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      Age- and Sex-Specific Mortality Associated With the 1918–1919 Influenza Pandemic in Kentucky

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          Abstract

          Background.  The reasons for the unusual age-specific mortality patterns of the 1918–1919 influenza pandemic remain unknown. Here we characterize pandemic-related mortality by single year of age in a unique statewide Kentucky data set and explore breakpoints in the age curves.

          Methods.  Individual death certificates from Kentucky during 1911–1919 were abstracted by medically trained personnel. Pandemic-associated excess mortality rates were calculated by subtracting observed rates during pandemic months from rates in previous years, separately for each single year of age and by sex.

          Results.  The age profile of excess mortality risk in fall 1918 was characterized by a maximum among infants, a minimum at ages 9–10 years, a maximum at ages 24–26 years, and a second minimum at ages 56–59 years. The excess mortality risk in young adults had been greatly attenuated by winter 1919. The age breakpoints of mortality risk did not differ between males and females.

          Conclusions.  The observed mortality breakpoints in male and female cohorts born during 1859–1862, 1892–1894, and 1908–1909 did not coincide with known dates of historical pandemics. The atypical age mortality patterns of the 1918–1919 pandemic cannot be explained by military crowding, war-related factors, or prior immunity alone and likely result from a combination of unknown factors.

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          Most cited references34

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          Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus.

          A new pandemic influenza A (H1N1) virus has emerged, causing illness globally, primarily in younger age groups. To assess the level of preexisting immunity in humans and to evaluate seasonal vaccine strategies, we measured the antibody response to the pandemic virus resulting from previous influenza infection or vaccination in different age groups. Using a microneutralization assay, we measured cross-reactive antibodies to pandemic H1N1 virus (2009 H1N1) in stored serum samples from persons who either donated blood or were vaccinated with recent seasonal or 1976 swine influenza vaccines. A total of 4 of 107 persons (4%) who were born after 1980 had preexisting cross-reactive antibody titers of 40 or more against 2009 H1N1, whereas 39 of 115 persons (34%) born before 1950 had titers of 80 or more. Vaccination with seasonal trivalent inactivated influenza vaccines resulted in an increase in the level of cross-reactive antibody to 2009 H1N1 by a factor of four or more in none of 55 children between the ages of 6 months and 9 years, in 12 to 22% of 231 adults between the ages of 18 and 64 years, and in 5% or less of 113 adults 60 years of age or older. Seasonal vaccines that were formulated with adjuvant did not further enhance cross-reactive antibody responses. Vaccination with the A/New Jersey/1976 swine influenza vaccine substantially boosted cross-reactive antibodies to 2009 H1N1 in adults. Vaccination with recent seasonal nonadjuvanted or adjuvanted influenza vaccines induced little or no cross-reactive antibody response to 2009 H1N1 in any age group. Persons under the age of 30 years had little evidence of cross-reactive antibodies to the pandemic virus. However, a proportion of older adults had preexisting cross-reactive antibodies. 2009 Massachusetts Medical Society
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            Characterization of the 1918 influenza virus polymerase genes.

            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.

              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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                Author and article information

                Contributors
                Journal
                J Infect Dis
                J. Infect. Dis
                jid
                jinfdis
                The Journal of Infectious Diseases
                Oxford University Press
                0022-1899
                1537-6613
                1 March 2013
                10 December 2012
                : 207
                : 5
                : 721-729
                Affiliations
                [1 ] Fogarty International Center
                [2 ] National Cancer Institute
                [3 ] National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland
                [4 ] Armed Forces Institute of Pathology, Washington, D. C.
                Author notes

                Present affiliations: American Society for Microbiology, Washington, D. C. (A. H. R.); Michael Best and Friedrich, Milwaukee, Wisconsin (T. A. J.).

                Correspondence: Jeffery K. Taubenberger, MD, PhD, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Dr, Rm 3E19A.2 MSC 3203, Bethesda, MD 20892-3203 ( taubenbergerj@ 123456niaid.nih.gov ).
                Article
                jis745
                10.1093/infdis/jis745
                3563305
                23230061
                36568bf9-4ee5-43a9-94b4-99075b8c0a1d
                Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2012.

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
                : 4 June 2012
                : 21 September 2012
                Categories
                Major Articles and Brief Reports
                Viruses

                Infectious disease & Microbiology
                pandemic,influenza,mortality,age patterns,gender,immunity,military
                Infectious disease & Microbiology
                pandemic, influenza, mortality, age patterns, gender, immunity, military

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