Early Indicators of Disease in Ferrets Infected with a High Dose of Avian Influenza H5N1
Identifieur interne : 000733 ( Pmc/Checkpoint ); précédent : 000732; suivant : 000734Early Indicators of Disease in Ferrets Infected with a High Dose of Avian Influenza H5N1
Auteurs : James P. Long [États-Unis] ; Eric M. Vela [États-Unis] ; Gregory V. Stark [États-Unis] ; Kelly J. Jones [États-Unis] ; Stephen T. Miller [États-Unis] ; John E. Bigger [États-Unis]Source :
- Scientific Reports [ 2045-2322 ] ; 2012.
Abstract
Avian influenza viruses are widespread in birds, contagious in humans, and are categorized as low pathogenicity avian influenza or highly pathogenic avian influenza. Ferrets are susceptible to infection with avian and human influenza A and B viruses and have been widely used as a model to study pathogenicity and vaccine efficacy. In this report, the natural history of the H5N1 influenza virus A/Vietnam/1203/04 influenza infection in ferrets was examined to determine clinical and laboratory parameters that may indicate (1) the onset of disease and (2) survival. In all, twenty of 24 animals infected with 7 × 105 TCID50 of A/Vietnam/1203/04 succumbed. A statistical analysis identified a combination of parameters including weight loss, nasal wash TCID50, eosinophils, and liver enzymes such as alanine amino transferase that might possibly serve as indicators of both disease onset and challenge survival.
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DOI: 10.1038/srep00972
PubMed: 23240077
PubMed Central: 3521156
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Early Indicators of Disease in Ferrets Infected with a High Dose of Avian Influenza H5N1</title><author><name sortKey="Long, James P" sort="Long, James P" uniqKey="Long J" first="James P." last="Long">James P. Long</name><affiliation wicri:level="2"><nlm:aff id="a1"><institution>Battelle 505 King Avenue Columbus</institution>, Ohio 43201</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea></wicri:cityArea></affiliation></author><author><name sortKey="Vela, Eric M" sort="Vela, Eric M" uniqKey="Vela E" first="Eric M." last="Vela">Eric M. Vela</name><affiliation wicri:level="2"><nlm:aff id="a1"><institution>Battelle 505 King Avenue Columbus</institution>, Ohio 43201</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea></wicri:cityArea></affiliation></author><author><name sortKey="Stark, Gregory V" sort="Stark, Gregory V" uniqKey="Stark G" first="Gregory V." last="Stark">Gregory V. Stark</name><affiliation wicri:level="2"><nlm:aff id="a1"><institution>Battelle 505 King Avenue Columbus</institution>, Ohio 43201</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea></wicri:cityArea></affiliation></author><author><name sortKey="Jones, Kelly J" sort="Jones, Kelly J" uniqKey="Jones K" first="Kelly J." last="Jones">Kelly J. 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Long</name><affiliation wicri:level="2"><nlm:aff id="a1"><institution>Battelle 505 King Avenue Columbus</institution>, Ohio 43201</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea></wicri:cityArea></affiliation></author><author><name sortKey="Vela, Eric M" sort="Vela, Eric M" uniqKey="Vela E" first="Eric M." last="Vela">Eric M. Vela</name><affiliation wicri:level="2"><nlm:aff id="a1"><institution>Battelle 505 King Avenue Columbus</institution>, Ohio 43201</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea></wicri:cityArea></affiliation></author><author><name sortKey="Stark, Gregory V" sort="Stark, Gregory V" uniqKey="Stark G" first="Gregory V." last="Stark">Gregory V. Stark</name><affiliation wicri:level="2"><nlm:aff id="a1"><institution>Battelle 505 King Avenue Columbus</institution>, Ohio 43201</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea></wicri:cityArea></affiliation></author><author><name sortKey="Jones, Kelly J" sort="Jones, Kelly J" uniqKey="Jones K" first="Kelly J." last="Jones">Kelly J. Jones</name><affiliation wicri:level="2"><nlm:aff id="a1"><institution>Battelle 505 King Avenue Columbus</institution>, Ohio 43201</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea></wicri:cityArea></affiliation></author><author><name sortKey="Miller, Stephen T" sort="Miller, Stephen T" uniqKey="Miller S" first="Stephen T." last="Miller">Stephen T. Miller</name><affiliation wicri:level="2"><nlm:aff id="a1"><institution>Battelle 505 King Avenue Columbus</institution>, Ohio 43201</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea></wicri:cityArea></affiliation></author><author><name sortKey="Bigger, John E" sort="Bigger, John E" uniqKey="Bigger J" first="John E." last="Bigger">John E. Bigger</name><affiliation wicri:level="2"><nlm:aff id="a1"><institution>Battelle 505 King Avenue Columbus</institution>, Ohio 43201</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea></wicri:cityArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Avian influenza viruses are widespread in birds, contagious in humans, and are categorized as low pathogenicity avian influenza or highly pathogenic avian influenza. Ferrets are susceptible to infection with avian and human influenza A and B viruses and have been widely used as a model to study pathogenicity and vaccine efficacy. In this report, the natural history of the H5N1 influenza virus A/Vietnam/1203/04 influenza infection in ferrets was examined to determine clinical and laboratory parameters that may indicate (1) the onset of disease and (2) survival. In all, twenty of 24 animals infected with 7 × 10<sup>5</sup> TCID<sub>50</sub> of A/Vietnam/1203/04 succumbed. A statistical analysis identified a combination of parameters including weight loss, nasal wash TCID<sub>50</sub>, eosinophils, and liver enzymes such as alanine amino transferase that might possibly serve as indicators of both disease onset and challenge survival.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Taubenberger, J K" uniqKey="Taubenberger J">J. K. Taubenberger</name></author><author><name sortKey="Morens, D M" uniqKey="Morens D">D. M. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Rep</journal-id><journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id><journal-title-group><journal-title>Scientific Reports</journal-title></journal-title-group><issn pub-type="epub">2045-2322</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23240077</article-id><article-id pub-id-type="pmc">3521156</article-id><article-id pub-id-type="pii">srep00972</article-id><article-id pub-id-type="doi">10.1038/srep00972</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Early Indicators of Disease in Ferrets Infected with a High Dose of Avian Influenza H5N1</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Long</surname><given-names>James P.</given-names></name><xref ref-type="corresp" rid="c1">a</xref><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Vela</surname><given-names>Eric M.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Stark</surname><given-names>Gregory V.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Jones</surname><given-names>Kelly J.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Miller</surname><given-names>Stephen T.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bigger</surname><given-names>John E.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><aff id="a1"><label>1</label><institution>Battelle 505 King Avenue Columbus</institution>, Ohio 43201</aff></contrib-group><author-notes><corresp id="c1"><label>a</label><email>longj@battelle.org</email></corresp></author-notes><pub-date pub-type="epub"><day>13</day><month>12</month><year>2012</year></pub-date><pub-date pub-type="collection"><year>2012</year></pub-date><volume>2</volume><elocation-id>972</elocation-id><history><date date-type="received"><day>31</day><month>05</month><year>2012</year></date><date date-type="accepted"><day>21</day><month>09</month><year>2012</year></date></history><permissions><copyright-statement>Copyright © 2012, Macmillan Publishers Limited. All rights reserved</copyright-statement><copyright-year>2012</copyright-year><copyright-holder>Macmillan Publishers Limited. All rights reserved</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc-nd/3.0/">http://creativecommons.org/licenses/by-nc-nd/3.0/</ext-link></license-p></license></permissions><abstract><p>Avian influenza viruses are widespread in birds, contagious in humans, and are categorized as low pathogenicity avian influenza or highly pathogenic avian influenza. Ferrets are susceptible to infection with avian and human influenza A and B viruses and have been widely used as a model to study pathogenicity and vaccine efficacy. In this report, the natural history of the H5N1 influenza virus A/Vietnam/1203/04 influenza infection in ferrets was examined to determine clinical and laboratory parameters that may indicate (1) the onset of disease and (2) survival. In all, twenty of 24 animals infected with 7 × 10<sup>5</sup> TCID<sub>50</sub> of A/Vietnam/1203/04 succumbed. A statistical analysis identified a combination of parameters including weight loss, nasal wash TCID<sub>50</sub>, eosinophils, and liver enzymes such as alanine amino transferase that might possibly serve as indicators of both disease onset and challenge survival.</p></abstract></article-meta></front><floats-group><fig id="f1"><label>Figure 1</label><caption><title>Clinical signs of disease in ferrets following infection with A/Vietnam/1203/04 virus.</title><p>Animals were monitored twice daily for clinical observations and at eight-hour intervals until 96 hours, using the following scoring system; 0 = alert and playful, 1 = alert but playful only when stimulated, 2 = alert but not playful when stimulated, and 3 = neither alert nor playful when stimulated. (A) Percentage of animals exhibiting clinical observations, (B) time of onset for clinical observations presenting during the first 96 hours following infection, and (C) activity score changes for influenza-infected animals.</p></caption><graphic xlink:href="srep00972-f1"></graphic></fig><fig id="f2"><label>Figure 2</label><caption><title>Survival of ferrets following challenge with 7 × 10<sup>5</sup> TCID<sub>50</sub> of A/Vietnam/1203/04 virus.</title><p>Kaplan-Meier Curves representing the survival distribution for ferrets over the 18-day period following challenge.</p></caption><graphic xlink:href="srep00972-f2"></graphic></fig><fig id="f3"><label>Figure 3</label><caption><title>Change in body temperature and body weight following infection with A/Vietnam/1203/04 virus.</title><p>Temperatures were taken twice daily prior to challenge and then at approximately eight-hour intervals from 8–96 hours by use of subcutaneous implantable temperature transponders. After 96 hours, temperatures were recorded twice daily. Body weights were taken every other day, beginning on day 0 until the end of the study (day 18) or death of the animal. Weights taken immediately prior to challenge on day 0 served as baseline. (A) Mean body temperature, (B) Mean temperature comparison between survivors and animals that succumbed to disease, (C) mean body weight, (D) mean change from baseline weight for influenza-infected animals by survival status.</p></caption><graphic xlink:href="srep00972-f3"></graphic></fig><fig id="f4"><label>Figure 4</label><caption><title>Hematology changes associated with A/Vietnam/1203/04 virus infection: (A) RDW, (B) platelets, (C) WBC count, (D) eosinophils, (E) monoocytes, (F) lymphocytes, (G) LUC, (H) neutrophils and (I) N/L ratio.</title></caption><graphic xlink:href="srep00972-f4"></graphic></fig><fig id="f5"><label>Figure 5</label><caption><title>Clinical chemistry changes associated with A/Vietnam/1203/04 virus infection: (A) AT, (B) ALT, (C) glucose.</title></caption><graphic xlink:href="srep00972-f5"></graphic></fig><fig id="f6"><label>Figure 6</label><caption><title>Replication of A/Vietnam/1203/04 in the upper respiratory tract of ferrets.</title><p>Following challenge, nasal washes were performed at 8, 16, 24, 48, 72 and 96 hours for determination of virus shedding. Results represent viral titers for nasal wash specimens by (A) TCID<sub>50</sub> analysis, and (B) qPCR.</p></caption><graphic xlink:href="srep00972-f6"></graphic></fig><table-wrap position="float" id="t1"><label>Table 1</label><caption><title>Experimental Design</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50">Group</th><th align="center" valign="top" charoff="50">Number of Animals</th><th align="center" valign="top" charoff="50">Sampling Time-points (Hours)<xref ref-type="fn" rid="t1-fn1">1</xref></th><th align="center" valign="top" charoff="50">Clinical Observations (Hours)<xref ref-type="fn" rid="t1-fn1">1</xref><sup>,</sup><xref ref-type="fn" rid="t1-fn2">2</xref></th><th align="center" valign="top" charoff="50">Temperature Recorded (Hours)<xref ref-type="fn" rid="t1-fn1">1</xref><sup>,</sup><xref ref-type="fn" rid="t1-fn3">3</xref></th><th align="center" valign="top" charoff="50">qPCR<xref ref-type="fn" rid="t1-fn4">4</xref></th><th align="center" valign="top" charoff="50">Hematology (Hours)<xref ref-type="fn" rid="t1-fn1">1</xref><sup>,</sup><xref ref-type="fn" rid="t1-fn5">5</xref></th><th align="center" valign="top" charoff="50">Clinical Chemistry (Hours)<xref ref-type="fn" rid="t1-fn1">1</xref><sup>,</sup><xref ref-type="fn" rid="t1-fn6">6</xref></th><th align="center" valign="top" charoff="50">Nasal Wash (Hours)<xref ref-type="fn" rid="t1-fn1">1</xref><sup>,</sup><xref ref-type="fn" rid="t1-fn7">7</xref></th></tr></thead><tbody valign="top"><tr><td align="center" valign="top" charoff="50">A Infected</td><td align="center" valign="top" charoff="50">8</td><td align="center" valign="top" charoff="50">8, 32, 56, 80 Moribund, terminal</td><td align="center" valign="top" charoff="50">8, 32, 56, 80</td><td align="center" valign="top" charoff="50">8, 32, 56, 80</td><td align="center" valign="top" charoff="50">8, 32, 56, 80 Moribund, terminal</td><td align="center" valign="top" charoff="50">8, 32, 56, 80 Moribund, terminal</td><td align="center" valign="top" charoff="50">8, 32, 56, 80 Moribund, terminal</td><td align="center" valign="top" charoff="50">8, 48</td></tr><tr><td align="center" valign="top" charoff="50">B Sham- infected</td><td align="center" valign="top" charoff="50">3</td><td align="center" valign="top" charoff="50">8, 32, 56, 80 Moribund, terminal</td><td align="center" valign="top" charoff="50">8, 32, 56, 80</td><td align="center" valign="top" charoff="50">8, 32, 56, 80</td><td align="center" valign="top" charoff="50">8, 32, 56, 80 Moribund, terminal</td><td align="center" valign="top" charoff="50">8, 32, 56, 80 Moribund, terminal</td><td align="center" valign="top" charoff="50">8, 32, 56, 80 Moribund, terminal</td><td align="center" valign="top" charoff="50">8, 48</td></tr><tr><td align="center" valign="top" charoff="50">C Infected</td><td align="center" valign="top" charoff="50">8</td><td align="center" valign="top" charoff="50">16, 40, 64, 88 Moribund, terminal</td><td align="center" valign="top" charoff="50">16, 40, 64, 88</td><td align="center" valign="top" charoff="50">16, 40, 64, 88</td><td align="center" valign="top" charoff="50">16, 40, 64, 88 Moribund, terminal</td><td align="center" valign="top" charoff="50">16, 40, 64, 88 Moribund, terminal</td><td align="center" valign="top" charoff="50">16, 40, 64, 88 Moribund, terminal</td><td align="center" valign="top" charoff="50">16, 72</td></tr><tr><td align="center" valign="top" charoff="50">D Sham- infected</td><td align="center" valign="top" charoff="50">3</td><td align="center" valign="top" charoff="50">16, 40, 64, 88 Moribund, terminal</td><td align="center" valign="top" charoff="50">16, 40, 64, 88</td><td align="center" valign="top" charoff="50">16, 40, 64, 88</td><td align="center" valign="top" charoff="50">16, 40, 64, 88 Moribund, terminal</td><td align="center" valign="top" charoff="50">16, 40, 64, 88 Moribund, terminal</td><td align="center" valign="top" charoff="50">16, 40, 64, 88 Moribund, terminal</td><td align="center" valign="top" charoff="50">16, 72</td></tr><tr><td align="center" valign="top" charoff="50">E Infected</td><td align="center" valign="top" charoff="50">8</td><td align="center" valign="top" charoff="50">24, 48, 72, 96 Moribund, terminal</td><td align="center" valign="top" charoff="50">24, 48, 72, 96</td><td align="center" valign="top" charoff="50">24, 48, 72, 96</td><td align="center" valign="top" charoff="50">24, 48, 72, 96 Moribund, terminal</td><td align="center" valign="top" charoff="50">24, 48, 72, 96 Moribund, terminal</td><td align="center" valign="top" charoff="50">24, 48, 72, 96 Moribund, terminal</td><td align="center" valign="top" charoff="50">24, 96</td></tr><tr><td align="center" valign="top" charoff="50">F Sham- infected</td><td align="center" valign="top" charoff="50">3</td><td align="center" valign="top" charoff="50">24, 48, 72, 96 Moribund, terminal</td><td align="center" valign="top" charoff="50">24, 48, 72, 96</td><td align="center" valign="top" charoff="50">24, 48, 72, 96</td><td align="center" valign="top" charoff="50">24, 48, 72, 96 Moribund, terminal</td><td align="center" valign="top" charoff="50">24, 48, 72, 96 Moribund, terminal</td><td align="center" valign="top" charoff="50">24, 48, 72, 96 Moribund, terminal</td><td align="center" valign="top" charoff="50">24, 96</td></tr></tbody></table><table-wrap-foot><fn id="t1-fn1"><p><sup>1</sup>Sampling time-points represent hours post-median challenge time ± 1 hour for each animal.</p></fn><fn id="t1-fn2"><p><sup>2</sup>Clinical observations were taken twice daily after 96 hours post-challenge for all groups.</p></fn><fn id="t1-fn3"><p><sup>3</sup>Temperatures were recorded twice daily after 96 hours post-challenge for all groups.</p></fn><fn id="t1-fn4"><p><sup>4</sup>Blood collected in EDTA tubes was used for real-time qPCR.</p></fn><fn id="t1-fn5"><p><sup>5</sup>Blood collected in EDTA tubes was used for hematology.</p></fn><fn id="t1-fn6"><p><sup>6</sup>Blood collected in SST tubes for serum was used for clinical chemistry.</p></fn><fn id="t1-fn7"><p><sup>7</sup>Nasal wash samples were tested using qPCR and TCID<sub>50</sub> assays.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t2"><label>Table 2</label><caption><title>Summary statistics for time to abnormal (days) for selected parameters by challenge group and survival status</title></caption><table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col><col align="center"></col><col align="center"></col><col align="center"></col></colgroup><thead valign="bottom"><tr><th align="left" valign="top" charoff="50">Parameter</th><th align="center" valign="top" charoff="50">Challenge</th><th align="center" valign="top" charoff="50">Mean time to abnormal in days (95% Confidence Interval)</th><th align="center" valign="top" charoff="50">Mean time to abnormal in days (Min, Max)</th></tr></thead><tbody valign="top"><tr><td align="center" valign="top" charoff="50">Weight</td><td align="center" valign="top" charoff="50">Flu Survivors</td><td align="center" valign="top" charoff="50">9.62 (7.22, 12.83)</td><td align="center" valign="top" charoff="50">(9.0, 11.0)</td></tr><tr><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">Flu Non-Survivors</td><td align="center" valign="top" charoff="50">6.25 (5.49, 7.13)</td><td align="center" valign="top" charoff="50">(3.0, 9.0)</td></tr><tr><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">Flu-Infected</td><td align="center" valign="top" charoff="50">6.65 (5.83, 7.59)</td><td align="center" valign="top" charoff="50">(3.0, 11.0)</td></tr><tr><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">Sham-Infected</td><td align="center" valign="top" charoff="50">NA</td><td align="center" valign="top" charoff="50">NA</td></tr><tr><td align="center" valign="top" charoff="50">Nasal Wash TCID<sub>50</sub></td><td align="center" valign="top" charoff="50">Flu Survivors</td><td align="center" valign="top" charoff="50">2.91 (1.85, 4.58)</td><td align="center" valign="top" charoff="50">(2.0, 4.0)</td></tr><tr><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">Flu Non-Survivors</td><td align="center" valign="top" charoff="50">1.56 (1.22, 2.00)</td><td align="center" valign="top" charoff="50">(0.7, 3.0)</td></tr><tr><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">Flu-Infected</td><td align="center" valign="top" charoff="50">1.74 (1.38, 2.19)</td><td align="center" valign="top" charoff="50">(0.7, 4.0)</td></tr><tr><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">Sham-Infected</td><td align="center" valign="top" charoff="50">NA</td><td align="center" valign="top" charoff="50">NA</td></tr><tr><td align="center" valign="top" charoff="50">Alanine Aminotransferase</td><td align="center" valign="top" charoff="50">Flu Survivors</td><td align="center" valign="top" charoff="50">18.00 ( -- )</td><td align="center" valign="top" charoff="50">(18.0, 18.0)</td></tr><tr><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">Flu Non-Survivors</td><td align="center" valign="top" charoff="50">2.61 (1.72, 3.95)</td><td align="center" valign="top" charoff="50">(0.3, 6.9)</td></tr><tr><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">Flu-Infected</td><td align="center" valign="top" charoff="50">3.39 (2.13, 5.40)</td><td align="center" valign="top" charoff="50">(0.3, 18.0)</td></tr><tr><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">Sham-Infected</td><td align="center" valign="top" charoff="50">18.00 ( -- )</td><td align="center" valign="top" charoff="50">(18.0, 18.0)</td></tr><tr><td align="center" valign="top" charoff="50">Eosinophils</td><td align="center" valign="top" charoff="50">Flu Survivors</td><td align="center" valign="top" charoff="50">3.81 (0.70, 20.67)</td><td align="center" valign="top" charoff="50">(1.7, 18.0)</td></tr><tr><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">Flu Non-Survivors</td><td align="center" valign="top" charoff="50">1.07 (0.72, 1.60)</td><td align="center" valign="top" charoff="50">(0.3, 6.2)</td></tr><tr><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">Flu-Infected</td><td align="center" valign="top" charoff="50">1.33 (0.87, 2.01)</td><td align="center" valign="top" charoff="50">(0.3, 18.0)</td></tr><tr><td align="center" valign="top" charoff="50"> </td><td align="center" valign="top" charoff="50">Sham-Infected</td><td align="center" valign="top" charoff="50">18.00 ( -- )</td><td align="center" valign="top" charoff="50">(18.0, 18.0)</td></tr></tbody></table><table-wrap-foot><fn id="t2-fn1"><p>NA: No animals in this group became abnormal.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><affiliations><list><country><li>États-Unis</li></country><region><li>Ohio</li></region></list><tree><country name="États-Unis"><region name="Ohio"><name sortKey="Long, James P" sort="Long, James P" uniqKey="Long J" first="James P." last="Long">James P. Long</name></region><name sortKey="Bigger, John E" sort="Bigger, John E" uniqKey="Bigger J" first="John E." last="Bigger">John E. Bigger</name><name sortKey="Jones, Kelly J" sort="Jones, Kelly J" uniqKey="Jones K" first="Kelly J." last="Jones">Kelly J. Jones</name><name sortKey="Miller, Stephen T" sort="Miller, Stephen T" uniqKey="Miller S" first="Stephen T." last="Miller">Stephen T. Miller</name><name sortKey="Stark, Gregory V" sort="Stark, Gregory V" uniqKey="Stark G" first="Gregory V." last="Stark">Gregory V. Stark</name><name sortKey="Vela, Eric M" sort="Vela, Eric M" uniqKey="Vela E" first="Eric M." last="Vela">Eric M. Vela</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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