BACKGROUND: Morbidity, severity, and mortality associated with annual influenza epidemics are of public health concern. We analyzed surveillance data on hospitalized laboratory-confirmed influenza cases admitted to intensive care units to identify common determinants for fatal outcome and inform and target public health prevention strategies, including risk communication. METHODS: We performed a descriptive analysis and used Poisson regression models with robust variance to estimate the association of age, sex, virus (sub)type, and underlying medical condition with fatal outcome using European Union data from 2009 to 2017. RESULTS: Of 13 368 cases included in the basic dataset, 2806 (21%) were fatal. Age ≥40 years and infection with influenza A virus were associated with fatal outcome. Of 5886 cases with known underlying medical conditions and virus A subtype included in a more detailed analysis, 1349 (23%) were fatal. Influenza virus A(H1N1)pdm09 or A(H3N2) infection, age ≥60 years, cancer, human immunodeficiency virus infection and/or other immune deficiency, and heart, kidney, and liver disease were associated with fatal outcome; the risk of death was lower for patients with chronic lung disease and for pregnant women. CONCLUSIONS: This study re-emphasises the importance of preventing influenza in the elderly and tailoring strategies to risk groups with underlying medical conditions.

Bruno Hubert Santé Public France Saint Maurice Cedex France

Department of Health Security National Institute for Health and Welfare Helsinki Finland

Department of Infectious Diseases Epidemiology National Institute of Public Health Prague Czech Republic

Department of Public Health of Regional Health Administration of Lisbon and Tagus Valley Lisboa Portugal

Health Service Executive Health Protection Surveillance Centre Dublin Ireland

Infectious Disease Prevention and Control Unit Health Regulation Malta

Instituto Nacional de Saúde Doutor Ricardo Jorge Lisboa Portugal

Medical University of Vienna Center for Virology Vienna Austria

National Centre of Epidemiology CIBER Epidemiología y Salud Pública Institute of Health Carlos 3 Madrid Spain

National Institute for Public Health and the Environment Bilthoven The Netherlands

National Institute of Public Health Romania National Centre for Communicable Diseases Surveillance and Control Bucuresti Romania

Office of the Chief Scientist European Centre for Disease Prevention and Control Solna Sweden

Public Health Authority of the Slovak Republic Bratislava Slovakia

Surveillance and Response Support European Centre for Disease Prevention and Control Solna Sweden

The Public Health Agency of Sweden Solna Sweden

Zobrazit více v PubMed

Nair H, Brooks WA, Katz M, et al. . Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis. Lancet 2011; 378:1917–30. PubMed

Fineberg HV. Pandemic preparedness and response–lessons from the H1N1 influenza of 2009. N Engl J Med 2014; 370:1335–42. PubMed

Hayward AC, Fragaszy EB, Bermingham A, et al. ; Flu Watch Group Comparative community burden and severity of seasonal and pandemic influenza: results of the Flu Watch cohort study. Lancet Respir Med 2014; 2:445–54. PubMed PMC

de Francisco Shapovalova N, Donadel M, Jit M, Hutubessy R. A systematic review of the social and economic burden of influenza in low- and middle-income countries. Vaccine 2015; 33:6537–44. PubMed

Iuliano AD, Roguski KM, Chang HH, et al. ; Global Seasonal Influenza-associated Mortality Collaborator Network Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet 2018; 391:1285–300. PubMed PMC

Snacken R, Brown C. New developments of influenza surveillance in Europe. Euro Surveill 2015; 20 Available at: https://www.eurosurveillance.org/content/10.2807/ese.20.04.21020-en PubMed

Dunning J, Baillie JK, Cao B, Hayden FG; International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) Antiviral combinations for severe influenza. Lancet Infect Dis 2014; 14:1259–70. PubMed PMC

Hayden FG, de Jong MD. Emerging influenza antiviral resistance threats. J Infect Dis 2011; 203:6–10. PubMed PMC

World Health Organization. Global Epidemiological Surveillance Standards for Influenza. Available at: http://www.who.int/influenza/resources/documents/WHO_Epidemiological_Influenza_Surveillance_Standards_2014.pdf?ua=1. Accessed 17 September 2017.

European Centre for Disease Prevention and Control (ECDC). Seasonal influenza vaccination in Europe; Vaccination recommendations and coverage rates in the EU Member States for eight influenza seasons, 2007–2008 to 2014–2015. Stockholm: ECDC; 2017.

Meerhoff TJ, Simaku A, Ulqinaku D, et al. . Surveillance for severe acute respiratory infections (SARI) in hospitals in the WHO European region - an exploratory analysis of risk factors for a severe outcome in influenza-positive SARI cases. BMC Infect Dis 2015; 15:1. PubMed PMC

Zolotusca L, Jorgensen P, Popovici O, et al. . Risk factors associated with fatal influenza, Romania, October 2009-May 2011. Influenza Other Respir Viruses 2014; 8:8–12. PubMed PMC

Zhang Q, Ji W, Guo Z, et al. . Risk factors and outcomes for pandemic H1N1 influenza compared with seasonal influenza in hospitalized children in China. Can J Infect Dis Med Microbiol 2012; 23:199–203. PubMed PMC

Van Kerkhove MD, Vandemaele KA, Shinde V, et al. ; WHO Working Group for Risk Factors for Severe H1N1pdm Infection Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: a global pooled analysis. PLoS Med 2011; 8:e1001053. PubMed PMC

Mertz D, Kim TH, Johnstone J, et al. . Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis. BMJ 2013; 347:f5061. PubMed PMC

Bonmarin I, Belchior E, Bergounioux J, et al. . Intensive care unit surveillance of influenza infection in France: the 2009/10 pandemic and the three subsequent seasons. Euro Surveill 2015; 20 Available at: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2015.20.46.30066 PubMed

Karlsson EA, Marcelin G, Webby RJ, Schultz-Cherry S. Review on the impact of pregnancy and obesity on influenza virus infection. Influenza Other Respir Viruses 2012; 6:449–60. PubMed PMC

Skowronski DM, De Serres G. Is routine influenza immunization warranted in early pregnancy? Vaccine 2009; 27:4754–70. PubMed

European Centre for Disease Prevention and Control (ECDC). Influenza surveillance in Europe, Season 2013–14. ECDC Surveillance Report 2014. Available at: https://www.ecdc.europa.eu/sites/default/files/media/en/publications/Publications/Influenza-2013-14-season-report.pdf. Accessed 30 September 2017.

European Centre for Disease prevention and Control (ECDC). Risk assessment of seasonal influenza, EU/EEA, 2016/2017, 24 December 2016. Available at: https://www.ecdc.europa.eu/en/publications-data/risk-assessment-seasonal-influenza-eueea-20162017-24-december-2016 Accessed 29 November 2017.

European Centre for Disease prevention and Control (ECDC). Risk assessment update: seasonal influenza, EU/EEA, 2016–2017. Available at: https://ecdc.europa.eu/en/publications-data/risk-assessment-update-seasonal-influenza-eueea-2016–2017. Accessed 29 November 2017.

Snacken R, Zucs P, Brown C, et al. . Influenza surveillance in Europe. Eur J Public Health 2011; 21:674–5. PubMed PMC

World Health Organization Regional Office for Europe and European Centre for Disease Prevention and Control. Influenza Surveillance Country, Territory and Area Profiles 2017. Available at: http://www.euro.who.int/__data/assets/pdf_file/0007/356119/InfluenzaSurveillanceProfiles_2017_en.pdf?ua=1. Accessed 4 March 2018.

World Health Organization Regional Office for Europe and European Centre for Disease Prevention and Control. Flu News Europe Joint ECDC-WHO/Europe weekly influenza update, System description. Available at: http://flunewseurope.org/system. Accessed 6 March 2018.

Barros AJ, Hirakata VN. Alternatives for logistic regression in cross-sectional studies: an empirical comparison of models that directly estimate the prevalence ratio. BMC Med Res Methodol 2003; 3:21. PubMed PMC

World Health Organization Regional Office for Europe. Influenza surveillance country profiles of WHO European Region Member States. 2017; Available at: http://www.euro.who.int/en/health-topics/communicable-diseases/influenza/surveillance-and-lab-network/influenza-surveillance-country-profiles/influenza-surveillance-country-profiles-of-who-european-region-member-states. Accessed 12 February 2018.

Snacken R, Quinten C, Devaux I, et al. . Surveillance of hospitalised severe cases of influenza A(H1N1)pdm09 and related fatalities in nine EU countries in 2010-2011. Influenza Other Respir Viruses 2012; 6:e93–6. PubMed PMC

Vestergaard LS, Nielsen J, Krause TG, et al. . Excess all-cause and influenza-attributable mortality in Europe, December 2016 to February 2017. Euro Surveill 2017; 22 Available at: https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2017.22.14.30506 PubMed PMC

Viboud C, Miller M, Olson D, Osterholm M, Simonsen L. Preliminary estimates of mortality and years of life lost associated with the 2009 A/H1N1 pandemic in the US and comparison with past influenza seasons. PLoS Curr. 2010; 2:RRN1153. PubMed PMC

Hartman L, Zhu Y, Edwards KM, et al. . Underdiagnosis of influenza virus infection in hospitalized older adults. J Am Geriatr Soc 2018; 66:467–72. PubMed PMC

Coleman BL, Fadel SA, Fitzpatrick T, Thomas SM. Risk factors for serious outcomes associated with influenza illness in high- versus low- and middle-income countries: Systematic literature review and meta-analysis. Influenza Other Respir Viruses 2018; 12:22–9. PubMed PMC

European Centre for Disease Prevention and Control (ECDC). Seasonal influenza vaccination in Europe, Overview of vaccination recommendations and coverage rates in the EU Member States for the 2012–13 influenza season. Technical Report Available at: https://www.ecdc.europa.eu/en/publications-data/seasonal-influenza-vaccination-europe-vaccination-recommendations-and-coverage Accessed 7 July 2016.

European Centre for Disease Prevention and Control (ECDC). Seasonal influenza vaccination and antiviral use in Europe, Overview of vaccination recommendations and coverage rates in the EU Member States for the 2013–14 and 2014–15 influenza seasons. Technical Report. Available at: http://ecdc.europa.eu/en/publications/Publications/Seasonal-influenza-vaccination-antiviral-use-europe.pdf. Accessed 15 July 2016.

Cohen C, Moyes J, Tempia S, et al. . Severe influenza-associated respiratory infection in high HIV prevalence setting, South Africa, 2009-2011. Emerg Infect Dis 2013; 19:1766–74. PubMed PMC

Cohen C, Simonsen L, Sample J, et al. . Influenza-related mortality among adults aged 25-54 years with AIDS in South Africa and the United States of America. Clin Infect Dis 2012; 55:996–1003. PubMed PMC

Martin-Loeches I, Díaz E, Vidaur L, et al. ; H1N1 SEMICYUC/REIPI/CIBERES Working group Pandemic and post-pandemic influenza A (H1N1) infection in critically ill patients. Crit Care 2011; 15:R286. PubMed PMC

European Centre for Disease Prevention and Control. HIV/AIDS Surveillance in Europe 2017–2016 Data. Stockholm: 2017. Available at: https://www.ecdc.europa.eu/en/publications-data/hivaids-surveillance-europe-2017-2016-data

Remschmidt C, Wichmann O, Harder T. Influenza vaccination in HIV-infected individuals: systematic review and assessment of quality of evidence related to vaccine efficacy, effectiveness and safety. Vaccine 2014; 32:5585–92. PubMed

López-Aldeguer J, Iribarren JA, Valencia E, et al. ; GESIDA 6409 Study Group Outcomes in HIV-infected patients admitted due to pandemic influenza. Enferm Infecc Microbiol Clin 2012; 30:608–12. PubMed

Myles P, Nguyen-Van-Tam JS, Semple MG, et al. ; Influenza Clinical Information Network FLU-CIN Differences between asthmatics and nonasthmatics hospitalised with influenza A infection. Eur Respir J 2013; 41:824–31. PubMed PMC

European Centre for Disease prevention and Control (ECDC). Expert Opinion on Neuraminidase Inhibitors for the Prevention and Treatment of Influenza – Review of Recent Systematic Reviews and Meta-Analyses. Stockholm: 2017. Available at: https://www.ecdc.europa.eu/en/publications-data/expert-opinion-neuraminidase-inhibitors-prevention-and-treatment-influenza-review

Effect of neuraminidase inhibitor (oseltamivir) treatment on outcome of hospitalised influenza patients, surveillance data from 11 EU countries, 2010 to 2020