Register-based cohort studies to estimate influenza vaccine effectiveness. THL, the National Institute of Finland Project Funding: Integrated Monitoring of Vaccines in Europe (I-MOVE+)This project has received funding from the European Union’s H2020 research and innovation programme under grant agreement No 634446. Development of Robust and Innovative Vaccines Effectiveness (DRIVE)This work has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777363.This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

1. PREVIOUS EXPOSURE TO
NATURAL INFECTION MATTERS
Ulrike Baum, Ritva Syrjänen, Kari Auranen, Niina Ikonen, Hanna Nohynek
The effect of influenza A infection in 2016/17 on influenza A and B infection in 2017/18 in the Finnish elderly
https://www.paivanlehti.fi/iskiko-flunssa-vai-influenssa-ja-kuinka-yskitaan-oikein/

2. DISCLOSURE
 Conflict of Interest
– None
 Project Funding
– Integrated Monitoring of Vaccines in Europe (I-MOVE+)
This project has received funding from the European Union’s H2020 research and innovation programme under grant agreement No 634446.
– Development of Robust and Innovative Vaccines Effectiveness (DRIVE)
This work has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777363.
This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.
 Travel Grant
– Funding Initiative at ESCAIDE 2018
The effect of influenza A infection in 2016/17 on influenza A and B infection in 2017/18 in the Finnish elderly

3. RESEARCH QUESTION
What happened to the more
than 7000 elderly 2016/17
influenza A cases in the
following season?
The effect of influenza A infection in 2016/17 on influenza A and B infection in 2017/18 in the Finnish elderly
https://ecdc.europa.eu/en/seasonal-influenza/season-2016-17

4. BACKGROUND
 Register-based cohort studies to estimate influenza vaccine
effectiveness
 Acquired active immunity
– Artificial through vaccination
– Natural through infection
 Exposure to natural infection very difficult to cover in large-
scale observational studies
The effect of influenza A infection in 2016/17 on influenza A and B infection in 2017/18 in the Finnish elderly

5. REGISTER-BASED COHORT STUDY
 Elderly aged 65-100 years
 Laboratory-confirmed
influenza A in 2016/17
 Laboratory-confirmed
influenza A or B in 2017/18
 Influenza vaccinations
2012/13-2017/18
 Potential confounders
Person
Identifier
Population
Information
System
National
Vaccination
Register
National
Infectious
Diseases
Register
Care
Register
for Health
Care
Register of
Primary
Health
Care Visits
The effect of influenza A infection in 2016/17 on influenza A and B infection in 2017/18 in the Finnish elderly
Baum, U. et al. (2018) ‘Cohort study design for estimating the effectiveness of seasonal influenza vaccines in real time based on
register data: The Finnish example’, Scandinavian Journal of Public Health. doi: 10.1177/1403494818808635.

6. BASELINE CHARACTERISTICS
The effect of influenza A infection in 2016/17 on influenza A and B infection in 2017/18 in the Finnish elderly
0%
20%
40%
60%
80%
100%
Relativefrequency
2016/17 influenza A cases (N=7407) Rest of the cohort (N=1,181,614)

7. 2017/18 INFLUENZA EPIDEMIC
0
200
400
600
800
40 42 44 46 48 50 52 2 4 6 8 10 12 14 16 18 20
Influenza A (7199 cases) Influenza B (5966 cases)
0%
25%
50%
75%
100%
40 42 44 46 48 50 52 2 4 6 8 10 12 14 16 18 20
Cumulative vaccination coverage
The effect of influenza A infection in 2016/17 on influenza A and B infection in 2017/18 in the Finnish elderly
0
25
50
75
100
40 42 44 46 48 50 52 2 4 6 8 10 12 14 16 18 20
Influenza A (16 cases) Influenza B (146 cases)
0%
25%
50%
75%
100%
40 42 44 46 48 50 52 2 4 6 8 10 12 14 16 18 20
Cumulative vaccination coverage
2016/17 influenza A cases (N=7407)
Rest of the cohort (N=1,181,614)

8. TIME-TO-EVENT ANALYSIS
 Comparison of the influenza A, influenza B respectively,
hazard rates in those who had a laboratory-confirmed
influenza A infection in 2016/17 with the corresponding
hazard rates in the rest of the cohort
* adjusted for age, sex, presence of chronic diseases, number of hospitalisations in 2016,
* influenza vaccination in 2017/18 and five previous seasons
The effect of influenza A infection in 2016/17 on influenza A and B infection in 2017/18 in the Finnish elderly
Outcome
Hazard ratio*
(95% confidence interval)
Influenza A 0.20 (0.12; 0.33)
Influenza B 2.48 (2.10; 2.93)

9. INTERPRETATION AND DISCUSSION
 Residual immunity against
influenza A
 Replacement towards
influenza B
 Increased frailty of previous
season’s influenza A cases
 Impact on vaccine
effectiveness estimates
The effect of influenza A infection in 2016/17 on influenza A and B infection in 2017/18 in the Finnish elderly
0
0,5
1
1,5
2
2,5
3
3,5
Influenza A Influenza B
Hazardratio

10. PREVIOUS EXPOSURE TO
NATURAL INFECTION MATTERS
Ulrike Baum, Ritva Syrjänen, Kari Auranen, Niina Ikonen, Hanna Nohynek
The effect of influenza A infection in 2016/17 on influenza A and B infection in 2017/18 in the Finnish elderly
https://www.paivanlehti.fi/iskiko-flunssa-vai-influenssa-ja-kuinka-yskitaan-oikein/