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The age distribution of mortality due to influenza: pandemic and peri-pandemic

Identifieur interne : 000591 ( Pmc/Curation ); précédent : 000590; suivant : 000592

The age distribution of mortality due to influenza: pandemic and peri-pandemic

Auteurs : Tom Reichert [États-Unis] ; Gerardo Chowell [États-Unis] ; Jonathan A. Mccullers [États-Unis]

Source :

RBID : PMC:3554498

Abstract

Background

Pandemic influenza is said to 'shift mortality' to younger age groups; but also to spare a subpopulation of the elderly population. Does one of these effects dominate? Might this have important ramifications?

Methods

We estimated age-specific excess mortality rates for all-years for which data were available in the 20th century for Australia, Canada, France, Japan, the UK, and the USA for people older than 44 years of age. We modeled variation with age, and standardized estimates to allow direct comparison across age groups and countries. Attack rate data for four pandemics were assembled.

Results

For nearly all seasons, an exponential model characterized mortality data extremely well. For seasons of emergence and a variable number of seasons following, however, a subpopulation above a threshold age invariably enjoyed reduced mortality. 'Immune escape', a stepwise increase in mortality among the oldest elderly, was observed a number of seasons after both the A(H2N2) and A(H3N2) pandemics. The number of seasons from emergence to escape varied by country. For the latter pandemic, mortality rates in four countries increased for younger age groups but only in the season following that of emergence. Adaptation to both emergent viruses was apparent as a progressive decrease in mortality rates, which, with two exceptions, was seen only in younger age groups. Pandemic attack rate variation with age was estimated to be similar across four pandemics with very different mortality impact.

Conclusions

In all influenza pandemics of the 20th century, emergent viruses resembled those that had circulated previously within the lifespan of then-living people. Such individuals were relatively immune to the emergent strain, but this immunity waned with mutation of the emergent virus. An immune subpopulation complicates and may invalidate vaccine trials. Pandemic influenza does not 'shift' mortality to younger age groups; rather, the mortality level is reset by the virulence of the emerging virus and is moderated by immunity of past experience. In this study, we found that after immune escape, older age groups showed no further mortality reduction, despite their being the principal target of conventional influenza vaccines. Vaccines incorporating variants of pandemic viruses seem to provide little benefit to those previously immune. If attack rates truly are similar across pandemics, it must be the case that immunity to the pandemic virus does not prevent infection, but only mitigates the consequences.


Url:
DOI: 10.1186/1741-7015-10-162
PubMed: 23234604
PubMed Central: 3554498

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PMC:3554498

Le document en format XML

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<p>Pandemic influenza is said to 'shift mortality' to younger age groups; but also to spare a subpopulation of the elderly population. Does one of these effects dominate? Might this have important ramifications?</p>
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<title>Methods</title>
<p>We estimated age-specific excess mortality rates for all-years for which data were available in the 20th century for Australia, Canada, France, Japan, the UK, and the USA for people older than 44 years of age. We modeled variation with age, and standardized estimates to allow direct comparison across age groups and countries. Attack rate data for four pandemics were assembled.</p>
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<p>For nearly all seasons, an exponential model characterized mortality data extremely well. For seasons of emergence and a variable number of seasons following, however, a subpopulation above a threshold age invariably enjoyed reduced mortality. 'Immune escape', a stepwise increase in mortality among the oldest elderly, was observed a number of seasons after both the A(H2N2) and A(H3N2) pandemics. The number of seasons from emergence to escape varied by country. For the latter pandemic, mortality rates in four countries increased for younger age groups but only in the season following that of emergence. Adaptation to both emergent viruses was apparent as a progressive decrease in mortality rates, which, with two exceptions, was seen only in younger age groups. Pandemic attack rate variation with age was estimated to be similar across four pandemics with very different mortality impact.</p>
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<p>In all influenza pandemics of the 20th century, emergent viruses resembled those that had circulated previously within the lifespan of then-living people. Such individuals were relatively immune to the emergent strain, but this immunity waned with mutation of the emergent virus. An immune subpopulation complicates and may invalidate vaccine trials. Pandemic influenza does not 'shift' mortality to younger age groups; rather, the mortality level is reset by the virulence of the emerging virus and is moderated by immunity of past experience. In this study, we found that after immune escape, older age groups showed no further mortality reduction, despite their being the principal target of conventional influenza vaccines. Vaccines incorporating variants of pandemic viruses seem to provide little benefit to those previously immune. If attack rates truly are similar across pandemics, it must be the case that immunity to the pandemic virus does not prevent infection, but only mitigates the consequences.</p>
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<journal-id journal-id-type="nlm-ta">BMC Med</journal-id>
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<journal-title>BMC Medicine</journal-title>
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<article-id pub-id-type="pmid">23234604</article-id>
<article-id pub-id-type="pmc">3554498</article-id>
<article-id pub-id-type="publisher-id">1741-7015-10-162</article-id>
<article-id pub-id-type="doi">10.1186/1741-7015-10-162</article-id>
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<subject>Research Article</subject>
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<title-group>
<article-title>The age distribution of mortality due to influenza: pandemic and peri-pandemic</article-title>
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<name>
<surname>Reichert</surname>
<given-names>Tom</given-names>
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<xref ref-type="aff" rid="I1">1</xref>
<email>treichert@entropyresearch.org</email>
</contrib>
<contrib contrib-type="author" id="A2">
<name>
<surname>Chowell</surname>
<given-names>Gerardo</given-names>
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<xref ref-type="aff" rid="I2">2</xref>
<xref ref-type="aff" rid="I3">3</xref>
<email>gchowell@asu.edu</email>
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<name>
<surname>McCullers</surname>
<given-names>Jonathan A</given-names>
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<xref ref-type="aff" rid="I4">4</xref>
<xref ref-type="aff" rid="I5">5</xref>
<email>Jon.McCullers@stjude.org</email>
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<aff id="I1">
<label>1</label>
Entropy Research Institute, 345 S. Great Road, Lincoln, 01773, Massachusetts, USA</aff>
<aff id="I2">
<label>2</label>
Mathematical, Computational and Modeling Sciences Center, School of Human Evolution and Social Change, Arizona State University, Tempe, 85287, Arizona, USA</aff>
<aff id="I3">
<label>3</label>
Division of Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, 31 Center Dr-MSC 2220, Bethesda, 20892-2220, Maryland, USA</aff>
<aff id="I4">
<label>4</label>
Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, 38104, Tennessee, USA</aff>
<aff id="I5">
<label>5</label>
Department of Pediatrics, University of Tennessee Health Sciences Center, 50 N. Dunlap, Memphis, 38104, Tennessee, USA</aff>
<pub-date pub-type="collection">
<year>2012</year>
</pub-date>
<pub-date pub-type="epub">
<day>12</day>
<month>12</month>
<year>2012</year>
</pub-date>
<volume>10</volume>
<fpage>162</fpage>
<lpage>162</lpage>
<history>
<date date-type="received">
<day>6</day>
<month>5</month>
<year>2012</year>
</date>
<date date-type="accepted">
<day>12</day>
<month>12</month>
<year>2012</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright ©2012 Reichert et al; licensee BioMed Central Ltd.</copyright-statement>
<copyright-year>2012</copyright-year>
<copyright-holder>Reichert et al; licensee BioMed Central Ltd.</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0">
<license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/2.0">http://creativecommons.org/licenses/by/2.0</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<self-uri xlink:href="http://www.biomedcentral.com/1741-7015/10/162"></self-uri>
<abstract>
<sec>
<title>Background</title>
<p>Pandemic influenza is said to 'shift mortality' to younger age groups; but also to spare a subpopulation of the elderly population. Does one of these effects dominate? Might this have important ramifications?</p>
</sec>
<sec>
<title>Methods</title>
<p>We estimated age-specific excess mortality rates for all-years for which data were available in the 20th century for Australia, Canada, France, Japan, the UK, and the USA for people older than 44 years of age. We modeled variation with age, and standardized estimates to allow direct comparison across age groups and countries. Attack rate data for four pandemics were assembled.</p>
</sec>
<sec>
<title>Results</title>
<p>For nearly all seasons, an exponential model characterized mortality data extremely well. For seasons of emergence and a variable number of seasons following, however, a subpopulation above a threshold age invariably enjoyed reduced mortality. 'Immune escape', a stepwise increase in mortality among the oldest elderly, was observed a number of seasons after both the A(H2N2) and A(H3N2) pandemics. The number of seasons from emergence to escape varied by country. For the latter pandemic, mortality rates in four countries increased for younger age groups but only in the season following that of emergence. Adaptation to both emergent viruses was apparent as a progressive decrease in mortality rates, which, with two exceptions, was seen only in younger age groups. Pandemic attack rate variation with age was estimated to be similar across four pandemics with very different mortality impact.</p>
</sec>
<sec>
<title>Conclusions</title>
<p>In all influenza pandemics of the 20th century, emergent viruses resembled those that had circulated previously within the lifespan of then-living people. Such individuals were relatively immune to the emergent strain, but this immunity waned with mutation of the emergent virus. An immune subpopulation complicates and may invalidate vaccine trials. Pandemic influenza does not 'shift' mortality to younger age groups; rather, the mortality level is reset by the virulence of the emerging virus and is moderated by immunity of past experience. In this study, we found that after immune escape, older age groups showed no further mortality reduction, despite their being the principal target of conventional influenza vaccines. Vaccines incorporating variants of pandemic viruses seem to provide little benefit to those previously immune. If attack rates truly are similar across pandemics, it must be the case that immunity to the pandemic virus does not prevent infection, but only mitigates the consequences.</p>
</sec>
</abstract>
<kwd-group>
<kwd>Pandemic influenza</kwd>
<kwd>mortality due to influenza</kwd>
<kwd>recycling</kwd>
<kwd>pandemic attack rates</kwd>
<kwd>vaccination</kwd>
<kwd>protective immunity</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>

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