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      1918 Influenza: the Mother of All Pandemics

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          Abstract

          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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          Characterization of the 1918 influenza virus polymerase genes.

          Jeffery K Taubenberger, Ann Reid, Raina M. Lourens … (2005)
          The influenza A viral heterotrimeric polymerase complex (PA, PB1, PB2) is known to be involved in many aspects of viral replication and to interact with host factors, thereby having a role in host specificity. The polymerase protein sequences from the 1918 human influenza virus differ from avian consensus sequences at only a small number of amino acids, consistent with the hypothesis that they were derived from an avian source shortly before the pandemic. However, when compared to avian sequences, the nucleotide sequences of the 1918 polymerase genes have more synonymous differences than expected, suggesting evolutionary distance from known avian strains. Here we present sequence and phylogenetic analyses of the complete genome of the 1918 influenza virus, and propose that the 1918 virus was not a reassortant virus (like those of the 1957 and 1968 pandemics), but more likely an entirely avian-like virus that adapted to humans. These data support prior phylogenetic studies suggesting that the 1918 virus was derived from an avian source. A total of ten amino acid changes in the polymerase proteins consistently differentiate the 1918 and subsequent human influenza virus sequences from avian virus sequences. Notably, a number of the same changes have been found in recently circulating, highly pathogenic H5N1 viruses that have caused illness and death in humans and are feared to be the precursors of a new influenza pandemic. The sequence changes identified here may be important in the adaptation of influenza viruses to humans.
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            Updating the accounts: global mortality of the 1918-1920 "Spanish" influenza pandemic.

            Juergen Mueller, Justin S. Hogg (2001)
            The influenza pandemic of 1918-20 is recognized as having generally taken place in three waves, starting in the northern spring and summer of 1918. This pattern of three waves, however, was not universal: in some locations influenza seems to have persisted into or returned in 1920. The recorded statistics of influenza morbidity and mortality are likely to be a significant understatement. Limitations of these data can include nonregistration, missing records, misdiagnosis, and nonmedical certification, and may also vary greatly between locations. Further research has seen the consistent upward revision of the estimated global mortality of the pandemic, which a 1920s calculation put in the vicinity of 21.5 million. A 1991 paper revised the mortality as being in the range 24.7-39.3 million. This paper suggests that it was of the order of 50 million. However, it must be acknowledged that even this vast figure may be substantially lower than the real toll, perhaps as much as 100 percent understated.
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              Pandemic versus epidemic influenza mortality: a pattern of changing age distribution.

              L Simonsen, M J Clarke, L B Schonberger … (1998)
              Almost all deaths related to current influenza epidemics occur among the elderly. However, mortality was greatest among the young during the 1918-1919 pandemic. This study compared the age distribution of influenza-related deaths in the United States during this century's three influenza A pandemics with that of the following epidemics. Half of influenza-related deaths during the 1968-1969 influenza A (H3N2) pandemic and large proportions of influenza-related deaths during the 1957-1958 influenza A (H2N2) and the 1918-1919 influenza A (H1N1) pandemics occurred among persons <65 years old. However, this group accounted for decrementally smaller proportions of deaths during the first decade following each pandemic. A model suggested that this mortality pattern may be explained by selective acquisition of protection against fatal illness among younger persons. The large proportion of influenza-related deaths during each pandemic and the following decade among persons <65 years old should be considered in planning for pandemics.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Emerg Infect Dis
                Journal ID (publisher-id): EID
                Title: Emerging Infectious Diseases
                Publisher: Centers for Disease Control and Prevention
                ISSN (Print): 1080-6040
                ISSN (Electronic): 1080-6059
                Publication date (Print): January 2006
                Volume: 12
                Issue: 1
                Pages: 15-22
                Affiliations
                [* ]Armed Forces Institute of Pathology, Rockville, Maryland, USA;
                [† ]National Institutes of Health, Bethesda, Maryland, USA
                Author notes
                Jeffery K. Taubenberger, Department of Molecular Pathology, Armed Forces Institute of Pathology, 1413 Research Blvd, Bldg 101, Rm 1057, Rockville, MD 20850-3125, USA; fax. 301-295-9507; email: taubenberger@ 123456afip.osd.mil
                Article
                Publisher ID: 05-0979
                DOI: 10.3201/eid1201.050979
                PMC ID: 3291398
                PubMed ID: 16494711
                SO-VID: 588c123b-6c03-4ca3-85d6-5329e6038600
                History
                Categories
                Subject: Historical Review

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: pandemic,history,influenza,pathogenesis
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: pandemic, history, influenza, pathogenesis

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