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Serological Response in RT-PCR Confirmed H1N1-2009 Influenza A by Hemagglutination Inhibition and Virus Neutralization Assays: An Observational Study

Identifieur interne : 000895 ( Pmc/Checkpoint ); précédent : 000894; suivant : 000896

Serological Response in RT-PCR Confirmed H1N1-2009 Influenza A by Hemagglutination Inhibition and Virus Neutralization Assays: An Observational Study

Auteurs : Mark I. Chen [Singapour] ; Ian G. Barr [Australie] ; Gerald C. H. Koh [Singapour] ; Vernon J. Lee [Singapour, Australie] ; Caroline P. S. Lee [Singapour] ; Robert Shaw [Australie] ; Cui Lin [Singapour] ; Jonathan Yap [Singapour] ; Alex R. Cook [Singapour] ; Boon Huan Tan [Singapour] ; Jin Phang Loh [Singapour] ; Timothy Barkham [Singapour] ; Vincent T. K. Chow [Singapour] ; Raymond T. P. Lin [Singapour] ; Yee-Sin Leo [Singapour]

Source :

RBID : PMC:2930007

Abstract

Background

We describe the serological response following H1N1-2009 influenza A infections confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR).

Methodology and Principal Findings

The study included patients admitted to hospital, subjects of a seroepidemiologic cohort study, and participants identified from outbreak studies in Singapore. Baseline (first available blood sample) and follow-up blood samples were analyzed for antibody titers to H1N1-2009 and recently circulating seasonal influenza A virus strains by hemagglutination inhibition (HI) and virus micro-neutralization (VM) assays. 267 samples from 118 cases of H1N1-2009 were analyzed. Geometric mean titers by HI peaked at 123 (95% confidence interval, CI 43-356) between days 30 to 39. The chance of observing seroconversion (four-fold or greater increase of antibodies) was maximized when restricting analysis to 45 participants with baseline sera collected within 5 days of onset and follow-up sera collected 15 or more days after onset; for these participants, 82% and 89% seroconverted to A/California/7/2009 H1N1 by HI and VM respectively. A four-fold or greater increase in cross-reactive antibody titers to seasonal A/Brisbane/59/2007 H1N1, A/Brisbane/10/2007 H3N2 and A/Wisconsin/15/2009 H3N2 occurred in 20%, 18% and 16% of participants respectively.

Conclusions and Significance

Appropriately timed paired serology detects 80–90% RT-PCR confirmed H1N1-2009; Antibodies from infection with H1N1-2009 cross-reacted with seasonal influenza viruses.


Url:
DOI: 10.1371/journal.pone.0012474
PubMed: 20814575
PubMed Central: 2930007


Affiliations:


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PMC:2930007

Le document en format XML

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<name sortKey="Tan, Boon Huan" sort="Tan, Boon Huan" uniqKey="Tan B" first="Boon Huan" last="Tan">Boon Huan Tan</name>
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<name sortKey="Loh, Jin Phang" sort="Loh, Jin Phang" uniqKey="Loh J" first="Jin Phang" last="Loh">Jin Phang Loh</name>
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<name sortKey="Barkham, Timothy" sort="Barkham, Timothy" uniqKey="Barkham T" first="Timothy" last="Barkham">Timothy Barkham</name>
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<addr-line>Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore, Singapore</addr-line>
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<name sortKey="Chow, Vincent T K" sort="Chow, Vincent T K" uniqKey="Chow V" first="Vincent T. K." last="Chow">Vincent T. K. Chow</name>
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<addr-line>Department of Microbiology, National University of Singapore, Singapore, Singapore</addr-line>
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<wicri:regionArea>Department of Microbiology, National University of Singapore, Singapore</wicri:regionArea>
<orgName type="university">Université nationale de Singapour</orgName>
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<name sortKey="Lin, Raymond T P" sort="Lin, Raymond T P" uniqKey="Lin R" first="Raymond T. P." last="Lin">Raymond T. P. Lin</name>
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<addr-line>National Public Health Laboratory, Ministry of Health, Singapore, Singapore</addr-line>
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<name sortKey="Leo, Yee Sin" sort="Leo, Yee Sin" uniqKey="Leo Y" first="Yee-Sin" last="Leo">Yee-Sin Leo</name>
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<title xml:lang="en" level="a" type="main">Serological Response in RT-PCR Confirmed H1N1-2009 Influenza A by Hemagglutination Inhibition and Virus Neutralization Assays: An Observational Study</title>
<author>
<name sortKey="Chen, Mark I" sort="Chen, Mark I" uniqKey="Chen M" first="Mark I." last="Chen">Mark I. Chen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<addr-line>Clinical Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Clinical Epidemiology, Tan Tock Seng Hospital, Singapore</wicri:regionArea>
<wicri:noRegion>Singapore</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="aff2">
<addr-line>Epidemiology and Public Health, National University of Singapore, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Epidemiology and Public Health, National University of Singapore, Singapore</wicri:regionArea>
<orgName type="university">Université nationale de Singapour</orgName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff3">
<addr-line>Duke-NUS Graduate Medical School, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Duke-NUS Graduate Medical School, Singapore</wicri:regionArea>
<wicri:noRegion>Singapore</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Barr, Ian G" sort="Barr, Ian G" uniqKey="Barr I" first="Ian G." last="Barr">Ian G. Barr</name>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<addr-line>World Health Organization Collaborating Centre for Reference and Research on Influenza, Melbourne, Victoria, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>World Health Organization Collaborating Centre for Reference and Research on Influenza, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Koh, Gerald C H" sort="Koh, Gerald C H" uniqKey="Koh G" first="Gerald C. H." last="Koh">Gerald C. H. Koh</name>
<affiliation wicri:level="4">
<nlm:aff id="aff2">
<addr-line>Epidemiology and Public Health, National University of Singapore, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Epidemiology and Public Health, National University of Singapore, Singapore</wicri:regionArea>
<orgName type="university">Université nationale de Singapour</orgName>
</affiliation>
<affiliation wicri:level="4">
<nlm:aff id="aff5">
<addr-line>Centre for Health Services Research, National University of Singapore, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Centre for Health Services Research, National University of Singapore, Singapore</wicri:regionArea>
<orgName type="university">Université nationale de Singapour</orgName>
</affiliation>
</author>
<author>
<name sortKey="Lee, Vernon J" sort="Lee, Vernon J" uniqKey="Lee V" first="Vernon J." last="Lee">Vernon J. Lee</name>
<affiliation wicri:level="4">
<nlm:aff id="aff2">
<addr-line>Epidemiology and Public Health, National University of Singapore, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Epidemiology and Public Health, National University of Singapore, Singapore</wicri:regionArea>
<orgName type="university">Université nationale de Singapour</orgName>
</affiliation>
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<nlm:aff id="aff5">
<addr-line>Centre for Health Services Research, National University of Singapore, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Centre for Health Services Research, National University of Singapore, Singapore</wicri:regionArea>
<orgName type="university">Université nationale de Singapour</orgName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff6">
<addr-line>Biodefence Centre, Ministry of Defence, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Biodefence Centre, Ministry of Defence, Singapore</wicri:regionArea>
<wicri:noRegion>Singapore</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff7">
<addr-line>Centre for Epidemiology and Population Health, Australian National University, Canberra, Australian Capital Territory, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Centre for Epidemiology and Population Health, Australian National University, Canberra, Australian Capital Territory</wicri:regionArea>
<wicri:noRegion>Australian Capital Territory</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Lee, Caroline P S" sort="Lee, Caroline P S" uniqKey="Lee C" first="Caroline P. S." last="Lee">Caroline P. S. Lee</name>
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<nlm:aff id="aff8">
<addr-line>Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore</wicri:regionArea>
<wicri:noRegion>Singapore</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Shaw, Robert" sort="Shaw, Robert" uniqKey="Shaw R" first="Robert" last="Shaw">Robert Shaw</name>
<affiliation wicri:level="1">
<nlm:aff id="aff4">
<addr-line>World Health Organization Collaborating Centre for Reference and Research on Influenza, Melbourne, Victoria, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>World Health Organization Collaborating Centre for Reference and Research on Influenza, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Lin, Cui" sort="Lin, Cui" uniqKey="Lin C" first="Cui" last="Lin">Cui Lin</name>
<affiliation wicri:level="1">
<nlm:aff id="aff9">
<addr-line>National Public Health Laboratory, Ministry of Health, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>National Public Health Laboratory, Ministry of Health, Singapore</wicri:regionArea>
<wicri:noRegion>Singapore</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Yap, Jonathan" sort="Yap, Jonathan" uniqKey="Yap J" first="Jonathan" last="Yap">Jonathan Yap</name>
<affiliation wicri:level="1">
<nlm:aff id="aff6">
<addr-line>Biodefence Centre, Ministry of Defence, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Biodefence Centre, Ministry of Defence, Singapore</wicri:regionArea>
<wicri:noRegion>Singapore</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Cook, Alex R" sort="Cook, Alex R" uniqKey="Cook A" first="Alex R." last="Cook">Alex R. Cook</name>
<affiliation wicri:level="4">
<nlm:aff id="aff10">
<addr-line>Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Department of Statistics and Applied Probability, National University of Singapore, Singapore</wicri:regionArea>
<orgName type="university">Université nationale de Singapour</orgName>
</affiliation>
</author>
<author>
<name sortKey="Tan, Boon Huan" sort="Tan, Boon Huan" uniqKey="Tan B" first="Boon Huan" last="Tan">Boon Huan Tan</name>
<affiliation wicri:level="1">
<nlm:aff id="aff11">
<addr-line>Detection and Diagnostics Laboratory, DSO National Laboratories, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Detection and Diagnostics Laboratory, DSO National Laboratories, Singapore</wicri:regionArea>
<wicri:noRegion>Singapore</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Loh, Jin Phang" sort="Loh, Jin Phang" uniqKey="Loh J" first="Jin Phang" last="Loh">Jin Phang Loh</name>
<affiliation wicri:level="1">
<nlm:aff id="aff11">
<addr-line>Detection and Diagnostics Laboratory, DSO National Laboratories, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Detection and Diagnostics Laboratory, DSO National Laboratories, Singapore</wicri:regionArea>
<wicri:noRegion>Singapore</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Barkham, Timothy" sort="Barkham, Timothy" uniqKey="Barkham T" first="Timothy" last="Barkham">Timothy Barkham</name>
<affiliation wicri:level="1">
<nlm:aff id="aff12">
<addr-line>Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore</wicri:regionArea>
<wicri:noRegion>Singapore</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Chow, Vincent T K" sort="Chow, Vincent T K" uniqKey="Chow V" first="Vincent T. K." last="Chow">Vincent T. K. Chow</name>
<affiliation wicri:level="4">
<nlm:aff id="aff13">
<addr-line>Department of Microbiology, National University of Singapore, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Department of Microbiology, National University of Singapore, Singapore</wicri:regionArea>
<orgName type="university">Université nationale de Singapour</orgName>
</affiliation>
</author>
<author>
<name sortKey="Lin, Raymond T P" sort="Lin, Raymond T P" uniqKey="Lin R" first="Raymond T. P." last="Lin">Raymond T. P. Lin</name>
<affiliation wicri:level="1">
<nlm:aff id="aff9">
<addr-line>National Public Health Laboratory, Ministry of Health, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>National Public Health Laboratory, Ministry of Health, Singapore</wicri:regionArea>
<wicri:noRegion>Singapore</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Leo, Yee Sin" sort="Leo, Yee Sin" uniqKey="Leo Y" first="Yee-Sin" last="Leo">Yee-Sin Leo</name>
<affiliation wicri:level="1">
<nlm:aff id="aff8">
<addr-line>Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore, Singapore</addr-line>
</nlm:aff>
<country xml:lang="fr">Singapour</country>
<wicri:regionArea>Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore</wicri:regionArea>
<wicri:noRegion>Singapore</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series>
<title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint>
<date when="2010">2010</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec>
<title>Background</title>
<p>We describe the serological response following H1N1-2009 influenza A infections confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR).</p>
</sec>
<sec>
<title>Methodology and Principal Findings</title>
<p>The study included patients admitted to hospital, subjects of a seroepidemiologic cohort study, and participants identified from outbreak studies in Singapore. Baseline (first available blood sample) and follow-up blood samples were analyzed for antibody titers to H1N1-2009 and recently circulating seasonal influenza A virus strains by hemagglutination inhibition (HI) and virus micro-neutralization (VM) assays. 267 samples from 118 cases of H1N1-2009 were analyzed. Geometric mean titers by HI peaked at 123 (95% confidence interval, CI 43-356) between days 30 to 39. The chance of observing seroconversion (four-fold or greater increase of antibodies) was maximized when restricting analysis to 45 participants with baseline sera collected within 5 days of onset and follow-up sera collected 15 or more days after onset; for these participants, 82% and 89% seroconverted to A/California/7/2009 H1N1 by HI and VM respectively. A four-fold or greater increase in cross-reactive antibody titers to seasonal A/Brisbane/59/2007 H1N1, A/Brisbane/10/2007 H3N2 and A/Wisconsin/15/2009 H3N2 occurred in 20%, 18% and 16% of participants respectively.</p>
</sec>
<sec>
<title>Conclusions and Significance</title>
<p>Appropriately timed paired serology detects 80–90% RT-PCR confirmed H1N1-2009; Antibodies from infection with H1N1-2009 cross-reacted with seasonal influenza viruses.</p>
</sec>
</div>
</front>
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<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">PLoS One</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosone</journal-id>
<journal-title-group>
<journal-title>PLoS ONE</journal-title>
</journal-title-group>
<issn pub-type="epub">1932-6203</issn>
<publisher>
<publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">20814575</article-id>
<article-id pub-id-type="pmc">2930007</article-id>
<article-id pub-id-type="publisher-id">10-PONE-RA-20010R1</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0012474</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline">
<subject>Immunology/Immunity to Infections</subject>
<subject>Virology/Diagnosis</subject>
<subject>Virology/Emerging Viral Diseases</subject>
<subject>Infectious Diseases/Viral Infections</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Serological Response in RT-PCR Confirmed H1N1-2009 Influenza A by Hemagglutination Inhibition and Virus Neutralization Assays: An Observational Study</article-title>
<alt-title alt-title-type="running-head">Antibody Response in H1N1-2009</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Chen</surname>
<given-names>Mark I.</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<xref ref-type="corresp" rid="cor1">
<sup>*</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Barr</surname>
<given-names>Ian G.</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Koh</surname>
<given-names>Gerald C. H.</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff5">
<sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lee</surname>
<given-names>Vernon J.</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="aff5">
<sup>5</sup>
</xref>
<xref ref-type="aff" rid="aff6">
<sup>6</sup>
</xref>
<xref ref-type="aff" rid="aff7">
<sup>7</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lee</surname>
<given-names>Caroline P. S.</given-names>
</name>
<xref ref-type="aff" rid="aff8">
<sup>8</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Shaw</surname>
<given-names>Robert</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lin</surname>
<given-names>Cui</given-names>
</name>
<xref ref-type="aff" rid="aff9">
<sup>9</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yap</surname>
<given-names>Jonathan</given-names>
</name>
<xref ref-type="aff" rid="aff6">
<sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cook</surname>
<given-names>Alex R.</given-names>
</name>
<xref ref-type="aff" rid="aff10">
<sup>10</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tan</surname>
<given-names>Boon Huan</given-names>
</name>
<xref ref-type="aff" rid="aff11">
<sup>11</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Loh</surname>
<given-names>Jin Phang</given-names>
</name>
<xref ref-type="aff" rid="aff11">
<sup>11</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Barkham</surname>
<given-names>Timothy</given-names>
</name>
<xref ref-type="aff" rid="aff12">
<sup>12</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chow</surname>
<given-names>Vincent T. K.</given-names>
</name>
<xref ref-type="aff" rid="aff13">
<sup>13</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lin</surname>
<given-names>Raymond T. P.</given-names>
</name>
<xref ref-type="aff" rid="aff9">
<sup>9</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Leo</surname>
<given-names>Yee-Sin</given-names>
</name>
<xref ref-type="aff" rid="aff8">
<sup>8</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1">
<label>1</label>
<addr-line>Clinical Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore</addr-line>
</aff>
<aff id="aff2">
<label>2</label>
<addr-line>Epidemiology and Public Health, National University of Singapore, Singapore, Singapore</addr-line>
</aff>
<aff id="aff3">
<label>3</label>
<addr-line>Duke-NUS Graduate Medical School, Singapore, Singapore</addr-line>
</aff>
<aff id="aff4">
<label>4</label>
<addr-line>World Health Organization Collaborating Centre for Reference and Research on Influenza, Melbourne, Victoria, Australia</addr-line>
</aff>
<aff id="aff5">
<label>5</label>
<addr-line>Centre for Health Services Research, National University of Singapore, Singapore, Singapore</addr-line>
</aff>
<aff id="aff6">
<label>6</label>
<addr-line>Biodefence Centre, Ministry of Defence, Singapore, Singapore</addr-line>
</aff>
<aff id="aff7">
<label>7</label>
<addr-line>Centre for Epidemiology and Population Health, Australian National University, Canberra, Australian Capital Territory, Australia</addr-line>
</aff>
<aff id="aff8">
<label>8</label>
<addr-line>Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore, Singapore</addr-line>
</aff>
<aff id="aff9">
<label>9</label>
<addr-line>National Public Health Laboratory, Ministry of Health, Singapore, Singapore</addr-line>
</aff>
<aff id="aff10">
<label>10</label>
<addr-line>Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore</addr-line>
</aff>
<aff id="aff11">
<label>11</label>
<addr-line>Detection and Diagnostics Laboratory, DSO National Laboratories, Singapore, Singapore</addr-line>
</aff>
<aff id="aff12">
<label>12</label>
<addr-line>Department of Laboratory Medicine, Tan Tock Seng Hospital, Singapore, Singapore</addr-line>
</aff>
<aff id="aff13">
<label>13</label>
<addr-line>Department of Microbiology, National University of Singapore, Singapore, Singapore</addr-line>
</aff>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Brown</surname>
<given-names>Justin</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">University of Georgia, United States of America</aff>
<author-notes>
<corresp id="cor1">* E-mail:
<email>Mark_IC_Chen@ttsh.com.sg</email>
</corresp>
<fn fn-type="con">
<p>Conceived and designed the experiments: MIC IGB GCHK VJL JY VTKC RTPL YSL. Performed the experiments: IGB CPL RS CL BHT JPL TB. Analyzed the data: MIC VJL ARC. Contributed reagents/materials/analysis tools: IGB RS CL RTPL. Wrote the paper: MIC GCHK VJL TB VTKC.</p>
</fn>
</author-notes>
<pub-date pub-type="collection">
<year>2010</year>
</pub-date>
<pub-date pub-type="epub">
<day>30</day>
<month>8</month>
<year>2010</year>
</pub-date>
<volume>5</volume>
<issue>8</issue>
<elocation-id>e12474</elocation-id>
<history>
<date date-type="received">
<day>20</day>
<month>6</month>
<year>2010</year>
</date>
<date date-type="accepted">
<day>4</day>
<month>8</month>
<year>2010</year>
</date>
</history>
<permissions>
<copyright-statement>Chen et al.</copyright-statement>
<copyright-year>2010</copyright-year>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p>
</license>
</permissions>
<abstract>
<sec>
<title>Background</title>
<p>We describe the serological response following H1N1-2009 influenza A infections confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR).</p>
</sec>
<sec>
<title>Methodology and Principal Findings</title>
<p>The study included patients admitted to hospital, subjects of a seroepidemiologic cohort study, and participants identified from outbreak studies in Singapore. Baseline (first available blood sample) and follow-up blood samples were analyzed for antibody titers to H1N1-2009 and recently circulating seasonal influenza A virus strains by hemagglutination inhibition (HI) and virus micro-neutralization (VM) assays. 267 samples from 118 cases of H1N1-2009 were analyzed. Geometric mean titers by HI peaked at 123 (95% confidence interval, CI 43-356) between days 30 to 39. The chance of observing seroconversion (four-fold or greater increase of antibodies) was maximized when restricting analysis to 45 participants with baseline sera collected within 5 days of onset and follow-up sera collected 15 or more days after onset; for these participants, 82% and 89% seroconverted to A/California/7/2009 H1N1 by HI and VM respectively. A four-fold or greater increase in cross-reactive antibody titers to seasonal A/Brisbane/59/2007 H1N1, A/Brisbane/10/2007 H3N2 and A/Wisconsin/15/2009 H3N2 occurred in 20%, 18% and 16% of participants respectively.</p>
</sec>
<sec>
<title>Conclusions and Significance</title>
<p>Appropriately timed paired serology detects 80–90% RT-PCR confirmed H1N1-2009; Antibodies from infection with H1N1-2009 cross-reacted with seasonal influenza viruses.</p>
</sec>
</abstract>
<counts>
<page-count count="7"></page-count>
</counts>
</article-meta>
</front>
</pmc>
<affiliations>
<list>
<country>
<li>Australie</li>
<li>Singapour</li>
</country>
<orgName>
<li>Université nationale de Singapour</li>
</orgName>
</list>
<tree>
<country name="Singapour">
<noRegion>
<name sortKey="Chen, Mark I" sort="Chen, Mark I" uniqKey="Chen M" first="Mark I." last="Chen">Mark I. Chen</name>
</noRegion>
<name sortKey="Barkham, Timothy" sort="Barkham, Timothy" uniqKey="Barkham T" first="Timothy" last="Barkham">Timothy Barkham</name>
<name sortKey="Chen, Mark I" sort="Chen, Mark I" uniqKey="Chen M" first="Mark I." last="Chen">Mark I. Chen</name>
<name sortKey="Chen, Mark I" sort="Chen, Mark I" uniqKey="Chen M" first="Mark I." last="Chen">Mark I. Chen</name>
<name sortKey="Chow, Vincent T K" sort="Chow, Vincent T K" uniqKey="Chow V" first="Vincent T. K." last="Chow">Vincent T. K. Chow</name>
<name sortKey="Cook, Alex R" sort="Cook, Alex R" uniqKey="Cook A" first="Alex R." last="Cook">Alex R. Cook</name>
<name sortKey="Koh, Gerald C H" sort="Koh, Gerald C H" uniqKey="Koh G" first="Gerald C. H." last="Koh">Gerald C. H. Koh</name>
<name sortKey="Koh, Gerald C H" sort="Koh, Gerald C H" uniqKey="Koh G" first="Gerald C. H." last="Koh">Gerald C. H. Koh</name>
<name sortKey="Lee, Caroline P S" sort="Lee, Caroline P S" uniqKey="Lee C" first="Caroline P. S." last="Lee">Caroline P. S. Lee</name>
<name sortKey="Lee, Vernon J" sort="Lee, Vernon J" uniqKey="Lee V" first="Vernon J." last="Lee">Vernon J. Lee</name>
<name sortKey="Lee, Vernon J" sort="Lee, Vernon J" uniqKey="Lee V" first="Vernon J." last="Lee">Vernon J. Lee</name>
<name sortKey="Lee, Vernon J" sort="Lee, Vernon J" uniqKey="Lee V" first="Vernon J." last="Lee">Vernon J. Lee</name>
<name sortKey="Leo, Yee Sin" sort="Leo, Yee Sin" uniqKey="Leo Y" first="Yee-Sin" last="Leo">Yee-Sin Leo</name>
<name sortKey="Lin, Cui" sort="Lin, Cui" uniqKey="Lin C" first="Cui" last="Lin">Cui Lin</name>
<name sortKey="Lin, Raymond T P" sort="Lin, Raymond T P" uniqKey="Lin R" first="Raymond T. P." last="Lin">Raymond T. P. Lin</name>
<name sortKey="Loh, Jin Phang" sort="Loh, Jin Phang" uniqKey="Loh J" first="Jin Phang" last="Loh">Jin Phang Loh</name>
<name sortKey="Tan, Boon Huan" sort="Tan, Boon Huan" uniqKey="Tan B" first="Boon Huan" last="Tan">Boon Huan Tan</name>
<name sortKey="Yap, Jonathan" sort="Yap, Jonathan" uniqKey="Yap J" first="Jonathan" last="Yap">Jonathan Yap</name>
</country>
<country name="Australie">
<noRegion>
<name sortKey="Barr, Ian G" sort="Barr, Ian G" uniqKey="Barr I" first="Ian G." last="Barr">Ian G. Barr</name>
</noRegion>
<name sortKey="Lee, Vernon J" sort="Lee, Vernon J" uniqKey="Lee V" first="Vernon J." last="Lee">Vernon J. Lee</name>
<name sortKey="Shaw, Robert" sort="Shaw, Robert" uniqKey="Shaw R" first="Robert" last="Shaw">Robert Shaw</name>
</country>
</tree>
</affiliations>
</record>

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