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      Molecular and point-of-care diagnostics for Ebola and new threats: National POCT policy and guidelines will stop epidemics

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      Expert Review of Molecular Diagnostics
      Informa UK Limited

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          Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection.

          Ebola virus (EBOV) infection causes a severe and fatal hemorrhagic disease that in many ways appears to be similar in humans and nonhuman primates; however, little is known about the development of EBOV hemorrhagic fever. In the present study, 21 cynomolgus monkeys were experimentally infected with EBOV and examined sequentially over a 6-day period to investigate the pathological events of EBOV infection that lead to death. Importantly, dendritic cells in lymphoid tissues were identified as early and sustained targets of EBOV, implicating their important role in the immunosuppression characteristic of EBOV infections. Bystander lymphocyte apoptosis, previously described in end-stage tissues, occurred early in the disease-course in intravascular and extravascular locations. Of note, apoptosis and loss of NK cells was a prominent finding, suggesting the importance of innate immunity in determining the fate of the host. Analysis of peripheral blood mononuclear cell gene expression showed temporal increases in tumor necrosis factor-related apoptosis-inducing ligand and Fas transcripts, revealing a possible mechanism for the observed bystander apoptosis, while up-regulation of NAIP and cIAP2 mRNA suggest that EBOV has evolved additional mechanisms to resist host defenses by inducing protective transcripts in cells that it infects. The sequence of pathogenetic events identified in this study should provide new targets for rational prophylactic and chemotherapeutic interventions.
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            Ebola virus: from discovery to vaccine.

            Ebola virus, being highly pathogenic for humans and non-human primates and the subject of former weapons programmes, is now one of the most feared pathogens worldwide. In addition, the lack of pre- and post-exposure interventions makes the development of rapid diagnostics, new antiviral agents and protective vaccines a priority for many nations. Further insight into the ecology, immunology and pathogenesis of Ebola virus will promote the delivery of these urgently required tools.
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              Diagnosis of Ebola Virus Disease: Past, Present, and Future.

              Laboratory diagnosis of Ebola virus disease plays a critical role in outbreak response efforts; however, establishing safe and expeditious testing strategies for this high-biosafety-level pathogen in resource-poor environments remains extremely challenging. Since the discovery of Ebola virus in 1976 via traditional viral culture techniques and electron microscopy, diagnostic methodologies have trended toward faster, more accurate molecular assays. Importantly, technological advances have been paired with increasing efforts to support decentralized diagnostic testing capacity that can be deployed at or near the point of patient care. The unprecedented scope of the 2014-2015 West Africa Ebola epidemic spurred tremendous innovation in this arena, and a variety of new diagnostic platforms that have the potential both to immediately improve ongoing surveillance efforts in West Africa and to transform future outbreak responses have reached the field. In this review, we describe the evolution of Ebola virus disease diagnostic testing and efforts to deploy field diagnostic laboratories in prior outbreaks. We then explore the diagnostic challenges pervading the 2014-2015 epidemic and provide a comprehensive examination of novel diagnostic tests that are likely to address some of these challenges moving forward.
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                Author and article information

                Journal
                Expert Review of Molecular Diagnostics
                Expert Review of Molecular Diagnostics
                Informa UK Limited
                1473-7159
                1744-8352
                June 18 2018
                July 03 2018
                July 20 2018
                July 03 2018
                : 18
                : 7
                : 657-673
                Affiliations
                [1 ] Point-of-Care Center for Teaching and Research (POCT•CTRTM), School of Medicine, UC Davis, and Knowledge Optimization®, Davis, CA
                Article
                10.1080/14737159.2018.1491793
                c2db34cf-bc6b-46a5-87c5-20e8f967bb06
                © 2018
                History

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