Unchanged Severity of Influenza A(H1N1)pdm09 Infection in Children during First Postpandemic Season

Altmann, Matthias; Fiebig, Lena; Buda, Silke; Kries, Rüdiger von; Dehnert, Manuel; Haas, Walter

doi:10.3201/eid1811.120719

Cited by 18 publications

(22 citation statements)

References 32 publications

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“…Contradictory findings have been reported in regard to varying disease severity during the pandemic season. Although some researchers did not observe any differences in disease severity between the first and second pandemic outbreaks in 2009 ( 13 , 14 ), another study showed a 4-fold increase in hospitalization and a 5-fold increase in number of deaths in the second wave ( 15 ). However, disease severity of postpandemic seasons has been rarely analyzed.…”

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confidence: 97%

Changes in Severity of Influenza A(H1N1)pdm09 Infection from Pandemic to First Postpandemic Season, Germany

Lehners¹,

Geis²,

Eisenbach³

et al. 2013

Emerg. Infect. Dis.

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We studied risk factors for a severe clinical outcome in hospitalized patients with laboratory-confirmed influenza A(H1N1)pdm09 infection at the University Hospital Heidelberg in the pandemic and first postpandemic seasons. We identified 102 patients in 2009–10 and 76 in 2010–11. The proportion of severely diseased patients dramatically increased from 14% in 2009–10 to 46% in 2010–11 as did the mortality rate (5%–12%). Patients in the first postpandemic season were significantly older (38 vs. 18 years) and more frequently had underlying medical conditions (75% vs. 51%). Overall, 50 patients (28%) had a severe clinical outcome, resulting in 14 deaths. Multivariate analysis showed that older male patients with chronic lung disease were at increased risk for a severe clinical outcome. In summary, the proportion of patients with severe disease and fatal cases increased in the postpandemic season. Therefore, patients with suspected infections should be promptly identified and receive early treatment.

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mentioning

confidence: 97%

Changes in Severity of Influenza A(H1N1)pdm09 Infection from Pandemic to First Postpandemic Season, Germany

Lehners¹,

Geis²,

Eisenbach³

et al. 2013

Emerg. Infect. Dis.

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“…There was no significant effect on pneumonia in children (RR 1.06, 95% CI 0.62 to 1.83; I 2 statistic = 0%). In two zanamivir adult trials, 81,82 pneumonia reporting was based on a stricter definition of X-ray confirmation and there was also no significant treatment effect (RR 1.02, 95% CI 0.35 to 3.02; I 2 statistic = 39%). In nine zanamivir trials, 77,79,80,87,89,91,[97][98][99] pneumonia was a self-reported, investigator-mediated, unverified outcome (see Figures 8 and 9).…”

Section: Pneumoniamentioning

confidence: 99%

“…83,92 were excluded from the meta-analysis because one was only a synopsis 83 and one compared zanamivir to usual care and not placebo. 92 We finally included 26 zanamivir trials: 14 on treatment in adults, [71][72][73]77,[80][81][82]87,89,91,95,[97][98][99] two in children 78,84 and 10 trials in prophylaxis. 70,79,85,86,88,90,93,94,96,100 Our attempt at collecting sufficient information from regulatory files to reconstruct missing CSRs also failed because the information appeared to be insufficient for a reliable reconstruction.…”

Section: Zanamivirmentioning

confidence: 99%

Neuraminidase inhibitors for influenza: a systematic review and meta-analysis of regulatory and mortality data

Heneghan

Onakpoya

Jones

et al. 2016

Health Technol Assess

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BackgroundNeuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide.ObjectivesTo (1) describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports (CSRs) of published and unpublished randomised, placebo-controlled trials and regulatory comments; and (2) determine the effect of oseltamivir (Tamiflu®, Roche) treatment on mortality in patients with 2009A/H1N1 influenza.MethodsWe searched trial registries, electronic databases and corresponded with regulators and sponsors to identify randomised trials of NIs. We requested full CSRs and accessed regulators’ comments. We included only those trials for which we had CSRs. To examine the effects of oseltamivir on 2009A/H1N1 influenza mortality, we requested individual patient data (IPD) from corresponding authors of all included observational studies.ResultsEffect of oseltamivir and zanamivir (Relenza®, GlaxoSmithKline) in the prevention and treatment of influenza: Oseltamivir reduced the time to first alleviation of symptoms in adults by 16.8 hours [95% confidence interval (CI) 8.4 to 25.1 hours]. Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days (95% CI 0.39 to 0.81 days). Oseltamivir reduced unverified pneumonia in adult treatment [risk difference (RD) 1.00%, 95% CI 0.22% to 1.49%]; similar findings were observed with zanamivir prophylaxis in adults (RD 0.32%, 95% CI 0.09% to 0.41%). Oseltamivir treatment of adults increased the risk of nausea (RD 3.66%, 95% CI 0.90% to 7.39%) and vomiting (RD 4.56%, 95% CI 2.39% to 7.58%). In the treatment of children, oseltamivir induced vomiting (RD 5.34%, 95% CI 1.75% to 10.29%). Both oseltamivir and zanamivir prophylaxis reduced the risk of symptomatic influenza in individuals (oseltamivir RD 3.05%, 95% CI 1.83% to 3.88%; zanamivir RD 1.98%, 95% CI 0.98% to 2.54%) and in households (oseltamivir RD 13.6%, 95% CI 9.52% to 15.47%; zanamivir RD 14.84%, 95% CI 12.18% to 16.55%). Oseltamivir increased psychiatric adverse events in the combined on- and off-treatment periods (RD 1.06%, 95% CI 0.07% to 2.76%) and the risk of headaches while on treatment (RD 3.15%, 95% CI 0.88% to 5.78%).Effect of oseltamivir on mortality in patients with 2009A/H1N1 influenza: Analysis of summary data of 30 studies as well as IPD of four studies showed evidence of time-dependent bias. After adjusting for time-dependent bias and potential confounding variables, competing risks analysis of the IPD showed insufficient evidence that oseltamivir reduced the risk of mortality (hazard ratio 1.03, 95% CI 0.64 to 1.65).ConclusionsOseltamivir and zanamivir cause small reductions in the time to first alleviation of influenza symptoms in adults. The use of oseltamivir increases the risk of nausea, vomiting, psychiatric events in adults and vomiting in children. Oseltamivir has no protective effect on mortality among patients with 2009A/H1N1 influenza. Prophylaxis with either NI may reduce symptomatic influenza in individuals and in households. The balance between benefits and harms should be considered when making decisions about use of NIs for either prophylaxis or treatment of influenza.Study registrationThis study is registered as PROSPERO CRD42012002245.FundingThe National Institute for Health Research Health Technology Assessment programme.

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“…Patients admitted to intensive care units were more frequently treated with antivirals: 91% in Canada and 90% in California . In comparison, a nationwide hospital‐based study in Germany showed that only 62% of children <15 years admitted to pediatric intensive care units were treated with oseltamivir both during the pandemic (H1N1) 2009 and the post‐pandemic season 2010/11 …”

Section: Discussionmentioning

confidence: 99%

Differential use of antivirals for treatment of patients with influenza A(H1N1)pdm09 in Germany

Reuß

Dehnert

Buda

et al. 2013

Influenza Resp Viruses

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BackgroundThe World Health Organization recommends early antiviral treatment for patients with severe influenza illness or those at increased risk for severe illness.ObjectivesThe aim of this study was to determine the proportion of cases with laboratory‐confirmed A(H1N1)pdm09 infection that have been treated with antivirals in Germany during the pandemic (H1N1) 2009 and to investigate factors associated with the use of antivirals.MethodsWe analyzed cases with laboratory‐confirmed A(H1N1)pdm09 infection notified to national health authorities in Germany between week 29/2009 and week 17/2010 using multivariable logistic regression. Severity of disease was defined by pneumonia or death.Results and conclusionsOf 160 804 cases with laboratory‐confirmed A(H1N1)pdm09 infection, 22% were treated with antivirals. Cases with severe disease were more likely to be treated with antivirals than cases without severe disease (odds ratio = 1·66; 95% confidence interval: 1·46–1·89). In the group with at least one underlying medical condition, only children aged between 1 and 4 years had significant lower odds for receiving antiviral treatment compared with cases in the age group 15 to 49 years (odds ratio = 0·75; 95% confidence interval: 0·6–0·94). In conclusion, the implementation of international recommendations on use of antivirals differed according to the age of patients in Germany during the pandemic (H1N1) 2009. This indicates that the potential of antivirals to prevent severe influenza might not have been fully exhausted. The reasons leading to the observed differences in patient management need to be investigated.

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Unchanged Severity of Influenza A(H1N1)pdm09 Infection in Children during First Postpandemic Season

Abstract: Improvement is needed in preventing severe disease and nosocomial transmission in children beyond pandemic situations.

Cited by 18 publications

References 32 publications

Changes in Severity of Influenza A(H1N1)pdm09 Infection from Pandemic to First Postpandemic Season, Germany

Changes in Severity of Influenza A(H1N1)pdm09 Infection from Pandemic to First Postpandemic Season, Germany

Neuraminidase inhibitors for influenza: a systematic review and meta-analysis of regulatory and mortality data

Differential use of antivirals for treatment of patients with influenza A(H1N1)pdm09 in Germany

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