Mid-season real-time estimates of seasonal influenza vaccine effectiveness in persons 65 years and older in register-based surveillance, Stockholm County, Sweden, and Finland, January 2017

摘要

Systems for register-based monitoring of vaccine effectiveness (VE) against laboratory-confirmed influenza (LCI) in real time were set up in Stockholm County, Sweden, and Finland, before start of the 2016/17 influenza season, using population-based cohort studies. Both in Stockholm and Finland, an early epidemic of influenza A(H3N2) peaked in week 52, 2016. Already during weeks 48 to 50, analyses of influenza VE in persons 65 years and above showed moderately good estimates of around 50%, then rapidly declined by week 2, 2017 to 28% and 32% in Stockholm and Finland, respectively. The sensitivity analyses, where time since vaccination was taken into account, could not demonstrate a clear decline, neither by calendar week nor by time since vaccination. Most (68%) of the samples collected from vaccinated patients belonged to the 3C.2a1 subclade with the additional amino acid substitution T135K in haemagglutinin (64%) or to subclade 3C.2a with the additional haemagglutinin substitutions T131K and R142K (36%). The proportion of samples containing these alterations increased during the studied period. These substitutions may be responsible for viral antigenic change and part of the observed VE drop. Another possible cause is poor vaccine immunogenicity in older persons. Improved influenza vaccines are needed, especially for the elderly. Keywords: Finland, Sweden, viral infections, influenza, influenza virus, surveillanceIntroductionSystems for register-based monitoring of vaccine effectiveness (VE) against laboratory-confirmed influenza (LCI) in real time were set up in Stockholm County, Sweden, and in Finland, before the start of the 2016/17 influenza season, using population-based cohort studies [1,2]. In both locations, after an initial moderately high VE of about 50%, a rapid and sharp 20% decline in VE was observed. In addition, reports from hospitals and outpatient clinics indicated that a majority of patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) were elderly people, i.e. those 65 years and above, and that many of them had been vaccinated with the seasonal influenza vaccine (SIV). We therefore wanted to calculate early and mid-season estimates of influenza VE and compare the results between the two populations. The aim was to evaluate VE for LCI in persons 65 years and above, an age group eligible for free SIV.MethodsIn both Stockholm County, Sweden, with 2 million inhabitants, and Finland with 5.5 million inhabitants, permanent residents have a unique personal identification number (PIN) based on which various national registers can be linked.In Stockholm County, we used the central database (VAL) for healthcare utilisation, consultations and diagnoses, the vaccination register (Vaccinera) and for the outcome, the national electronic surveillance system (SmiNet) for the reporting of communicable diseases. Data from VAL, Vaccinera and SmiNet were linked using the same PIN (for details on data sources see [1,3,4]). VAL was used for obtaining data on in- and outpatient diagnoses, comorbidities, age and sex as well as the Stockholm Mosaic system. The latter is a proxy for socioeconomic status based on 11 mutually exclusive categories, e.g. living in a low-income urban apartment block, multicultural suburb, affluent inner city, countryside, by which the County (including Stockholm city) can be divided into 120 smaller urban agglomerations [5]. Vaccinera contains all data, starting from 2009, on influenza and pneumococcal vaccination of persons aged 65 years and older or belonging to medical risk groups. Since the SIV programme in Stockholm offers persons 65 years and older vaccination free of charge and registration is mandatory and required for reimbursements to the healthcare provider, it can be assumed that all vaccinated persons in that age group are included in this database. SmiNet includes all diagnoses of influenza A and B starting from 1 December 2015 when they became notifiable diseases.In Finland, the Population Information System (PIS) [5], the National Vaccination Register (NVR) [6] and the National Infectious Diseases Register (NIDR) [7] are also linked through a unique PIN. The PIS provides information on every person’s date of birth, sex, date of death, and residential history. Also the NVR contains individual-level data, e.g. vaccine type and lot number as well as date of vaccination, for all vaccinations given within public primary healthcare (the system responsible for delivering the national immunisation programme), including free SIV for certain age and risk groups. The coverage of the NVR is assumed to reach 100% when excluding the population (