1918 review add rd

1918 review add rd - PERSPECTIVE 1918 Influenza the Mother...

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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 tis- sues. 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. “Curiouser and curiouser!” cried Alice Lewis Carroll, Alice’s Adventures in Wonderland, 1865 A n estimated one third of the world’s population (or 500 million persons) were infected and had clinical- ly apparent illnesses ( 1,2 ) during the 1918–1919 influenza pandemic. The disease was exceptionally severe. Case- fatality rates were >2.5%, compared to <0.1% in other influenza pandemics ( 3,4 ). Total deaths were estimated at 50 million ( 5–7 ) and were arguably as high as 100 mil- lion ( 7 ). The impact of this pandemic was not limited to 1918–1919. All influenza A pandemics since that time, and indeed almost all cases of influenza A worldwide (except- ing human infections from avian viruses such as H5N1 and H7N7), have been caused by descendants of the 1918 virus, including “drifted” H1N1 viruses and reassorted H2N2 and H3N2 viruses. The latter are composed of key genes from the 1918 virus, updated by subsequently-incor- porated avian influenza genes that code for novel surface proteins, making the 1918 virus indeed the “mother” of all pandemics. In 1918, the cause of human influenza and its links to avian and swine influenza were unknown. Despite clinical and epidemiologic similarities to influenza pandemics of 1889, 1847, and even earlier, many questioned whether such an explosively fatal disease could be influenza at all. That question did not begin to be resolved until the 1930s, when closely related influenza viruses (now known to be H1N1 viruses) were isolated, first from pigs and shortly thereafter from humans. Seroepidemiologic studies soon linked both of these viruses to the 1918 pandemic ( 8 ). Subsequent research indicates that descendants of the 1918 virus still persists enzootically in pigs. They probably also circulated continuously in humans, undergoing gradual antigenic drift and causing annual epidemics, until the 1950s. With the appearance of a new H2N2 pandemic strain in 1957 (“Asian flu”), the direct H1N1 viral descen- dants of the 1918 pandemic strain disappeared from human circulation entirely, although the related lineage persisted enzootically in pigs. But in 1977, human H1N1 viruses suddenly “reemerged” from a laboratory freezer (
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1918 review add rd - PERSPECTIVE 1918 Influenza the Mother...

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