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<!DOCTYPE html> <html lang="en" dir="ltr" xmlns="http://www.w3.org/1999/xhtml" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <head prefix="og: http://ogp.me/ns# article: http://ogp.me/ns/article# book: http://ogp.me/ns/book#" >  <link rel="dns-prefetch" href="//d33xdlntwy0kbs.cloudfront.net" /> <link rel="dns-prefetch" href="//cdn.jsdelivr.net" /> <link rel="dns-prefetch" href="//www.google.com" /> <link rel="dns-prefetch" href="//scholar.google.com" /> <link rel="dns-prefetch" href="//www.googletagmanager.com" /> <link rel="dns-prefetch" href="//rum-static.pingdom.net" /> <meta http-equiv="Content-Type" content="text/html; charset=utf-8" /> <link rel="shortcut icon" href="https://www.medrxiv.org/sites/default/files/images/favicon.ico" type="image/vnd.microsoft.icon" /> <meta name="viewport" content="width=device-width, initial-scale=1" /> <meta name="article_thumbnail" content="https://www.medrxiv.org/content/medrxiv/early/2022/04/12/2021.08.31.21262916/embed/inline-graphic-1.gif" /> <meta name="type" content="article" /> <meta name="category" content="article" /> <meta name="HW.identifier" content="/medrxiv/early/2022/04/12/2021.08.31.21262916.atom" /> <meta name="HW.pisa" content="medrxiv;2021.08.31.21262916v5" /> <meta name="DC.Format" content="text/html" /> <meta name="DC.Language" content="en" /> <meta name="DC.Title" content="Ensemble model estimates of the global burden of measles morbidity and mortality from 2000 to 2019: a modeling study" /> <meta name="DC.Identifier" content="10.1101/2021.08.31.21262916" /> <meta name="DC.Date" content="2022-04-12" /> <meta name="DC.Publisher" content="Cold Spring Harbor Laboratory Press" /> <meta name="DC.Rights" content="© 2022, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-NoDerivs 4.0 International), CC BY-ND 4.0, as described at http://creativecommons.org/licenses/by-nd/4.0/" /> <meta name="DC.AccessRights" content="restricted" /> <meta name="DC.Description" content="Background Measles remains a significant source of childhood morbidity and mortality worldwide. Two doses of measles containing vaccine are recommended for all children and delivered through a combination of routine and supplemental immunization activities. Uncertainty about the degree to which second dose opportunities reach previously unvaccinated children presents a challenge in the assessment of vaccination programs and the estimation of the global burden of measles disease and mortality. Methods We fit an ensemble of models that represent alternative assumptions about the degree to which second dose opportunities reach previously unvaccinated children to routine measles surveillance from 100 countries. Using maximum likelihood we selected the best fit model for each country. We compare the resulting estimates of the burden of measles disease and mortality to existing methods for estimating the burden of measles that assume that second dose opportunities are independent of receipt of the first dose. Findings We find that 78 of 100 countries are best-fit by a model that assumes that second doses that are delivered through supplemental campaigns are preferentially delivered to children who have received a first dose. Using a country-specific best-fit model we estimate that measles mortality has declined by 73% from 2000-2019 compared to an estimated decline of 83% using an assumption of independent doses in all countries. Interpretation Despite large decreases in measles cases over the last two decades, the observed trajectories in most countries suggest that supplemental immunization activities are disproportionately reaching previously vaccinated children. To accelerate measles reduction goals efforts to reach unvaccinated children through supplemental activities and second dose opportunities should be intensified. Funding Bill and Melinda Gates Foundation, World Health Organization ### Competing Interest Statement MF has received funding from the Bill and Melinda Gates Foundation, the US Centers for Disease Control and Prevention, and the World Health Organization. MF and KE have received funding from Gavi, the vaccine alliance. MP was a CDC detailee to WHO from 2016-2021. ### Funding Statement MF, SH, HS, BL, KE were supported by a grant from Gavi, the vaccine alliance. MF was supported by a grant from the Bill and Melinda Gates Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Our work with the anonymized and aggregated data provided by WHO and used in the study does not quality as human subjects research as defined by the university IRB. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data referred to this manuscript are available at the websites referenced in the text. <https://apps.who.int/immunization_monitoring/globalsummary/timeseries/tsincidencemeasles.html> <https://population.un.org/wpp/> [https://cdn.who.int/media/docs/default-source/immunization/data\_statistics/summary\_measles\_sias.xls?sfvrsn=77c794e8\_6][1] [1]: https://cdn.who.int/media/docs/default-source/immunization/data_statistics/summary_measles_sias.xls?sfvrsn=77c794e8_6" /> <meta name="DC.Contributor" content="Heather Santos" /> <meta name="DC.Contributor" content="Kirsten Eilertson" /> <meta name="DC.Contributor" content="Brian Lambert" /> <meta name="DC.Contributor" content="Sarah Hauryski" /> <meta name="DC.Contributor" content="Minal Patel" /> <meta name="DC.Contributor" content="Matthew Ferrari" /> <meta name="article:published_time" content="2022-04-12" /> <meta name="citation_title" content="Ensemble model estimates of the global burden of measles morbidity and mortality from 2000 to 2019: a modeling study" /> <meta name="citation_abstract" lang="en" content="<h3>Abstract</h3> <h3>Background</h3> <p>Measles remains a significant source of childhood morbidity and mortality worldwide. Two doses of measles containing vaccine are recommended for all children and delivered through a combination of routine and supplemental immunization activities. Uncertainty about the degree to which second dose opportunities reach previously unvaccinated children presents a challenge in the assessment of vaccination programs and the estimation of the global burden of measles disease and mortality.</p><h3>Methods</h3> <p>We fit an ensemble of models that represent alternative assumptions about the degree to which second dose opportunities reach previously unvaccinated children to routine measles surveillance from 100 countries. Using maximum likelihood we selected the best fit model for each country. We compare the resulting estimates of the burden of measles disease and mortality to existing methods for estimating the burden of measles that assume that second dose opportunities are independent of receipt of the first dose.</p><h3>Findings</h3> <p>We find that 78 of 100 countries are best-fit by a model that assumes that second doses that are delivered through supplemental campaigns are preferentially delivered to children who have received a first dose. Using a country-specific best-fit model we estimate that measles mortality has declined by 73% from 2000-2019 compared to an estimated decline of 83% using an assumption of independent doses in all countries.</p><h3>Interpretation</h3> <p>Despite large decreases in measles cases over the last two decades, the observed trajectories in most countries suggest that supplemental immunization activities are disproportionately reaching previously vaccinated children. To accelerate measles reduction goals efforts to reach unvaccinated children through supplemental activities and second dose opportunities should be intensified.</p><h3>Funding</h3> <p>Bill and Melinda Gates Foundation, World Health Organization</p>" /> <meta name="citation_journal_title" content="medRxiv" /> <meta name="citation_publisher" content="Cold Spring Harbor Laboratory Press" /> <meta name="citation_publication_date" content="2022/01/01" /> <meta name="citation_mjid" content="medrxiv;2021.08.31.21262916v5" /> <meta name="citation_id" content="2021.08.31.21262916v5" /> <meta name="citation_public_url" content="https://www.medrxiv.org/content/10.1101/2021.08.31.21262916v5" /> <meta name="citation_abstract_html_url" content="https://www.medrxiv.org/content/10.1101/2021.08.31.21262916v5.abstract" /> <meta name="citation_full_html_url" content="https://www.medrxiv.org/content/10.1101/2021.08.31.21262916v5.full" /> <meta name="citation_pdf_url" content="https://www.medrxiv.org/content/medrxiv/early/2022/04/12/2021.08.31.21262916.full.pdf" /> <meta name="citation_doi" content="10.1101/2021.08.31.21262916" /> <meta name="citation_num_pages" content="15" /> <meta name="citation_article_type" content="Article" /> <meta name="citation_firstpage" content="2021.08.31.21262916" /> <meta name="citation_author" content="Heather Santos" /> <meta name="citation_author_institution" content="Drexel University School of Public Health" /> <meta name="citation_author" content="Kirsten Eilertson" /> <meta name="citation_author_institution" content="Department of Statistics, Colorado State University" /> <meta name="citation_author" content="Brian Lambert" /> <meta name="citation_author_institution" content="Center for Infectious Disease Dynamics, The Pennsylvania State University" /> <meta name="citation_author_orcid" content="http://orcid.org/0000-0002-8595-2726" /> <meta name="citation_author" content="Sarah Hauryski" /> <meta name="citation_author_institution" content="Center for Infectious Disease Dynamics, The Pennsylvania State University" /> <meta name="citation_author" content="Minal Patel" /> <meta name="citation_author_institution" content="Department of Immunizations, Vaccines, and Biologicals, World Health Organization" /> <meta name="citation_author" content="Matthew Ferrari" /> <meta name="citation_author_institution" content="Center for Infectious Disease Dynamics, The Pennsylvania State University" /> <meta name="citation_author_email" content="mferrari@psu.edu" /> <meta name="citation_author_orcid" content="http://orcid.org/0000-0001-5251-8168" /> <meta name="citation_reference" content="Patel MK. 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Available from: https://www.who.int/publications/m/item/immunization-agenda-2030-a-global-strategy-to-leave-no-one-behind" /> <meta name="twitter:title" content="Ensemble model estimates of the global burden of measles morbidity and mortality from 2000 to 2019: a modeling study" /> <meta name="twitter:site" content="@medrxivpreprint" /> <meta name="twitter:card" content="summary" /> <meta name="twitter:image" content="https://www.medrxiv.org/sites/default/files/images/medrxiv_logo_homepage7-5-small-test-up.png" /> <meta name="twitter:description" content="Background Measles remains a significant source of childhood morbidity and mortality worldwide. Two doses of measles containing vaccine are recommended for all children and delivered through a combination of routine and supplemental immunization activities. Uncertainty about the degree to which second dose opportunities reach previously unvaccinated children presents a challenge in the assessment of vaccination programs and the estimation of the global burden of measles disease and mortality. Methods We fit an ensemble of models that represent alternative assumptions about the degree to which second dose opportunities reach previously unvaccinated children to routine measles surveillance from 100 countries. Using maximum likelihood we selected the best fit model for each country. We compare the resulting estimates of the burden of measles disease and mortality to existing methods for estimating the burden of measles that assume that second dose opportunities are independent of receipt of the first dose. Findings We find that 78 of 100 countries are best-fit by a model that assumes that second doses that are delivered through supplemental campaigns are preferentially delivered to children who have received a first dose. Using a country-specific best-fit model we estimate that measles mortality has declined by 73% from 2000-2019 compared to an estimated decline of 83% using an assumption of independent doses in all countries. Interpretation Despite large decreases in measles cases over the last two decades, the observed trajectories in most countries suggest that supplemental immunization activities are disproportionately reaching previously vaccinated children. To accelerate measles reduction goals efforts to reach unvaccinated children through supplemental activities and second dose opportunities should be intensified. Funding Bill and Melinda Gates Foundation, World Health Organization ### Competing Interest Statement MF has received funding from the Bill and Melinda Gates Foundation, the US Centers for Disease Control and Prevention, and the World Health Organization. MF and KE have received funding from Gavi, the vaccine alliance. MP was a CDC detailee to WHO from 2016-2021. ### Funding Statement MF, SH, HS, BL, KE were supported by a grant from Gavi, the vaccine alliance. MF was supported by a grant from the Bill and Melinda Gates Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Our work with the anonymized and aggregated data provided by WHO and used in the study does not quality as human subjects research as defined by the university IRB. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data referred to this manuscript are available at the websites referenced in the text. <https://apps.who.int/immunization_monitoring/globalsummary/timeseries/tsincidencemeasles.html> <https://population.un.org/wpp/> [https://cdn.who.int/media/docs/default-source/immunization/data\_statistics/summary\_measles\_sias.xls?sfvrsn=77c794e8\_6][1] [1]: https://cdn.who.int/media/docs/default-source/immunization/data_statistics/summary_measles_sias.xls?sfvrsn=77c794e8_6" /> <meta name="og-title" property="og:title" content="Ensemble model estimates of the global burden of measles morbidity and mortality from 2000 to 2019: a modeling study" /> <meta name="og-url" property="og:url" content="https://www.medrxiv.org/content/10.1101/2021.08.31.21262916v5" /> <meta name="og-site-name" property="og:site_name" content="medRxiv" /> <meta name="og-description" property="og:description" content="Background Measles remains a significant source of childhood morbidity and mortality worldwide. Two doses of measles containing vaccine are recommended for all children and delivered through a combination of routine and supplemental immunization activities. Uncertainty about the degree to which second dose opportunities reach previously unvaccinated children presents a challenge in the assessment of vaccination programs and the estimation of the global burden of measles disease and mortality. Methods We fit an ensemble of models that represent alternative assumptions about the degree to which second dose opportunities reach previously unvaccinated children to routine measles surveillance from 100 countries. Using maximum likelihood we selected the best fit model for each country. We compare the resulting estimates of the burden of measles disease and mortality to existing methods for estimating the burden of measles that assume that second dose opportunities are independent of receipt of the first dose. Findings We find that 78 of 100 countries are best-fit by a model that assumes that second doses that are delivered through supplemental campaigns are preferentially delivered to children who have received a first dose. Using a country-specific best-fit model we estimate that measles mortality has declined by 73% from 2000-2019 compared to an estimated decline of 83% using an assumption of independent doses in all countries. Interpretation Despite large decreases in measles cases over the last two decades, the observed trajectories in most countries suggest that supplemental immunization activities are disproportionately reaching previously vaccinated children. To accelerate measles reduction goals efforts to reach unvaccinated children through supplemental activities and second dose opportunities should be intensified. Funding Bill and Melinda Gates Foundation, World Health Organization ### Competing Interest Statement MF has received funding from the Bill and Melinda Gates Foundation, the US Centers for Disease Control and Prevention, and the World Health Organization. MF and KE have received funding from Gavi, the vaccine alliance. MP was a CDC detailee to WHO from 2016-2021. ### Funding Statement MF, SH, HS, BL, KE were supported by a grant from Gavi, the vaccine alliance. MF was supported by a grant from the Bill and Melinda Gates Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Our work with the anonymized and aggregated data provided by WHO and used in the study does not quality as human subjects research as defined by the university IRB. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data referred to this manuscript are available at the websites referenced in the text. <https://apps.who.int/immunization_monitoring/globalsummary/timeseries/tsincidencemeasles.html> <https://population.un.org/wpp/> [https://cdn.who.int/media/docs/default-source/immunization/data\_statistics/summary\_measles\_sias.xls?sfvrsn=77c794e8\_6][1] [1]: https://cdn.who.int/media/docs/default-source/immunization/data_statistics/summary_measles_sias.xls?sfvrsn=77c794e8_6" /> <meta name="og-type" property="og:type" content="article" /> <meta name="og-image" property="og:image" content="https://www.medrxiv.org/sites/default/files/images/medrxiv_logo_homepage7-5-small-test-up.png" /> <meta name="citation_date" content="2022-04-12" /> <link rel="alternate" type="text/plain" title="Full Text (Plain)" href="/content/10.1101/2021.08.31.21262916v5.full.txt" /> <link rel="alternate" type="application/vnd.ms-powerpoint" title="Powerpoint" href="/content/10.1101/2021.08.31.21262916v5.ppt" /> <link 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clearfix"> <div class="content clearfix"> <div class="panel-display panels-960-layout jcore-2col-layout" > <div class="panel-row-wrapper clearfix"> <div class="main-content-wrapper grid-17 suffix-1 alpha"> <div class="panel-panel panel-region-content"> <div class="inside"><div class="panel-pane pane-highwire-article-citation" > <div class="pane-content"> <div class="highwire-article-citation highwire-citation-type-highwire-article node501478" data-node-nid="501478" id="node-501478--2582751760" data-pisa="medrxiv;2021.08.31.21262916v5" data-pisa-master="medrxiv;2021.08.31.21262916" data-apath="/medrxiv/early/2022/04/12/2021.08.31.21262916.atom" data-hw-author-tooltip-instance=""><div class="highwire-cite highwire-cite-highwire-article highwire-citation-medrxiv-article-top clearfix has-author-tooltip" > <h1 class="highwire-cite-title" id="page-title">Ensemble model estimates of the global burden of measles morbidity and mortality from 2000 to 2019: a modeling study</h1> <div class="highwire-cite-authors" ><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Heather</span> <span class="nlm-surname">Santos</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Kirsten</span> <span class="nlm-surname">Eilertson</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="2"><a href="http://orcid.org/0000-0002-8595-2726" target="_blank" class="hw-author-orcid-logo link-icon-only link-icon"><span class="hw-icon-orcid hw-icon-color-orcid"></span> <span class="title element-invisible">View ORCID Profile</span></a><span class="nlm-given-names">Brian</span> <span class="nlm-surname">Lambert</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Sarah</span> <span class="nlm-surname">Hauryski</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Minal</span> <span class="nlm-surname">Patel</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="5"><a href="http://orcid.org/0000-0001-5251-8168" target="_blank" class="hw-author-orcid-logo link-icon-only link-icon"><span class="hw-icon-orcid hw-icon-color-orcid"></span> <span class="title element-invisible">View ORCID Profile</span></a><span class="nlm-given-names">Matthew</span> <span class="nlm-surname">Ferrari</span></span></span></div> <div class="highwire-cite-metadata" ><span class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">doi:</span> https://doi.org/10.1101/2021.08.31.21262916 </span></div> </div> <div id="hw-article-author-popups-node-501478--2582751760" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">Heather Santos </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span><span class='nlm-institution'>Drexel University School of Public Health</span>, Philadelphia, Pennsylvania</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Heather%2BSantos%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Santos%20H&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AHeather%2BSantos%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">Kirsten Eilertson </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>2</span><span class='nlm-institution'>Department of Statistics, Colorado State University</span>, Fort Collins, CO, <span class='nlm-country'>USA</span></div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Kirsten%2BEilertson%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Eilertson%20K&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AKirsten%2BEilertson%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">Brian Lambert </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>3</span><span class='nlm-institution'>Center for Infectious Disease Dynamics, The Pennsylvania State University</span>, University Park, PA, <span class='nlm-country'>USA</span></div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Brian%2BLambert%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Lambert%20B&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3ABrian%2BLambert%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-8595-2726" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Brian Lambert</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">Sarah Hauryski </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>3</span><span class='nlm-institution'>Center for Infectious Disease Dynamics, The Pennsylvania State University</span>, University Park, PA, <span class='nlm-country'>USA</span></div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Sarah%2BHauryski%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Hauryski%20S&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3ASarah%2BHauryski%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">Minal Patel </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>4</span><span class='nlm-institution'>Department of Immunizations, Vaccines, and Biologicals, World Health Organization</span>, Geneva, <span class='nlm-country'>Switzerland</span></div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Minal%2BPatel%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Patel%20M&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AMinal%2BPatel%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">Matthew Ferrari </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>3</span><span class='nlm-institution'>Center for Infectious Disease Dynamics, The Pennsylvania State University</span>, University Park, PA, <span class='nlm-country'>USA</span></div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Matthew%2BFerrari%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Ferrari%20M&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AMatthew%2BFerrari%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link"><a href="http://orcid.org/0000-0001-5251-8168" target="_blank" class="" data-icon-position="" 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href="/content/10.1101/2021.08.31.21262916v5.full.pdf+html" class="panels-ajax-tab-tab" data-panel-name="biorxiv_tab_pdf" data-target-id="highwire_article_tabs" data-entity-context="node:501478" data-trigger="full.pdf+html" data-url-enabled="1"><i class="icon-file-alt"></i> Preview PDF</a><a href="/panels_ajax_tab/biorxiv_tab_pdf/node:501478/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li></ul></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-panel-tabs-container" > <div class="pane-content"> <div data-panels-ajax-tab-preloaded="biorxiv_tab_art" id="panels-ajax-tab-container-highwire_article_tabs" class="panels-ajax-tab-container"><div class="panels-ajax-tab-loading" style ="display:none"><img class="loading" src="https://www.medrxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif" alt="Loading" title="Loading" /></div><div class="panels-ajax-tab-wrap-biorxiv_tab_art"><div class="panel-display panel-1col clearfix" > <div class="panel-panel panel-col"> <div><div class="panel-pane pane-highwire-markup" > <div class="pane-content"> <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" data-highwire-cite-ref-tooltip-instance="highwire_reflinks_tooltip" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article abstract-view "><span class="highwire-journal-article-marker-start"></span><div class="section abstract" id="abstract-1"><h2 class="">Abstract</h2><div id="sec-1" class="subsection"><p id="p-2"><strong>Background</strong> Measles remains a significant source of childhood morbidity and mortality worldwide. Two doses of measles containing vaccine are recommended for all children and delivered through a combination of routine and supplemental immunization activities. Uncertainty about the degree to which second dose opportunities reach previously unvaccinated children presents a challenge in the assessment of vaccination programs and the estimation of the global burden of measles disease and mortality.</p></div><div id="sec-2" class="subsection"><p id="p-3"><strong>Methods</strong> We fit an ensemble of models that represent alternative assumptions about the degree to which second dose opportunities reach previously unvaccinated children to routine measles surveillance from 100 countries. Using maximum likelihood we selected the best fit model for each country. We compare the resulting estimates of the burden of measles disease and mortality to existing methods for estimating the burden of measles that assume that second dose opportunities are independent of receipt of the first dose.</p></div><div id="sec-3" class="subsection"><p id="p-4"><strong>Findings</strong> We find that 78 of 100 countries are best-fit by a model that assumes that second doses that are delivered through supplemental campaigns are preferentially delivered to children who have received a first dose. Using a country-specific best-fit model we estimate that measles mortality has declined by 73% from 2000-2019 compared to an estimated decline of 83% using an assumption of independent doses in all countries.</p></div><div id="sec-4" class="subsection"><p id="p-5"><strong>Interpretation</strong> Despite large decreases in measles cases over the last two decades, the observed trajectories in most countries suggest that supplemental immunization activities are disproportionately reaching previously vaccinated children. To accelerate measles reduction goals efforts to reach unvaccinated children through supplemental activities and second dose opportunities should be intensified.</p></div><div id="sec-5" class="subsection"><p id="p-6"><strong>Funding</strong> Bill and Melinda Gates Foundation, World Health Organization</p></div></div><h3>Competing Interest Statement</h3><p id="p-7">MF has received funding from the Bill and Melinda Gates Foundation, the US Centers for Disease Control and Prevention, and the World Health Organization. MF and KE have received funding from Gavi, the vaccine alliance. MP was a CDC detailee to WHO from 2016-2021.</p><h3>Funding Statement</h3><p id="p-8">MF, SH, HS, BL, KE were supported by a grant from Gavi, the vaccine alliance. MF was supported by a grant from the Bill and Melinda Gates Foundation.</p><h3>Author Declarations</h3><p id="p-9">I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.</p><p id="p-10">Yes</p><p id="p-11">The details of the IRB/oversight body that provided approval or exemption for the research described are given below:</p><p id="p-12">Our work with the anonymized and aggregated data provided by WHO and used in the study does not quality as human subjects research as defined by the university IRB.</p><p id="p-13">I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.</p><p id="p-14">Yes</p><p id="p-15">I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).</p><p id="p-16">Yes</p><p id="p-17">I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.</p><p id="p-18">Yes</p><div class="section fn-group" id="fn-group-1"><h2>Footnotes</h2><ul><li class="fn-update fn-group-summary-of-updates" id="fn-1"><p id="p-19">Fixed an error in the definition of theta in text.</p></li></ul></div><div class="section data-availability" id="sec-18"><h2 class="">Data Availability</h2><p id="p-67">The data referred to this manuscript are available at the websites referenced in the text.</p><p id="p-68"> <a href="https://apps.who.int/immunization_monitoring/globalsummary/timeseries/tsincidencemeasles.html">https://apps.who.int/immunization_monitoring/globalsummary/timeseries/tsincidencemeasles.html</a> </p><p id="p-69"> <a href="https://population.un.org/wpp/">https://population.un.org/wpp/</a> </p><p id="p-70"> <a href="https://cdn.who.int/media/docs/default-source/immunization/data_statistics/summary_measles_sias.xls?sfvrsn=77c794e8_6">https://cdn.who.int/media/docs/default-source/immunization/data_statistics/summary_measles_sias.xls?sfvrsn=77c794e8_6</a> </p></div><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-biorxiv-copyright" > <div class="pane-content"> <div class="field field-name-field-highwire-copyright field-type-text field-label-inline clearfix"><div class="field-label">Copyright </div><div class="field-items"><div class="field-item 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highwire-citation-type-highwire-article cite-tool-node501478--5" data-node-nid="501478" id="citation-node-501478--61741574560" data-pisa="medrxiv;2021.08.31.21262916v5" data-pisa-master="medrxiv;2021.08.31.21262916" data-seqnum="501478" data-apath="/medrxiv/early/2022/04/12/2021.08.31.21262916.atom"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-biorxiv-article-pap-list clearfix" > <div class="highwire-cite-title" > <div class="highwire-cite-title">Ensemble model estimates of the global burden of measles morbidity and mortality from 2000 to 2019: a modeling study</div> </div> <div class="highwire-cite-authors" ><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Heather</span> <span class="nlm-surname">Santos</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Kirsten</span> <span class="nlm-surname">Eilertson</span></span>, <span 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