Annual influenza epidemics in the United States occur in the late fall and often lasts to early spring.1 It is usually a self-limiting disease but can result in increased hospitalizations and mortality.2,3 Rates of infection are highest among children, but risks of complications are highest in adults ≥65 years old, children <5 years old, and those with underlying chronic disease.1 Annual influenza vaccination is the main strategy in preventing seasonal influenza infections and its complications.1 Current advisory committee on immunization practices (ACIP) guidelines recommend routine influenza vaccination to all individuals 6 months and older, trivalent inactivated vaccine (TIV) for all individuals 6 months or older or the live attenuated influenza vaccine (LAIV) for healthy non-pregnant people 2-49 years old. Efficacy of these vaccines have been studied using various endpoints including immunogenicity, laboratory-confirmed influenza infections, hospitalizations and mortality.1
Osterholm and colleagues published a systematic review and meta-analysis of randomized controlled trials and observational studies examining influenza vaccine efficacy and effectiveness.4 Only studies reporting influenza infections confirmed by RT-PCR or viral culture testing were included as these tests have higher sensitivity and specificity than other laboratory tests such as rapid antigen tests. Clinical diagnosis of influenza can be unreliable as symptoms can be similar to other respiratory infections.5 Meta-analysis was only performed when there were 3 or more RCTs with equivalent age ranges and vaccine characteristics.
Seventeen RCTs were identified assessing TIV and/or LAIV, 10 of which assessed TIV during 12 influenza seasons. All but one RCT were conducted in healthy individuals including children 6-23 months and adults 18-64 years old. The trivalent inactivated vaccine was effective in 8 out of 12 (67%) seasonal analyses. Pooled vaccine efficacy of 8 RCTs in adults 18-64 years old found 59% efficacy using random-effects odds ratio (95% CI 51-67). Ten RCTs assessed LAIV during 12 influenza seasons as well (3 studies evaluated both TIV and LAIV). Similar to TIV, all were conducted in healthy individuals including children aged 6 months to 7 years, adults 18-49 years old, and adults >60 years old. All RCTs in 6 months – 7 year olds showed vaccine efficacy and a pooled analysis found 84% efficacy using random-effects odds ratio (95% CI 69-91). No meta-analysis was performed of those trials including the 18-49 year olds despite meeting the pre-specified criteria for pooled analysis.
Fourteen observational studies were identified, 9 studies reported on seasonal influenza vaccines and 5 reported on monovalent pH1N1 vaccine. Seasonal influenza vaccines studies included cohorts < 59 months old or > 50 years old. Significant vaccine effectiveness was shown in 6 of 17 (35%) seasons. A potential reason for the low effectiveness rate is that these studies only included medically-attended influenza infections. Therefore patients with milder influenza episodes who did not seek medical attention were not included. All 5 H1N1 studies found significant vaccine effectiveness.
While this review showed little RCT evidence to support TIV efficacy outside of healthy adults and LAIV efficacy outside of children aged 6 months-7 years, RCTs cannot be conducted ethically ...