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Eurosurveillance, Volume 22, Issue 7, 16 February 2017
Rapid communication
Kissling, Rondy, and I-MOVE/I-MOVE+ study team: Early 2016/17 vaccine effectiveness estimates against influenza A(H3N2): I-MOVE multicentre case control studies at primary care and hospital levels in Europe

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Citation style for this article: Kissling E, Rondy M, I-MOVE/I-MOVE+ study team. Early 2016/17 vaccine effectiveness estimates against influenza A(H3N2): I-MOVE multicentre case control studies at primary care and hospital levels in Europe. Euro Surveill. 2017;22(7):pii=30464. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2017.22.7.30464

Received:09 February 2017; Accepted:16 February 2017


The 2016/17 influenza season in Europe is marked by the predominant circulation of influenza A(H3N2) viruses [1], with significant pressure on hospitals, mostly due to patients aged 65 years and older developing severe disease [1]. Many European countries have reported excess all-cause mortality [2]. Initial estimates based on Swedish and Finnish electronic databases suggest low influenza vaccine effectiveness (IVE) among older adults [3,4]. We measured early IVE at primary care and hospital levels against laboratory-confirmed influenza A(H3N2) in Europe.

Primary care and hospital-based multicentre case control studies in Europe to measure influenza vaccine effectiveness

We conducted separate multicentre primary care and hospital-based case–control studies and analyses using the test-negative design (TND). We have described the methods in detail previously [5-7].

In the primary care study, comprising 893 practitioners (including general practitioners and paediatricians) in 12 countries, we included a systematic sample of all community-dwelling patients presenting to their practitioner with influenza-like illness (ILI), as defined by the European Union ILI case definition (sudden onset of symptoms and at least one of the following systemic symptoms: fever or feverishness, malaise, headache, myalgia, and at least one of the following respiratory symptoms: cough, sore throat, shortness of breath). In the hospital study, comprising 27 hospitals from 11 countries, we included community-dwelling patients aged 65 years and older admitted to hospital for influenza-related clinical conditions with symptoms compatible with severe acute respiratory infection (SARI). Each study site adapted a generic protocol to their local setting [8,9].

At each study site, the study period commenced more than 14 days after the start of the vaccination campaign and lasted from the week of the first influenza case to the date of sending data for the interim analysis at the end of January 2017.

A case of confirmed influenza was an ILI (primary care) or SARI (hospital) patient who was swabbed and tested positive for influenza A(H3N2) virus using real-time RT-PCR. Controls were ILI (primary care) or SARI (hospital) patients who tested negative for any influenza virus using RT-PCR.

We excluded patients with contraindications for influenza vaccination, SARI patients discharged from a previous hospital stay within 48 hours of symptom onset (hospital), those with a previous laboratory-confirmed influenza in the season, those refusing to participate or unable to consent, those who had received antiviral drugs before swabbing (primary care), those swabbed more than 7 days after symptom onset, patients with missing laboratory results and any patients positive to any influenza virus other than influenza A(H3N2).

Practitioners and hospital teams collected clinical and epidemiological information including date of symptom onset and date of swabbing, 2016/17 seasonal vaccination status, date of vaccination and vaccine product administered, 2015/16 seasonal vaccination status, sex, age, presence of chronic conditions, whether the patient belonged to a target group for influenza vaccination (primary care) and number of hospitalisations for chronic conditions in the past 12 months.

We defined individuals as vaccinated if they had received at least one dose of the 2016/17 influenza vaccine at least 15 days before ILI/SARI symptom onset. We excluded individuals vaccinated less than 15 days before symptom onset and individuals with unknown vaccination date.

At primary care level, nine study sites (France, Germany, Hungary, Ireland, the Netherlands, Portugal, Romania, Spain and Sweden) participated in a sub-study using an in-depth laboratory protocol, and randomly selected positive influenza A(H3N2) specimens for genetic sequencing.

We pooled individual patient data in each study and computed the pooled IVE as ((1−OR of vaccination between cases and controls) × 100) using logistic regression with study site as a fixed effect. We conducted a complete case analysis excluding patients with missing values for any of the variables in the model. All IVE estimates were adjusted for study site, calendar time of onset and age (where sample size allowed). Further potential confounding factors included sex, underlying chronic conditions and hospitalisations in the past year.

We stratified IVE by age group. We measured IVE among the target groups for influenza vaccination at primary care level, defined as older adults (aged over 54, 59 or 64 years depending on study site), individuals with chronic conditions and other groups for whom the vaccine was recommended in a given country (e.g. pregnant women, healthcare workers and other professional groups, depending on the study site).

Influenza vaccine effectiveness in primary care

In the primary care analysis, we included 2,250 cases of influenza A(H3N2) and 2,773 negative controls.

The 2016/17 seasonal influenza vaccine coverage was 10.3% among influenza A(H3N2) cases and 10.9% among controls. Compared with cases, a greater proportion of controls belonged to the age group of 0–4-year-olds (26.1% vs 12.3%) and a lower proportion belonged to the age group of 5–14-year-olds (12.1% vs 22.7%) (Table 1).

Table 1

Influenza A(H3N2) cases and controls included in the 2016/17 season influenza vaccine effectiveness analysis, I-MOVE/I-MOVE+ multicentre case control studies (primary care (n = 5,023) and hospital (n = 635) levels) Europe, influenza season 2016/17

Variables Primary care level Hospital level
Number of A(H3N2) n = 2,250 Number of controls
n = 2,773
Number of A(H3N2)
n = 267
Number of controls
n = 368
n Total % n Total % n Total % n Total %
Median age (years) 29 28 79 80
Age groups (years)
0–4 276 2,242 12.3 723 2,766 26.1 NA NA
5–14 508 2,242 22.7 336 2,766 12.1 NA NA
15–64 1,177 2,242 52.5 1,438 2,766 52.0 NA NA
65–79 234 2,242 10.4 214 2,766 7.7 138 267 51.7 185 368 50.3
≥ 80 47 2,242 2.1 55 2,766 2.0 129 267 48.3 183 368 49.7
Missing 8 7 0 0
Sex
Female 1,126 2,237 50.3 1,407 2,758 51.0 141 267 52.8 190 368 51.6
Missing 13 15 0 0
Chronic conditions
At least one chronic condition 451 2,237 20.2 542 2,743 19.8 237 255 92.9 321 344 93.3
Missing 13 30 12 24
At least one hospitalisation in the previous 12 months for chronic conditions 26 2,196 1.2 57 2,686 2.1 66 247 26.7 146 334 43.7
Missing 54 87 20 34
Target group for vaccination
Belongs to a target group for vaccination 616 2,241 27.5 706 2,755 25.6 267 267 100.0 368 368 100.0
Missing 9 18 0 0
Swab delay
Swabbed within 3 days of symptom onset 2,024 2,250 90.0 2,291 2,773 82.6 154 267 57.7 212 368 57.6
Vaccination status
Seasonal flu vaccination 16–17 231 2,250 10.3 301 2,773 10.9 108 267 40.4 191 368 51.9
Seasonal flu vaccination 15–16 223 2,196 10.2 316 2,665 11.9 117 252 46.4 199 362 55.0
Missing 54 108 15 6
Previous and current season influenza vaccination
Not vaccinated in any season 1,929 2,196 87.8 2,284 2,665 85.7 128 252 50.8 147 362 40.6
Current season vaccination only 44 2,196 2.0 65 2,665 2.4 7 252 2.8 16 362 4.4
Previous season vaccination only 43 2,196 2.0 95 2,665 3.6 20 252 7.9 28 362 7.7
Current and previous season vaccination 180 2,196 8.2 221 2,665 8.3 97 252 38.5 171 362 47.2
Missing 54 108 15 6
Type of vaccine
Not vaccinated 2019 2,215 91.2 2,472 2,725 90.7 159 261 60.9 177 359 49.3
Inactivated subunit egg 97 2,215 4.4 108 2,725 4.0 65 261 24.9 101 359 28.1
Inactivated split virion egg 71 2,215 3.2 118 2,725 4.3 32 261 12.3 74 359 20.6
Adjuvanted 18 2,215 0.8 21 2,725 0.8 5 261 1.9 7 359 1.9
Quadrivalent vaccine 10 2,215 0.5 6 2,725 0.2 0 261 0.0 0 359 0.0
Missing vaccine type 35 48 6 9
Month of onset
October 2016 4 2,250 0.2 84 2,773 3.0 0 267 0.0 0 368 0.0
November 2016 154 2,250 6.8 759 2,773 27.4 3 267 1.1 6 368 1.6
December 2016 1,199 2,250 53.3 1,194 2,773 43.1 174 267 65.2 236 368 64.1
January 2017 893 2,250 39.7 736 2,773 26.5 90 267 33.7 126 368 34.2
Study sites
Croatia 13 2,250 0.6 13 2,773 0.5 NA NA
Finland NA NA 14 267 5.2 17 368 4.6
France 584 2,250 26.0 609 2,773 22.0 35 267 13.1 116 368 31.5
Germany 28 2,250 12.8 873 2,773 31.5 NA NA
Hungary 39 2,250 1.7 84 2,773 3.0 NA NA
Ireland 135 2,250 6.0 113 2,773 4.1 NA NA
Italy 411 2,250 18.3 367 2,773 13.2 37 267 13.9 58) 368 15.8
Lithuania NA NA 30 267 11.2 18 368 4.9
Navarra NA NA 20 267 7.5 34 368 9.2
The Netherlands 47 2,250 2.1 142 2,773 5.1 6 267 2.2 19 368 5.2
Poland 9 2,250 0.4 33 2,773 1.2 NA NA
Portugal 156 2,250 6.9 80 2,773 2.9 36 267 13.5 14 368 3.8
Romania 27 2,250 1.2 9 2,773 0.3 60 267 22.5 37 368 10.1
Spain 474 2,250 21.1 303 2,773 10.9 29 267 10.9 55 368 14.9
Sweden 66 2,250 2.9 147 2,773 5.3 NA NA

NA: Not applicable.

Nine study sites sequenced 204 randomly selected specimens out of 1,817 (11.2%) (Table 2). Of these, 156 (76.5%) belonged to the 3C.2a1 clade A/Bolzano/7/2016, 46 (22.5%) to A/Hong Kong/4801/2014 (3C.2a) and two (1.0%) to A/Switzerland/9715293/2013 (3C.3a).

Table 2

Influenza A(H3N2) viruses characterised by clade, amino acid substitutions and study site, at nine participating laboratories, I-MOVE/I-MOVE+ primary care multicentre case control study, Europe, influenza season 2016/17 (n = 1,817)

Characterised viruses (clade) Germany
n = 289
France
n = 584
Hungary
n = 39
Ireland
n = 135
The Netherlands
n = 47
Portugal
n = 156
Romania
n = 27
Spain
n = 474
Sweden
n = 66
Total
n = 1,817
n % n % n % n % n % n % n % n % n % n %
A/HongKong/4801/2014 (3C.2a) 10 6 3 0 8 8 4 3 4 46
N121K + S144K 3 30 6 100 3 100 0 1 12 8 100 4 100 3 100 3 75 31 67
A/Bolzano/7/2016 (3C.2a1) 33 19 3 5 20 23 8 36 9 156
N171K + N121K + I140M 10 30 0 0 0 7 35 2 9 4 50 8 22 3 33 34 22
N171K + N121K + T135K 2 6 0 2 67 0 3 15 0 0 1 3 3 33 11 7
N171K + N121K + K92R + H311Q 8 24 0 1 33 1 20 4 20 4 17 0 10 28 0 28 18
N171K + R142G 7 21 3 16 0 3 60 3 15 17 74 0 1 3 1 11 35 22
A/Switzerland/9715293/2013 (3C.3a) 0 0 0 2 0 0 0 0 0 2
Total sequenced/total A(H3N2) 43 15 25 4 6 15 7 5 28 60 31 20 12 44 39 8 13 20 204 11

Among the 156 viruses of the 3C.2a1 clade, further genetic groups have emerged in 108 (69.2%) (Table 2). These include 34 viruses in group 1 (22%), harbouring the I140M substitution located in the antigenic site A of the haemagglutinin, in addition to changes in amino acid positions 171 and 121, both located in the antigenic site D. Eleven viruses belonged to group 2 (7%), carrying the T135K mutation located in the antigenic site A and resulting in the loss of a glycosylation site, in addition to the already mentioned changes in positions 171 and 121. Twenty-eight viruses belonged to genetic group 3 (18%), carrying the K92R and H311Q substitutions located in the antigenic sites E and C, respectively, in addition to changes in positions 171 and 121. Finally, 35 viruses belonged to group 4 (22%), carrying the R142G mutation located in the antigenic site A and the N171K substitution. Thirty-one viruses (67%) belonging to the 3C.2a clade (A/HongKong/4801/2014) carried the substitutions N121K and S144K, the latter located in the antigenic site position A.

Adjusted IVE against influenza A(H3N2) across all age groups was 38.0% (95% CI: 21.3 to 51.2). It was 44.1% (95% CI: −12.3 to 72.2), 46.9% (95% CI: 25.2 to 62.3) and 23.4% (95% CI: −15.4 to 49.1) in 0–14, 15–64 and ≥ 65 year-olds, respectively. The IVE in the target group for vaccination was 25.7% (95% CI: 1.5 to 43.9) (Table 3).

Table 3

Pooled adjusted seasonal vaccine effectiveness against laboratory-confirmed influenza A(H3N2) by age group and target group for vaccination, I-MOVE/I-MOVE+ multicentre case control studies (primary care (n = 4,937) and hospital (n = 635)), influenza season 2016/17

Analyses Adjustment / stratification Cases Controls Adjusted VE 95% CI
All Vaccinated % All Vaccinated %
Primary care
All ages


Adjusted by study site only 2,216 229 10 2,721 297 11 10.9 −8.3 to 26.6
Adjusted by calendar time and study site 2,216 229 10 2,721 297 11 27.9 11.9 to 41.1
Adjusted by calendar time, age and study site 2,216 229 10 2,721 297 11 38.4   22.2 to 51.3  
Fully adjusted: calendar time, age, study site, presence of chronic conditions, sex 2,216 229 10 2,721 297 11 38.0 21.3 to 51.2
By age group (years)a

0–14 773 20 3 1,043 27 3 44.1 −12.3 to 72.2
15–64 1,164 69 6 1,410 126 9 46.9 25.2 to 62.3
≥ 65 278 140 50 268 144 54 23.4 −15.4 to 49.1
Target group for vaccinationa All ages 606 201 33 698 235 34 25.7 1.5 to 43.9
Hospital
≥ 65 years


Adjusted by study site only 267 108 40 368 191 52 −0.7 −46.8 to 30.9
Adjusted by calendar time and study site 267 108 40 368 191 52 3 −42.2 to 33.8
Adjusted by calendar time, age and study site 267 108 40 368 191 52 2.5 −43.6 to 33.8
Fully adjusted: time, age, study site, sex, chronic condition (lung, heart, renal disease, diabetes, cancer, obesity) and hospitalisation in the past year 240 95 40 316 162 51 2.0 −51.7 to 36.8
By age group (years)b
65–79 130 38 29 165 70 42 7.9 −67.3 to 49.3
≥ 80 115 59 51 167 102 61 2.4 −81.3 to 47.5

CI: confidence interval; VE: vaccine effectiveness at hospital level.

a Adjusted by study site, age, calendar time, presence of chronic conditions and sex.

b Adjusted by calendar time, age and study site.

Influenza vaccine effectiveness at hospital level

In the hospital study, we included 267 cases of influenza A(H3N2) and 368 negative controls.

The 2016/17 seasonal influenza vaccine coverage was 40.4% among influenza A(H3N2) cases and 51.9% among controls. A higher proportion of controls were vaccinated with inactivated split-virion vaccine group (20.6% vs 12.3%). A higher proportion of controls had been hospitalised for chronic conditions in the past twelve months (43.7% vs 26.7%) (Table 1).

Adjusted IVE against influenza A(H3N2) among those aged 65 years and older was 2.5% (95% CI: −43.6 to 33.8), it was 7.9% (95% CI: −67.3 to 49.3) among those aged 65 to 79 years and 2.4% (95% CI: −81.3 to 47.5) among those aged 80 years and older (Table 3).

Discussion

In primary care, early estimates suggest moderate IVE against influenza A(H3N2) among 0–64-year-olds and low IVE in the target group for influenza vaccination. Among those aged 65 years and older, IVE was low at both primary care and hospital level, however precision was low.

Viruses of the 3C.2a1 clade (A/Bolzano/7/2016) predominated in the study sites participating in the laboratory protocol. Compared to the vaccine virus A/HongKong/4801/2014, they had the N171K substitution and in addition, most of them had the N121K substitution. This clade appears to be antigenically similar to the A(H3N2) vaccine component. However, our sequencing results suggest that this cluster is continuing to evolve: 70% of sequenced viruses had further mutations, forming clusters defined by new HA1 amino acid substitutions in antigenic sites, including antigenic site A. We did not measure IVE against A/Bolzano/7/2016 viruses, as estimates were not robust because of the small sample size.

The 2016/17 early primary care IVE estimate among all ages was 38% (95% CI: 21.3 to 51.2), similar to the early estimates from the Canadian Sentinel Practitioner Surveillance [10] and comparable to early estimates against influenza A(H3N2) in previous seasons: 43% (95% CI: -0.4 to 67.7) in 2011/12 and 41.9% (95% CI: −67.1 to 79.8) in 2012/13 [11,12]. This season, we reached better precision thanks to a larger sample size.

The IVE estimates among those aged 65 years and older and target groups for vaccination were low and, despite low precision, reinforce the risk assessment from the European Centre for Disease Prevention and Control (ECDC), which suggests to consider administering antiviral drugs to populations vulnerable to severe influenza irrespective of vaccination status, in line with national and international recommendations [1].

These early results are included in the Global Influenza Vaccine Effectiveness (GIVE) report to contribute to the World Health Organization consultation and information meeting on the composition of influenza virus vaccines for use in the 2017/18 northern hemisphere influenza season [13].

Conclusion

The early season estimates presented here corroborate the suboptimal performance of inactivated influenza vaccine against influenza A(H3N2) that the I-MOVE team and others have reported in the previous post-2009 pandemic seasons [14,15].


I-MOVE/I-MOVE + study team

Authors contributing to the primary care and hospital study

EpiConcept, France

Esther Kissling, EpiConcept

Alain Moren, EpiConcept

Marc Rondy, EpiConcept

Marta Valenciano, EpiConcept

Croatia

Bernard Kaić, Croatian Institute of Public Health
Sanja Kurečić Filipović, Croatian Institute of Public Health
Iva Pem-Novosel, Croatian Institute of Public Health
Zvjezdana Lovrić, Croatian Institute of Public Health

Hungary

Judit Kriszttina Horváth, National Center for Epidemiology, Department of Disease Prevention and Surveillance

Annmária Ferenczi, National Center for Epidemiology, Department of Disease Prevention and Surveillance

Beatrix Oroszi, National Center for Epidemiology

Zita Vizler, Office of the Chief Medical Officer

Éva Hercegh, National Center for Epidemiology, Influenza Virus Laboratory

Bálin Szala, National Center for Epidemiology, Influenza Virus Laboratory

Italy

Valeria Alfonsi, Istituto Superiore di Sanità

Antonino Bella, Istituto Superiore di Sanità
Caterina Rizzo, Istituto Superiore di Sanità

Poland

Iwona Paradowska-Stankiewicz, National Institute of Public Health-National Institute of Hygiene, Warsaw 
Monika Korczyńska, National Institute of Public Health-National Institute of Hygiene, Warsaw

Lidia Brydak, National Institute of Public Health-National Institute of Hygiene, Warsaw

Portugal

Baltazar Nunes, Departamento de Epidemiologia, Instituto Nacional de Saúde Dr. Ricardo Jorge

Ausenda Machado, Departamento de Epidemiologia, Instituto Nacional de Saúde Dr. Ricardo Jorge

Ana Paula Rodrigues, Departamento de Epidemiologia, Instituto Nacional de Saúde Dr. Ricardo Jorge

Verónica Gomez, Departamento de Epidemiologia, Instituto Nacional de Saúde Dr. Ricardo Jorge

Irina Kislaya, Departamento de Epidemiologia, Instituto Nacional de Saúde Dr. Ricardo Jorge

Mafalda Sousa Uva, Departamento de Epidemiologia, Instituto Nacional de Saúde Dr. Ricardo Jorge

Raquel Guiomar, Departamento de Doenças Infeciosas, Instituto Nacional de Saúde Dr. Ricardo Jorge

Pedro Pechirra, Departamento de Doenças Infeciosas, Instituto Nacional de Saúde Dr. Ricardo Jorge

Paula Cristóvão, Departamento de Doenças Infeciosas, Instituto Nacional de Saúde Dr. Ricardo Jorge

Patrícia Conde, Departamento de Doenças Infeciosas, Instituto Nacional de Saúde Dr. Ricardo Jorge

Inês Costa, Departamento de Doenças Infeciosas, Instituto Nacional de Saúde Dr. Ricardo Jorge

Romania

Daniela Pitigoi, University of Medicine and Pharmacy Carol Davila, National Institute for Research Cantacuzino, Bucharest, Romania 

Emilia Lupulescu, National Institute for Research Cantacuzino 

Alina Elena Ivanciuc, National  Institute for  Research Cantacuzino 

Mihaela Lazar, National Institute for Research Cantacuzino 

Carmen Maria Cherciu,  National Institute for Research  Cantacuzino 

Spain

Amparo Larrauri, National Centre of Epidemiology, CIBER  Epidemiología y Salud Pública (CIBERESP), Institute of Health Carlos III

Alin Gherasim, National Centre of Epidemiology, Institute of Health Carlos III

Francisco Pozo, National Centre for Microbiology, National Influenza Reference Laboratory, WHO-National Influenza Centre, Institute of Health Carlos III

Luis García Comas. Dirección General de Salud Pública. Comunidad de Madrid

Fernando Gonzalez Carril, Departamento de Salud, Gobierno del País Vasco

Jesus Castilla, Instituto de Salud Pública de Navarra, IdiSNA, Pamplona, CIBER  Epidemiología y Salud Pública (CIBERESP)

Carmen Quiñones, Dirección General de Salud Pública y Consumo de La Rioja

Jaume Giménez, Servicio de Epidemiología, Dirección General de Salut Pública, Mallorca, Baleares

Daniel Castrillejo, Servicio de Epidemiología. DGSC, Ciudad Autónoma de Melilla

Madalen Oribe Amores, Subdirección de Salud Pública de Gipuzkoa, País Vasco m-

Miriam García, Dirección General de Salud Pública, Aragón

The Netherlands

Adam Meijer, National Institute for Public Health and the Environment (RIVM)

Authors contributing to the primary care study

France

Alessandra Falchi, EA7310, Laboratoire de Virologie, Université de Corse-Inserm, F-20250, Corse

Ana-Maria Vilcu, Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique (IPLESP UMRS 1136)

Cécile Souty, Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique (IPLESP UMRS 1136)

Thierry Blanchon, Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d’épidémiologie et de Santé Publique

Sylvie Behillil, Coordinating Center of the National Reference Center for influenza viruses, Unit of Molecular Genetics of RNA Viruses, Institut Pasteur, UMR3569 CNRS, University Paris Diderot Sornonne Paris Cité, Institut Pasteur

Vincent Enouf, Coordinating Center of the National Reference Center for influenza viruses, Unit of Molecular Genetics of RNA Viruses, Institut Pasteur, UMR3569 CNRS, University Paris Diderot Sornonne Paris Cité, Institut Pasteur

Sylvie van der Werf, Coordinating Center of the National Reference Center for influenza viruses, Unit of Molecular Genetics of RNA Viruses, Institut Pasteur, UMR3569 CNRS, University Paris Diderot Sornonne Paris Cité, Institut Pasteur

Bruno Lina, Laboratoire de Virologie, CNR des virus influenza, Institut des Agents Infectieux, Groupement Hospitalier Nord des HCL, Lyon, France; Laboratoire Virpath, CIRI Inserm U1111, CNRS 5308, ENS, UCBL, Faculté de Médecine LYON Est, Université de Lyon, Lyon, France

Martine Valette, Laboratoire de Virologie, CNR des virus influenza, Institut des Agents Infectieux, Groupement Hospitalier Nord des HCL, Lyon, France

Germany

Anicka Reuss, Department for Infectious Disease Epidemiology, Robert Koch Institute

Ute Preuss, Department for Infectious Disease Epidemiology, Robert Koch Institute

Silke Buda, Department for Infectious Disease Epidemiology, Robert Koch Institute

Kerstin Prahm, Department for Infectious Disease Epidemiology, Robert Koch Institute

Brunhilde Schweiger, National Reference Center for Influenza, Robert Koch Institute

Marianne Wedde, National Reference Center for Influenza, Robert Koch Institute

Maria Martin, National Reference Center for Influenza, Robert Koch Institute

Barbara Biere, National Reference Center for Influenza, Robert Koch Institute

Ireland

Joan O’Donnell, HSE-Health Protection Surveillance Centre

Lisa Domegan, HSE-Health Protection Surveillance Centre

Anita Kelly, HSE-Health Protection Surveillance Centre

Michael Joyce, Irish College of General Practitioners

Claire Collins, Irish College of General Practitioners

Cillian de Gascun, National Virus Reference Laboratory, University College Dublin

Jeff Connell, National Virus Reference Laboratory, University College Dublin

Grainne Tuite, National Virus Reference Laboratory, University College Dublin

Margaret Duffy, National Virus Reference Laboratory, University College Dublin

Joanne Moran, National Virus Reference Laboratory, University College Dublin

Bridget Hogg, National Virus Reference Laboratory, University College Dublin

Linda Dunford, National Virus Reference Laboratory, University College Dublin

Sweden

Mia Brytting, the Public Health Agency of Sweden

Katherina Zakikhany, the Public Health Agency of Sweden

The Netherlands

Marit de Lange, National Institute for Public Health and the Environment (RIVM)

Gé Donker, Netherlands Institute for Health Services Research (NIVEL)

European Centre for Disease Prevention and Control (ECDC)

Kari Johansen, European Centre for Disease Prevention and Control

Pasi Penttinen, European Centre for Disease Prevention and Control

Authors contributing to the hospital study

Finland

Ritva Syrjänen, National Institute for Health and Welfare (THL), Impact Assessment
Niina Ikonen, National Institute for Health and Welfare (THL), Viral Infections

Hanna Nohynek, National Institute for Health and Welfare (THL), Vaccination Programme

Anu Haveri, National Institute for Health and Welfare (THL), Viral Infections

France

Odile Launay, Inserm, F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC); CIC De Vaccinologie, Cochin-Pasteur, APHP, Université Paris Descartes, Sorbonne

Florence Galtier. Inserm, F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC); CIC 1411, hôpital St Eloi, CHU de Montpellier

Philippe Vanems, Inserm, F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC); Infection Control and Epidemiology Unit, Hôpital Edouard Herriot, Hospices Civils de Lyon; Emerging Pathogens Laboratory - Fondation Mérieux, Centre International de Recherce en Infectiologie, INSERM U1111, Centre National de la Recherche Scientifiqe (CNRS), UMR5308; Ecole Nationale Supérieure (ENS) de Lyon, Université Claude Bernard Lyon

Fabrice Lainé, Inserm, F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC); CIC 1414- Pôle Santé Publique, CHU de Rennes - Hôpital Pontchaillou, Rennes

Nezha Lenzi, Inserm, F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC)

Hungary

Katalin Antmann, Hospital Hygiene Department Semmelweis University

Kamilla Nagy, Hospital Hygiene Department, Univeristy of Szeged

Lithuania

Giedre Gefenaite, Department of Infectious diseases, Lithuanian University of Health Sciences

Monika Kuliešė, Department of Infectious diseases, Lithuanian University of Health Sciences

Aukse Mickiene, Department of Infectious diseases, Lithuanian University of Health Sciences

Ligita Jancoriene, Clinic of Infectious, Chest Diseases, Dermatovenerology and Allergology, Vilnius University Faculty of Medicine; University Hospital of Infectious Diseases and Tuberculosis, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Centre of Infectious Diseases

Birute Zablockiene, Clinic of Infectious, Chest Diseases, Dermatovenerology and Allergology, Vilnius University Faculty of Medicine; University Hospital of Infectious Diseases and Tuberculosis, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Centre of Infectious Diseases

Gyte Damuleviciene, Department of Geriatrics, Lithuanian University of Health Sciences

Rita Grimalauskaite, Department of Geriatrics, Lithuanian University of Health Sciences

Alfredas Bagdonas, Department of Internal Diseases, Lithuanian University of Health Sciences

Navarre, Spain

Itziar Casado, Instituto de Salud Pública de Navarra, IdiSNA, Pamplona;CIBER Epidemiología y Salud Pública

Jorge Díaz-González, Instituto de Salud Pública de Navarra, IdiSNA, Pamplona; CIBER Epidemiología y Salud Pública

Jesús Castilla, Instituto de Salud Pública de Navarra, IdiSNA, Pamplona; CIBER Epidemiología y Salud Pública

Romania

Maria Nitescu: Matei Bals Hospital

Emanoil Ceausu: Victor Babes Hospital

Codrina Bejan: Sfanta Parascheva Hospital

The Netherlands

Sierk Marbus, National Institute for Public Health and the Environment (RIVM)

Acknowledgements

Funding: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634446 to conduct the study in individuals aged 65 years or more.

ECDC has contributed to fund the coordination and some study sites under the Framework contract No ECDC/2014/026 for the individuals aged less than 65 years.

The Lithuanian study sites were supported by a grant from Research Council of Lithuania (SEN-03/2015).

The I-MOVE/I-MOVE+ study team is very grateful to all patients, general practitioners, paediatricians, hospital teams, laboratory teams, regional epidemiologists who have contributed to the study.

We acknowledge the authors, originating and submitting laboratories of the sequences from GISAID’s EpiFlu Database used for this study. All submitters of data may be contacted directly via the GISAID website www.gisaid.org

Conflict of interest

None declared.

Authors’ contributions

Esther Kissling: coordination I-MOVE/I-MOVE+ primary care network, study design, analysis of primary care data, interpretation of results, manuscript writing

Marc Rondy: coordination I-MOVE+ hospital network, study design, analysis of hospital data, interpretation of results, manuscript writing

Both authors contributed equally to the study and manuscript.

I-MOVE/I-MOVE+ study team:

Primary care and hospital sites at national/regional level: data collection, data validation, results interpretation, review of manuscript. Laboratories: virological analysis, genetic characterisation, interpretation of results.

Francisco Pozo: coordinated the I-MOVE/I-MOVE+ virological analysis of the primary care study.

Alain Moren, Marta Valenciano: study design, coordination of I-MOVE/I-MOVE+ network, interpretation of results, contribution to manuscript writing.

Kari Johansen, Pasi Penttinen: study design, interpretation of results, review of manuscript.


References

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