadherence and endothelial damage

<p>Abstract</p> <p>Background</p> <p>The adhesion of <it>Plasmodium falciparum </it>parasitized red blood cell (PRBC) to human endothelial cells (EC) induces inflammatory processes, coagulation cascades, oxidative stress and apoptosis. These pathological processes are suspected to be responsible for the blood-brain-barrier and other organs' endothelial dysfunctions observed in fatal cases of malaria. Atorvastatin, a drug that belongs to the lowering cholesterol molecule family of statins, has been shown to ameliorate endothelial functions and is widely used in patients with cardiovascular disorders.</p> <p>Methods</p> <p>The effect of this compound on PRBC induced endothelial impairments was assessed using endothelial co-culture models.</p> <p>Results</p> <p>Atorvastatin pre-treatment of EC was found to reduce the expression of adhesion molecules and <it>P. falciparum </it>cytoadherence, to protect cells against PRBC-induced apoptosis and to enhance endothelial monolayer integrity during co-incubation with parasites.</p> <p>Conclusions</p> <p>These results might suggest a potential interest use of atorvastatin as a protective treatment to interfere with the pathophysiological cascades leading to severe malaria.</p

Retraction.

This is a retraction of 'Gradual emergence followed by exponential spread of the SARS-CoV-2 Omicron variant in Africa' 10.1126/science.add873

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

Rôle de l'endothélium vasculaire dans les paludismes sévères

Le paludisme est la maladie parasitaire la plus mortelle avec environ 781000 morts en 2009. Ces morts sont essentiellement dus aux formes sévères de la maladie qui touchent des organes vitaux tels que le poumon et le cerveau. Mais il existe aussi des formes asymptomatiques et simples. Cependant, les causes de l apparition d une forme de paludisme plutôt qu une autre ne sont toujours pas connues. Dans l organisme le parasite infecte les hématies et est en contact avec les endothéliums vasculaires des différents organes cibles. Donc nous pensons que les différentes formes de paludisme peuvent être dues à des interactions différentes entre le parasite et ses organes cibles. C est pourquoi nous avons comparé différents mécanismes induits par plusieurs souches parasitaires provenant de patients atteints de paludisme asymptomatique à grave sur endothéliums vasculaires, pulmonaire (EP) et cérébrale (EC), humains. Ceci dans le but de savoir si ces endothéliums jouent un rôle dans l apparition des paludismes sévères. Nos résultats montrent que c est le cas. D abord, nous avons remarqué que les hématies parasitées adhèrent massivement sur l EP par rapport à l EC. Ensuite, l EP est fortement activé après contact avec les hématies parasitées tandis que l EC l est moins. Enfin, toutes les souches testées induisent la mort des cellules endothéliales pulmonaires alors que seules certaines induisent celle des cellules endothéliales cérébrales. En conclusion, le couple souche parasitaire-type d endothélium joue un rôle dans l apparition des différentes formes de paludisme. Donc l endothélium est au cœur de la pathologiePARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF

A Sanger approach based on overlapping fragments to screen SARS-CoV-2 variants

Since the beginning of the COVID-19 pandemic, the SARS-CoV-2 virus has undergone various genetic mutations which have led to the emergence of variants. The World Health Organization (WHO) defines Variants of Concern (VOCs) and Variants of Interest (VOIs) according to several criteria. These include significant changes in the transmissibility and pathogenicity of the virus characterized by mutations in the spike gene coding the spike glycoprotein. In this study, we designed ten Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) assays in order to identify mutations of SARS-CoV-2 in overlapping fragments. Each assay contained mutations on the fragments sequenced by a Sanger method. The genomic analysis of the fragments allowed to identify the variant according to the position of the mutations. The assembly of the 10 fragments refined the analysis, highlighting all the mutations present in the S gene. Finally, a comparison of methods using a Next-Generation Sequencing (NGS) approches for samples enabled the method to be validated. By this method we have highlighted a characteristic mutation of the lineage B of SARS-CoV-2. We showed the circulation of SARS-CoV-2 belonging to lineage A and B in the beginning of the pandemic in Gabon. We have identified the Alpha, Delta and Omicron variants. This method would allow laboratories with limited financial means or without NGS instrument to obtain sequences of the S gene. This method wase very effective to highlight the circulation of variants, in particular VOCs and VOIs, in this developing country, Gabon, during the COVID-19 pandemic

Phylogenetic tree based on a 439-basepair fragment of the polymerase gene (L) of members of the <i>Paramyxoviridae</i> family.

<p>Sequences generated in this study are highlighted in red. Bayesian posterior probabilities are shown; values <0.80 were removed for clarity. The viruses are designated as follows (virus abbreviation/typical host/accession numbers of reference sequences in brackets): HeV  =  Hendra virus, NiV  =  Nipah virus, BatPV  =  Bat paramyxovirus, BeiPV  =  Beilong virus, JPV  = J virus, MosPV  =  Mossman virus, TupPV  =  Tupaia paramyxovirus, NarPV  =  Nariva virus, PDV  =  Phocine distemper virus, CDV  =  Canine distemper virus, CeMV DMV  =  Cetacean morbillivirus strain dolphin morbillivirus, MeV  =  Measles virus, PPRV  =  Peste-des-petits ruminants virus, RPV  =  Rinderpest virus, FdlPV  =  Fer-de-lance virus, PSPV  =  Pacific salmon paramyxovirus, ASPV  =  Atlantic salmon paramyxovirus, SeV  =  Sendai virus, bPIV3  =  Bovine parainfluenza virus 3, hPIV1  =  Human parainfluenza virus 1, hPIV3  =  Human parainfluenza virus 3, SwPIV3  =  Swine parainfluenza virus 3, NDV  =  Newcastle disease virus, PigeonPMV  =  Pigeon paramyxovirus, AMPV9  =  Avian paramyxovirus type 9, AMPV6  =  Avian paramyxovirus type 6, AMPV2  =  Avian paramyxovirus type 2, AMPV3  =  Avian paramyxovirus type 3, AMPV4  =  Avian paramyxovirus type 4, PIV5  =  parainfluenza virus 5, SV41  =  Simian virus 41, MenPV  =  Menangle paramyxovirus, MprPV  =  Mapuera virus, MuV  =  Mumpsvirus, PorPV  =  Porcine rubulavirus, TioPV  =  Tioman paramyxovirus, hPIV2  =  Human parainfluenza virus 2, hMPV  =  Human metapneumovirus, MPV  =  Murine pneumonia virus, bRSV  =  Bovine respiratory syncytial virus, hRSV  =  Human respiratory syncytial virus, APV  =  Avian Pneumovirus, ThkPV-1  =  Tuhoko virus 1, ThkPV-2  =  Tuhoko virus 2, ThkPV-3  =  Tuhoko virus 3.</p

Virus distribution in organs from <i>Coleura afra</i> individuals.

<p>Virus distribution is shown in terms of C<i>t</i> values on the y-axis for each bat organ tested (x-axis). <i>n</i> represents the number of organs available for the study.</p

Results of real-time PCR on organs from <i>Coleura afra</i> individuals.

<p>Numbers indicate the cycle threshold (C<i>t</i>). ND, not done because of missing samples.</p><p>Undet, C<i>t</i> undetermined.</p><p>Results of real-time PCR on organs from <i>Coleura afra</i> individuals.</p

Overview of specimens collected in Belinga caves and tested by specific BelPV qPCR assay.

<p>Overview of specimens collected in Belinga caves and tested by specific BelPV qPCR assay.</p

Evidence for circulation of Rift Valley fever virus in wildlife and domestic animals in a forest environment in Gabon, Central Africa.

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis caused by the Rift Valley fever virus (RVFV) that can infect domestic and wild animals. Although the RVFV transmission cycle has been well documented across Africa in savanna ecosystems, little is known about its transmission in tropical rainforest settings, particularly in Central Africa. We therefore conducted a survey in northeastern Gabon to assess RVFV circulation among wild and domestic animals. Among 163 wildlife samples tested using RVFV-specific RT-qPCR, four ruminants belonging to subfamily Cephalophinae were detected positive. The phylogenetic analysis revealed that the four RVFV sequences clustered together with a virus isolated in Namibia within the well-structured Egyptian clade. A cross-sectional survey conducted on sheep, goats and dogs living in villages within the same area determined the IgG RVFV-specific antibody prevalence using cELISA. Out of the 306 small ruminants tested (214 goats, 92 sheep), an overall antibody prevalence of 15.4% (95% CI [11.5-19.9]) was observed with a higher rate in goats than in sheep (20.1% versus 3.3%). RVFV-specific antibodies were detected in a single dog out of the 26 tested. Neither age, sex of domestic animals nor season was found to be significant risk factors of RVFV occurrence. Our findings highlight sylvatic circulation of RVFV for the first time in Gabon. These results stress the need to develop adequate surveillance plan measures to better control the public health threat of RVFV. [Abstract copyright: Copyright: © 2024 Becquart 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.