Estimating the annual attack rate of seasonal influenza among unvaccinated individuals: A systematic review and meta-analysis

Introduction: Seasonal influenza affects millions of people globally each year, causing significant morbidity and mortality. However, there remains substantial uncertainty about the attack rate (incidence) of influenza, particularly in unvaccinated individuals. Methods: We undertook a systematic review of vaccine randomised controlled trials (RCTs) that reported on laboratory-confirmed seasonal influenza in the placebo arm. We calculated the influenza attack rate from included studies as the number of laboratory-confirmed positive seasonal influenza cases in the placebo arm divided by the total number of subjects in this arm. A random effects meta-analysis was conducted to estimate the influenza attack rate among unvaccinated individuals (both symptomatic only as well as symptomatic and asymptomatic combined). Results: We included 32 RCTs that had a total of 13,329 participants. The pooled estimates for symptomatic influenza were 12.7% (95%Cl 8.5%, 18.6%) for children (<18 years), 4.4% (95%Cl 3.0%, 6.3%) for adults, and 7.2% (95%Cl 4.3%, 12.0%) for older people (65 years and above). The pooled estimates for symptomatic and asymptomatic influenza combined for all influenza were 22.5% (95%Cl 9.0%, 46.0%) for children and 10.7% (95%Cl 4.5%, 23.2%) for adults. Only one study was identified for symptomatic and asymptomatic combined in older people which had a rate of 8.8% (95%Cl 7.0%, 10.8%). There was substantial heterogeneity between studies. Conclusion: Overall, we found that approximately 1 in 5 unvaccinated children and 1 in 10 unvaccinated adults were estimated to be infected by seasonal influenza annually, with rates of symptomatic influenza roughly half of these estimates. Our findings help to establish the background risk of seasonal influenza infection in unvaccinated individuals. (C) 2018 Elsevier Ltd. All rights reserved.