Although vaccination remains the best way to prevent influenza, the pooled efficacy of trivalent inactivated vaccine is approximately 60% while that of live attenuated vaccine is about 80%. The authors of this study highlight the lack of rigorous data supporting influenza vaccination, particularly in those groups most at risk.
The authors performed a systematic review and meta-analysis of influenza vaccine efficacy and effectiveness using only studies that used laboratory confirmed influenza as an endpoint (either by PCR or culture). The authors chose these stringent criteria as serologic confirmation of influenza is confounded by vaccine effect and influenza-like illness is a very non-specific endpoint. Efficacy was assessed using randomized-controlled trials, which were placebo controlled and effectiveness was assessed using observational trials. Only vaccines licensed in the USA were included. Vaccine challenge studies were excluded as they did not represent natural infection. Studies which reported efficacy or effectiveness against only one strain were excluded as were studies that looked at pandemic H1N1. Vaccine efficacy and effectiveness were analyzed by age group and season.
17 randomized-controlled trials covering 24 flu seasons and 53,983 patients met inclusion criteria. Trivalent inactivated vaccine (TIV) was assessed in 10 trials and showed efficacy in 8 of 12 (67%) seasons with a pooled vaccine efficacy of 59% (95% CI 61-67). No trials showing efficacy were found in 2 major ACIP recommendation groups, children age 2-17 and adults age >65 years, and only a single trial showed efficacy in children age 6-24 months. Live attenuated influenza vaccine (LAIV) showed efficacy in 9 of 12 (75%) seasons with a pooled efficacy of 83% (95% CI 69-91). All 8 trials in children age 6 months to 7 years showed efficacy as did a trial in adults >60, while 3 trials in those aged 18-49 years did not show efficacy. Effectiveness was assessed using 9 published reports covering 17 seasonal or cohort analyses and found to be effective in only 35% (6/17 seasons). The percentage of trials showing effectiveness of influenza vaccine varied by ACIP risk group: children 6-59 months 38% (3/8), adults >65 yrs 50% (1/2), and individuals with ACIP age or risk criteria 33% (1-3). Five trials of monovalent pandemic H1N1 vaccine (all with adjuvants outside the US) showed a median effectiveness of 69% (range 60-93%).
This study highlights the data gaps we have regarding influenza vaccine efficacy in certain groups, particularly those at the highest risk of complication from infection. The primary strength of this study was the author’s choice of a strict standard for influenza detection to minimize bias and confounding and to provide the most accurate estimate of the actual efficacy and effectiveness of influenza vaccine. The weakness is that no other endpoint was assessed such as mortality (although this is easily confounded), complications, or hospitalization.
What are the take-away messages from this study? First, preferred use of LAIV should be considered in young children. Second, more data is needed in those most at risk to prove vaccine efficacy and identify those where alternative strategies may be needed (high dose vaccine, etc.).
Third, the authors did not assess modification of illness severity or transmission and influenza vaccine likely has some effect on this. Forth, we should continue to vaccinate healthcare workers as influenza vaccine is still the most effective method for preventing nosocomial transmission of influenza. Fifth, we should keep in mind influenza vaccine likely does provide some protection even to those who do not respond via “herd immunity.” Finally, we are in need of a more effective influenza vaccine. In the event of a high mortality, high transmissibility global influenza pandemic, an efficacy of 60% will not be adequate.
Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12:36-44. http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(11)70295-X/abstract