Abstract
We measured early 2016/17 season influenza vaccine effectiveness (IVE) against influenza A(H3N2) in Europe using multicentre case control studies at primary care and hospital levels. IVE at primary care level was 44.1%, 46.9% and 23.4% among 0–14, 15–64 and ≥ 65 year-olds, and 25.7% in the influenza vaccination target group. At hospital level, IVE was 2.5%, 7.9% and 2.4% among ≥ 65, 65–79 and ≥ 80 year-olds. As in previous seasons, we observed suboptimal IVE against influenza A(H3N2).
Keywords: influenza, influenza like illness, ILI, severe acute respiratory infection, SARI, vaccine effectiveness, vaccines, immunisation
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].
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
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)
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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