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      Tracking virus outbreaks in the twenty-first century

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          Abstract

          Emerging viruses have the potential to impose substantial mortality, morbidity and economic burdens on human populations. Tracking the spread of infectious diseases to assist in their control has traditionally relied on the analysis of case data gathered as the outbreak proceeds. Here, we describe how many of the key questions in infectious disease epidemiology, from the initial detection and characterization of outbreak viruses, to transmission chain tracking and outbreak mapping, can now be much more accurately addressed using recent advances in virus sequencing and phylogenetics. We highlight the utility of this approach with the hypothetical outbreak of an unknown pathogen, ‘Disease X’, suggested by the World Health Organization to be a potential cause of a future major epidemic. We also outline the requirements and challenges, including the need for flexible platforms that generate sequence data in real-time, and for these data to be shared as widely and openly as possible.

          Abstract

          This Review Article describes how recent advances in viral genome sequencing and phylogenetics have enabled key issues associated with outbreak epidemiology to be more accurately addressed, and highlights the requirements and challenges for generating, sharing and using such data when tackling a viral outbreak.

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          Most cited references70

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          Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

          A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
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            Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome

            The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent. Clinical specimens from patients with SARS were searched for unknown viruses with the use of cell cultures and molecular techniques. A novel coronavirus was identified in patients with SARS. The virus was isolated in cell culture, and a sequence 300 nucleotides in length was obtained by a polymerase-chain-reaction (PCR)-based random-amplification procedure. Genetic characterization indicated that the virus is only distantly related to known coronaviruses (identical in 50 to 60 percent of the nucleotide sequence). On the basis of the obtained sequence, conventional and real-time PCR assays for specific and sensitive detection of the novel virus were established. Virus was detected in a variety of clinical specimens from patients with SARS but not in controls. High concentrations of viral RNA of up to 100 million molecules per milliliter were found in sputum. Viral RNA was also detected at extremely low concentrations in plasma during the acute phase and in feces during the late convalescent phase. Infected patients showed seroconversion on the Vero cells in which the virus was isolated. The novel coronavirus might have a role in causing SARS. Copyright 2003 Massachusetts Medical Society
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              A novel coronavirus associated with severe acute respiratory syndrome.

              A worldwide outbreak of severe acute respiratory syndrome (SARS) has been associated with exposures originating from a single ill health care worker from Guangdong Province, China. We conducted studies to identify the etiologic agent of this outbreak. We received clinical specimens from patients in seven countries and tested them, using virus-isolation techniques, electron-microscopical and histologic studies, and molecular and serologic assays, in an attempt to identify a wide range of potential pathogens. None of the previously described respiratory pathogens were consistently identified. However, a novel coronavirus was isolated from patients who met the case definition of SARS. Cytopathological features were noted in Vero E6 cells inoculated with a throat-swab specimen. Electron-microscopical examination revealed ultrastructural features characteristic of coronaviruses. Immunohistochemical and immunofluorescence staining revealed reactivity with group I coronavirus polyclonal antibodies. Consensus coronavirus primers designed to amplify a fragment of the polymerase gene by reverse transcription-polymerase chain reaction (RT-PCR) were used to obtain a sequence that clearly identified the isolate as a unique coronavirus only distantly related to previously sequenced coronaviruses. With specific diagnostic RT-PCR primers we identified several identical nucleotide sequences in 12 patients from several locations, a finding consistent with a point-source outbreak. Indirect fluorescence antibody tests and enzyme-linked immunosorbent assays made with the new isolate have been used to demonstrate a virus-specific serologic response. This virus may never before have circulated in the U.S. population. A novel coronavirus is associated with this outbreak, and the evidence indicates that this virus has an etiologic role in SARS. Because of the death of Dr. Carlo Urbani, we propose that our first isolate be named the Urbani strain of SARS-associated coronavirus. Copyright 2003 Massachusetts Medical Society
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                Author and article information

                Contributors
                jason.ladner@nau.edu
                a.rambaut@ed.ac.uk
                edward.holmes@sydney.edu.au
                Journal
                Nat Microbiol
                Nat Microbiol
                Nature Microbiology
                Nature Publishing Group UK (London )
                2058-5276
                13 December 2018
                2019
                : 4
                : 1
                : 10-19
                Affiliations
                [1 ]ISNI 0000000122199231, GRID grid.214007.0, Department of Immunology and Microbiology, , The Scripps Research Institute, ; La Jolla, CA USA
                [2 ]ISNI 0000000419368710, GRID grid.47100.32, Department of Epidemiology of Microbial Diseases, , Yale School of Public Health, ; New Haven, CT USA
                [3 ]ISNI 0000 0004 1936 8040, GRID grid.261120.6, Pathogen and Microbiome Institute, , Northern Arizona University, ; Flagstaff, AZ USA
                [4 ]ISNI 0000 0001 0668 7884, GRID grid.5596.f, Department of Microbiology and Immunology, Rega Institute, , KU Leuven - University of Leuven, ; Leuven, Belgium
                [5 ]ISNI 0000 0004 1936 8948, GRID grid.4991.5, Department of Zoology, , University of Oxford, ; Oxford, UK
                [6 ]ISNI 0000 0004 1936 7988, GRID grid.4305.2, Institute of Evolutionary Biology, , University of Edinburgh, ; Edinburgh, UK
                [7 ]ISNI 0000 0004 0533 8254, GRID grid.453035.4, Fogarty International Center, National Institutes of Health, ; Bethesda, MD USA
                [8 ]ISNI 0000 0004 1936 834X, GRID grid.1013.3, Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and Sydney Medical School, Charles Perkins Centre, , The University of Sydney, ; Sydney, New South Wales Australia
                [9 ]Scripps Research Translational Institute, La Jolla, CA USA
                Author information
                http://orcid.org/0000-0001-7751-4366
                http://orcid.org/0000-0003-4337-3707
                http://orcid.org/0000-0001-9596-3552
                http://orcid.org/0000-0001-6431-5982
                Article
                296
                10.1038/s41564-018-0296-2
                6345516
                30546099
                17de9342-5815-4a6d-9838-bb115a926d8a
                © Springer Nature Limited 2018

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 26 May 2018
                : 19 October 2018
                Categories
                Review Article
                Custom metadata
                © The Author(s), under exclusive licence to Springer Nature Limited 2019

                molecular evolution,genomics,infectious diseases
                molecular evolution, genomics, infectious diseases

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