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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">2009 Pandemic Influenza A (H1N1) </title><author><name sortKey="Shieh, Wun Ju" sort="Shieh, Wun Ju" uniqKey="Shieh W" first="Wun-Ju" last="Shieh">Wun-Ju Shieh</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Blau, Dianna M" sort="Blau, Dianna M" uniqKey="Blau D" first="Dianna M." last="Blau">Dianna M. Blau</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Denison, Amy M" sort="Denison, Amy M" uniqKey="Denison A" first="Amy M." last="Denison">Amy M. Denison</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Deleon Carnes, Marlene" sort="Deleon Carnes, Marlene" uniqKey="Deleon Carnes M" first="Marlene" last="Deleon-Carnes">Marlene Deleon-Carnes</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Adem, Patricia" sort="Adem, Patricia" uniqKey="Adem P" first="Patricia" last="Adem">Patricia Adem</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Bhatnagar, Julu" sort="Bhatnagar, Julu" uniqKey="Bhatnagar J" first="Julu" last="Bhatnagar">Julu Bhatnagar</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Sumner, John" sort="Sumner, John" uniqKey="Sumner J" first="John" last="Sumner">John Sumner</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Liu, Lindy" sort="Liu, Lindy" uniqKey="Liu L" first="Lindy" last="Liu">Lindy Liu</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Patel, Mitesh" sort="Patel, Mitesh" uniqKey="Patel M" first="Mitesh" last="Patel">Mitesh Patel</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Batten, Brigid" sort="Batten, Brigid" uniqKey="Batten B" first="Brigid" last="Batten">Brigid Batten</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Greer, Patricia" sort="Greer, Patricia" uniqKey="Greer P" first="Patricia" last="Greer">Patricia Greer</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Jones, Tara" sort="Jones, Tara" uniqKey="Jones T" first="Tara" last="Jones">Tara Jones</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Smith, Chalanda" sort="Smith, Chalanda" uniqKey="Smith C" first="Chalanda" last="Smith">Chalanda Smith</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Bartlett, Jeanine" sort="Bartlett, Jeanine" uniqKey="Bartlett J" first="Jeanine" last="Bartlett">Jeanine Bartlett</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Montague, Jeltley" sort="Montague, Jeltley" uniqKey="Montague J" first="Jeltley" last="Montague">Jeltley Montague</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="White, Elizabeth" sort="White, Elizabeth" uniqKey="White E" first="Elizabeth" last="White">Elizabeth White</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Rollin, Dominique" sort="Rollin, Dominique" uniqKey="Rollin D" first="Dominique" last="Rollin">Dominique Rollin</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Gao, Rongbao" sort="Gao, Rongbao" uniqKey="Gao R" first="Rongbao" last="Gao">Rongbao Gao</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Seales, Cynthia" sort="Seales, Cynthia" uniqKey="Seales C" first="Cynthia" last="Seales">Cynthia Seales</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Jost, Heather" sort="Jost, Heather" uniqKey="Jost H" first="Heather" last="Jost">Heather Jost</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Metcalfe, Maureen" sort="Metcalfe, Maureen" uniqKey="Metcalfe M" first="Maureen" last="Metcalfe">Maureen Metcalfe</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Goldsmith, Cynthia S" sort="Goldsmith, Cynthia S" uniqKey="Goldsmith C" first="Cynthia S." last="Goldsmith">Cynthia S. Goldsmith</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Humphrey, Charles" sort="Humphrey, Charles" uniqKey="Humphrey C" first="Charles" last="Humphrey">Charles Humphrey</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Schmitz, Ann" sort="Schmitz, Ann" uniqKey="Schmitz A" first="Ann" last="Schmitz">Ann Schmitz</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Drew, Clifton" sort="Drew, Clifton" uniqKey="Drew C" first="Clifton" last="Drew">Clifton Drew</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Paddock, Christopher" sort="Paddock, Christopher" uniqKey="Paddock C" first="Christopher" last="Paddock">Christopher Paddock</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Uyeki, Timothy M" sort="Uyeki, Timothy M" uniqKey="Uyeki T" first="Timothy M." last="Uyeki">Timothy M. Uyeki</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Zaki, Sherif R" sort="Zaki, Sherif R" uniqKey="Zaki S" first="Sherif R." last="Zaki">Sherif R. Zaki</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20508031</idno><idno type="pmc">2893660</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893660</idno><idno type="RBID">PMC:2893660</idno><idno type="doi">10.2353/ajpath.2010.100115</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000153</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000153</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">2009 Pandemic Influenza A (H1N1) </title><author><name sortKey="Shieh, Wun Ju" sort="Shieh, Wun Ju" uniqKey="Shieh W" first="Wun-Ju" last="Shieh">Wun-Ju Shieh</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Blau, Dianna M" sort="Blau, Dianna M" uniqKey="Blau D" first="Dianna M." last="Blau">Dianna M. Blau</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Denison, Amy M" sort="Denison, Amy M" uniqKey="Denison A" first="Amy M." last="Denison">Amy M. Denison</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Deleon Carnes, Marlene" sort="Deleon Carnes, Marlene" uniqKey="Deleon Carnes M" first="Marlene" last="Deleon-Carnes">Marlene Deleon-Carnes</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Adem, Patricia" sort="Adem, Patricia" uniqKey="Adem P" first="Patricia" last="Adem">Patricia Adem</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Bhatnagar, Julu" sort="Bhatnagar, Julu" uniqKey="Bhatnagar J" first="Julu" last="Bhatnagar">Julu Bhatnagar</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Sumner, John" sort="Sumner, John" uniqKey="Sumner J" first="John" last="Sumner">John Sumner</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Liu, Lindy" sort="Liu, Lindy" uniqKey="Liu L" first="Lindy" last="Liu">Lindy Liu</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Patel, Mitesh" sort="Patel, Mitesh" uniqKey="Patel M" first="Mitesh" last="Patel">Mitesh Patel</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Batten, Brigid" sort="Batten, Brigid" uniqKey="Batten B" first="Brigid" last="Batten">Brigid Batten</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Greer, Patricia" sort="Greer, Patricia" uniqKey="Greer P" first="Patricia" last="Greer">Patricia Greer</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Jones, Tara" sort="Jones, Tara" uniqKey="Jones T" first="Tara" last="Jones">Tara Jones</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Smith, Chalanda" sort="Smith, Chalanda" uniqKey="Smith C" first="Chalanda" last="Smith">Chalanda Smith</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Bartlett, Jeanine" sort="Bartlett, Jeanine" uniqKey="Bartlett J" first="Jeanine" last="Bartlett">Jeanine Bartlett</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Montague, Jeltley" sort="Montague, Jeltley" uniqKey="Montague J" first="Jeltley" last="Montague">Jeltley Montague</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="White, Elizabeth" sort="White, Elizabeth" uniqKey="White E" first="Elizabeth" last="White">Elizabeth White</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Rollin, Dominique" sort="Rollin, Dominique" uniqKey="Rollin D" first="Dominique" last="Rollin">Dominique Rollin</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Gao, Rongbao" sort="Gao, Rongbao" uniqKey="Gao R" first="Rongbao" last="Gao">Rongbao Gao</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Seales, Cynthia" sort="Seales, Cynthia" uniqKey="Seales C" first="Cynthia" last="Seales">Cynthia Seales</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Jost, Heather" sort="Jost, Heather" uniqKey="Jost H" first="Heather" last="Jost">Heather Jost</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Metcalfe, Maureen" sort="Metcalfe, Maureen" uniqKey="Metcalfe M" first="Maureen" last="Metcalfe">Maureen Metcalfe</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Goldsmith, Cynthia S" sort="Goldsmith, Cynthia S" uniqKey="Goldsmith C" first="Cynthia S." last="Goldsmith">Cynthia S. Goldsmith</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Humphrey, Charles" sort="Humphrey, Charles" uniqKey="Humphrey C" first="Charles" last="Humphrey">Charles Humphrey</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Schmitz, Ann" sort="Schmitz, Ann" uniqKey="Schmitz A" first="Ann" last="Schmitz">Ann Schmitz</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Drew, Clifton" sort="Drew, Clifton" uniqKey="Drew C" first="Clifton" last="Drew">Clifton Drew</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Paddock, Christopher" sort="Paddock, Christopher" uniqKey="Paddock C" first="Christopher" last="Paddock">Christopher Paddock</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Uyeki, Timothy M" sort="Uyeki, Timothy M" uniqKey="Uyeki T" first="Timothy M." last="Uyeki">Timothy M. Uyeki</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author><author><name sortKey="Zaki, Sherif R" sort="Zaki, Sherif R" uniqKey="Zaki S" first="Sherif R." last="Zaki">Sherif R. Zaki</name><affiliation><nlm:aff id="N0x3989fc0N0x200a718"></nlm:aff></affiliation></author></analytic><series><title level="j">The American Journal of Pathology</title><idno type="ISSN">0002-9440</idno><idno type="eISSN">1525-2191</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>In the spring of 2009, a novel influenza A (H1N1) virus emerged in North America and spread worldwide to cause the first influenza pandemic since 1968. During the first 4 months, over 500 deaths in the United States had been associated with confirmed 2009 pandemic influenza A (H1N1) [2009 H1N1] virus infection. Pathological evaluation of respiratory specimens from initial influenza-associated deaths suggested marked differences in viral tropism and tissue damage compared with seasonal influenza and prompted further investigation. Available autopsy tissue samples were obtained from 100 US deaths with laboratory-confirmed 2009 H1N1 virus infection. Demographic and clinical data of these case-patients were collected, and the tissues were evaluated by multiple laboratory methods, including histopathological evaluation, special stains, molecular and immunohistochemical assays, viral culture, and electron microscopy. The most prominent histopathological feature observed was diffuse alveolar damage in the lung in all case-patients examined. Alveolar lining cells, including type I and type II pneumocytes, were the primary infected cells. Bacterial co-infections were identified in >25% of the case-patients. Viral pneumonia and immunolocalization of viral antigen in association with diffuse alveolar damage are prominent features of infection with 2009 pandemic influenza A (H1N1) virus. Underlying medical conditions and bacterial co-infections contributed to the fatal outcome of this infection. More studies are needed to understand the multifactorial pathogenesis of this infection.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Pathol</journal-id><journal-title>The American Journal of Pathology</journal-title><issn pub-type="ppub">0002-9440</issn><issn pub-type="epub">1525-2191</issn><publisher><publisher-name>American Society for Investigative Pathology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20508031</article-id><article-id pub-id-type="pmc">2893660</article-id><article-id pub-id-type="doi">10.2353/ajpath.2010.100115</article-id><article-categories><subj-group subj-group-type="heading"><subject>Regular Articles</subject><subj-group><subject>Immunopathology and Infectious Diseases</subject></subj-group></subj-group></article-categories><title-group><article-title>2009 Pandemic Influenza A (H1N1) </article-title><subtitle>Pathology and Pathogenesis of 100 Fatal Cases in the United States</subtitle></title-group><contrib-group><contrib contrib-type="author"><name><surname>Shieh</surname><given-names>Wun-Ju</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Blau</surname><given-names>Dianna M.</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Denison</surname><given-names>Amy M.</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>DeLeon-Carnes</surname><given-names>Marlene</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Adem</surname><given-names>Patricia</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Bhatnagar</surname><given-names>Julu</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Sumner</surname><given-names>John</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Liu</surname><given-names>Lindy</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Patel</surname><given-names>Mitesh</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Batten</surname><given-names>Brigid</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Greer</surname><given-names>Patricia</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Jones</surname><given-names>Tara</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Smith</surname><given-names>Chalanda</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Bartlett</surname><given-names>Jeanine</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Montague</surname><given-names>Jeltley</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>White</surname><given-names>Elizabeth</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Rollin</surname><given-names>Dominique</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Gao</surname><given-names>Rongbao</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">†</xref></contrib><contrib contrib-type="author"><name><surname>Seales</surname><given-names>Cynthia</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Jost</surname><given-names>Heather</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Metcalfe</surname><given-names>Maureen</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Goldsmith</surname><given-names>Cynthia S.</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Humphrey</surname><given-names>Charles</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Schmitz</surname><given-names>Ann</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Drew</surname><given-names>Clifton</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Paddock</surname><given-names>Christopher</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><contrib contrib-type="author"><name><surname>Uyeki</surname><given-names>Timothy M.</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">‡</xref></contrib><contrib contrib-type="author"><name><surname>Zaki</surname><given-names>Sherif R.</given-names></name><xref ref-type="aff" rid="N0x3989fc0N0x200a718">*</xref></contrib><aff id="N0x3989fc0N0x200a718">From the Infectious Diseases Pathology Branch,<label>*</label> Division of Viral and Rickettsial Diseases, and the Epidemiology and Prevention Branch,<label>‡</label> Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia; and the Influenza Department,<label>†</label> National Institute for Viral Disease Control and Prevention, Centers for Disease Control and Prevention, Beijing, China</aff></contrib-group><pub-date pub-type="ppub"><month>7</month><year>2010</year></pub-date><volume>177</volume><issue>1</issue><fpage>166</fpage><lpage>175</lpage><history><date date-type="accepted"><day>3</day><month>3</month><year>2010</year></date></history><permissions><copyright-statement>Copyright © American Society for Investigative Pathology</copyright-statement><copyright-year>2010</copyright-year></permissions><self-uri xlink:title="pdf" xlink:href="zjh00710000166.pdf"></self-uri><abstract><p>In the spring of 2009, a novel influenza A (H1N1) virus emerged in North America and spread worldwide to cause the first influenza pandemic since 1968. During the first 4 months, over 500 deaths in the United States had been associated with confirmed 2009 pandemic influenza A (H1N1) [2009 H1N1] virus infection. Pathological evaluation of respiratory specimens from initial influenza-associated deaths suggested marked differences in viral tropism and tissue damage compared with seasonal influenza and prompted further investigation. Available autopsy tissue samples were obtained from 100 US deaths with laboratory-confirmed 2009 H1N1 virus infection. Demographic and clinical data of these case-patients were collected, and the tissues were evaluated by multiple laboratory methods, including histopathological evaluation, special stains, molecular and immunohistochemical assays, viral culture, and electron microscopy. The most prominent histopathological feature observed was diffuse alveolar damage in the lung in all case-patients examined. Alveolar lining cells, including type I and type II pneumocytes, were the primary infected cells. Bacterial co-infections were identified in >25% of the case-patients. Viral pneumonia and immunolocalization of viral antigen in association with diffuse alveolar damage are prominent features of infection with 2009 pandemic influenza A (H1N1) virus. Underlying medical conditions and bacterial co-infections contributed to the fatal outcome of this infection. More studies are needed to understand the multifactorial pathogenesis of this infection.</p></abstract></article-meta></front><floats-wrap><fig position="float" id="F1-8671"><label>Figure 1</label><caption><p>Histopathological findings in airway and lung; H&E staining. Original magnification: ×50 (<bold>A, B, E,</bold> and <bold>G</bold>); ×25 (<bold>C</bold> and <bold>D</bold>); ×100 (<bold>F</bold>). <bold>A:</bold> Inflammation in the airway is usually mild and predominantly composed of mononuclear cells. <bold>B:</bold> The lungs show various phases of diffuse alveolar damage, including fibrinous inflammation, intra-alveolar hemorrhage (<bold>C</bold>), intra-alveolar edema and hyaline membrane formation (<bold>D</bold> and <bold>E</bold>), type II pneumocytes hyperplasia (<bold>F</bold>), and organizing fibrosis (<bold>G</bold>).</p></caption><graphic xlink:href="zjh0071086710001"></graphic></fig><fig position="float" id="F2-8671"><label>Figure 2</label><caption><p>Immunolocalization of 2009 H1N1 influenza viral antigens and ultrastructural features: immunoalkaline phosphate staining, naphthol fast red substrate with light hematoxylin counterstain (<bold>A</bold>–<bold>G</bold>); double immunostaining with immunoperoxidase and immunoalkaline phosphatase, naphthol fast red substrate with light hematoxylin counterstain (<bold>H</bold>–<bold>J</bold>); and thin-sectioned electron microscopy (<bold>K</bold> and <bold>L</bold>). Original magnification: ×50 (<bold>A, D,</bold> and <bold>F</bold>); ×25 (<bold>B</bold>); ×12.5 (<bold>C</bold>); ×100 (<bold>E</bold> and <bold>G</bold>); ×158 (<bold>H</bold>–<bold>J</bold>). Scale bars = 500 nm (<bold>K</bold>); 100 nm (<bold>L</bold>). <bold>A:</bold> Viral antigens are detected in the nuclei of infected airway epithelial cells. <bold>B:</bold> Viral antigens are seen in submucosal glands. <bold>C</bold>–<bold>E:</bold> Viral antigens are predominantly present in the nuclei of alveolar lining cells, including type I and type II pneumocytes; many of them have detached and are in the alveolar space. <bold>F:</bold> Immunostaining of viral antigens is seen in hyaline membranes lining alveoli. <bold>G:</bold> Viral antigens are located in endothelial cells. <bold>H</bold> and <bold>I:</bold> Double staining reveals influenza viral antigens (brown) are predominantly in pneumocytes (red, co-labeled with cytokeratin [<bold>H</bold>]), specifically in type II pneumocytes (red, co-labeled with surfactant [<bold>I</bold>]). Viral antigen (brown) can also be seen in occasional macrophages (red, co-labeled with CD68 [<bold>J</bold>]). <bold>K:</bold> Electron micrograph showing infected cell (<bold>asterisk</bold>) with extracellular virus particles, associated with dense material. <bold>L:</bold> Virions consist of internal nucleocapsids surrounded by an envelope with surface projections.</p></caption><graphic xlink:href="zjh0071086710002"></graphic></fig><fig position="float" id="F3-8671"><label>Figure 3</label><caption><p>Bacterial co-infections detected with histopathology, special stains, and IHC. <bold>A, D,</bold> and <bold>G:</bold> H&E staining; <bold>B, E,</bold> and <bold>H:</bold> immunoalkaline phosphate staining, naphthol fast red substrate with light hematoxylin counterstain; <bold>C</bold> and <bold>F:</bold> Lilly-Twort tissue Gram staining. Original magnification: ×25 (<bold>A, D,</bold> and <bold>G</bold>); ×100 (<bold>B</bold> and <bold>E</bold>); ×158 (<bold>C</bold> and <bold>F</bold>); ×50 (<bold>H</bold>). <bold>A:</bold> Abundant neutrophilic infiltrate in the alveoli indicative of an acute pneumonic process. <bold>B:</bold> Extracellular and intracellular immunostaining of <italic>S. pneumoniae</italic> antigens. <bold>C:</bold> Gram-positive cocci in the serial section as <bold>B.</bold> <bold>D:</bold> Abundant neutrophilic infiltrate in the alveoli of another patient with pneumonia. <bold>E:</bold> Extracellular and intracellular immunostaining of Group A <italic>Streptococcus</italic> antigens. <bold>F:</bold> Gram-positive cocci in the serial section as <bold>E.</bold> <bold>G:</bold> Prominent necrosis and neutrophilic infiltrate indicative of a necrotizing pneumonia. <bold>H:</bold> Abundant immunostaining of <italic>S. aureus</italic>.</p></caption><graphic xlink:href="zjh0071086710003"></graphic></fig><table-wrap position="float" id="T1-8671"><label>Table 1</label><caption><p>Characteristics of Confirmed 2009 H1N1 Case-Patients with Autopsy Samples Evaluated for Pathologic Features</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="1" align="center" valign="bottom">Characteristic</th><th colspan="1" rowspan="1" align="center" valign="bottom">No. (%)</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">Male patients</td><td colspan="1" rowspan="1" align="center" valign="top">51 (51)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Age group</td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> 0–9</td><td colspan="1" rowspan="1" align="center" valign="top">4 (4)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> 10–19</td><td colspan="1" rowspan="1" align="center" valign="top">13 (13)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> 20–29</td><td colspan="1" rowspan="1" align="center" valign="top">17 (17)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> 30–39</td><td colspan="1" rowspan="1" align="center" valign="top">24 (24)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> 40–49</td><td colspan="1" rowspan="1" align="center" valign="top">22 (22)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> 50–59</td><td colspan="1" rowspan="1" align="center" valign="top">17 (17)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> ≥60</td><td colspan="1" rowspan="1" align="center" valign="top">3 (3)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Medical history (<italic>n</italic> = 93)</td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> At least one pre-existing condition</td><td colspan="1" rowspan="1" align="center" valign="top">79 (85)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Obesity<xref rid="TFN1-1-8671" ref-type="other">*</xref></td><td colspan="1" rowspan="1" align="center" valign="top">43 (46)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Extreme obesity<xref rid="TFN1-1-8671" ref-type="other">*</xref></td><td colspan="1" rowspan="1" align="center" valign="top">16 (17)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Cardiovascular disease</td><td colspan="1" rowspan="1" align="center" valign="top">23 (25)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Asthma</td><td colspan="1" rowspan="1" align="center" valign="top">20 (22)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Diabetes</td><td colspan="1" rowspan="1" align="center" valign="top">12 (13)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Pregnancy</td><td colspan="1" rowspan="1" align="center" valign="top">6 (6)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> HIV infection</td><td colspan="1" rowspan="1" align="center" valign="top">4 (4)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Duration of illness, median days (range)</td><td colspan="1" rowspan="1" align="center" valign="top">8 (1–44 days)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Clinical symptoms (<italic>n</italic> = 72)</td><td colspan="1" rowspan="1" align="center" valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Fever</td><td colspan="1" rowspan="1" align="center" valign="top">59 (82)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Cough</td><td colspan="1" rowspan="1" align="center" valign="top">48 (67)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Shortness of breath</td><td colspan="1" rowspan="1" align="center" valign="top">42 (58)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Headache</td><td colspan="1" rowspan="1" align="center" valign="top">11 (15)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Fatigue/weakness</td><td colspan="1" rowspan="1" align="center" valign="top">10 (14)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Sore throat</td><td colspan="1" rowspan="1" align="center" valign="top">11 (15)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Vomiting</td><td colspan="1" rowspan="1" align="center" valign="top">16 (22)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Diarrhea</td><td colspan="1" rowspan="1" align="center" valign="top">8 (11)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Hospitalized (<italic>n</italic> = 87)</td><td colspan="1" rowspan="1" align="center" valign="top">58 (67)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Invasive mechanical ventilation (<italic>n</italic> = 57)</td><td colspan="1" rowspan="1" align="center" valign="top">42 (74)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Antiviral treatment (<italic>n</italic> = 67)</td><td colspan="1" rowspan="1" align="center" valign="top">44 (66)</td></tr></tbody></table><table-wrap-foot><fn id="TFN1-1-8671"><label>*</label><p>Obesity is defined as body mass index ≥30 and extreme obesity as body mass index ≥40. </p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="T2-8671"><label>Table 2</label><caption><p>Histopathological Features in Respiratory Tract Specimens of 2009 H1N1 Fatal Case-Patients (<italic>N</italic> = 100)</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="1" align="center" valign="bottom">Histopathologic feature</th><th colspan="1" rowspan="1" align="center" valign="bottom">No. (%) of case-patients with feature</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">Trachea and bronchi (<italic>n</italic> = 85)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Inflammation and edema</td><td colspan="1" rowspan="1" align="char" char="." valign="top">56 (66)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Necrosis</td><td colspan="1" rowspan="1" align="char" char="." valign="top">22 (26)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Hemorrhage</td><td colspan="1" rowspan="1" align="char" char="." valign="top">15 (18)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Lung<xref rid="TFN2-1-8671" ref-type="other">*</xref> (<italic>n</italic> = 100)</td><td colspan="1" rowspan="1" align="char" char="." valign="top"></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Edema</td><td colspan="1" rowspan="1" align="char" char="." valign="top">63 (63)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Hyaline membranes</td><td colspan="1" rowspan="1" align="char" char="." valign="top">59 (59)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Fibrin</td><td colspan="1" rowspan="1" align="char" char="." valign="top">58 (58)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Hemorrhage</td><td colspan="1" rowspan="1" align="char" char="." valign="top">58 (58)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Inflammation</td><td colspan="1" rowspan="1" align="char" char="." valign="top">48 (48)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Type II pneumocyte hyperplasia</td><td colspan="1" rowspan="1" align="char" char="." valign="top">46 (46)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Neutrophilic bronchopneumonia</td><td colspan="1" rowspan="1" align="char" char="." valign="top">29 (29)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Organizing fibrosis</td><td colspan="1" rowspan="1" align="char" char="." valign="top">28 (28)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top"> Squamous metaplasia</td><td colspan="1" rowspan="1" align="char" char="." valign="top">12 (12)</td></tr></tbody></table><table-wrap-foot><fn id="TFN2-1-8671"><label>*</label><p>Edema, fibrin, and hemorrhage were seen in alveolar spaces; inflammation and organizing fibrosis primarily involved interstitium but were also focally seen within alveolar spaces. </p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="T3-8671"><label>Table 3</label><caption><p>Diagnostic Results for Respiratory Tissues Evaluated from 100 Fatal Cases of 2009 H1N1</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="2" rowspan="1" align="center" valign="bottom">Influenza A
<hr></hr></th><th colspan="2" rowspan="1" align="center" valign="bottom">Bacterial co-infections
<hr></hr></th><th colspan="1" rowspan="2" align="center" valign="bottom">Total no. of case-patients</th></tr><tr><th colspan="1" rowspan="1" align="center" valign="bottom">RT-PCR<xref rid="TFN3-1-8671" ref-type="other">*</xref></th><th colspan="1" rowspan="1" align="center" valign="bottom">IHC</th><th colspan="1" rowspan="1" align="center" valign="bottom">PCR</th><th colspan="1" rowspan="1" align="center" valign="bottom">IHC</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">+</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="char" char="." valign="top">33</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">+</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="char" char="." valign="top">29</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">+</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="char" char="." valign="top">14</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">+</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="char" char="." valign="top">10</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">+</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">A/unsub</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="char" char="." valign="top">2</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">A/unsub</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="char" char="." valign="top">8</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">−</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1</td></tr><tr><td colspan="4" rowspan="1" align="left" valign="top">Total</td><td colspan="1" rowspan="1" align="char" char="." valign="top">100</td></tr></tbody></table><table-wrap-foot><fn id="TFN3-1-8671"><label>*</label><p>Of the 100 case-patients included in this study, 90 were positive for influenza A in respiratory tissue evaluated, either for 2009 H1N1 (+) or nonsubtypeable (A/unsub). The 10 case-patients that were PCR negative (−) were confirmed by outside laboratory results from clinical samples. </p></fn></table-wrap-foot></table-wrap></floats-wrap></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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