Evaluating the Effectiveness of Influenza Vaccine in People with At-Risk Medical Conditions: A Test-Negative Design Case-Control Study for the Seasonal Influenza Vaccine Effectiveness II (SIVE II) Project

Background: Seasonal trivalent inactivated influenza (TIV) vaccine effectiveness (VE) against laboratory confirmed influenza in adults with at-risk medical conditions is not well established. Previous studies have been hampered by small sample sizes to assess VE for each at-risk medical condition recommended for vaccination. Larger better powered studies investigating how influenza VE varied in those with specific risk factors associated with poor influenza outcomes is therefore required. Methods: A test-negative design case-control study of influenza VE was carried out in adults with at-risk medical conditions in Scotland between 2010/11 to 2015/16. We used individual patient-level health administrative data from 223 primary care practices linked with hospital and laboratory data (n=10275 swabs from n=9147 individuals). Generalised additive logistic regression was used to provide adjusted VE estimates between adults (aged >18 years) with laboratory-confirmed influenza compared to those with a negative test for influenza. Findings: Significant positive VE was found for all adults with chronic heart disease (31%; 95% confidence interval [CI]: 10 to 48), diabetes (34%; 95%CI: 12 to 51), impaired immune function (51%; 95%CI: 13 to 72), chronic kidney disease (40%; 95%CI: 17 to 57) and Body Mass Index (BMI) >30 to <40 kg/m2 (62%; 95%CI: 26 to 81). Significant VE was demonstrated for impaired immune function amongst most age groups including younger adults (18-54 years; 68%; 95%CI: 17 to 88) and those aged 85 years and over (42%; 95%CI: 4 to 65). The oldest adults aged 85 years and over had a significant positive VE for chronic respiratory disease (20%; 95%CI: 3 to 34), diabetes (34%; 95%CI: 11 to 51), and impaired immune function (42%; 95%CI: 4 to 65). Non-significant VE was found for those with chronic neurological disease (18%; 95%CI: -16 to 43). Interpretation: The amount of vaccine protection against laboratory-confirmed influenza varied amongst adults with at-risk medical conditions in different age groups. Seasonal influenza vaccination programmes should additionally consider those with BMI >30 to <40 kg/m2. Available alternate vaccines which aim to improve immune response should be considered for at-risk groups with consistently low TIV VE (e.g. neurological disease). Funding Statement: National Institute for Health Research Health Technology Assessment Programme (project number 13/34/14), Health Data Research UK, Asthma UK Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The Privacy Advisory Committee of the Information Services Division, NSS, approved the linkage and the statistical analysis of the anonymised data used in this study. Ethical permission was granted from the National Research Ethics Service Committee, West Midlands - Edgbaston [15/WM/0035].