Godoy et al. BMC Infectious Diseases (2020) 20:80 https://doi.org/10.1186/s12879-020-4792-7 RESEARCH ARTICLE Open Access Hospital-acquired influenza infections detected by a surveillance system over six seasons, from 2010/2011 to 2015/2016 P. Godoy1,2,3* , N. Torner1,2,4, N. Soldevila2,4, C. Rius2,5, M. Jane1,2, A. Martínez1,2,4, JA. Caylà2,5, A. Domínguez2,4 and the Working Group on the Surveillance of Severe Influenza Hospitalized Cases in Catalonia Abstract Background: In addition to outbreaks of nosocomial influenza, sporadic nosocomial influenza infections also occur but are generally not reported in the literature. This study aimed to determine the epidemiologic characteristics of cases of nosocomial influenza compared with the remaining severe cases of severe influenza in acute hospitals in Catalonia (Spain) which were identified by surveillance. Methods: An observational case-case epidemiological study was carried out in patients aged ≥18 years from Catalan 12 hospitals between 2010 and 2016. For each laboratory-confirmed influenza case (nosocomial or not) we collected demographic, virological and clinical characteristics. We defined patients with nosocomial influenza as those admitted to a hospital for a reason other than acute respiratory infection in whom ILI symptoms developed ≥48 h after admission and influenza virus infection was confirmed using RT-PCR. Mixed-effects regression was used to estimate the crude and adjusted OR. Results: One thousand seven hundred twenty-two hospitalized patients with severe laboratory-confirmed influenza virus infection were included: 96 (5.6%) were classified as nosocomial influenza and more frequently had > 14 days of hospital stay (42.7% vs. 27.7%, P < .001) and higher mortality (18.8% vs. 12.6%, P < .02). The variables associated with nosocomial influenza cases in acute-care hospital settings were chronic renal disease (aOR 2.44 95% CI 1.44– 4.15) and immunodeficiency (aOR 1.79 95% CI 1.04–3.06). Conclusions: Nosocomial infections are a recurring problem associated with high rates of chronic diseases and death. These findings underline the need for adherence to infection control guidelines. Keywords: Healthcare-associated infection, Hospitalized patients, Influenza, Nosocomial infection Background timing and spread of influenza and detect variations in Each year, 5–20% of the population are infected by the circulating influenza viruses [2, 3]. influenza virus [1]. Among adults aged ≥65 years and pa- The Department of Health of Catalonia (Spain) intro- tients with underlying chronic diseases influenza is a duced the surveillance of patients hospitalized with leading cause of severe illness and death. Sentinel sur- laboratory-confirmed influenza to supplement the infor- veillance of patients hospitalized due to severe mation provided by the influenza sentinel surveillance laboratory-confirmed influenza is critical to control the system, based on primary healthcare physicians, in Octo- ber 2010 [4]. During periods of increased influenza activ- ity in the community and the subsequent increase in the number of patients with influenza in hospitals, the risk * Correspondence: pere.godoy@gencat.cat 1 Epidemiology Service. Agència de Salut Pública de Catalunya, Generalitat de of nosocomial transmission from infected patients in- Catalunya, Barcelona, Spain creases [5]. 2 CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Godoy et al. BMC Infectious Diseases (2020) 20:80 Page 2 of 7 Nosocomial influenza is a recognized public health and review of medical records. This included socio- problem in acute-care hospital settings [5] and has been demographic data, obesity (body mass index [BMI] > 40), associated with significant morbidity, mortality and high pregnancy, major chronic conditions (chronic obstructive economic costs due to longer hospital stays. It is likely pulmonary disease [COPD]), diabetes, chronic renal dis- to be under-recognized due to rapid patient turnover ease, immunodeficiency (HIV infection or other), chronic and delays in diagnosis. cardiovascular disease, and chronic liver disease). Outbreaks of influenza have been reported in different hospital wards [6–11]. In addition, sporadic nosocomial Laboratory data influenza infections may occur but are generally not Patient samples were first tested in the laboratories of the identified or reported [5]. participating hospitals using an in-house real-time RT-PCR This study aimed to determine the epidemiologic char- for influenza A and B after manual nucleic acid extraction. acteristics of nosocomial influenza cases in acute-care Samples with unsubtyped influenza virus were sent to the hospital settings in Catalonia (Spain) identified by sur- Catalan Influenza Reference Laboratory to determine the veillance rather than through outbreak control activity subtype. Molecular subtyping was used to determine the H during six consecutive influenza seasons (2010–2011 to subtype for influenza A and the lineage for influenza B. 2015–2016). Subtyping failed in some cases due to a low viral load and such samples were classified as “unidentifiable”. Methods Epidemiological study Statistical analysis The general methods of this study have been published We compared the baseline characteristics of nosocomial elsewhere [12, 13]. In summary, we conducted an obser- influenza cases with those of other hospitalized cases of vational case-case epidemiological study of the charac- severe influenza. The baseline variables considered were: teristics and risk factors of nosocomial influenza cases in sex, age (18–64, 65–74 and ≥ 75 years), virus type, major patients hospitalized due to laboratory-confirmed influ- chronic conditions (COPD, diabetes, obesity [BMI > 40], enza in acute-care hospital settings. chronic renal disease, immunodeficiency [HIV infection Catalonia (Spain) initiated, in 2010, the surveillance of or other]), chronic cardiovascular disease, and chronic patients hospitalized due to laboratory-confirmed influ- liver disease), complications, hospital stay, seasonal influ- enza. The system included a catchment area of 4,644, enza, and antiviral treatment. The chi-square test and 543 persons. During each influenza season, the 12 hospi- Fisher’s exact test were used for categorical variables and tals included in the surveillance system report on pa- the median test for continuous variables. tients hospitalized with severe laboratory-confirmed The length of stay was calculated as from the first day influenza admitted to one of these hospitals. of hospital admission in patients with community- acquired influenza and from the onset of influenza Study population and data collected symptoms in patients with nosocomial influenza. To as- The study population was reported cases aged ≥18 years sess the relationships between the dependent variable hospitalized with severe laboratory-confirmed influenza (nosocomial influenza cases Yes/No) and the independ- virus infection during six influenza seasons (2010–2011 ent variables studied, a case-case bivariate analysis was to 2015–2016). We included patients hospitalized ≥24 h made. Possible interactions between independent vari- in any participating hospitals who presented an ables were analyzed by logistic regression. Independent influenza-like-illness (ILI). A sentinel physician who variables were checked for collinearity using the variance screened all patients with severe ILI enlisted patients in inflation factor. Because there were differences between each participating hospital. All patients had a nasopha- hospitals in nosocomial influenza cases, a mixed-effects ryngeal or throat swab (bronchoalveolar lavage fluid or logistic regression model with the variable hospital as a tracheal aspirate for intensive care unit (ICU) patients) random intercept was constructed to estimate the crude and influenza virus infection was detected using reverse and adjusted odds ratios (OR) and their corresponding transcription polymerase chain reaction (RT-PCR). 95% confidence intervals (CI). A multivariate analysis From this source of acute-care hospital influenza pa- was performed using the mixed-effects logistic regres- tients, we defined patients with nosocomial influenza as sion model that included the variables described. The those admitted to a hospital for a reason other than final model was selected using the backward procedure, acute respiratory infection in whom ILI symptoms devel- with a cut-off point of p < 0.2. oped ≥48 h after admission and influenza virus infection was confirmed using RT-PCR. Ethics approval and consent to participate A structured questionnaire was used by public health of- As this study was undertaken as part of a national sur- ficers to collect data from each reported case by interview veillance system, ethical approval was not required [14]. Godoy et al. BMC Infectious Diseases (2020) 20:80 Page 3 of 7 Results highlight the importance of the nosocomial transmission A total of 1722 patients aged ≥18 years hospitalized with of influenza in acute hospitals in a study with a multi- laboratory-confirmed influenza were recorded: 805 center design, a large number of patients and an ex- (46.7%) were aged 18–64 years and 917 (53.3%) ≥ 65 tended study period of six consecutive influenza seasons. years and 743 (43.1%) were female. During the six sea- Our results are consistent with other studies that show sons studied, 1480 (85.9%) patients were infected with sporadic nosocomial cases of influenza are a public influenza A viruses (572 H1N1 and 331 H3N2) and 241 health problem in acute-care hospital settings. Enstone (14%) with influenza B viruses. et al. in the United Kingdom detected 30 nosocomial Of the 1722 patients, 96 (5.6%) were admitted to a cases (2.0%) in 1520 hospitalized patients with influenza hospital for a reason other than acute respiratory infec- from 75 hospitals [15]; Macesic et al. in Australia re- tion and developed ILI symptoms ≥48 h after admission corded 26 nosocomial cases (4.3%) in 598 hospitalized and were classified as nosocomial influenza. Of these 96 patients with influenza from 15 hospitals [16]; and Álva- cases, 35 (36.5%) were aged 18–64 years, 22 (22.9%) were rez-Lerma et al in Spain documented 224 nosocomial aged 64–74 years, 39 (40.6%) ≥ 75 years and 43 (44.8%) cases (9.3%) in 2421 hospitalized patients with influenza were female. Eighty (83.3%) patients presented ≥1 influ- from 148 intensive care units [17]. Patients with enza risk factor and 36 (37.5%) had received the influ- hospital-acquired influenza infection had a profile that enza vaccine (Table 1). differed from that of patients with community-acquired There were differences between nosocomial influenza infections; they were older, more likely to have chronic patients and those who were not. Nosocomial influenza diseases (diabetes, chronic renal disease, immunodefi- cases had a higher frequency of age 65–74 years (22.9% ciency and chronic cardiovascular disease) and had vs. 18.8%, P < .13), and ≥ 75 years (40.6% vs. 33.9%, higher mortality (18.8%). Similarly, other studies present P < .15), diabetes (35.4% vs. 24.4%, P = .02), chronic renal poor outcomes. While the mortality of nosocomial cases disease (29.2% vs. 12.8% P < .001), immunodeficiency in the study by Enstone et. al was 26.7% [15], in the (28.1% vs. 18.9% P < .001), chronic cardiovascular disease study by Álvarez-Lerma et al. it was 39.2% [17]; in both (39.6% vs. 28.8% P < .02) and chronic liver disease (8.3% studies mortality was notably higher than that due to vs. 6.4% P = .25). Influenza vaccination uptake was community-acquired influenza [15, 17]. Compared with higher in nosocomial influenza patients (37.5% vs. 25.6%, community-acquired influenza cases, we found a signifi- P = .03) (Table 1). cantly longer stay in patients with nosocomial influenza. Likewise, nosocomial influenza patients more fre- Nosocomial influenza has previously been associated quently received antiviral treatment within 48 h of symp- with longer hospitalization as well as increased use of tom onset (67.4% vs. 23.9%, P = .01) and had a lower diagnostic resources and treatments [5]. frequency of pneumonia (54.2% vs. 76.4%, P < .001). Even though vaccination rates were very low in pa- However, nosocomial influenza patients required more tients with both hospital-acquired and community- days of hospital stay (median: 13 (2–76) vs. 9 (0–137), acquired influenza virus infection, a higher proportion of P = .001) and a higher mortality rate was observed nosocomial influenza patients had been vaccinated. This (18.8% vs. 12.6%, P < .02) (Table 2). No interaction was has been observed in other studies [15–17] and may be found between the variables investigated, and there was related to the greater number of comorbidities (COPD, no collinearity between the variables. diabetes, chronic renal disease, immunodeficiency and In the multivariable regression model, the variables as- chronic cardiovascular disease) for which vaccination is sociated with nosocomial influenza cases were chronic recommended [18]. renal disease (aOR 2.44 95% CI 1.44–4.15) and immuno- As with nosocomial influenza outbreaks [19, 20], spor- deficiency (aOR 1.79 95% CI 1.04–3.06) (Table 3). adic nosocomial cases of influenza detected by surveil- Nosocomial influenza cases were a risk factor for death lance during the influenza season may have special (OR 1.86 95% CI 1.07–3.23). Furthermore, in the multi- interest, as they could suggest failures in hospital infec- variable regression model the risk of death was slightly tion control. The case series in this study was detected higher (aOR 3.26 95% CI 1.53–6.92) after adjustment for in settings where clinical management and infection the other variables in the model (Table 4). control precautions were determined by guidelines [21], and with data recorded by experienced public health Discussion staff [4]. This study, based on the surveillance of hospitalized There is no standardized definition of nosocomial in- cases of severe laboratory-confirmed influenza, shows fluenza infection. The mean hospital stay before symp- that 5.65% of influenza cases in acute hospitals were due tom onset in this study was 14.3 days and we applied a to nosocomial transmission and were associated with cutoff point of ≥2 days after admission in nosocomial chronic diseases and a high risk of death. The results cases. This case definition was based on a review of Godoy et al. BMC Infectious Diseases (2020) 20:80 Page 4 of 7 Table 1 Demographic characteristics and comorbidities of patients with community-acquired or nosocomial influenza, Catalonia (Spain) Variables Hospital acquired Community acquired Crude OR P value (N = 96) (N = 1626) (95% CI) Age 18–64 35 (36.5%) 770 (47.4%) Ref. 65–74 22 (22.9%) 305 (18.8%) 1.53 (0.88–2.66) 0.13 > =75 39 (40.6%) 551 (33.9%) 1.42 (0.88–2.29) 0.15 Sex Female 43 (44.8%) 700 (43.1%) 1.07 (0.70–1.62) 0.75 Male 53 (55.2%) 926 (56.9%) Ref. COPD Yes 26 (27.1%) 414 (25.5%) 1.06 (0.68–1.70) 0.79 No 70 (72.9%) 1212 (74.5%) Ref. Obesity Yes 14 (14.6%) 168 (10.3%) 1.29 (0.71–2.35) 0.41 No 82 (85.4%) 1458 (89.7%) Ref. Diabetes Yes 34 (35.4%) 396 (24.4%) 1.66 (1.07–2.57) 0.02 No 62 (64.6%) 1230 (75.6%) Ref. Chronic renal disease Yes 28 (29.2%) 208 (12.8%) 3.05 (1.89–4.92) < 0.001 No 68 (70.8%) 1418 (87.2%) Ref. Immunodeficiency Yes 27 (28.1%) 307 (18.9%) 1.96 (1.21–3.17) 0.01 No 69 (71.9%) 1319 (81.1%) Ref. Heart disease Yes 38 (39.6%) 469 (28.8%) 1.67 (1.09–2.57) 0.02 No 58 (60.4%) 1157 (71.2%) Ref. Liver disease Yes 8 (8.3%) 1034 (6.4%) 1.57 (0.73–3.37) 0.25 No 88 (91.7%) 1522 (93.6%) Ref. Virus type A 79 (82.3%) 1401 (86.1%) Ref. B 17 (17.7%) 224 (13.8%) 1.49 (0.86–2.59) 0.15 C 0 (0.0%) 1 (0.1%) – – Seasonal influenza vaccination Yes 36 (37.5%) 412 (25.6%) 1.62 (1.05–2.52) 0.03 No 60 (62.5%) 1198 (74.4%) Ref. OR Odds ratio, CI Confidence interval health care-associated influenza that showed a median Health care-associated influenza cases could signal threshold delay between admission and symptom onset failures in hospital infection control, as transmission of 48 h (range: 24–96 h) [22, 23], suggesting that the er- may have been due to an infectious health care worker roneous inclusion of community cases of influenza as [24] or to the contaminated hands of a health care nosocomial cases is quite improbable. Nevertheless, a worker [5]. However, infection by other patients could standardized definition is lacking, and this should be re- also have occurred. Munier-Marion et al. reported that solved in the future. hospitalizations in double-occupancy rooms are an Godoy et al. BMC Infectious Diseases (2020) 20:80 Page 5 of 7 Table 2 Antiviral treatment, complications and risk of death in patients with community-acquired and nosocomial influenza, Catalonia (Spain) Variables Hospital acquired Community acquired Crude OR P value (N = 96) (N = 1626) (95% CI) Antiviral treatment Yes 89 (92.7%) 1485 (91.3%) 1.06 (0.48–2.34) 0.89 No 7 (7.3%) 141 (8.7%) Ref. Antiviral treatment ≤ 48 h before symptom onset 62 (67.4%) 375 (23.9%) 2.94 (1.30–6.66) 0.01 > 48 h before symptom onset 23 (25.0%) 1051 (67.1%) 0.42 (0.18–1.00) 0.05 No 7 (7.6%) 141 (9.0%) Ref. Hospital stay; median (range) 13 (2–76) 9 (0–137) 0.001 Hospital stay 0–14 days 55 (57.3%) 1174 (72.3%) Ref. > 14 days 41 (42.7%) 450 (27.7%) 2.04 (1.33–3.14) < 0.001 Pneumonia Yes 52 (54.2%) 1237 (76.4%) 0.34 (0.22–0.53) < 0.001 No 44 (45.8%) 383 (23.6%) Ref. ARDS Yes 33 (34.4%) 626 (39.3%) 0.86 (0.52–1.42) 0.57 No 63 (65.6%) 965 (60.7%) Ref. Multiorgan failure Yes 10 (10.6%) 166 (10.5%) 1.10 (0.56–2.19) 0.78 No 84 (89.4%) 1416 (89.5%) Ref. ICU admission Yes 31 (32.3%) 561 (34.5%) 1.00 (0.64–1.56) 0.99 No 65 (67.7%) 1065 (65.5%) Ref. Death Yes 18 (18.8%) 205 (12.6%) 1.91 (1.11–3.31) 0.02 No 78 (81.3%) 1421 (87.4%) Ref. ARDS Acute respiratory distress syndrome, ICU Intensive care unit, OR Odds ratio, CI Confidence interval important risk factor for hospital-acquired influenza together these measures may help reduce the number of [25]. Another possibility may be transmission from pa- acquired-hospital influenza cases. Furthermore, the tients’ visitors [5, 25]. study suggested a high risk of death in elderly patients Strategies to reduce influenza transmission in health with nosocomial influenza with chronic renal disease or facilities should include different methods. Patients with immunosuppressive diseases and those with stem cell risk factors should be vaccinated before the start of the transplantation or cancer. Health care workers caring for influenza season. In addition, all their contacts and these patients should be vaccinated every season and health care workers should also be vaccinated. Barrier mandatory vaccination may be considered. precautions, compliance with hand hygiene and exclu- Our study is based on a case-case analysis of patients sion of sick workers should also be ensured. The influ- hospitalized with severe laboratory-confirmed influenza. enza vaccine is recommended and funded for older The strengths of the study include the large number of people and risk groups in most European countries, al- patients hospitalized for influenza, the multicenter de- though its effectiveness is not absolute [18]. Reducing sign, the uniform patient screening by hospitals, the diag- transmission from advising of not working or not visit- nostic confirmation of all patients and the extended ing hospitals when people are sick and applying barrier study period of six consecutive influenza seasons. precautions has some limitations due to the possibility However, the study has also limitations. Some patients of influenza transmission before the onset of symptoms may have been discharged before the onset of hospital- or with minimal symptomatology [24]. Nevertheless, acquired influenza. Furthermore, some patients may Godoy et al. BMC Infectious Diseases (2020) 20:80 Page 6 of 7 Table 3 Multivariate logistic regression model of nosocomial influenza may be underestimated. These results suggest influenza risk factors, Catalonia (Spain) the need to improve infection control guidelines and the Variables Adjusted OR (95% CI) P value vaccination of health care workers and ensure clinical Chronic renal disease suspicion of influenza in high risk areas. In addition, Yes 2.44 (1.44–4.15) < 0.001 people should be recommended not to visit hospitals when they are ill. No Ref. Immunodeficiency Abbreviations ARDS: Acute respiratory distress syndrome; BMI: Body mass index; Yes 1.79 (1.04–3.06) 0.03 COPD: Chronic obstructive pulmonary disease; ICU: Intensive care unit; No Ref. ILI: Influenza-like-illness; RT-PCR: Polymerase chain reaction Liver disease Acknowledgements Yes 1.72 (0.75–3.96) 0.19 The Working Group on Surveillance of Severe Influenza Hospitalized Cases in Catalonia is composed of: No Ref. Alsedà M, Álvarez J, Arias C, Balañà PJ, Barrabeig I, Camps N, Carol M, Ferràs J, Antiviral treatment Ferrús G, Follia N, Godoy P, Bach P, Jané M, Martínez A, Minguell S, Parrón I, Plasència E, Sala-Farré MR, Torner N, Torra R, Torres J (Public Health Agency ≤ 48 h before symptom onset 3.43 (1.45–8.12) 0.01 of Catalonia); Caylà J, Gorrindo P, Rius C (Public Health Agency of Barcelona); > 48 h before symptom onset 0.51 (0.21–1.26) 0.15 Marcos MA, Mosquera MDM, Vilella A (H Clínic, Barcelona); Antón A, Pumar- ola T, Campins M (H Universitari Vall d’Hebrón, Barcelona); García D (H Josep No Ref. Trueta, Girona); Espejo E (H Terrassa); Freixas N, Riera Garcia M (Mútua Ter- rassa); Maraver E, Mas D, Perez R, (H Altahia Manresa); Rebull J (H.Verge de la Hospital stay Cinta, Tortosa); Pou J (H Sant Joan de Déu, Esplugues); García-Pardo G, Olona 0–14 days Ref. M (H Joan XXIII, Tarragona); Barcenilla F, Castellana D (H Arnau de Vilanova, Lleida) Navarro-Rubio G (Consorci Sanitari Parc Taulí, Sabadell); Force LL (H > 14 days 2.57 (1.59–4.16) < 0.001 Mataró). Pneumonia Authors’ contributions Yes 0.42 (0.26–0.68) < 0.001 NT, MJ, AM, AD and PG designed the study protocol. JC, CR, NT, MJ, AM and No Ref. PG organized the logistics. JC, CR, NT, and PG participated in the detection of cases, gathering epidemiological information and taking clinical samples ARDS and sending samples to the laboratory. NS, AD and PG conducted the Yes 0.60 (0.34–1.05) 0.07 epidemiological and statistical analyses of the study. The authors in The Working Group on Surveillance of Severe Influenza Hospitalized Cases in No Ref. Catalonia participated in the detection of cases, gathering epidemiological Death information and taking clinical samples and sending samples to the laboratory. PG made a first draft of the paper and all authors made relevant Yes 2.25 (1.18–4.26) 0.01 contributions to successive versions. All authors reviewed and approved the No Ref. final version of the article. ARDS Acute respiratory distress syndrome, ICU Intensive care unit, OR Odds Funding ratio, CI Confidence interval This study was funded by the Program of Surveillance, Prevention and Control of Transmissible Diseases (PREVICET) of CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid and the Catalan have minor symptoms which might not be detected and Agency for the Management of Grants for University Research (AGAUR Grant therefore the real number of nosocomial cases might Number 2017/SGR 1342). The funding body had no influence on the design, have been underestimated. collection, analysis and interpretation of data or in the manuscript writing. Availability of data and materials Conclusions The datasets used and/or analyzed during this study are available from the This study shows that nosocomial transmission is a re- corresponding author on reasonable request. current problem and the total effect of nosocomial Ethics approval and consent to participate As this study was undertaken as part of a national surveillance system, Table 4 Multivariate logistic analysis of nosocomial influenza as ethical approval was not required and data collation was covered by existing a risk factor for death information governance approvals. Death No death Crude P Adjusted P value Consent for publication OR value OR Not applicable. (N = 223) (N = 1499) (95% CI) (95% CI) Hospital 18 (8.1%) 78 (5.2%) 1.86 0.03 3.26 0.002 Competing interests acquired (1.07– (1.53– The authors declare that they have no competing interests. 3.23) 6.92) Author details Community 205 1421 Ref. Ref. 1 Epidemiology Service. Agència de Salut Pública de Catalunya, Generalitat de acquired (91.9%) (94.8%) Catalunya, Barcelona, Spain. 2CIBER de Epidemiología y Salud Pública Adjusted for age, antiviral treatment, pneumonia, multiorgan failure, intensive (CIBERESP), Barcelona, Spain. 3Institut de Recerca Biomédica de Lleida, care unit, renal failure, immunodeficiency and chronic liver disease IRBLleida, Lleida, Spain. 4Departamento de Medicina, Universidad de Godoy et al. BMC Infectious Diseases (2020) 20:80 Page 7 of 7 Barcelona, Barcelona, Spain. 5Agència de Salut Pública de Barcelona, paediatric oncology ward in Italy, October–November 2009. Barcelona, Spain. Eurosurveillance. 2010;15(1). 20. Lalayanni C, Sirigou A, Iskas M, Smias C, Sakellari I, Anagnostopoulos A. Received: 18 November 2018 Accepted: 14 January 2020 Outbreak of novel influenza A (H1N1) in an adult haematology department and haematopoietic cell transplantation unit: clinical presentation and outcome. J Inf Secur. 2010;61:270–2. 21. Abraham MK, Perkins J, Vilke GM, Coyne CJ. Influenza in the emergency References department: vaccination, diagnosis, and treatment: clinical practice paper 1. World Health Organization. Influenza (seasonal). Fact sheet. 2016. Available approved by American Academy of Emergency Medicine Clinical Guidelines from: http://www.who.int/mediacentre/factsheets/fs211/en/ Committee. J Emerg Med. 2016;50(3):536–42. 2. World Health Organization. Global epidemiological surveillance standards 22. Munier-Marion E, Benet T, Vanhems P. Definition of healthcare-associated for influenza: World Health Organ; 2013. Available: http://who.int/influenza/ influenza: a review and results from an international survey. Influenza Other resources/documents/WHO_Epidemiological_Influenza_Surveillance_ Respir Viruses. 2017;11(5):367–71. Standards_2014.pdf?ua=1 23. Lessler J, Reich NG, Brookmeyer R, Perl TM, Nelson KE, Cummings DAT. 3. Chaves SS, Aragon D, Bennett N, Cooper T, D’Mello T, Farley M, et al. Incubation periods of acute respiratory viral infections: a systematic review. Patients hospitalized with laboratory-confirmed influenza during the 2010- Lancet Infect Dis. 2009;9(5):291–300. 2011 influenza season: exploring disease severity by virus type and subtype. 24. Patrozou E, Mermel LA. Does influenza transmission occur from J Infect Dis. 2013;208(8):1305–14. asymptomatic infection or prior to symptom onset? Public Health Rep. 4. Torner N, Martínez A, Basile L, Plasencia E, Barrabeig I, Follia N, et al. 2009;124(2):193–6. Vigilància epidemiològica dels casos greus hospitalitzats confirmats de grip. 25. Munier-Marion E, Benet T, Regis C, Lina B, Morfin F, Vanhems P. Xarxa sentinella PIDIRAC (Catalunya 2010–2015). Butll Epidemiol Catalunya. Hospitalization in double-occupancy rooms and the risk of hospital- 2016;37:234–53 Available from: http://canalsalut.gencat.cat/ca/actualitat/ acquired influenza: a prospective cohort study. Clin Microbiol Infect. 2016; llista_butlletins/salut_publica/butlleti_epidemiologic_de_catalunya/. 22(5):461.e7–9. 5. Salgado CD, Farr BM, Hall KK, Hayden FG. Influenza in the acute hospital setting. Lancet Infect Dis. 2002;2:145–55. Publisher’s Note 6. Sartor C, Zandotti C, Romain F, Jacomo V, Simon S, Atlan-Gepner C, et al. Springer Nature remains neutral with regard to jurisdictional claims in Disruption of services in an internal medicine unit due to a nosocomial published maps and institutional affiliations. influenza outbreak. Infect Control Hosp Epidemiol. 2002;23(10):615–9. 7. Vu D, Peck AJ, Nichols WG, Varley C, Englund JA, Corey L, et al. Safety and tolerability of oseltamivir prophylaxis in hematopoietic stem cell transplant recipients: a retrospective case-control study. Clin Infect Dis. 2007;45(2):187–93. 8. Schepetiuk S, Papanaoum K, Qiao M. Spread of influenza a virus infection in hospitalised patients with cancer. Aust NZ J Med. 1998;28:475–6. 9. Tsagris V, Nika A, Kyriakou D, Kapetanakis I, Harahousou E, Stripeli F, et al. Influenza A/H1N1/2009 outbreak in a neonatal intensive care unit. J Hosp Infect. 2012;81(1):36–40. 10. Ye M, Jacobs A, Khan MN, Jaipaul J, Oda J, Johnson M, et al. Evaluation of the use of oseltamivir prophylaxis in the control of influenza outbreaks in long-term care facilities in Alberta, Canada: a retrospective provincial database analysis. BMJ Open. 2016;6:e011686. 11. Yousuf HM, Englund J, Couch R, Rolston K, Luna M, Goodrich J, et al. Influenza among hospitalized adults with leukemia. Clin Infect Dis. 1997; 24(6):1095–9. 12. Godoy P, Romero A, Soldevila N, Torner N, Jané M, Martínez A, et al. Influenza vaccine effectiveness in reducing severe outcomes over six influenza seasons, a case-case analysis, Spain, 2010/11 to 2015/16. Euro Surveill. 2018;23(43). 13. Domínguez A, Romero-Tamarit A, Soldevila N, Godoy P, Martínez A, Torner N, et al. Effectiveness of antiviral treatment in preventing death in severe hospitalised influenza cases over six seasons. Epidemiol Infect. 2018;146(7): 799–808. 14. Generalitat de Catalunya. Decret 2013/2015, de 15 de setembre, pel qual es crea la Xarxa de Vigilància Epidemiològica i es regulen els sistemes de notificacio de malalties de declaració obligatòria i els brots epidèmics. DOGC. 2015;6958:1–19. 15. Enstone JE, Myles PR, Openshaw PJM, Gadd EM, Lim WS. Nosocomial pandemic (H1N1) 2009, United Kingdom, 2009–2010. Emerg Infect Dis. 2011;17:592–8. 16. Macesic N, Kotsimbos TC, Kelly PCA. Hospital-acquired influenza in an Australian sentinel surveillance system. Med J Aust. 2013;198:370–2. 17. Alvarez-Lerma F, Marin-Corral J, Vila C, Masclans JR, Loeches IM, Barbadillo S, et al. Characteristics of patients with hospital-acquired influenza A (H1N1)pdm09 virus admitted to the intensive care unit. J Hosp Infect. 2017; 95(2):200–6. 18. Mereckiene J, Cotter S, Nicoll A, Lopalco P, Noori T, Weber J, et al. Seasonal influenza immunisation in Europe. Overview of recommendations and vaccination coverage for three seasons: pre-pandemic (2008/09), pandemic (2009/10) and post-pandemic (2010/11). Eurosurveillance. 2014;19(16):20780. 19. Chironna M, Tafuri S, Santoro N, Prato R, Quarto M, Germinario CA. A nosocomial outbreak of 2009 pandemic influenza A(H1N1) in a