Analysis of severe cases of epidemic influenza and its lethality in the last 5 flu seasons

Reina, Jordi; López de Bilbao, Carmen; Riera, Melchor
doi:10.1016/j.medcle.2018.05.021
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">During the influenza A &#40;H1N1&#41; pdm09 pandemic of 2009&#44; the need for active surveillance of severe forms of influenza requiring hospitalization was observed&#46; The objectives of this surveillance are to provide an estimate of severity in seasonal epidemics or influenza pandemics&#44; to determine the impact they have on different health services&#46; Likewise&#44; it allows to identify and characterize the risk groups regarding the presentation of these cases by the different circulating influenza viruses or their association to certain underlying diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Patients with influenza symptoms confirmed by the laboratory and requiring hospital admission due to the severity of their condition&#44; that is&#44; pneumonia&#44; multiorgan failure&#44; respiratory distress or admission to the ICU&#44; are considered severe cases of influenza&#59; likewise&#44; it includes patients who develop the above signs and symptoms during their hospital stay due to another cause&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We have reviewed the severe cases of influenza with hospital admission observed in the last 5 flu epidemic seasons in the University Hospital Son Espases&#44; which acts as a reference hospital for this disease and covers a population of 200&#44;000 inhabitants&#46; Influenza confirmation was performed on patients&#8217; respiratory samples using a commercially available molecular amplification technique that identifies and differentiates influenza types and subtypes &#40;Allplex&#8482;&#44; Seegene&#44; Seoul&#44; South Korea&#41;&#46; Patient data were extracted from the medical records and Virology laboratory&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Throughout the last 5 flu seasons&#44; 256 cases of severe flu have been detected&#46; Of these&#44; 121 &#40;47&#46;2&#37;&#41; occurred in women and 135 &#40;52&#46;8&#37;&#41; in men &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; 29 &#40;11&#46;3&#37;&#41; patients died&#44; 19 &#40;65&#46;5&#37;&#41; were women and 10 &#40;34&#46;5&#37;&#41; were men&#46; Of the total number of women with severe influenza&#44; 19 died &#40;15&#46;7&#37;&#41;&#44; and of the total of men&#44; 10 &#40;7&#46;4&#37;&#41; died &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Mortality rates in women have ranged from 7&#46;1&#37; in the 2012&#8211;2013 season&#44; with a mixed flu circulation A &#40;H1N1&#41; pdm09 and influenza B&#44; up to 25&#37; in the 2016&#8211;2017 season&#44; with influenza A &#40;H3N2&#41; being the most predominant&#46; In men&#44; the lowest percentage was detected in the 2012&#8211;2013 season&#44; with 4&#46;1&#37;&#44; and the highest&#44; in the 2015&#8211;2016 season&#44; with 11&#46;3&#37;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">A progressive increase in the case-fatality rate associated with severe influenza has been observed from the 2012&#8211;2013 season &#40;5&#46;3&#37;&#41; to the 2016&#8211;2017 season &#40;18&#46;5&#37;&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; The low case-fatality rate of severe influenza B cases is verified throughout the study period&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Of all severe cases&#44; 40&#46;2&#37; were caused by influenza A &#40;H1N1&#41; pdm09&#44; 41&#46;1&#37; by influenza A &#40;H3N2&#41; and 18&#46;7&#37; by influenza B&#46; The case-fatality rate associated with influenza subtypes were 10&#46;6&#37; for A &#40;H1N1&#41; pdm09&#44; 16&#46;1&#37; for A &#40;H3N2&#41; and 2&#46;1&#37; for influenza B&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The criteria for admission of severe cases were pneumonia &#40;43&#46;5&#37;&#41;&#44; admission to the ICU &#40;29&#46;2&#37;&#41;&#44; respiratory distress &#40;22&#46;7&#37;&#41; and multi-organ failure &#40;4&#46;4&#37;&#41; &#40;one patient could meet more than one clinical criterion simultaneously&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">This study highlights a progressive case-fatality rate increase in severe cases of influenza&#59; and although there were only 27 of them in the last season&#44; their case-fatality rate was 18&#46;5&#37;&#44; the highest of the entire study&#46; This case-fatality rate seems to be associated both with the flu infection itself &#40;pathogenicity&#41; and with the host characteristics&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The lower case-fatality rate of severe cases caused by subtype A &#40;H1N1&#41; pdm09 is confirmed&#44; even though the number of cases is almost the same as that caused by subtype A &#40;H3N2&#41;&#44; as observed in the pandemic of 2009&#44; and that could be due to the fact that it mainly affects previously healthy young people&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">A higher case-fatality rate has been detected in severe cases of influenza affecting the female population &#40;15&#46;7&#37; versus 7&#46;4&#37;&#41;&#59; this could be due to the longer life expectancy of women and the increased vulnerability over the years&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">On the other hand&#44; there is evidence that severe cases caused by subtype A &#40;H3N2&#41; show a higher case-fatality rate&#44; probably because they mainly affect the elderly population&#44; with significant underlying diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> Therefore&#44; initiating specific antiviral treatment as soon as possible after the suspicion or diagnosis of influenza is recommended&#44; regardless of whether the subtype involved in the severe case is known or not&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">A lower incidence of severe cases caused by influenza B has been observed &#40;it has only represented 18&#46;7&#37; of all severe cases&#41; and is associated with a very low case-fatality rate &#40;2&#46;1&#37;&#41; compared to influenza A&#46; Influenza B mainly affects the paediatric and youth population and hardly associates significant complications&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In short&#44; case-fatality rate in severe hospitalized flu cases seems to depend basically on the influenza type and subtype involved&#44; which in turn vary in each seasonal flu epidemic&#46; In our study&#44; it could be inferred that the sex of the patient would be a predisposing factor to a higher influenza fatality&#44; although a much larger study would be necessary to confirm it&#46;</p></span>"
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Women&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Men&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A &#40;H1N1&#41; pdm09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">A &#40;H3N2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2012&#8211;2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&#47;1<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38&#47;2 &#40;5&#46;3&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2013&#8211;2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">32&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35&#47;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&#47;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60&#47;5 &#40;8&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2014&#8211;2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">33&#47;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50&#47;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">61&#47;8 &#40;13&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2015&#8211;2016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26&#47;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44&#47;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&#47;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70&#47;9 &#40;12&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2016&#8211;2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&#47;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&#47;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&#47;5 &#40;18&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">121&#47;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">135&#47;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">103&#47;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">105&#47;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">48&#47;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">256&#47;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&#46;7<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#46;3&nbsp;\t\t\t\t\t\t\n
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