Suchergebnisse

Background: Current outbreaks of COVID-19 are threatening the health care systems of several countries around the world. Control measures, based on isolation, contact tracing, and quarantine, can decrease and delay the burden of the ongoing epidemic. With respect to the ongoing COVID-19 epidemic, recent modeling work shows that these interventions may be inadequate to control local outbreaks, even when perfect isolation is assumed. The effect of infectiousness prior to symptom onset combined with asymptomatic infectees further complicates the use of contact tracing. We aim to study whether antivirals, which decrease the viral load and reduce infectiousness, could be integrated into control measures in order to augment the feasibility of controlling the epidemic. Methods: Using a simulation-based model of viral transmission, we tested the efficacy of different intervention measures to control local COVID-19 outbreaks. For individuals that were identified through contact tracing, we evaluate two procedures: monitoring individuals for symptoms onset and testing of individuals. Additionally, we investigate the implementation of an antiviral compound combined with the contact tracing process. Results: For an infectious disease in which asymptomatic and presymptomatic infections are plausible, an intervention measure based on contact tracing performs better when combined with testing instead of monitoring, provided that the test is able to detect infections during the incubation period. Antiviral drugs, in combination with contact tracing, quarantine, and isolation, result in a significant decrease of the final size and the peak incidence, and increase the probability that the outbreak will fade out. Conclusion: In all tested scenarios, the model highlights the benefits of control measures based on the testing of traced individuals. In addition, the administration of an antiviral drug, together with quarantine, isolation, and contact tracing, is shown to decrease the spread of the epidemic. This control measure could be an effective strategy to control local and re-emerging outbreaks of COVID-19. ; This work is funded by the EpiPose project from the European Union's SC1-PHE-CORONAVIRUS-2020 programme, project number 101003688, by the European Union's Horizon 2020 research and innovation programme (grant agreement 682540-TransMID), the European Union's Horizon 2020 research and innovation program under grant agreement no. 101003627 (SCORE project), and the Stichting Antoine Faes. A.T. acknowledges support from the special research fund of the University of Antwerp. P.L. was supported by funding from the Flemish Government under the "Onderzoeksprogramma Artificiele Intelligentie (AI) Vlaanderen" programme. ; Hens, N (corresponding author), Univ Antwerp, Ctr Hlth Econ Res & Modelling Infect Dis, Antwerp, Belgium; Hasselt Univ, Interuniv Inst Biostatist & Stat Bioinformat, Data Sci Inst, Hasselt, Belgium. niel.hens@uhasselt.be

WOS: 000388677600001 ; PubMed ID: 27667586 ; In countries from which Crimean-Congo haemorrhagic fever (CCHF) is absent, the causative virus, CCHF virus (CCHFV), is classified as a hazard group 4 agent and handled in containment level (CL)-4. In contrast, most endemic countries out of necessity have had to perform diagnostic tests under biosafety level (BSL)-2 or -3 conditions. In particular, Turkey and several of the Balkan countries have safely processed more than 100 000 samples over many years in BSL-2 laboratories. It is therefore advocated that biosafety requirements for CCHF diagnostic procedures should be revised, to allow the tests required to be performed under enhanced BSL-2 conditions with appropriate biosafety laboratory equipment and personal protective equipment used according to standardized protocols in the countries affected. Downgrading of CCHFV research work from CL-4, BSL-4 to CL-3, BSL-3 should also be considered. ; European Commission under Health Cooperation Work Program of 7th Framework Program [260427] ; Funding was received through CCH Fever Network (Collaborative Project) supported by the European Commission under the Health Cooperation Work Program of the 7th Framework Program (grant agreement no. 260427) (http://www.cch-fever.eu/). The views expressed by state-employed American co-authors are their personal views, and do not necessarily represent the views of the US government agencies they work for. The views expressed by the ECDC coauthor are his personal views, and do not necessarily represent the views of the European agency he is working for.

Flaviviridae are small enveloped viruses hosting a positive-sense single-stranded RNA genome. Besides yellow fever virus, a landmark case in the history of virology, members of the Flavivirus genus, such as West Nile virus and dengue virus, are increasingly gaining attention due to their re-emergence and incidence in different areas of the world. Additional environmental and demographic considerations suggest that novel or known flaviviruses will continue to emerge in the future. Nevertheless, up to few years ago flaviviruses were considered low interest candidates for drug design. At the start of the European Union VIZIER Project, in 2004, just two crystal structures of protein domains from the flaviviral replication machinery were known. Such pioneering studies, however, indicated the flaviviral replication complex as a promising target for the development of antiviral compounds. Here we review structural and functional aspects emerging from the characterization of two main components (NS3 and NS5 proteins) of the flavivirus replication complex. Most of the reviewed results were achieved within the European Union VIZIER Project, and cover topics that span from viral genomics to structural biology and inhibition mechanisms. The ultimate aim of the reported approaches is to shed light on the design and development of antiviral drug leads.

This project has received funding from the Covid-19-Fund KU Leuven / University Hospitals Leuven, the COVID-19 call of the Research Foundation - Flanders (FWO) (grant G0G4820N), the European Union's Horizon 2020 research and innovation program (Grant 101,003,627, Swift COronavirus therapeutics REsponse project) and the Bill and Melinda Gates Foundation (Grant INV-00,636). LLi is member of the Institute of Tropical Medicine's Outbreak Research Team which is financially supported by the Department of Economy, Science and Innovation (EWI) of the Flemish government. BV is supported by a research grant of the Frans Van de Werf Fund for Clinical Cardiovascular Research. P. Verhamme, TV, P. Vermeersch are senior clinical investigators of the FWO. We thank Johnson & Johnson for determining drug concentrations in hamster samples and for providing. guidance on the dosing. We thank Lindsey Bervoets, Carolien De Keyzer, Elke Maas and Jasper Rymentants for the technical support with the animal experiments. TNDD is funded by the Horizon 2020 grant OrganoVIR 812,673 on the project 'Organoids for Virus Research - An innovative training-ITN programme'. XW and XZ received funding of the China Scholarship Council (CSC) (grant number 201,806,170,087 and 201,906,170,033). Part of this research work was performed using the 'Caps-It' research infrastructure (project ZW13 02) that was financially supported by the Hercules Foundation (FWO) and Rega Foundation, KU Leuven.