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      The origins of the great pandemic

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          Abstract

          The timing and location of the first cases of the 1918 influenza pandemic are still controversial, a century after the pandemic became widely recognized. Here, we critically review competing hypotheses on the timing and geographical origin of this important outbreak and provide new historical insights into debates within military circles as to the nature of putative pre-1918 influenza activity. We also synthesize current knowledge about why the 1918 pandemic was so intense in young adults. Although it is still not clear precisely when and where the outbreak began and symptom-based reports are unlikely to reveal the answer, indirect methods including phylogenetics provide important clues, and we consider whether intense influenza activity as far back as 1915 in the USA may have been caused by viral strains closely related to the 1918 one.

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          1918 Influenza: the Mother of All Pandemics

          The "Spanish" influenza pandemic of 1918–1919, which caused ≈50 million deaths worldwide, remains an ominous warning to public health. Many questions about its origins, its unusual epidemiologic features, and the basis of its pathogenicity remain unanswered. The public health implications of the pandemic therefore remain in doubt even as we now grapple with the feared emergence of a pandemic caused by H5N1 or other virus. However, new information about the 1918 virus is emerging, for example, sequencing of the entire genome from archival autopsy tissues. But, the viral genome alone is unlikely to provide answers to some critical questions. Understanding the 1918 pandemic and its implications for future pandemics requires careful experimentation and in-depth historical analysis.
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            A synchronized global sweep of the internal genes of modern avian influenza virus.

            Zoonotic infectious diseases such as influenza continue to pose a grave threat to human health. However, the factors that mediate the emergence of RNA viruses such as influenza A virus (IAV) are still incompletely understood. Phylogenetic inference is crucial to reconstructing the origins and tracing the flow of IAV within and between hosts. Here we show that explicitly allowing IAV host lineages to have independent rates of molecular evolution is necessary for reliable phylogenetic inference of IAV and that methods that do not do so, including 'relaxed' molecular clock models, can be positively misleading. A phylogenomic analysis using a host-specific local clock model recovers extremely consistent evolutionary histories across all genomic segments and demonstrates that the equine H7N7 lineage is a sister clade to strains from birds--as well as those from humans, swine and the equine H3N8 lineage--sharing an ancestor with them in the mid to late 1800s. Moreover, major western and eastern hemisphere avian influenza lineages inferred for each gene coalesce in the late 1800s. On the basis of these phylogenies and the synchrony of these key nodes, we infer that the internal genes of avian influenza virus (AIV) underwent a global selective sweep beginning in the late 1800s, a process that continued throughout the twentieth century and up to the present. The resulting western hemispheric AIV lineage subsequently contributed most of the genomic segments to the 1918 pandemic virus and, independently, the 1963 equine H3N8 panzootic lineage. This approach provides a clear resolution of evolutionary patterns and processes in IAV, including the flow of viral genes and genomes within and between host lineages.
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              Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York City.

              The 1918 "Spanish flu" was the fastest spreading and most deadly influenza pandemic in recorded history. Hypotheses of its origin have been based on a limited collection of case and outbreak reports from before its recognized European emergence in the summer of 1918. These anecdotal accounts, however, remain insufficient for determining the early diffusion and impact of the pandemic virus. Using routinely collected monthly age-stratified mortality data, we show that an unmistakable shift in the age distribution of epidemic deaths occurred during the 1917/1918 influenza season in New York City. The timing, magnitude, and age distribution of this mortality shift provide strong evidence that an early wave of the pandemic virus was present in New York City during February-April 1918.
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                Author and article information

                Journal
                Evol Med Public Health
                Evol Med Public Health
                emph
                Evolution, Medicine, and Public Health
                Oxford University Press
                2050-6201
                2019
                21 January 2019
                21 January 2019
                : 2019
                : 1
                : 18-25
                Affiliations
                [1 ]Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ, USA
                [2 ]Sydenham House, Applethwaite, Keswick, UK
                [3 ]6 Northolme Road, London, UK
                Author notes
                Corresponding author. Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. Tel: +1-520-626-3456; E-mail: worobey@ 123456email.arizona.edu
                Article
                eoz001
                10.1093/emph/eoz001
                6381288
                18db26da-6d89-4438-873a-86e83ca46455
                © The Author(s) 2019. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 June 2018
                : 15 January 2019
                Page count
                Pages: 8
                Funding
                Funded by: David and Lucile Packard Foundation 10.13039/100000008
                Funded by: Jim Cox and Douglas Gill
                Categories
                Review

                influenza,1918,pandemic,geography,origin
                influenza, 1918, pandemic, geography, origin

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