Prioritization of Influenza Pandemic Vaccination to Minimize Years of Life Lost
Identifieur interne : 001554 ( Istex/Corpus ); précédent : 001553; suivant : 001555Prioritization of Influenza Pandemic Vaccination to Minimize Years of Life Lost
Auteurs : Mark A. Miller ; Cecile Viboud ; Donald R. Olson ; Rebecca F. Grais ; Maia A. Rabaa ; Lone SimonsenSource :
- The Journal of Infectious Diseases [ 0022-1899 ] ; 2008.
Abstract
Background. How to allocate limited vaccine supplies in the event of an influenza pandemic is currently under debate. Conventional vaccination strategies focus on those at highest risk for severe outcomes, including seniors, but do not consider (1) the signature pandemic pattern in which mortality risk is shifted to younger ages, (2) likely reduced vaccine response in seniors, and (3) differences in remaining years of life with age. Methods. We integrated these factors to project the age-specific years of life lost (YLL) and saved in a future pandemic, on the basis of mortality patterns from 3 historical pandemics, age-specific vaccine efficacy, and the 2000 US population structure. Results. For a 1918-like scenario, the absolute mortality risk is highest in people <45 years old; in contrast, seniors (those ≥65 years old) have the highest mortality risk in the 1957 and 1968 scenarios. The greatest YLL savings would be achieved by targeting different age groups in each scenario; people <45 years old in the 1918 scenario, people 45–64 years old in the 1968 scenario, and people >45 years old in the 1957 scenario. Conclusions. Our findings shift the focus of pandemic vaccination strategies onto younger populations and illustrate the need for real-time surveillance of mortality patterns in a future pandemic. Flexible setting of vaccination priority is essential to minimize mortality.
Url:
DOI: 10.1086/589716
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ISTEX:544B402E32A7C1B0C58B23C463C0BF5515A1A7B3Le document en format XML
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Miller</name><affiliation><mods:affiliation>Fogarty International Center, National Institutes of Health, Bethesda, Maryland</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: millemar@mail.nih.gov</mods:affiliation></affiliation><affiliation><mods:affiliation>Reprints or correspondence: Dr. Mark Miller, Div. of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, 16 Center Dr., Bethesda, MD 20892 (millemar@mail.nih.gov).</mods:affiliation></affiliation></author><author><name sortKey="Viboud, Cecile" sort="Viboud, Cecile" uniqKey="Viboud C" first="Cecile" last="Viboud">Cecile Viboud</name><affiliation><mods:affiliation>Fogarty International Center, National Institutes of Health, Bethesda, Maryland</mods:affiliation></affiliation></author><author><name sortKey="Olson, Donald R" sort="Olson, Donald R" uniqKey="Olson D" first="Donald R." last="Olson">Donald R. Olson</name><affiliation><mods:affiliation>New York City Department of Health and Mental Hygiene, New York, New York</mods:affiliation></affiliation></author><author><name sortKey="Grais, Rebecca F" sort="Grais, Rebecca F" uniqKey="Grais R" first="Rebecca F." last="Grais">Rebecca F. Grais</name><affiliation><mods:affiliation>Fogarty International Center, National Institutes of Health, Bethesda, Maryland</mods:affiliation></affiliation></author><author><name sortKey="Rabaa, Maia A" sort="Rabaa, Maia A" uniqKey="Rabaa M" first="Maia A." last="Rabaa">Maia A. 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Miller</name><affiliation><mods:affiliation>Fogarty International Center, National Institutes of Health, Bethesda, Maryland</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: millemar@mail.nih.gov</mods:affiliation></affiliation><affiliation><mods:affiliation>Reprints or correspondence: Dr. Mark Miller, Div. of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, 16 Center Dr., Bethesda, MD 20892 (millemar@mail.nih.gov).</mods:affiliation></affiliation></author><author><name sortKey="Viboud, Cecile" sort="Viboud, Cecile" uniqKey="Viboud C" first="Cecile" last="Viboud">Cecile Viboud</name><affiliation><mods:affiliation>Fogarty International Center, National Institutes of Health, Bethesda, Maryland</mods:affiliation></affiliation></author><author><name sortKey="Olson, Donald R" sort="Olson, Donald R" uniqKey="Olson D" first="Donald R." last="Olson">Donald R. 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Rabaa</name><affiliation><mods:affiliation>Fogarty International Center, National Institutes of Health, Bethesda, Maryland</mods:affiliation></affiliation></author><author><name sortKey="Simonsen, Lone" sort="Simonsen, Lone" uniqKey="Simonsen L" first="Lone" last="Simonsen">Lone Simonsen</name><affiliation><mods:affiliation>Department of Global Health, School of Public Health and Health Services, George Washington University, Washington, DC</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">The Journal of Infectious Diseases</title><title level="j" type="abbrev">The Journal of Infectious Diseases</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><publisher>The University of Chicago Press</publisher><date when="2008-08-01">2008</date><biblScope unit="vol">198</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="305">305</biblScope><biblScope unit="page" to="311">311</biblScope></imprint><idno type="ISSN">0022-1899</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-1899</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Background. How to allocate limited vaccine supplies in the event of an influenza pandemic is currently under debate. Conventional vaccination strategies focus on those at highest risk for severe outcomes, including seniors, but do not consider (1) the signature pandemic pattern in which mortality risk is shifted to younger ages, (2) likely reduced vaccine response in seniors, and (3) differences in remaining years of life with age. Methods. We integrated these factors to project the age-specific years of life lost (YLL) and saved in a future pandemic, on the basis of mortality patterns from 3 historical pandemics, age-specific vaccine efficacy, and the 2000 US population structure. Results. For a 1918-like scenario, the absolute mortality risk is highest in people <45 years old; in contrast, seniors (those ≥65 years old) have the highest mortality risk in the 1957 and 1968 scenarios. The greatest YLL savings would be achieved by targeting different age groups in each scenario; people <45 years old in the 1918 scenario, people 45–64 years old in the 1968 scenario, and people >45 years old in the 1957 scenario. Conclusions. Our findings shift the focus of pandemic vaccination strategies onto younger populations and illustrate the need for real-time surveillance of mortality patterns in a future pandemic. 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Grais</name><affiliations><json:string>Fogarty International Center, National Institutes of Health, Bethesda, Maryland</json:string></affiliations></json:item><json:item><name>Maia A. Rabaa</name><affiliations><json:string>Fogarty International Center, National Institutes of Health, Bethesda, Maryland</json:string></affiliations></json:item><json:item><name>Lone Simonsen</name><affiliations><json:string>Department of Global Health, School of Public Health and Health Services, George Washington University, Washington, DC</json:string></affiliations></json:item></author><arkIstex>ark:/67375/HXZ-VMW0NGNP-F</arkIstex><language><json:string>unknown</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>Background. How to allocate limited vaccine supplies in the event of an influenza pandemic is currently under debate. Conventional vaccination strategies focus on those at highest risk for severe outcomes, including seniors, but do not consider (1) the signature pandemic pattern in which mortality risk is shifted to younger ages, (2) likely reduced vaccine response in seniors, and (3) differences in remaining years of life with age. Methods. We integrated these factors to project the age-specific years of life lost (YLL) and saved in a future pandemic, on the basis of mortality patterns from 3 historical pandemics, age-specific vaccine efficacy, and the 2000 US population structure. Results. For a 1918-like scenario, the absolute mortality risk is highest in people >45 years old; in contrast, seniors (those ≥65 years old) have the highest mortality risk in the 1957 and 1968 scenarios. The greatest YLL savings would be achieved by targeting different age groups in each scenario; people >45 years old in the 1918 scenario, people 45–64 years old in the 1968 scenario, and people >45 years old in the 1957 scenario. Conclusions. Our findings shift the focus of pandemic vaccination strategies onto younger populations and illustrate the need for real-time surveillance of mortality patterns in a future pandemic. 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12]</json:string><json:string>[36]</json:string><json:string>[9]</json:string><json:string>[16, 17]</json:string><json:string>[2]</json:string><json:string>[35]</json:string><json:string>[19]</json:string><json:string>[9, 12]</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/HXZ-VMW0NGNP-F</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - microbiology</json:string><json:string>2 - infectious diseases</json:string><json:string>2 - immunology</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - biomedical research</json:string><json:string>3 - microbiology</json:string></scienceMetrix><scopus><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Infectious Diseases</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Immunology and 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Vaccination to Minimize Years of Life Lost</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>The University of Chicago Press</publisher><availability><licence>© 2008 by the Infectious Diseases Society of America</licence></availability><date type="Copyright" when="2008">2008</date><date when="2008-08-01">2008</date></publicationStmt><notesStmt><note type="content-type" source="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="publication-type" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note></notesStmt><sourceDesc><biblStruct type="article"><analytic><title level="a" type="main" xml:lang="en">Prioritization of Influenza Pandemic Vaccination to Minimize Years of Life Lost</title><author xml:id="author-0000" role="corresp"><persName><surname>Miller</surname><forename type="first">Mark A.</forename></persName><affiliation><orgName type="institution">Fogarty International Center</orgName><orgName type="institution">National Institutes of Health</orgName><address><addrLine>Bethesda, Maryland</addrLine></address></affiliation><email>millemar@mail.nih.gov</email></author><author xml:id="author-0001"><persName><surname>Viboud</surname><forename type="first">Cecile</forename></persName><affiliation><orgName type="institution">Fogarty International Center</orgName><orgName type="institution">National Institutes of Health</orgName><address><addrLine>Bethesda, Maryland</addrLine></address></affiliation></author><author xml:id="author-0002"><persName><surname>Olson</surname><forename type="first">Donald R.</forename></persName><affiliation><orgName type="department">New York City Department of Health and Mental Hygiene</orgName><address><addrLine>New York, New York</addrLine></address></affiliation></author><author xml:id="author-0003"><persName><surname>Grais</surname><forename type="first">Rebecca F.</forename></persName><affiliation><orgName type="institution">Fogarty International Center</orgName><orgName type="institution">National Institutes of Health</orgName><address><addrLine>Bethesda, Maryland</addrLine></address></affiliation></author><author xml:id="author-0004"><persName><surname>Rabaa</surname><forename type="first">Maia A.</forename></persName><affiliation><orgName type="institution">Fogarty International Center</orgName><orgName type="institution">National Institutes of Health</orgName><address><addrLine>Bethesda, Maryland</addrLine></address></affiliation></author><author xml:id="author-0005"><persName><surname>Simonsen</surname><forename type="first">Lone</forename></persName><affiliation><orgName type="department">Department of Global Health</orgName><orgName type="department">School of Public Health and Health Services</orgName><orgName type="institution">George Washington University</orgName><address><addrLine>Washington, 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<ref target="http://www.tei-c.org/">We use TEI</ref></desc></application></appInfo></encodingDesc><profileDesc><abstract><p><hi rend="bold"><hi rend="italic">Background.</hi></hi> How to allocate limited vaccine supplies in the event of an influenza pandemic is currently under debate. Conventional vaccination strategies focus on those at highest risk for severe outcomes, including seniors, but do not consider (1) the signature pandemic pattern in which mortality risk is shifted to younger ages, (2) likely reduced vaccine response in seniors, and (3) differences in remaining years of life with age.</p><p><hi rend="bold"><hi rend="italic">Methods.</hi></hi> We integrated these factors to project the age-specific years of life lost (YLL) and saved in a future pandemic, on the basis of mortality patterns from 3 historical pandemics, age-specific vaccine efficacy, and the 2000 US population structure.</p><p><hi rend="bold"><hi rend="italic">Results.</hi></hi> For a 1918-like scenario, the absolute mortality risk is highest in people <45 years old; in contrast, seniors (those ≥65 years old) have the highest mortality risk in the 1957 and 1968 scenarios. The greatest YLL savings would be achieved by targeting different age groups in each scenario; people <45 years old in the 1918 scenario, people 45–64 years old in the 1968 scenario, and people >45 years old in the 1957 scenario.</p><p><hi rend="bold"><hi rend="italic">Conclusions.</hi></hi> Our findings shift the focus of pandemic vaccination strategies onto younger populations and illustrate the need for real-time surveillance of mortality patterns in a future pandemic. Flexible setting of vaccination priority is essential to minimize mortality.</p></abstract><textClass ana="subject"><keywords scheme="heading"><term>Major Articles and Brief Reports</term></keywords></textClass><langUsage><language ident="EN"></language></langUsage></profileDesc><revisionDesc><change when="2019-12-09" who="#istex" xml:id="pub2tei">formatting</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/HXZ-VMW0NGNP-F/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup, element #text not found" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article">
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<title-group>
<article-title>Prioritization of Influenza Pandemic Vaccination to Minimize Years of Life Lost</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name><surname>Miller</surname><given-names>Mark A.</given-names></name>
<xref ref-type="aff" rid="AU1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="COR1"></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Viboud</surname><given-names>Cecile</given-names></name>
<xref ref-type="aff" rid="AU1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Olson</surname><given-names>Donald R.</given-names></name>
<xref ref-type="aff" rid="AU2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Grais</surname><given-names>Rebecca F.</given-names></name>
<xref ref-type="aff" rid="AU1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Rabaa</surname><given-names>Maia A.</given-names></name>
<xref ref-type="aff" rid="AU1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Simonsen</surname><given-names>Lone</given-names></name>
<xref ref-type="aff" rid="AU3"><sup>3</sup></xref>
</contrib>
<aff id="AU1"><label>1</label><institution>Fogarty International Center, National Institutes of Health</institution>, <addr-line>Bethesda, Maryland</addr-line></aff>
<aff id="AU2"><label>2</label><institution>New York City Department of Health and Mental Hygiene</institution>, <addr-line>New York, New York</addr-line></aff>
<aff id="AU3"><label>3</label><institution>Department of Global Health, School of Public Health and Health Services, George Washington University</institution>, <addr-line>Washington, DC</addr-line></aff>
</contrib-group>
<author-notes>
<corresp id="COR1">Reprints or correspondence: Dr. Mark Miller, Div. of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, 16 Center Dr., Bethesda, MD 20892 (<email>millemar@mail.nih.gov</email>).</corresp>
</author-notes>
<pub-date pub-type="ppub">
<day>1</day>
<month>8</month>
<year>2008</year>
</pub-date>
<volume>198</volume>
<issue>3</issue>
<fpage>305</fpage>
<lpage>311</lpage>
<history>
<date date-type="received">
<day>1</day>
<month>11</month>
<year>2007</year>
</date>
<date date-type="accepted">
<day>14</day>
<month>2</month>
<year>2008</year>
</date>
</history>
<copyright-statement>© 2008 by the Infectious Diseases Society of America</copyright-statement>
<copyright-year>2008</copyright-year>
<abstract>
<p><bold><italic>Background.</italic></bold> How to allocate limited vaccine supplies in the event of an influenza pandemic is currently under debate. Conventional vaccination strategies focus on those at highest risk for severe outcomes, including seniors, but do not consider (1) the signature pandemic pattern in which mortality risk is shifted to younger ages, (2) likely reduced vaccine response in seniors, and (3) differences in remaining years of life with age.</p>
<p><bold><italic>Methods.</italic></bold> We integrated these factors to project the age-specific years of life lost (YLL) and saved in a future pandemic, on the basis of mortality patterns from 3 historical pandemics, age-specific vaccine efficacy, and the 2000 US population structure.</p>
<p><bold><italic>Results.</italic></bold> For a 1918-like scenario, the absolute mortality risk is highest in people <45 years old; in contrast, seniors (those ≥65 years old) have the highest mortality risk in the 1957 and 1968 scenarios. The greatest YLL savings would be achieved by targeting different age groups in each scenario; people <45 years old in the 1918 scenario, people 45–64 years old in the 1968 scenario, and people >45 years old in the 1957 scenario.</p>
<p><bold><italic>Conclusions.</italic></bold> Our findings shift the focus of pandemic vaccination strategies onto younger populations and illustrate the need for real-time surveillance of mortality patterns in a future pandemic. Flexible setting of vaccination priority is essential to minimize mortality.</p>
</abstract>
</article-meta>
</front>
<body>
<p>The Centers for Disease Control and Prevention (CDC) has estimated that the population of the United States at increased risk for influenza is 91 million, whereas the total population targeted for vaccination is ∼218 million [<xref ref-type="bibr" rid="R1">1</xref>], which will lead to a clear resource-allocation dilemma in the event of a pandemic. Pandemic influenza preparedness strategies focus on the prevention of severe outcomes as the guiding principle for the utilization of vaccines and therapeutics. The US pandemic preparedness draft plan provides guidance for vaccine allocation, prioritizing key government and health care workers as well as emergency responders. In the general population, seniors (those ≥65 years of age) are prioritized over younger healthy adults in all 3 of the pandemic scenarios considered, which range from mild to severe [<xref ref-type="bibr" rid="R2">2</xref>]. Government officials are seeking input from the public to refine this proposed prioritization strategy. In the meantime, several bioethicists and scientists have questioned the prioritization of seniors over younger persons and sparked a recent policy debate centered around the question of whom should be vaccinated first [<xref ref-type="bibr" rid="R3">3</xref>–<xref ref-type="bibr" rid="R8">8</xref>]. Essentially, ethicists criticize the inherent axiom that any life lost has the same value, regardless of whether the deceased was 5 or 99 years old.</p>
<p>When considering the best approach to mitigate the impact of mortality in a pandemic, the age-specific historical experience of mortality risk must be taken into consideration. Mortality during influenza pandemics has ranged from relatively mild (1968) to catastrophic (1918) [<xref ref-type="bibr" rid="R9">9</xref>]. Although severe influenza predominantly affects the elderly and infirm in interpandemic seasons, mortality shifts toward younger adults in pandemic years [<xref ref-type="bibr" rid="R10">10</xref>]. The 1918 pandemic is an extreme case, in which young adults were at highest risk of death, whereas seniors were essentially spared relative to the immediately preceding influenza seasons [<xref ref-type="bibr" rid="R11">11</xref>]; a similar phenomenon was seen in the 1968 pandemic [<xref ref-type="bibr" rid="R9">9</xref>, <xref ref-type="bibr" rid="R12">12</xref>]. Decisions on vaccine allocation should also incorporate information on the decline in vaccine response with age due to immune senescence [<xref ref-type="bibr" rid="R13">13</xref>], an issue that has been overlooked in current pandemic plans. A recent literature review of randomized, placebo-controlled vaccine response found that influenza vaccine efficacy is reduced by 25%–50% in seniors, compared with that in younger adults [<xref ref-type="bibr" rid="R14">14</xref>]. Incorporating the phenomenon of declining response with age in a priority setting will also intuitively drive the priority groups toward younger ages.</p>
<p>In this article, we propose the integration of these concepts and explore a quantitative approach to be used to set priorities for vaccination in pandemic planning. Measurement of the potential years of life lost (YLL) during influenza pandemics is a quantitative tool that integrates mortality risks in various age groups with age differences in life expectancy. The YLL measure implies a differential between the prevention of death in younger and older persons [<xref ref-type="bibr" rid="R15">15</xref>] and is commonly used as a metric in public health decision making, particularly for vaccination recommendations [<xref ref-type="bibr" rid="R16">16</xref>, <xref ref-type="bibr" rid="R17">17</xref>]. Intuitively, the use of YLL instead of the customary number of deaths would generate a very different weighting of age group priorities, simply because YLL “values” the prevention of the death of a younger person more highly than that of an older individual. Although YLL measures were recently applied to the estimation of seasonal influenza economic costs [<xref ref-type="bibr" rid="R18">18</xref>], this important metric has not been incorporated into the current debate about optimal control of pandemic influenza thus far.</p>
<p>Health economics analyses conventionally consider complex health outcome metrics such as quality-adjusted life years and disability-adjusted life years (DALYs) [<xref ref-type="bibr" rid="R19">19</xref>], which incorporates both YLL and years of life spent in poor health or with disability after a disease episode. These metrics are useful for evaluating the burdens of chronic diseases or injuries [<xref ref-type="bibr" rid="R20">20</xref>] but do not add much to the assessment of influenza vaccine strategies, given that influenza is an acute viral infection from which survivors usually fully recover in a week or two with no life-long sequelae. Furthermore, when death and life with disability are integrated in a single measure of DALYs, different weights on these health outcomes must be set a priori, a sometimes difficult and debated approach [<xref ref-type="bibr" rid="R21">21</xref>]. In addition, because the YLL metric does not put different weights on remaining years of life based on disability or societal preferences related to the value of life at different ages, it tends to overestimate disease burden in seniors compared with the DALY metric [<xref ref-type="bibr" rid="R22">22</xref>]. Hence, in this work, we focus on YLL, a conservative metric that captures the major health burden of pandemic influenza with no need to set arbitrary values on quality of life.</p>
<p>Although the importance of assessing YLL has been suggested as an important consideration for vaccine allocation in pandemic situations [<xref ref-type="bibr" rid="R3">3</xref>, <xref ref-type="bibr" rid="R6">6</xref>], here we provide the first quantitative estimates of this metric. We project the age-specific YLL and the benefits of vaccination in a future pandemic, integrating historical mortality rates, life expectancy, and age-specific vaccine efficacy. The purpose of this analysis is to provide an alternative quantitative tool to help guide pandemic vaccine priority setting and achieve the greatest possible population impact, by preventing the loss of as many years of life as possible.</p>
<sec sec-type="methods">
<title>Methods</title>
<p>We estimated influenza-related deaths by age for the 1918, 1957, and 1968 pandemics. For the earliest 2 pandemics, we relied on age-specific mortality estimates available in the literature, based on New York City data for the 1918 pandemic [<xref ref-type="bibr" rid="R9">9</xref>, <xref ref-type="bibr" rid="R11">11</xref>] and national US data for the 1957 pandemic [<xref ref-type="bibr" rid="R23">23</xref>, <xref ref-type="bibr" rid="R24">24</xref>]. We used data from New York City for the 1918 pandemic because the overall death rate there for the main pandemic wave in 1918–1919 was equal to that in the entire United States (53 deaths per 10,000 population), and reliable age-specific mortality estimates were available only for New York City [<xref ref-type="bibr" rid="R11">11</xref>]. Data were available for 6 age groups for the 1918 pandemic (<5, 5–14, 15–24, 25–44, 45–64, and ≥65 years) and for 7 age groups for the 1957 pandemic (<1, 1–14, 15–24, 25–44, 45–64, 65–74, and ≥75 years). For the 1968 pandemic, we used monthly national vital statistics by age (<1, 1–4, 5–19, 20–44, 45–64, 65–74, and ≥75 years) [<xref ref-type="bibr" rid="R25">25</xref>]. Estimates of excess deaths for all 3 pandemics were based on the same Serfling-like seasonal regression approach long used by the CDC and others [<xref ref-type="bibr" rid="R11">11</xref>, <xref ref-type="bibr" rid="R24">24</xref>, <xref ref-type="bibr" rid="R25">25</xref>]. We applied this approach to all-cause mortality to capture the overall mortality burden of past influenza pandemics [<xref ref-type="bibr" rid="R9">9</xref>].</p>
<p>Next, to project deaths and YLL in a future pandemic, we modeled scenarios in which pandemics with mortality patterns similar to those of the 1918, 1957, or 1968 pandemics occur in a contemporary setting. We calculated “period expected” YLL [<xref ref-type="bibr" rid="R19">19</xref>] by applying historical age-specific death rates for the 1918, 1957, and 1968 pandemics to the age structure of the US population in 2000 and standard life expectancy at age of death in 2000 from the midpoint of each age category for the 6 (1918 pandemic) or 7 (1957 and 1968 pandemics) age categories available [<xref ref-type="bibr" rid="R26">26</xref>]. For example, in the 1918-like scenario, projections of YLL numbers among people <45 years old were calculated as follows:
<disp-formula>
<graphic position="anchor" xlink:href="198-3-305-eq001.tif"></graphic>
</disp-formula>
where DR<sub>1918,<italic>i</italic></sub> is the historical age-specific death rate in the 1918 pandemic for age subgroup <italic>i;</italic> Pop<sub>2000,<italic>i</italic></sub> is the 2000 population size of group <italic>i;</italic> LE<sub>2000,<italic>i</italic></sub> is the 2000 life expectancy of an individual at age <italic>i;</italic> and <italic>i</italic> represents the 4 age subgroups <45 years old available in the historical 1918 mortality data. We then derived projected YLL rates in people <45 years old for the 1918-like scenario, as follows:
<disp-formula>
<graphic position="anchor" xlink:href="198-3-305-eq002.tif"></graphic>
</disp-formula></p>
<p>Our algorithm follows a standard approach [<xref ref-type="bibr" rid="R27">27</xref>] in that we do not use a social discount rate that favors life saved in the near future; nor do we use age-specific coefficients to weight deaths in young adults more heavily than those in children or seniors. Such a weighting and discounting system can be used in DALYs [<xref ref-type="bibr" rid="R19">19</xref>] but relies on disputed value judgments based on economic considerations [<xref ref-type="bibr" rid="R21">21</xref>].</p>
<p>To account for differences in population sizes by age group, it is important to show excess mortality and YLL as incidence rates for the 3 pandemic scenarios. For each scenario, we also present the relative risk (RR) of mortality and YLL for those aged <45 years and 45–64 years, compared with the reference group of persons aged ≥65 years (the age group currently prioritized for vaccination). These 3 age groups were the only ones compatible with comparisons across all 3 scenarios, given the limited availability of historical age-specific mortality data.</p>
<p>To incorporate the expected age-specific benefits of a pandemic vaccine, we used estimates of seasonal influenza vaccine immunogenicity stratified by age groups. A recent study indicated that the antibody response in seniors was only approximately one-fourth to one-half as rigorous as that in adults <65 years old [<xref ref-type="bibr" rid="R14">14</xref>]. Assuming that the vaccine efficacy in terms of preventing deaths is between 70% and 90% of deaths in persons <65 years old [<xref ref-type="bibr" rid="R28">28</xref>, <xref ref-type="bibr" rid="R29">29</xref>], this result suggests that the corresponding vaccine efficacy for seniors is between 17% and 53% [<xref ref-type="bibr" rid="R14">14</xref>]. Using this range of relative immunogenicity, we estimated the direct effects of vaccination in the different age groups, measured as YLL and deaths prevented per dose of administered vaccine.</p>
</sec>
<sec sec-type="results">
<title>Results</title>
<p>Aside from the sheer magnitude of deaths in the 1918 pandemic, the disproportionate age pattern of deaths is of note; deaths occurred predominantly in young adults, and seniors were spared [<xref ref-type="bibr" rid="R9">9</xref>]. The mortality rate of 560 deaths per 100,000 population in persons <45 years old was 3.75 times greater than that in persons ≥65 years old (<xref ref-type="fig" rid="F3">table 1</xref>). By contrast, in the moderate 1957 pandemic, the overall mortality rate was 6.4 per 100,000 in persons <45 years old, only 0.02 times that in persons ≥65 years old. Similarly, in the mild 1968 pandemic, seniors experienced the highest mortality rate, although the differential with younger age groups was less pronounced than for the 1957 pandemic.</p>
<p>When YLL are considered rather than simply deaths, the impact of pandemics is more pronounced in younger populations. <xref ref-type="fig" rid="F1">Figure 1</xref> compares mortality and YLL rates by age in the 1918, 1957, and 1968 pandemic scenarios, where projections are based on the 2000 US population. With the exception of the 1918 pandemic, persons ≥65 years old have higher rates of influenza-related deaths than those <65 years old. However, when YLL rates are considered, the projected burden shifts toward younger populations. For the 1957 and 1968 pandemic scenarios in particular, the YLL metric reduces the differences in rates between seniors and younger people. We also note that 56%–99% of YLL would occur in persons <65 years old, depending on the scenario considered (see <xref ref-type="fig" rid="F2">figure 2</xref> for numbers of deaths and YLL).</p>
<p>Taking into account differential vaccine efficacy with age produces an even greater shift in vaccine benefits toward younger age groups (<xref ref-type="fig" rid="F3">table 1</xref>). Using the 3 age groups for which we have mortality data from all 3 historic pandemics (<45, 45–64, and ≥65 years old), we can define the optimal age group for targeted influenza vaccination as the one that maximizes the YLL prevented per vaccine dose. The optimal group comprises people <45 years old for the 1918-like scenario and people 45–64 years old for the 1968-like scenario (RR > 1 in <xref ref-type="fig" rid="F3">table 1</xref>). For the 1957-like scenario, the range of YLL prevented per dose in people 45–64 years old overlaps with that in people ≥65 years old; we cannot resolve whether vaccinating the middle-age group would be better than vaccinating seniors, and we therefore conclude that these age groups would be equally good choices.</p>
</sec>
<sec sec-type="discussion">
<title>Discussion</title>
<p>Some years ago, a CDC health economics study of pandemic influenza noted that nearly opposite age- and high-risk-group priorities would be generated if, instead of death counts, prioritization was based on a more complex measure of health outcomes that had characteristics similar to our proposed YLL measure [<xref ref-type="bibr" rid="R30">30</xref>]. However, the important finding—that priority setting critically depends on what outcomes we want to prevent—did not get the attention it deserved until recent commentaries were made by bioethicists [<xref ref-type="bibr" rid="R3">3</xref>, <xref ref-type="bibr" rid="R6">6</xref>, <xref ref-type="bibr" rid="R8">8</xref>].</p>
<p>Focusing on vaccination of seniors in preference to younger populations fails to account for 4 important factors in pandemic situations: (1) the differential in YLL for deaths in younger versus older persons; (2) reduced vaccine immunogenicity in seniors; (3) the observed shift in mortality to younger groups during pandemics; and (4) the indirect (herd immunity) effects of vaccination. In this article, we offer a comprehensive quantitative study that seeks to account for the first 3 of these factors and project the potential impact per vaccine dose in different age groups on the basis of past pandemic mortality patterns extrapolated to the current US population structure. This is particularly relevant given the history of inadequate vaccine supply [<xref ref-type="bibr" rid="R31">31</xref>] and the need to prioritize vaccination to maximize health benefits per administered vaccine dose [<xref ref-type="bibr" rid="R16">16</xref>, <xref ref-type="bibr" rid="R17">17</xref>]. For 2 of 3 pandemic scenarios studied, our new integrated approach to project the likely benefits of a pandemic vaccination effort prioritizes persons <65 years old over seniors and differs from the US pandemic preparedness draft plan [<xref ref-type="bibr" rid="R2">2</xref>] as well as 14 of 28 national plans that specifically prioritized vaccine [<xref ref-type="bibr" rid="R32">32</xref>]. Importantly, if vaccine resources were limited, the greatest YLL mortality benefits would be achieved by targeting different age groups in each pandemic scenario; people <45 years old in the 1918 scenario, people 45–64 years old in the 1968 scenario, and people >45 years old in the 1957 scenario. Unfortunately, the US draft plan [<xref ref-type="bibr" rid="R2">2</xref>] currently considers young, healthy adults to be the lowest priority for vaccination in all 3 scenarios, even though historical events suggest that mortality could be disproportionately high in this age group.</p>
<p>Pandemics differ from influenza epidemics not necessarily in causing more deaths but in causing proportionally more deaths in younger age groups [<xref ref-type="bibr" rid="R10">10</xref>]. Pandemic impact is not always evident if one simply compares the total number of influenza-related deaths between pandemic and interpandemic seasons, especially in the case of the mild 1968 pandemic [<xref ref-type="bibr" rid="R9">9</xref>, <xref ref-type="bibr" rid="R25">25</xref>]. Although the greatest mortality and YLL burden during <italic>interpandemic</italic> influenza occur in seniors (data not shown), in a future pandemic situation the majority of YLL (56%–99%) are expected to occur in persons <65 years old, regardless of which of the 3 scenarios reflecting our past experience with pandemic influenza is considered. The heavier YLL burden in younger age groups is truly a characteristic of pandemic influenza and is not found for seasonal influenza, thus confirming that the YLL metric is sensitive and specific to the mortality age pattern in influenza pandemics.</p>
<p>The mortality age shift observed during past pandemics may result from the recycling of influenza viral antigens over time [<xref ref-type="bibr" rid="R33">33</xref>], thus conferring protection against severe disease in the most senior age groups [<xref ref-type="bibr" rid="R11">11</xref>, <xref ref-type="bibr" rid="R12">12</xref>], possibly combined with a shift in disease transmission patterns [<xref ref-type="bibr" rid="R34">34</xref>]. In particular, recent analyses of monthly data from the 1918 pandemic in New York City and Denmark document little excess mortality in seniors [<xref ref-type="bibr" rid="R11">11</xref>, <xref ref-type="bibr" rid="R35">35</xref>], suggesting a sparing of the elderly. This pattern challenges the classically described W-shaped age-specific mortality curve, which was based on crude annual mortality data rather than monthly excess mortality [<xref ref-type="bibr" rid="R36">36</xref>]. In addition, for the 1918 pandemic, the curious age pattern of young adults having the highest mortality risk may be further explained by an unusual immune pathology that affected young adults [<xref ref-type="bibr" rid="R37">37</xref>]. Because the contributions of the 2 possibilities—recycling and immune pathology—cannot be resolved for the 1918 pandemic [<xref ref-type="bibr" rid="R37">37</xref>], projections of a future pandemic impact cannot unequivocally evaluate the full range of possible age patterns. We note that recycling is not an issue for a contemporary pandemic threat such as A/H5N1, yet the age distribution of human cases and deaths so far is reminiscent of that of the 1918 pandemic, with the highest impact being among the young [<xref ref-type="bibr" rid="R38">38</xref>]. Clearly, more research is warranted to help us fully understand and potentially predict the age distribution of deaths for pandemic influenza.</p>
<p>We note some limitations of our study. We assigned YLL for life tables from age groups of the total US population and did not stratify by underlying medical conditions or socioeconomic risk factors, which may affect life expectancy. However, although seasonal influenza generally kills exclusively “high-risk” persons with underlying predisposing medical conditions, deaths in historic influenza pandemics occurred predominantly among previously healthy individuals [<xref ref-type="bibr" rid="R11">11</xref>, <xref ref-type="bibr" rid="R12">12</xref>], so this is unlikely to be a serious limitation. Furthermore, to estimate the influenza mortality burden, we exclusively studied all-cause excess mortality, a measure that is thought to best reflect the total burden of influenza but is imprecise relative to other outcomes, such as excess pneumonia and influenza mortality [<xref ref-type="bibr" rid="R9">9</xref>]. However, applying the same methodology to deaths from pneumonia and influenza leads to the same qualitative conclusions in terms of optimal age groups for vaccination (data not shown).</p>
<p>We also limited our analysis to New York City data and assumed that there was little regional geographical variation in the age pattern of pandemic influenza deaths across the United States. Although considerable variability in the overall impact of the 1918 flu was reported across US cities [<xref ref-type="bibr" rid="R39">39</xref>, <xref ref-type="bibr" rid="R40">40</xref>], there is no evidence that the general age pattern of deaths differed. Furthermore, unusually high mortality among young adults in 1918 has been consistently found in locales as diverse as the United States, the United Kingdom, Scandinavia, and Australia [<xref ref-type="bibr" rid="R11">11</xref>, <xref ref-type="bibr" rid="R41">41</xref>–<xref ref-type="bibr" rid="R43">43</xref>]. In particular, a sensitivity analysis based on historical data from Copenhagen [<xref ref-type="bibr" rid="R35">35</xref>] suggested that the death and YLL burden in people <45 years old was similar in Copenhagen and New York City. By contrast, older age groups experienced a lower burden in Copenhagen than in New York City, such that targeting younger age groups for vaccination is even more dramatically beneficial in the Copenhagen-based 1918 scenario (<xref ref-type="fig" rid="F4">table 2</xref>). We also recognize that the overall pandemic mortality impact has historically played out in several waves in the first 3–5 years [<xref ref-type="bibr" rid="R9">9</xref>], but we have considered only the primary pandemic wave in our scenarios. However, it is in the first year of a pandemic that vaccine resources are likely to be most scarce.</p>
<p>Finally, our analysis considers only the direct benefits of vaccination. Previous research suggests that community-wide protection against influenza may be best achieved by vaccinating those who are responsible for most transmission, particularly children [<xref ref-type="bibr" rid="R44">44</xref>–<xref ref-type="bibr" rid="R46">46</xref>]. A priori, incorporating the <italic>indirect</italic> effect of vaccination (herd immunity) through an age-structured transmission model can only shift the optimal vaccination policy further away from seniors, because epidemics are driven by transmission in younger age groups. Recent mathematical modeling efforts have highlighted the possibility that vaccination of high-transmitter groups could indirectly mitigate the overall pandemic disease burden [<xref ref-type="bibr" rid="R47">47</xref>–<xref ref-type="bibr" rid="R50">50</xref>]. However, these studies focused on the optimal strategy for reducing morbidity rather than mortality [<xref ref-type="bibr" rid="R48">48</xref>–<xref ref-type="bibr" rid="R50">50</xref>], and they did not differentiate between deaths in younger and older persons in terms of life expectancy [<xref ref-type="bibr" rid="R3">3</xref>, <xref ref-type="bibr" rid="R47">47</xref>]. In such modeling exercises, the optimal strategy critically depends on whether available vaccine resources are sufficient to achieve herd immunity by vaccinating high-transmitter groups. In turn, model results are highly sensitive to the level of mixing between the different age groups [<xref ref-type="bibr" rid="R48">48</xref>], viral transmissibility [<xref ref-type="bibr" rid="R47">47</xref>, <xref ref-type="bibr" rid="R48">48</xref>], and age-specific case fatality rates, the values of which need to be fixed a priori but remain unclear for pandemic influenza. Irrespective of the feasibility of achieving indirect protection, we have shown that simply considering the <italic>direct</italic> benefits of vaccination in terms of YLL is enough to refocus current priority groups toward younger ages. Hence, our quantitative study rooted in analysis of historical mortality data adds complementary elements to the current debate on who should be prioritized for pandemic influenza vaccination; these new considerations [<xref ref-type="bibr" rid="R47">47</xref>–<xref ref-type="bibr" rid="R50">50</xref>] all shift attention away from seniors and toward either younger adults or children as more cost-effective targets.</p>
<p>Although projections of past pandemic experience to the present-day population are naturally fraught with uncertainties, they provide guidance for future policies and highlight the most relevant issues. Our estimation is not an endorsement of any particular policy but highlights how the choice of health outcome metrics such as YLL can influence the prioritization of age groups to vaccinate in pandemic settings. It also shows that the vaccine priority scheme for seasonal influenza is not optimized to mitigate the impact of pandemic influenza. Finally, although our analysis of mortality patterns for pandemic influenza is restricted to only 3 historic scenarios for which age-stratified data are available, each scenario prioritizes a different age group. These results suggest the need for pandemic plans to have an element of flexibility that allows the prioritization of age groups for immunization at the start of a pandemic to be modified as age-specific epidemiological data on the novel virus become available in real time. This is a challenge in both developed and developing countries, because conventional mortality reporting often lags by 2 or 3 years, and new systems for near real-time reporting of mortality need to be designed, implemented, and tested before a pandemic occurs. Equally important, the question of who should be vaccinated first needs to be debated and reasoned through now, before the onset of a public health emergency, while we have the time to reflect on which decision-making metric is the most appropriate.</p>
</sec>
</body>
<back>
<ack>
<title>Acknowledgment</title>
<p>We thank Robert Taylor for his role in editing the manuscript.</p>
</ack>
<ref-list>
<title>References</title>
<ref id="R1">
<label>1</label>
<nlm-citation citation-type="web">
<collab collab-type="author">US Centers for Disease Control and Prevention</collab>
<source>Estimates of influenza vaccination target population sizes in 2006 and recent vaccine uptake levels</source>
<access-date>11 December 2006</access-date>
<comment>Available at: <ext-link ext-link-type="uri" xlink:href="http://www.cdc.gov/flu/professionals/vaccination/pdf/targetpopchart.pdf">http://www.cdc.gov/flu/professionals/vaccination/pdf/targetpopchart.pdf</ext-link></comment>
</nlm-citation>
</ref>
<ref id="R2">
<label>2</label>
<nlm-citation citation-type="web">
<collab collab-type="author">US Department of Health and Human Services</collab>
<source>Draft guidance on allocating and targeting pandemic influenza vaccine</source>
<access-date>27 October 2007</access-date>
<comment>Available at: <ext-link ext-link-type="uri" xlink:href="http://www.pandemicflu.gov/vaccine/prioritization.html">http://www.pandemicflu.gov/vaccine/prioritization.html</ext-link></comment>
</nlm-citation>
</ref>
<ref id="R3">
<label>3</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Emanuel</surname><given-names>EJ</given-names></name>
<name><surname>Wertheimer</surname><given-names>A</given-names></name>
</person-group>
<article-title>Public health: who should get influenza vaccine when not all can?</article-title>
<source>Science</source>
<year>2006</year>
<volume>312</volume>
<fpage>854</fpage>
<lpage>5</lpage>
</nlm-citation>
</ref>
<ref id="R4">
<label>4</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Frey</surname><given-names>HS</given-names></name>
</person-group>
<article-title>The ethics of influenza vaccination</article-title>
<source>Science</source>
<year>2006</year>
<volume>313</volume>
<fpage>758</fpage>
<lpage>60</lpage>
<comment>author reply 758–60</comment>
</nlm-citation>
</ref>
<ref id="R5">
<label>5</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Galvani</surname><given-names>AP</given-names></name>
<name><surname>Medlock</surname><given-names>J</given-names></name>
<name><surname>Chapman</surname><given-names>GB</given-names></name>
</person-group>
<article-title>The ethics of influenza vaccination</article-title>
<source>Science</source>
<year>2006</year>
<volume>313</volume>
<fpage>758</fpage>
<lpage>60</lpage>
<comment>author reply 758–60</comment>
</nlm-citation>
</ref>
<ref id="R6">
<label>6</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Gostin</surname><given-names>LO</given-names></name>
</person-group>
<article-title>Medical countermeasures for pandemic influenza: ethics and the law</article-title>
<source>JAMA</source>
<year>2006</year>
<volume>295</volume>
<fpage>554</fpage>
<lpage>6</lpage>
</nlm-citation>
</ref>
<ref id="R7">
<label>7</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Silverstein</surname><given-names>RP</given-names></name>
</person-group>
<article-title>The ethics of influenza vaccination</article-title>
<source>Science</source>
<year>2006</year>
<volume>313</volume>
<fpage>758</fpage>
<lpage>60</lpage>
<comment>author reply 758–60</comment>
</nlm-citation>
</ref>
<ref id="R8">
<label>8</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Zimmerman</surname><given-names>RK</given-names></name>
</person-group>
<article-title>Rationing of influenza vaccine during a pandemic: ethical analyses</article-title>
<source>Vaccine</source>
<year>2007</year>
<volume>25</volume>
<fpage>2019</fpage>
<lpage>26</lpage>
</nlm-citation>
</ref>
<ref id="R9">
<label>9</label>
<nlm-citation citation-type="book">
<person-group person-group-type="author">
<name><surname>Simonsen</surname><given-names>L</given-names></name>
<name><surname>Olson</surname><given-names>D</given-names></name>
<name><surname>Viboud</surname><given-names>C</given-names></name>
<name><surname>Miller</surname><given-names>M</given-names></name>
</person-group>
<article-title>Pandemic influenza and mortality: past evidence and projections for the future</article-title>
<source>Forum on microbial threats. Pandemic influenza: assessing capabilities for prevention and response</source>
<year>2004</year>
<publisher-loc>Washington, DC</publisher-loc>
<publisher-name>Institute of Medicine, National Academy of Sciences</publisher-name>
</nlm-citation>
</ref>
<ref id="R10">
<label>10</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Simonsen</surname><given-names>L</given-names></name>
<name><surname>Clarke</surname><given-names>MJ</given-names></name>
<name><surname>Schonberger</surname><given-names>LB</given-names></name>
<name><surname>Arden</surname><given-names>NH</given-names></name>
<name><surname>Cox</surname><given-names>NJ</given-names></name>
<name><surname>Fukuda</surname><given-names>K</given-names></name>
</person-group>
<article-title>Pandemic versus epidemic influenza mortality: a pattern of changing age distribution</article-title>
<source>J Infect Dis</source>
<year>1998</year>
<volume>178</volume>
<fpage>53</fpage>
<lpage>60</lpage>
</nlm-citation>
</ref>
<ref id="R11">
<label>11</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Olson</surname><given-names>DR</given-names></name>
<name><surname>Simonsen</surname><given-names>L</given-names></name>
<name><surname>Edelson</surname><given-names>PJ</given-names></name>
<name><surname>Morse</surname><given-names>SS</given-names></name>
</person-group>
<article-title>Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York City</article-title>
<source>Proc Natl Acad Sci USA</source>
<year>2005</year>
<volume>102</volume>
<fpage>11059</fpage>
<lpage>63</lpage>
</nlm-citation>
</ref>
<ref id="R12">
<label>12</label>
<nlm-citation citation-type="book">
<person-group person-group-type="author">
<name><surname>Simonsen</surname><given-names>L</given-names></name>
<name><surname>Reichert</surname><given-names>TA</given-names></name>
<name><surname>Miller</surname><given-names>M</given-names></name>
</person-group>
<article-title>The virtues of antigenic sin: consequences of pandemic recycling on influenza-associated mortality</article-title>
<source>Options for the control of influenza V. International Congress Series 1263</source>
<year>2003</year>
<publisher-loc>Okinawa, Japan</publisher-loc>
<publisher-name>Elsevier</publisher-name>
</nlm-citation>
</ref>
<ref id="R13">
<label>13</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Vallejo</surname><given-names>AN</given-names></name>
</person-group>
<article-title>Immune remodeling: lessons from repertoire alterations during chronological aging and in immune-mediated disease</article-title>
<source>Trends Mol Med</source>
<year>2007</year>
<volume>13</volume>
<fpage>94</fpage>
<lpage>102</lpage>
</nlm-citation>
</ref>
<ref id="R14">
<label>14</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Goodwin</surname><given-names>K</given-names></name>
<name><surname>Viboud</surname><given-names>C</given-names></name>
<name><surname>Simonsen</surname><given-names>L</given-names></name>
</person-group>
<article-title>Antibody response to influenza vaccination in the elderly: a quantitative review</article-title>
<source>Vaccine</source>
<year>2006</year>
<volume>24</volume>
<fpage>1159</fpage>
<lpage>69</lpage>
</nlm-citation>
</ref>
<ref id="R15">
<label>15</label>
<nlm-citation citation-type="journal">
<article-title>Techniques to measure the impact of mortality: years of potential life lost</article-title>
<source>Epidemiol Bull</source>
<year>2003</year>
<volume>24</volume>
<fpage>1</fpage>
<lpage>4</lpage>
</nlm-citation>
</ref>
<ref id="R16">
<label>16</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Edmunds</surname><given-names>WJ</given-names></name>
<name><surname>Brisson</surname><given-names>M</given-names></name>
<name><surname>Rose</surname><given-names>JD</given-names></name>
</person-group>
<article-title>The epidemiology of herpes zoster and potential cost-effectiveness of vaccination in England and Wales</article-title>
<source>Vaccine</source>
<year>2001</year>
<volume>19</volume>
<fpage>3076</fpage>
<lpage>90</lpage>
</nlm-citation>
</ref>
<ref id="R17">
<label>17</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Lieu</surname><given-names>TA</given-names></name>
<name><surname>Ray</surname><given-names>GT</given-names></name>
<name><surname>Black</surname><given-names>SB</given-names></name>
<etal></etal></person-group>
<article-title>Projected cost-effectiveness of pneumococcal conjugate vaccination of healthy infants and young children</article-title>
<source>JAMA</source>
<year>2000</year>
<volume>283</volume>
<fpage>1460</fpage>
<lpage>8</lpage>
</nlm-citation>
</ref>
<ref id="R18">
<label>18</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Molinari</surname><given-names>NA</given-names></name>
<name><surname>Ortega-Sanchez</surname><given-names>IR</given-names></name>
<name><surname>Messonnier</surname><given-names>ML</given-names></name>
<etal></etal></person-group>
<article-title>The annual impact of seasonal influenza in the US: measuring disease burden and costs</article-title>
<source>Vaccine</source>
<year>2007</year>
<volume>25</volume>
<fpage>5086</fpage>
<lpage>96</lpage>
</nlm-citation>
</ref>
<ref id="R19">
<label>19</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Murray</surname><given-names>CJ</given-names></name>
</person-group>
<article-title>Quantifying the burden of disease: the technical basis for disability-adjusted life years</article-title>
<source>Bull World Health Organ</source>
<year>1994</year>
<volume>72</volume>
<fpage>429</fpage>
<lpage>45</lpage>
</nlm-citation>
</ref>
<ref id="R20">
<label>20</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>McKenna</surname><given-names>MT</given-names></name>
<name><surname>Michaud</surname><given-names>CM</given-names></name>
<name><surname>Murray</surname><given-names>CJ</given-names></name>
<name><surname>Marks</surname><given-names>JS</given-names></name>
</person-group>
<article-title>Assessing the burden of disease in the United States using disability-adjusted life years</article-title>
<source>Am J Prev Med</source>
<year>2005</year>
<volume>28</volume>
<fpage>415</fpage>
<lpage>23</lpage>
</nlm-citation>
</ref>
<ref id="R21">
<label>21</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Cohen</surname><given-names>J</given-names></name>
</person-group>
<article-title>The Global Burden of Disease Study: a useful projection of future global health?</article-title>
<source>J Public Health Med</source>
<year>2000</year>
<volume>22</volume>
<fpage>518</fpage>
<lpage>24</lpage>
</nlm-citation>
</ref>
<ref id="R22">
<label>22</label>
<nlm-citation citation-type="book">
<person-group person-group-type="author">
<name><surname>Mathers</surname><given-names>CD</given-names></name>
<name><surname>Salomon</surname><given-names>JA</given-names></name>
<name><surname>Ezzati</surname><given-names>M</given-names></name>
<name><surname>Begg</surname><given-names>S</given-names></name>
<name><surname>Vander Hoorn</surname><given-names>S</given-names></name>
<name><surname>Lopez</surname><given-names>AD</given-names></name>
</person-group>
<person-group person-group-type="editor">
<name><surname>Lopez</surname><given-names>AD</given-names></name>
<name><surname>Mathers</surname><given-names>CD</given-names></name>
<name><surname>Ezzati</surname><given-names>M</given-names></name>
<name><surname>Jamison</surname><given-names>DT</given-names></name>
<name><surname>Murray</surname><given-names>CJ</given-names></name>
</person-group>
<article-title>Sensitivity and uncertainty analyses for burden of disease and risk factor estimates</article-title>
<source>Global burden of disease and risk factors</source>
<year>2006</year>
<publisher-loc>New York</publisher-loc>
<publisher-name>Oxford University Press</publisher-name>
<fpage>399</fpage>
<lpage>426</lpage>
</nlm-citation>
</ref>
<ref id="R23">
<label>23</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Housworth</surname><given-names>WJ</given-names></name>
<name><surname>Spoon</surname><given-names>MM</given-names></name>
</person-group>
<article-title>The age distribution of excess mortality during A2 Hong Kong influenza epidemics compared with earlier A2 outbreaks</article-title>
<source>Am J Epidemiol</source>
<year>1971</year>
<volume>94</volume>
<fpage>348</fpage>
<lpage>50</lpage>
</nlm-citation>
</ref>
<ref id="R24">
<label>24</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Serfling</surname><given-names>RE</given-names></name>
<name><surname>Sherman</surname><given-names>IL</given-names></name>
<name><surname>Houseworth</surname><given-names>WJ</given-names></name>
</person-group>
<article-title>Excess pneumonia-influenza mortality by age and sex in three major influenza A2 epidemics, United States, 1957-58, 1960 and 1963</article-title>
<source>Am J Epidemiol</source>
<year>1967</year>
<volume>86</volume>
<fpage>433</fpage>
<lpage>41</lpage>
</nlm-citation>
</ref>
<ref id="R25">
<label>25</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Viboud</surname><given-names>C</given-names></name>
<name><surname>Grais</surname><given-names>RF</given-names></name>
<name><surname>Lafont</surname><given-names>BAP</given-names></name>
<etal></etal></person-group>
<article-title>Multinational impact of the 1968 Hong Kong influenza pandemic: evidence for a smoldering pandemic</article-title>
<source>J Infect Dis</source>
<year>2005</year>
<volume>192</volume>
<fpage>233</fpage>
<lpage>48</lpage>
</nlm-citation>
</ref>
<ref id="R26">
<label>26</label>
<nlm-citation citation-type="web">
<collab collab-type="author">US National Center for Health Statistics</collab>
<source>United States life tables, 1999–2003</source>
<access-date>11 December 2006</access-date>
<comment>Available at: <ext-link ext-link-type="uri" xlink:href="http://www.cdc.gov/nchs/datawh/statab/unpubd/mortabs/lewk3_10.htm">http://www.cdc.gov/nchs/datawh/statab/unpubd/mortabs/lewk3_10.htm</ext-link></comment>
</nlm-citation>
</ref>
<ref id="R27">
<label>27</label>
<nlm-citation citation-type="journal">
<article-title>Premature mortality in the United States: public health issues in the use of years of potential life lost</article-title>
<source>MMWR Morb Mortal Wkly Rep</source>
<year>1986</year>
<volume>35</volume>
<fpage>1S</fpage>
<lpage>11S</lpage>
</nlm-citation>
</ref>
<ref id="R28">
<label>28</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Demicheli</surname><given-names>V</given-names></name>
<name><surname>Rivetti</surname><given-names>D</given-names></name>
<name><surname>Deeks</surname><given-names>JJ</given-names></name>
<name><surname>Jefferson</surname><given-names>TO</given-names></name>
</person-group>
<article-title>Vaccines for preventing influenza in healthy adults</article-title>
<source>Cochrane Database Syst Rev</source>
<year>2004</year>
<comment>CD001269</comment>
</nlm-citation>
</ref>
<ref id="R29">
<label>29</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Harper</surname><given-names>SA</given-names></name>
<name><surname>Fukuda</surname><given-names>K</given-names></name>
<name><surname>Uyeki</surname><given-names>TM</given-names></name>
<name><surname>Cox</surname><given-names>NJ</given-names></name>
<name><surname>Bridges</surname><given-names>CB</given-names></name>
</person-group>
<article-title>Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP)</article-title>
<source>MMWR Recomm Rep</source>
<year>2004</year>
<volume>53</volume>
<fpage>1</fpage>
<lpage>40</lpage>
</nlm-citation>
</ref>
<ref id="R30">
<label>30</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Meltzer</surname><given-names>MI</given-names></name>
<name><surname>Cox</surname><given-names>NJ</given-names></name>
<name><surname>Fukuda</surname><given-names>K</given-names></name>
</person-group>
<article-title>The economic impact of pandemic influenza in the United States: priorities for intervention</article-title>
<source>Emerg Infect Dis</source>
<year>1999</year>
<volume>5</volume>
<fpage>659</fpage>
<lpage>71</lpage>
</nlm-citation>
</ref>
<ref id="R31">
<label>31</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Wynia</surname><given-names>MK</given-names></name>
</person-group>
<article-title>Ethics and public health emergencies: rationing vaccines</article-title>
<source>Am J Bioeth</source>
<year>2006</year>
<volume>6</volume>
<fpage>4</fpage>
<lpage>7</lpage>
</nlm-citation>
</ref>
<ref id="R32">
<label>32</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Uscher-Pines</surname><given-names>L</given-names></name>
<name><surname>Omer</surname><given-names>SB</given-names></name>
<name><surname>Barnett</surname><given-names>DJ</given-names></name>
<name><surname>Burke</surname><given-names>TA</given-names></name>
<name><surname>Balicer</surname><given-names>RD</given-names></name>
</person-group>
<article-title>Priority setting for pandemic influenza: an analysis of national preparedness plans</article-title>
<source>PLoS Med</source>
<year>2006</year>
<volume>3</volume>
<fpage>e436</fpage>
</nlm-citation>
</ref>
<ref id="R33">
<label>33</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Dowdle</surname><given-names>WR</given-names></name>
</person-group>
<article-title>Influenza A virus recycling revisited</article-title>
<source>Bull World Health Organ</source>
<year>1999</year>
<volume>77</volume>
<fpage>820</fpage>
<lpage>8</lpage>
</nlm-citation>
</ref>
<ref id="R34">
<label>34</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Epstein</surname><given-names>SL</given-names></name>
</person-group>
<article-title>Prior H1N1 influenza infection and susceptibility of Cleveland Family Study participants during the H2N2 pandemic of 1957: an experiment of nature</article-title>
<source>J Infect Dis</source>
<year>2006</year>
<volume>193</volume>
<fpage>49</fpage>
<lpage>53</lpage>
</nlm-citation>
</ref>
<ref id="R35">
<label>35</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Andreasen</surname><given-names>V</given-names></name>
<name><surname>Viboud</surname><given-names>C</given-names></name>
<name><surname>Simonsen</surname><given-names>L</given-names></name>
</person-group>
<article-title>Epidemiologic characterization of the 1918 influenza pandemic summer wave in Copenhagen: implications for pandemic control strategies</article-title>
<source>J Infect Dis</source>
<year>2008</year>
<volume>197</volume>
<fpage>270</fpage>
<lpage>8</lpage>
</nlm-citation>
</ref>
<ref id="R36">
<label>36</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Dauer</surname><given-names>C</given-names></name>
<name><surname>Serfling</surname><given-names>R</given-names></name>
</person-group>
<article-title>Mortality from influenza, 1957–1958 and 1959–1960</article-title>
<source>Am Rev Respir Dis</source>
<year>1961</year>
<volume>83</volume>
<fpage>15</fpage>
<lpage>26</lpage>
</nlm-citation>
</ref>
<ref id="R37">
<label>37</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Palese</surname><given-names>P</given-names></name>
<name><surname>Tumpey</surname><given-names>TM</given-names></name>
<name><surname>Garcia-Sastre</surname><given-names>A</given-names></name>
</person-group>
<article-title>What can we learn from reconstructing the extinct 1918 pandemic influenza virus?</article-title>
<source>Immunity</source>
<year>2006</year>
<volume>24</volume>
<fpage>121</fpage>
<lpage>4</lpage>
</nlm-citation>
</ref>
<ref id="R38">
<label>38</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Smallman-Raynor</surname><given-names>M</given-names></name>
<name><surname>Cliff</surname><given-names>AD</given-names></name>
</person-group>
<article-title>Avian influenza A (H5N1) age distribution in humans</article-title>
<source>Emerg Infect Dis</source>
<year>2007</year>
<volume>13</volume>
<fpage>510</fpage>
<lpage>2</lpage>
</nlm-citation>
</ref>
<ref id="R39">
<label>39</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Bootsma</surname><given-names>MC</given-names></name>
<name><surname>Ferguson</surname><given-names>NM</given-names></name>
</person-group>
<article-title>The effect of public health measures on the 1918 influenza pandemic in U.S. cities</article-title>
<source>Proc Natl Acad Sci USA</source>
<year>2007</year>
<volume>104</volume>
<fpage>7588</fpage>
<lpage>93</lpage>
</nlm-citation>
</ref>
<ref id="R40">
<label>40</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Hatchett</surname><given-names>RJ</given-names></name>
<name><surname>Mecher</surname><given-names>CE</given-names></name>
<name><surname>Lipsitch</surname><given-names>M</given-names></name>
</person-group>
<article-title>Public health interventions and epidemic intensity during the 1918 influenza pandemic</article-title>
<source>Proc Natl Acad Sci USA</source>
<year>2007</year>
<volume>104</volume>
<fpage>7582</fpage>
<lpage>7</lpage>
</nlm-citation>
</ref>
<ref id="R41">
<label>41</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Curson</surname><given-names>P</given-names></name>
<name><surname>McCracken</surname><given-names>K</given-names></name>
</person-group>
<article-title>An Australian perspective of the 1918-1919 influenza pandemic</article-title>
<source>NSW Public Health Bull</source>
<year>2006</year>
<volume>17</volume>
<fpage>103</fpage>
<lpage>7</lpage>
</nlm-citation>
</ref>
<ref id="R42">
<label>42</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Langford</surname><given-names>C</given-names></name>
</person-group>
<article-title>The age pattern of mortality in the 1918-19 influenza pandemic: an attempted explanation based on data for England and Wales</article-title>
<source>Med Hist</source>
<year>2002</year>
<volume>46</volume>
<fpage>1</fpage>
<lpage>20</lpage>
</nlm-citation>
</ref>
<ref id="R43">
<label>43</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Mamelund</surname><given-names>SE</given-names></name>
</person-group>
<article-title>A socially neutral disease? Individual social class, household wealth and mortality from Spanish influenza in two socially contrasting parishes in Kristiania 1918–19</article-title>
<source>Soc Sci Med</source>
<year>2006</year>
<volume>62</volume>
<fpage>923</fpage>
<lpage>40</lpage>
</nlm-citation>
</ref>
<ref id="R44">
<label>44</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Brownstein</surname><given-names>JS</given-names></name>
<name><surname>Kleinman</surname><given-names>KP</given-names></name>
<name><surname>Mandl</surname><given-names>KD</given-names></name>
</person-group>
<article-title>Identifying pediatric age groups for influenza vaccination using a real-time regional surveillance system</article-title>
<source>Am J Epidemiol</source>
<year>2005</year>
<volume>162</volume>
<fpage>686</fpage>
<lpage>93</lpage>
</nlm-citation>
</ref>
<ref id="R45">
<label>45</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Halloran</surname><given-names>ME</given-names></name>
<name><surname>Longini</surname><given-names>IM</given-names><suffix>Jr</suffix></name>
</person-group>
<article-title>Public health: community studies for vaccinating schoolchildren against influenza</article-title>
<source>Science</source>
<year>2006</year>
<volume>311</volume>
<fpage>615</fpage>
<lpage>6</lpage>
</nlm-citation>
</ref>
<ref id="R46">
<label>46</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Olson</surname><given-names>DR</given-names></name>
<name><surname>Heffernan</surname><given-names>RT</given-names></name>
<name><surname>Paladini</surname><given-names>M</given-names></name>
<name><surname>Konty</surname><given-names>K</given-names></name>
<name><surname>Weiss</surname><given-names>D</given-names></name>
<name><surname>Mostashari</surname><given-names>F</given-names></name>
</person-group>
<article-title>Monitoring the impact of influenza by age: emergency department fever and respiratory complaint surveillance in New York City</article-title>
<source>PLoS Med</source>
<year>2007</year>
<volume>4</volume>
<fpage>e247</fpage>
</nlm-citation>
</ref>
<ref id="R47">
<label>47</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Bansal</surname><given-names>S</given-names></name>
<name><surname>Pourbohloul</surname><given-names>B</given-names></name>
<name><surname>Meyers</surname><given-names>LA</given-names></name>
</person-group>
<article-title>A comparative analysis of influenza vaccination programs</article-title>
<source>PLoS Med</source>
<year>2006</year>
<volume>3</volume>
<fpage>e387</fpage>
</nlm-citation>
</ref>
<ref id="R48">
<label>48</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Dushoff</surname><given-names>J</given-names></name>
<name><surname>Plotkin</surname><given-names>JB</given-names></name>
<name><surname>Viboud</surname><given-names>C</given-names></name>
<etal></etal></person-group>
<article-title>Vaccinating to protect a vulnerable subpopulation</article-title>
<source>PLoS Med</source>
<year>2007</year>
<volume>4</volume>
<fpage>e174</fpage>
</nlm-citation>
</ref>
<ref id="R49">
<label>49</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Ferguson</surname><given-names>NM</given-names></name>
<name><surname>Cummings</surname><given-names>DA</given-names></name>
<name><surname>Fraser</surname><given-names>C</given-names></name>
<name><surname>Cajka</surname><given-names>JC</given-names></name>
<name><surname>Cooley</surname><given-names>PC</given-names></name>
<name><surname>Burke</surname><given-names>DS</given-names></name>
</person-group>
<article-title>Strategies for mitigating an influenza pandemic</article-title>
<source>Nature</source>
<year>2006</year>
<volume>442</volume>
<fpage>448</fpage>
<lpage>52</lpage>
</nlm-citation>
</ref>
<ref id="R50">
<label>50</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Germann</surname><given-names>TC</given-names></name>
<name><surname>Kadau</surname><given-names>K</given-names></name>
<name><surname>Longini</surname><given-names>IM</given-names><suffix>Jr</suffix></name>
<name><surname>Macken</surname><given-names>CA</given-names></name>
</person-group>
<article-title>Mitigation strategies for pandemic influenza in the United States</article-title>
<source>Proc Natl Acad Sci USA</source>
<year>2006</year>
<volume>103</volume>
<fpage>5935</fpage>
<lpage>40</lpage>
</nlm-citation>
</ref>
</ref-list>
<sec sec-type="display-objects">
<title>Figures and Tables</title>
<fig id="F1" position="float">
<label>Figure 1</label>
<caption>
<p>Comparison of projected rates of influenza-related deaths and years of life lost (YLL) for 3 pandemic scenarios. Solid lines show YLL, and dashed lines show deaths (both per 100,000 population). Estimates are based on historical age-specific influenza-related mortality rates from the 1918 pandemic <italic>(A)</italic>, the 1957 pandemic <italic>(B)</italic>, and the 1968 pandemic <italic>(C)</italic>, projected onto the 2000 US population structure and life expectancies. The age groups studied vary between the pandemics due to the availability of historical data [<xref ref-type="bibr" rid="R11">11</xref>, <xref ref-type="bibr" rid="R23">23</xref>, <xref ref-type="bibr" rid="R25">25</xref>].</p>
</caption>
<graphic mimetype="image" xlink:href="198-3-305-fig001.tif"></graphic>
</fig>
<fig id="F2" position="float">
<label>Figure 2</label>
<caption>
<p>Comparison of projected nos. of influenza-related deaths and years of life lost (YLL) for 3 pandemic scenarios.</p>
</caption>
<graphic mimetype="image" xlink:href="198-3-305-fig002.tif"></graphic>
</fig>
<fig id="F3" position="float">
<label>Table 1</label>
<caption>
<p>Mortality per 100,000 population, estimated no. of prevented deaths, and years of life lost prevented per vaccine dose, by age group and relative risk.</p>
</caption>
<graphic mimetype="image" xlink:href="198-3-305-tbl001.tif"></graphic>
</fig>
<fig id="F4" position="float">
<label>Table 2</label>
<caption>
<p>Sensitivity analysis for the 1918 scenario, using excess mortality rates derived from historical data from Copenhagen [<xref ref-type="bibr" rid="R35">35</xref>].</p>
</caption>
<graphic mimetype="image" xlink:href="198-3-305-tbl002.tif"></graphic>
</fig>
</sec>
<fn-group>
<fn fn-type="other">
<p>Potential conflicts of interest: none reported.</p></fn>
<fn fn-type="presented-by">
<p>Presented in part: Options for the Control of Influenza VI, Toronto, 16–23 June 2007 (abstract O104); Ninth Annual Conference on Vaccine Research, Baltimore, 8–10 May 2006 (presentation S6).</p>
</fn>
<fn fn-type="financial-disclosure">
<p>Financial support: National Institutes of Health; Fogarty International Center; National Institute of Allergy and Infectious Disease.</p></fn>
<fn fn-type="other">
<p>This article reflects the opinions of the authors and in no way reflects current policies of the Department of Health and Human Services of the United States government.</p>
</fn>
</fn-group>
</back>
</article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Prioritization of Influenza Pandemic Vaccination to Minimize Years of Life Lost</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Prioritization of Influenza Pandemic Vaccination to Minimize Years of Life Lost</title></titleInfo><name type="personal" displayLabel="corresp"><namePart type="given">Mark A.</namePart><namePart type="family">Miller</namePart><affiliation>Fogarty International Center, National Institutes of Health, Bethesda, Maryland</affiliation><affiliation>E-mail: millemar@mail.nih.gov</affiliation><affiliation>Reprints or correspondence: Dr. Mark Miller, Div. of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, 16 Center Dr., Bethesda, MD 20892 (millemar@mail.nih.gov).</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Cecile</namePart><namePart type="family">Viboud</namePart><affiliation>Fogarty International Center, National Institutes of Health, Bethesda, Maryland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Donald R.</namePart><namePart type="family">Olson</namePart><affiliation>New York City Department of Health and Mental Hygiene, New York, New York</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rebecca F.</namePart><namePart type="family">Grais</namePart><affiliation>Fogarty International Center, National Institutes of Health, Bethesda, Maryland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Maia A.</namePart><namePart type="family">Rabaa</namePart><affiliation>Fogarty International Center, National Institutes of Health, Bethesda, Maryland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lone</namePart><namePart type="family">Simonsen</namePart><affiliation>Department of Global Health, School of Public Health and Health Services, George Washington University, Washington, DC</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>The University of Chicago Press</publisher><dateIssued encoding="w3cdtf">2008-08-01</dateIssued><dateCreated encoding="w3cdtf">2008-02-14</dateCreated><copyrightDate encoding="w3cdtf">2008</copyrightDate></originInfo><abstract>Background. How to allocate limited vaccine supplies in the event of an influenza pandemic is currently under debate. Conventional vaccination strategies focus on those at highest risk for severe outcomes, including seniors, but do not consider (1) the signature pandemic pattern in which mortality risk is shifted to younger ages, (2) likely reduced vaccine response in seniors, and (3) differences in remaining years of life with age. Methods. We integrated these factors to project the age-specific years of life lost (YLL) and saved in a future pandemic, on the basis of mortality patterns from 3 historical pandemics, age-specific vaccine efficacy, and the 2000 US population structure. Results. For a 1918-like scenario, the absolute mortality risk is highest in people <45 years old; in contrast, seniors (those ≥65 years old) have the highest mortality risk in the 1957 and 1968 scenarios. The greatest YLL savings would be achieved by targeting different age groups in each scenario; people <45 years old in the 1918 scenario, people 45–64 years old in the 1968 scenario, and people >45 years old in the 1957 scenario. Conclusions. Our findings shift the focus of pandemic vaccination strategies onto younger populations and illustrate the need for real-time surveillance of mortality patterns in a future pandemic. Flexible setting of vaccination priority is essential to minimize mortality.</abstract><relatedItem type="host"><titleInfo><title>The Journal of Infectious Diseases</title></titleInfo><titleInfo type="abbreviated"><title>The Journal of Infectious Diseases</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><identifier type="ISSN">0022-1899</identifier><identifier type="eISSN">1537-6613</identifier><identifier type="PublisherID">jid</identifier><identifier type="PublisherID-hwp">jinfdis</identifier><part><date>2008</date><detail type="volume"><caption>vol.</caption><number>198</number></detail><detail type="issue"><caption>no.</caption><number>3</number></detail><extent unit="pages"><start>305</start><end>311</end></extent></part></relatedItem><relatedItem type="references" displayLabel="R1"><titleInfo><title></title></titleInfo><name type="corporate"><namePart>US Centers for Disease Control and Prevention</namePart></name><genre>web</genre><note>Available at: http://www.cdc.gov/flu/professionals/vaccination/pdf/targetpopchart.pdf</note><note>US Centers for Disease Control and Prevention Estimates of influenza vaccination target population sizes in 2006 and recent vaccine uptake levels 11 December 2006 Available at: http://www.cdc.gov/flu/professionals/vaccination/pdf/targetpopchart.pdf</note></relatedItem><relatedItem type="references" displayLabel="R2"><titleInfo><title></title></titleInfo><name type="corporate"><namePart>US Department of Health and Human Services</namePart></name><genre>web</genre><note>Available at: http://www.pandemicflu.gov/vaccine/prioritization.html</note><note>US Department of Health and Human Services Draft guidance on allocating and targeting pandemic influenza vaccine 27 October 2007 Available at: http://www.pandemicflu.gov/vaccine/prioritization.html</note></relatedItem><relatedItem type="references" displayLabel="R3"><titleInfo><title>Public health: who should get influenza vaccine when not all can?</title></titleInfo><name type="personal"><namePart type="given">EJ</namePart><namePart type="family">Emanuel</namePart></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Wertheimer</namePart></name><genre>journal</genre><note>EmanuelEJ WertheimerA Public health: who should get influenza vaccine when not all can? Science 2006 312 854 5</note><relatedItem type="host"><titleInfo><title>Science</title></titleInfo><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>312</number></detail><extent unit="pages"><start>854</start><end>5</end><list>854-5</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R4"><titleInfo><title>The ethics of influenza vaccination</title></titleInfo><name type="personal"><namePart type="given">HS</namePart><namePart type="family">Frey</namePart></name><genre>journal</genre><note>author reply 758–60</note><note>FreyHS The ethics of influenza vaccination Science 2006 313 758 60 author reply 758–60</note><relatedItem type="host"><titleInfo><title>Science</title></titleInfo><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>313</number></detail><extent unit="pages"><start>758</start><end>60</end><list>758-60</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R5"><titleInfo><title>The ethics of influenza vaccination</title></titleInfo><name type="personal"><namePart type="given">AP</namePart><namePart type="family">Galvani</namePart></name><name type="personal"><namePart type="given">J</namePart><namePart type="family">Medlock</namePart></name><name type="personal"><namePart type="given">GB</namePart><namePart type="family">Chapman</namePart></name><genre>journal</genre><note>author reply 758–60</note><note>GalvaniAP MedlockJ ChapmanGB The ethics of influenza vaccination Science 2006 313 758 60 author reply 758–60</note><relatedItem type="host"><titleInfo><title>Science</title></titleInfo><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>313</number></detail><extent unit="pages"><start>758</start><end>60</end><list>758-60</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R6"><titleInfo><title>Medical countermeasures for pandemic influenza: ethics and the law</title></titleInfo><name type="personal"><namePart type="given">LO</namePart><namePart type="family">Gostin</namePart></name><genre>journal</genre><note>GostinLO Medical countermeasures for pandemic influenza: ethics and the law JAMA 2006 295 554 6</note><relatedItem type="host"><titleInfo><title>JAMA</title></titleInfo><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>295</number></detail><extent unit="pages"><start>554</start><end>6</end><list>554-6</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R7"><titleInfo><title>The ethics of influenza vaccination</title></titleInfo><name type="personal"><namePart type="given">RP</namePart><namePart type="family">Silverstein</namePart></name><genre>journal</genre><note>author reply 758–60</note><note>SilversteinRP The ethics of influenza vaccination Science 2006 313 758 60 author reply 758–60</note><relatedItem type="host"><titleInfo><title>Science</title></titleInfo><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>313</number></detail><extent unit="pages"><start>758</start><end>60</end><list>758-60</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R8"><titleInfo><title>Rationing of influenza vaccine during a pandemic: ethical analyses</title></titleInfo><name type="personal"><namePart type="given">RK</namePart><namePart type="family">Zimmerman</namePart></name><genre>journal</genre><note>ZimmermanRK Rationing of influenza vaccine during a pandemic: ethical analyses Vaccine 2007 25 2019 26</note><relatedItem type="host"><titleInfo><title>Vaccine</title></titleInfo><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>25</number></detail><extent unit="pages"><start>2019</start><end>26</end><list>2019-26</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R9"><titleInfo><title>Pandemic influenza and mortality: past evidence and projections for the future</title></titleInfo><name type="personal"><namePart type="given">L</namePart><namePart type="family">Simonsen</namePart></name><name type="personal"><namePart type="given">D</namePart><namePart type="family">Olson</namePart></name><name type="personal"><namePart type="given">C</namePart><namePart type="family">Viboud</namePart></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Miller</namePart></name><genre>book</genre><note>SimonsenL OlsonD ViboudC MillerM Pandemic influenza and mortality: past evidence and projections for the future Forum on microbial threats. Pandemic influenza: assessing capabilities for prevention and response 2004 Washington, DC Institute of Medicine, National Academy of Sciences</note><relatedItem type="host"><titleInfo><title>Forum on microbial threats. Pandemic influenza: assessing capabilities for prevention and response</title></titleInfo><originInfo><publisher>Institute of Medicine, National Academy of Sciences. </publisher><place><placeTerm type="text">Washington, DC</placeTerm></place></originInfo><part><date>2004</date></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R10"><titleInfo><title>Pandemic versus epidemic influenza mortality: a pattern of changing age distribution</title></titleInfo><name type="personal"><namePart type="given">L</namePart><namePart type="family">Simonsen</namePart></name><name type="personal"><namePart type="given">MJ</namePart><namePart type="family">Clarke</namePart></name><name type="personal"><namePart type="given">LB</namePart><namePart type="family">Schonberger</namePart></name><name type="personal"><namePart type="given">NH</namePart><namePart type="family">Arden</namePart></name><name type="personal"><namePart type="given">NJ</namePart><namePart type="family">Cox</namePart></name><name type="personal"><namePart type="given">K</namePart><namePart type="family">Fukuda</namePart></name><genre>journal</genre><note>SimonsenL ClarkeMJ SchonbergerLB ArdenNH CoxNJ FukudaK Pandemic versus epidemic influenza mortality: a pattern of changing age distribution J Infect Dis 1998 178 53 60</note><relatedItem type="host"><titleInfo><title>J Infect Dis</title></titleInfo><part><date>1998</date><detail type="volume"><caption>vol.</caption><number>178</number></detail><extent unit="pages"><start>53</start><end>60</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R11"><titleInfo><title>Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York City</title></titleInfo><name type="personal"><namePart type="given">DR</namePart><namePart type="family">Olson</namePart></name><name type="personal"><namePart type="given">L</namePart><namePart type="family">Simonsen</namePart></name><name type="personal"><namePart type="given">PJ</namePart><namePart type="family">Edelson</namePart></name><name type="personal"><namePart type="given">SS</namePart><namePart type="family">Morse</namePart></name><genre>journal</genre><note>OlsonDR SimonsenL EdelsonPJ MorseSS Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York City Proc Natl Acad Sci USA 2005 102 11059 63</note><relatedItem type="host"><titleInfo><title>Proc Natl Acad Sci USA</title></titleInfo><part><date>2005</date><detail type="volume"><caption>vol.</caption><number>102</number></detail><extent unit="pages"><start>11059</start><end>63</end><list>11059-63</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R12"><titleInfo><title>The virtues of antigenic sin: consequences of pandemic recycling on influenza-associated mortality</title></titleInfo><name type="personal"><namePart type="given">L</namePart><namePart type="family">Simonsen</namePart></name><name type="personal"><namePart type="given">TA</namePart><namePart type="family">Reichert</namePart></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Miller</namePart></name><genre>book</genre><note>SimonsenL ReichertTA MillerM The virtues of antigenic sin: consequences of pandemic recycling on influenza-associated mortality Options for the control of influenza V. International Congress Series 1263 2003 Okinawa, Japan Elsevier</note><relatedItem type="host"><titleInfo><title>Options for the control of influenza V. International Congress Series 1263</title></titleInfo><originInfo><publisher>Elsevier. </publisher><place><placeTerm type="text">Okinawa, Japan</placeTerm></place></originInfo><part><date>2003</date></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R13"><titleInfo><title>Immune remodeling: lessons from repertoire alterations during chronological aging and in immune-mediated disease</title></titleInfo><name type="personal"><namePart type="given">AN</namePart><namePart type="family">Vallejo</namePart></name><genre>journal</genre><note>VallejoAN Immune remodeling: lessons from repertoire alterations during chronological aging and in immune-mediated disease Trends Mol Med 2007 13 94 102</note><relatedItem type="host"><titleInfo><title>Trends Mol Med</title></titleInfo><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>13</number></detail><extent unit="pages"><start>94</start><end>102</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R14"><titleInfo><title>Antibody response to influenza vaccination in the elderly: a quantitative review</title></titleInfo><name type="personal"><namePart type="given">K</namePart><namePart type="family">Goodwin</namePart></name><name type="personal"><namePart type="given">C</namePart><namePart type="family">Viboud</namePart></name><name type="personal"><namePart type="given">L</namePart><namePart type="family">Simonsen</namePart></name><genre>journal</genre><note>GoodwinK ViboudC SimonsenL Antibody response to influenza vaccination in the elderly: a quantitative review Vaccine 2006 24 1159 69</note><relatedItem type="host"><titleInfo><title>Vaccine</title></titleInfo><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>24</number></detail><extent unit="pages"><start>1159</start><end>69</end><list>1159-69</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R15"><titleInfo><title>Techniques to measure the impact of mortality: years of potential life lost</title></titleInfo><genre>journal</genre><note>Techniques to measure the impact of mortality: years of potential life lost Epidemiol Bull 2003 24 1 4</note><relatedItem type="host"><titleInfo><title>Epidemiol Bull</title></titleInfo><part><date>2003</date><detail type="volume"><caption>vol.</caption><number>24</number></detail><extent unit="pages"><start>1</start><end>4</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R16"><titleInfo><title>The epidemiology of herpes zoster and potential cost-effectiveness of vaccination in England and Wales</title></titleInfo><name type="personal"><namePart type="given">WJ</namePart><namePart type="family">Edmunds</namePart></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Brisson</namePart></name><name type="personal"><namePart type="given">JD</namePart><namePart type="family">Rose</namePart></name><genre>journal</genre><note>EdmundsWJ BrissonM RoseJD The epidemiology of herpes zoster and potential cost-effectiveness of vaccination in England and Wales Vaccine 2001 19 3076 90</note><relatedItem type="host"><titleInfo><title>Vaccine</title></titleInfo><part><date>2001</date><detail type="volume"><caption>vol.</caption><number>19</number></detail><extent unit="pages"><start>3076</start><end>90</end><list>3076-90</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R17"><titleInfo><title>Projected cost-effectiveness of pneumococcal conjugate vaccination of healthy infants and young children</title></titleInfo><name type="personal"><namePart type="given">TA</namePart><namePart type="family">Lieu</namePart></name><name type="personal"><namePart type="given">GT</namePart><namePart type="family">Ray</namePart></name><name type="personal"><namePart type="given">SB</namePart><namePart type="family">Black</namePart></name><genre>journal</genre><note>LieuTA RayGT BlackSB Projected cost-effectiveness of pneumococcal conjugate vaccination of healthy infants and young children JAMA 2000 283 1460 8</note><relatedItem type="host"><titleInfo><title>JAMA</title></titleInfo><part><date>2000</date><detail type="volume"><caption>vol.</caption><number>283</number></detail><extent unit="pages"><start>1460</start><end>8</end><list>1460-8</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R18"><titleInfo><title>The annual impact of seasonal influenza in the US: measuring disease burden and costs</title></titleInfo><name type="personal"><namePart type="given">NA</namePart><namePart type="family">Molinari</namePart></name><name type="personal"><namePart type="given">IR</namePart><namePart type="family">Ortega-Sanchez</namePart></name><name type="personal"><namePart type="given">ML</namePart><namePart type="family">Messonnier</namePart></name><genre>journal</genre><note>MolinariNA Ortega-SanchezIR MessonnierML The annual impact of seasonal influenza in the US: measuring disease burden and costs Vaccine 2007 25 5086 96</note><relatedItem type="host"><titleInfo><title>Vaccine</title></titleInfo><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>25</number></detail><extent unit="pages"><start>5086</start><end>96</end><list>5086-96</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R19"><titleInfo><title>Quantifying the burden of disease: the technical basis for disability-adjusted life years</title></titleInfo><name type="personal"><namePart type="given">CJ</namePart><namePart type="family">Murray</namePart></name><genre>journal</genre><note>MurrayCJ Quantifying the burden of disease: the technical basis for disability-adjusted life years Bull World Health Organ 1994 72 429 45</note><relatedItem type="host"><titleInfo><title>Bull World Health Organ</title></titleInfo><part><date>1994</date><detail type="volume"><caption>vol.</caption><number>72</number></detail><extent unit="pages"><start>429</start><end>45</end><list>429-45</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R20"><titleInfo><title>Assessing the burden of disease in the United States using disability-adjusted life years</title></titleInfo><name type="personal"><namePart type="given">MT</namePart><namePart type="family">McKenna</namePart></name><name type="personal"><namePart type="given">CM</namePart><namePart type="family">Michaud</namePart></name><name type="personal"><namePart type="given">CJ</namePart><namePart type="family">Murray</namePart></name><name type="personal"><namePart type="given">JS</namePart><namePart type="family">Marks</namePart></name><genre>journal</genre><note>McKennaMT MichaudCM MurrayCJ MarksJS Assessing the burden of disease in the United States using disability-adjusted life years Am J Prev Med 2005 28 415 23</note><relatedItem type="host"><titleInfo><title>Am J Prev Med</title></titleInfo><part><date>2005</date><detail type="volume"><caption>vol.</caption><number>28</number></detail><extent unit="pages"><start>415</start><end>23</end><list>415-23</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R21"><titleInfo><title>The Global Burden of Disease Study: a useful projection of future global health?</title></titleInfo><name type="personal"><namePart type="given">J</namePart><namePart type="family">Cohen</namePart></name><genre>journal</genre><note>CohenJ The Global Burden of Disease Study: a useful projection of future global health? J Public Health Med 2000 22 518 24</note><relatedItem type="host"><titleInfo><title>J Public Health Med</title></titleInfo><part><date>2000</date><detail type="volume"><caption>vol.</caption><number>22</number></detail><extent unit="pages"><start>518</start><end>24</end><list>518-24</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R22"><titleInfo><title>Sensitivity and uncertainty analyses for burden of disease and risk factor estimates</title></titleInfo><name type="personal"><namePart type="given">CD</namePart><namePart type="family">Mathers</namePart></name><name type="personal"><namePart type="given">JA</namePart><namePart type="family">Salomon</namePart></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Ezzati</namePart></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Begg</namePart></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Vander Hoorn</namePart></name><name type="personal"><namePart type="given">AD</namePart><namePart type="family">Lopez</namePart></name><name type="personal"><namePart type="given">AD</namePart><namePart type="family">Lopez</namePart></name><name type="personal"><namePart type="given">CD</namePart><namePart type="family">Mathers</namePart></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Ezzati</namePart></name><name type="personal"><namePart type="given">DT</namePart><namePart type="family">Jamison</namePart></name><name type="personal"><namePart type="given">CJ</namePart><namePart type="family">Murray</namePart></name><genre>book</genre><note>MathersCD SalomonJA EzzatiM BeggS Vander HoornS LopezAD LopezAD MathersCD EzzatiM JamisonDT MurrayCJ Sensitivity and uncertainty analyses for burden of disease and risk factor estimates Global burden of disease and risk factors 2006 New York Oxford University Press 399 426</note><relatedItem type="host"><titleInfo><title>Global burden of disease and risk factors</title></titleInfo><originInfo><publisher>Oxford University Press. </publisher><place><placeTerm type="text">New York</placeTerm></place></originInfo><part><date>2006</date><extent unit="pages"><start>399</start><end>426</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R23"><titleInfo><title>The age distribution of excess mortality during A2 Hong Kong influenza epidemics compared with earlier A2 outbreaks</title></titleInfo><name type="personal"><namePart type="given">WJ</namePart><namePart type="family">Housworth</namePart></name><name type="personal"><namePart type="given">MM</namePart><namePart type="family">Spoon</namePart></name><genre>journal</genre><note>HousworthWJ SpoonMM The age distribution of excess mortality during A2 Hong Kong influenza epidemics compared with earlier A2 outbreaks Am J Epidemiol 1971 94 348 50</note><relatedItem type="host"><titleInfo><title>Am J Epidemiol</title></titleInfo><part><date>1971</date><detail type="volume"><caption>vol.</caption><number>94</number></detail><extent unit="pages"><start>348</start><end>50</end><list>348-50</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R24"><titleInfo><title>Excess pneumonia-influenza mortality by age and sex in three major influenza A2 epidemics, United States, 1957-58, 1960 and 1963</title></titleInfo><name type="personal"><namePart type="given">RE</namePart><namePart type="family">Serfling</namePart></name><name type="personal"><namePart type="given">IL</namePart><namePart type="family">Sherman</namePart></name><name type="personal"><namePart type="given">WJ</namePart><namePart type="family">Houseworth</namePart></name><genre>journal</genre><note>SerflingRE ShermanIL HouseworthWJ Excess pneumonia-influenza mortality by age and sex in three major influenza A2 epidemics, United States, 1957-58, 1960 and 1963 Am J Epidemiol 1967 86 433 41</note><relatedItem type="host"><titleInfo><title>Am J Epidemiol</title></titleInfo><part><date>1967</date><detail type="volume"><caption>vol.</caption><number>86</number></detail><extent unit="pages"><start>433</start><end>41</end><list>433-41</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R25"><titleInfo><title>Multinational impact of the 1968 Hong Kong influenza pandemic: evidence for a smoldering pandemic</title></titleInfo><name type="personal"><namePart type="given">C</namePart><namePart type="family">Viboud</namePart></name><name type="personal"><namePart type="given">RF</namePart><namePart type="family">Grais</namePart></name><name type="personal"><namePart type="given">BAP</namePart><namePart type="family">Lafont</namePart></name><genre>journal</genre><note>ViboudC GraisRF LafontBAP Multinational impact of the 1968 Hong Kong influenza pandemic: evidence for a smoldering pandemic J Infect Dis 2005 192 233 48</note><relatedItem type="host"><titleInfo><title>J Infect Dis</title></titleInfo><part><date>2005</date><detail type="volume"><caption>vol.</caption><number>192</number></detail><extent unit="pages"><start>233</start><end>48</end><list>233-48</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R26"><titleInfo><title></title></titleInfo><name type="corporate"><namePart>US National Center for Health Statistics</namePart></name><genre>web</genre><note>Available at: http://www.cdc.gov/nchs/datawh/statab/unpubd/mortabs/lewk3_10.htm</note><note>US National Center for Health Statistics United States life tables, 1999–2003 11 December 2006 Available at: http://www.cdc.gov/nchs/datawh/statab/unpubd/mortabs/lewk3_10.htm</note></relatedItem><relatedItem type="references" displayLabel="R27"><titleInfo><title>Premature mortality in the United States: public health issues in the use of years of potential life lost</title></titleInfo><genre>journal</genre><note>Premature mortality in the United States: public health issues in the use of years of potential life lost MMWR Morb Mortal Wkly Rep 1986 35 1S 11S</note><relatedItem type="host"><titleInfo><title>MMWR Morb Mortal Wkly Rep</title></titleInfo><part><date>1986</date><detail type="volume"><caption>vol.</caption><number>35</number></detail><extent unit="pages"><start>1S</start><end>11S</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R28"><titleInfo><title>Vaccines for preventing influenza in healthy adults</title></titleInfo><name type="personal"><namePart type="given">V</namePart><namePart type="family">Demicheli</namePart></name><name type="personal"><namePart type="given">D</namePart><namePart type="family">Rivetti</namePart></name><name type="personal"><namePart type="given">JJ</namePart><namePart type="family">Deeks</namePart></name><name type="personal"><namePart type="given">TO</namePart><namePart type="family">Jefferson</namePart></name><genre>journal</genre><note>CD001269</note><note>DemicheliV RivettiD DeeksJJ JeffersonTO Vaccines for preventing influenza in healthy adults Cochrane Database Syst Rev 2004 CD001269</note><relatedItem type="host"><titleInfo><title>Cochrane Database Syst Rev</title></titleInfo><part><date>2004</date></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R29"><titleInfo><title>Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP)</title></titleInfo><name type="personal"><namePart type="given">SA</namePart><namePart type="family">Harper</namePart></name><name type="personal"><namePart type="given">K</namePart><namePart type="family">Fukuda</namePart></name><name type="personal"><namePart type="given">TM</namePart><namePart type="family">Uyeki</namePart></name><name type="personal"><namePart type="given">NJ</namePart><namePart type="family">Cox</namePart></name><name type="personal"><namePart type="given">CB</namePart><namePart type="family">Bridges</namePart></name><genre>journal</genre><note>HarperSA FukudaK UyekiTM CoxNJ BridgesCB Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR Recomm Rep 2004 53 1 40</note><relatedItem type="host"><titleInfo><title>MMWR Recomm Rep</title></titleInfo><part><date>2004</date><detail type="volume"><caption>vol.</caption><number>53</number></detail><extent unit="pages"><start>1</start><end>40</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R30"><titleInfo><title>The economic impact of pandemic influenza in the United States: priorities for intervention</title></titleInfo><name type="personal"><namePart type="given">MI</namePart><namePart type="family">Meltzer</namePart></name><name type="personal"><namePart type="given">NJ</namePart><namePart type="family">Cox</namePart></name><name type="personal"><namePart type="given">K</namePart><namePart type="family">Fukuda</namePart></name><genre>journal</genre><note>MeltzerMI CoxNJ FukudaK The economic impact of pandemic influenza in the United States: priorities for intervention Emerg Infect Dis 1999 5 659 71</note><relatedItem type="host"><titleInfo><title>Emerg Infect Dis</title></titleInfo><part><date>1999</date><detail type="volume"><caption>vol.</caption><number>5</number></detail><extent unit="pages"><start>659</start><end>71</end><list>659-71</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R31"><titleInfo><title>Ethics and public health emergencies: rationing vaccines</title></titleInfo><name type="personal"><namePart type="given">MK</namePart><namePart type="family">Wynia</namePart></name><genre>journal</genre><note>WyniaMK Ethics and public health emergencies: rationing vaccines Am J Bioeth 2006 6 4 7</note><relatedItem type="host"><titleInfo><title>Am J Bioeth</title></titleInfo><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>6</number></detail><extent unit="pages"><start>4</start><end>7</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R32"><titleInfo><title>Priority setting for pandemic influenza: an analysis of national preparedness plans</title></titleInfo><name type="personal"><namePart type="given">L</namePart><namePart type="family">Uscher-Pines</namePart></name><name type="personal"><namePart type="given">SB</namePart><namePart type="family">Omer</namePart></name><name type="personal"><namePart type="given">DJ</namePart><namePart type="family">Barnett</namePart></name><name type="personal"><namePart type="given">TA</namePart><namePart type="family">Burke</namePart></name><name type="personal"><namePart type="given">RD</namePart><namePart type="family">Balicer</namePart></name><genre>journal</genre><note>Uscher-PinesL OmerSB BarnettDJ BurkeTA BalicerRD Priority setting for pandemic influenza: an analysis of national preparedness plans PLoS Med 2006 3 e436</note><relatedItem type="host"><titleInfo><title>PLoS Med</title></titleInfo><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>3</number></detail><extent unit="pages"><start>e436</start></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R33"><titleInfo><title>Influenza A virus recycling revisited</title></titleInfo><name type="personal"><namePart type="given">WR</namePart><namePart type="family">Dowdle</namePart></name><genre>journal</genre><note>DowdleWR Influenza A virus recycling revisited Bull World Health Organ 1999 77 820 8</note><relatedItem type="host"><titleInfo><title>Bull World Health Organ</title></titleInfo><part><date>1999</date><detail type="volume"><caption>vol.</caption><number>77</number></detail><extent unit="pages"><start>820</start><end>8</end><list>820-8</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R34"><titleInfo><title>Prior H1N1 influenza infection and susceptibility of Cleveland Family Study participants during the H2N2 pandemic of 1957: an experiment of nature</title></titleInfo><name type="personal"><namePart type="given">SL</namePart><namePart type="family">Epstein</namePart></name><genre>journal</genre><note>EpsteinSL Prior H1N1 influenza infection and susceptibility of Cleveland Family Study participants during the H2N2 pandemic of 1957: an experiment of nature J Infect Dis 2006 193 49 53</note><relatedItem type="host"><titleInfo><title>J Infect Dis</title></titleInfo><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>193</number></detail><extent unit="pages"><start>49</start><end>53</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R35"><titleInfo><title>Epidemiologic characterization of the 1918 influenza pandemic summer wave in Copenhagen: implications for pandemic control strategies</title></titleInfo><name type="personal"><namePart type="given">V</namePart><namePart type="family">Andreasen</namePart></name><name type="personal"><namePart type="given">C</namePart><namePart type="family">Viboud</namePart></name><name type="personal"><namePart type="given">L</namePart><namePart type="family">Simonsen</namePart></name><genre>journal</genre><note>AndreasenV ViboudC SimonsenL Epidemiologic characterization of the 1918 influenza pandemic summer wave in Copenhagen: implications for pandemic control strategies J Infect Dis 2008 197 270 8</note><relatedItem type="host"><titleInfo><title>J Infect Dis</title></titleInfo><part><date>2008</date><detail type="volume"><caption>vol.</caption><number>197</number></detail><extent unit="pages"><start>270</start><end>8</end><list>270-8</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R36"><titleInfo><title>Mortality from influenza, 1957–1958 and 1959–1960</title></titleInfo><name type="personal"><namePart type="given">C</namePart><namePart type="family">Dauer</namePart></name><name type="personal"><namePart type="given">R</namePart><namePart type="family">Serfling</namePart></name><genre>journal</genre><note>DauerC SerflingR Mortality from influenza, 1957–1958 and 1959–1960 Am Rev Respir Dis 1961 83 15 26</note><relatedItem type="host"><titleInfo><title>Am Rev Respir Dis</title></titleInfo><part><date>1961</date><detail type="volume"><caption>vol.</caption><number>83</number></detail><extent unit="pages"><start>15</start><end>26</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R37"><titleInfo><title>What can we learn from reconstructing the extinct 1918 pandemic influenza virus?</title></titleInfo><name type="personal"><namePart type="given">P</namePart><namePart type="family">Palese</namePart></name><name type="personal"><namePart type="given">TM</namePart><namePart type="family">Tumpey</namePart></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Garcia-Sastre</namePart></name><genre>journal</genre><note>PaleseP TumpeyTM Garcia-SastreA What can we learn from reconstructing the extinct 1918 pandemic influenza virus? Immunity 2006 24 121 4</note><relatedItem type="host"><titleInfo><title>Immunity</title></titleInfo><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>24</number></detail><extent unit="pages"><start>121</start><end>4</end><list>121-4</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R38"><titleInfo><title>Avian influenza A (H5N1) age distribution in humans</title></titleInfo><name type="personal"><namePart type="given">M</namePart><namePart type="family">Smallman-Raynor</namePart></name><name type="personal"><namePart type="given">AD</namePart><namePart type="family">Cliff</namePart></name><genre>journal</genre><note>Smallman-RaynorM CliffAD Avian influenza A (H5N1) age distribution in humans Emerg Infect Dis 2007 13 510 2</note><relatedItem type="host"><titleInfo><title>Emerg Infect Dis</title></titleInfo><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>13</number></detail><extent unit="pages"><start>510</start><end>2</end><list>510-2</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R39"><titleInfo><title>The effect of public health measures on the 1918 influenza pandemic in U.S. cities</title></titleInfo><name type="personal"><namePart type="given">MC</namePart><namePart type="family">Bootsma</namePart></name><name type="personal"><namePart type="given">NM</namePart><namePart type="family">Ferguson</namePart></name><genre>journal</genre><note>BootsmaMC FergusonNM The effect of public health measures on the 1918 influenza pandemic in U.S. cities Proc Natl Acad Sci USA 2007 104 7588 93</note><relatedItem type="host"><titleInfo><title>Proc Natl Acad Sci USA</title></titleInfo><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>104</number></detail><extent unit="pages"><start>7588</start><end>93</end><list>7588-93</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R40"><titleInfo><title>Public health interventions and epidemic intensity during the 1918 influenza pandemic</title></titleInfo><name type="personal"><namePart type="given">RJ</namePart><namePart type="family">Hatchett</namePart></name><name type="personal"><namePart type="given">CE</namePart><namePart type="family">Mecher</namePart></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Lipsitch</namePart></name><genre>journal</genre><note>HatchettRJ MecherCE LipsitchM Public health interventions and epidemic intensity during the 1918 influenza pandemic Proc Natl Acad Sci USA 2007 104 7582 7</note><relatedItem type="host"><titleInfo><title>Proc Natl Acad Sci USA</title></titleInfo><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>104</number></detail><extent unit="pages"><start>7582</start><end>7</end><list>7582-7</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R41"><titleInfo><title>An Australian perspective of the 1918-1919 influenza pandemic</title></titleInfo><name type="personal"><namePart type="given">P</namePart><namePart type="family">Curson</namePart></name><name type="personal"><namePart type="given">K</namePart><namePart type="family">McCracken</namePart></name><genre>journal</genre><note>CursonP McCrackenK An Australian perspective of the 1918-1919 influenza pandemic NSW Public Health Bull 2006 17 103 7</note><relatedItem type="host"><titleInfo><title>NSW Public Health Bull</title></titleInfo><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>17</number></detail><extent unit="pages"><start>103</start><end>7</end><list>103-7</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R42"><titleInfo><title>The age pattern of mortality in the 1918-19 influenza pandemic: an attempted explanation based on data for England and Wales</title></titleInfo><name type="personal"><namePart type="given">C</namePart><namePart type="family">Langford</namePart></name><genre>journal</genre><note>LangfordC The age pattern of mortality in the 1918-19 influenza pandemic: an attempted explanation based on data for England and Wales Med Hist 2002 46 1 20</note><relatedItem type="host"><titleInfo><title>Med Hist</title></titleInfo><part><date>2002</date><detail type="volume"><caption>vol.</caption><number>46</number></detail><extent unit="pages"><start>1</start><end>20</end></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R43"><titleInfo><title>A socially neutral disease? Individual social class, household wealth and mortality from Spanish influenza in two socially contrasting parishes in Kristiania 1918–19</title></titleInfo><name type="personal"><namePart type="given">SE</namePart><namePart type="family">Mamelund</namePart></name><genre>journal</genre><note>MamelundSE A socially neutral disease? Individual social class, household wealth and mortality from Spanish influenza in two socially contrasting parishes in Kristiania 1918–19 Soc Sci Med 2006 62 923 40</note><relatedItem type="host"><titleInfo><title>Soc Sci Med</title></titleInfo><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>62</number></detail><extent unit="pages"><start>923</start><end>40</end><list>923-40</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R44"><titleInfo><title>Identifying pediatric age groups for influenza vaccination using a real-time regional surveillance system</title></titleInfo><name type="personal"><namePart type="given">JS</namePart><namePart type="family">Brownstein</namePart></name><name type="personal"><namePart type="given">KP</namePart><namePart type="family">Kleinman</namePart></name><name type="personal"><namePart type="given">KD</namePart><namePart type="family">Mandl</namePart></name><genre>journal</genre><note>BrownsteinJS KleinmanKP MandlKD Identifying pediatric age groups for influenza vaccination using a real-time regional surveillance system Am J Epidemiol 2005 162 686 93</note><relatedItem type="host"><titleInfo><title>Am J Epidemiol</title></titleInfo><part><date>2005</date><detail type="volume"><caption>vol.</caption><number>162</number></detail><extent unit="pages"><start>686</start><end>93</end><list>686-93</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R45"><titleInfo><title>Public health: community studies for vaccinating schoolchildren against influenza</title></titleInfo><name type="personal"><namePart type="given">ME</namePart><namePart type="family">Halloran</namePart></name><name type="personal"><namePart type="given">IM</namePart><namePart type="family">Longini Jr</namePart></name><genre>journal</genre><note>HalloranME LonginiIMJr Public health: community studies for vaccinating schoolchildren against influenza Science 2006 311 615 6</note><relatedItem type="host"><titleInfo><title>Science</title></titleInfo><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>311</number></detail><extent unit="pages"><start>615</start><end>6</end><list>615-6</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R46"><titleInfo><title>Monitoring the impact of influenza by age: emergency department fever and respiratory complaint surveillance in New York City</title></titleInfo><name type="personal"><namePart type="given">DR</namePart><namePart type="family">Olson</namePart></name><name type="personal"><namePart type="given">RT</namePart><namePart type="family">Heffernan</namePart></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Paladini</namePart></name><name type="personal"><namePart type="given">K</namePart><namePart type="family">Konty</namePart></name><name type="personal"><namePart type="given">D</namePart><namePart type="family">Weiss</namePart></name><name type="personal"><namePart type="given">F</namePart><namePart type="family">Mostashari</namePart></name><genre>journal</genre><note>OlsonDR HeffernanRT PaladiniM KontyK WeissD MostashariF Monitoring the impact of influenza by age: emergency department fever and respiratory complaint surveillance in New York City PLoS Med 2007 4 e247</note><relatedItem type="host"><titleInfo><title>PLoS Med</title></titleInfo><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>4</number></detail><extent unit="pages"><start>e247</start></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R47"><titleInfo><title>A comparative analysis of influenza vaccination programs</title></titleInfo><name type="personal"><namePart type="given">S</namePart><namePart type="family">Bansal</namePart></name><name type="personal"><namePart type="given">B</namePart><namePart type="family">Pourbohloul</namePart></name><name type="personal"><namePart type="given">LA</namePart><namePart type="family">Meyers</namePart></name><genre>journal</genre><note>BansalS PourbohloulB MeyersLA A comparative analysis of influenza vaccination programs PLoS Med 2006 3 e387</note><relatedItem type="host"><titleInfo><title>PLoS Med</title></titleInfo><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>3</number></detail><extent unit="pages"><start>e387</start></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R48"><titleInfo><title>Vaccinating to protect a vulnerable subpopulation</title></titleInfo><name type="personal"><namePart type="given">J</namePart><namePart type="family">Dushoff</namePart></name><name type="personal"><namePart type="given">JB</namePart><namePart type="family">Plotkin</namePart></name><name type="personal"><namePart type="given">C</namePart><namePart type="family">Viboud</namePart></name><genre>journal</genre><note>DushoffJ PlotkinJB ViboudC Vaccinating to protect a vulnerable subpopulation PLoS Med 2007 4 e174</note><relatedItem type="host"><titleInfo><title>PLoS Med</title></titleInfo><part><date>2007</date><detail type="volume"><caption>vol.</caption><number>4</number></detail><extent unit="pages"><start>e174</start></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R49"><titleInfo><title>Strategies for mitigating an influenza pandemic</title></titleInfo><name type="personal"><namePart type="given">NM</namePart><namePart type="family">Ferguson</namePart></name><name type="personal"><namePart type="given">DA</namePart><namePart type="family">Cummings</namePart></name><name type="personal"><namePart type="given">C</namePart><namePart type="family">Fraser</namePart></name><name type="personal"><namePart type="given">JC</namePart><namePart type="family">Cajka</namePart></name><name type="personal"><namePart type="given">PC</namePart><namePart type="family">Cooley</namePart></name><name type="personal"><namePart type="given">DS</namePart><namePart type="family">Burke</namePart></name><genre>journal</genre><note>FergusonNM CummingsDA FraserC CajkaJC CooleyPC BurkeDS Strategies for mitigating an influenza pandemic Nature 2006 442 448 52</note><relatedItem type="host"><titleInfo><title>Nature</title></titleInfo><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>442</number></detail><extent unit="pages"><start>448</start><end>52</end><list>448-52</list></extent></part></relatedItem></relatedItem><relatedItem type="references" displayLabel="R50"><titleInfo><title>Mitigation strategies for pandemic influenza in the United States</title></titleInfo><name type="personal"><namePart type="given">TC</namePart><namePart type="family">Germann</namePart></name><name type="personal"><namePart type="given">K</namePart><namePart type="family">Kadau</namePart></name><name type="personal"><namePart type="given">IM</namePart><namePart type="family">Longini Jr</namePart></name><name type="personal"><namePart type="given">CA</namePart><namePart type="family">Macken</namePart></name><genre>journal</genre><note>GermannTC KadauK LonginiIMJr MackenCA Mitigation strategies for pandemic influenza in the United States Proc Natl Acad Sci USA 2006 103 5935 40</note><relatedItem type="host"><titleInfo><title>Proc Natl Acad Sci USA</title></titleInfo><part><date>2006</date><detail type="volume"><caption>vol.</caption><number>103</number></detail><extent unit="pages"><start>5935</start><end>40</end><list>5935-40</list></extent></part></relatedItem></relatedItem><identifier type="istex">544B402E32A7C1B0C58B23C463C0BF5515A1A7B3</identifier><identifier type="ark">ark:/67375/HXZ-VMW0NGNP-F</identifier><identifier type="DOI">10.1086/589716</identifier><accessCondition type="use and reproduction" 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