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A Meta-analysis of Serologic and Field Studies

Walter E. P. Beyer, MD, PhD; Iris A. de Bruijn, MSc; Abraham M. Palache, MSc, PhD; Ruud G. J. Westendorp, MD, PhD; Albert D. M. E. Osterhaus, DVM, PhD

Arch Intern Med. 1999;159:182-188.

Background  According to common recommendations, influenza vaccination should be performed annually. It has been suggested that vaccination in previous years reduces vaccine efficacy in the long term.

Objective  To determine whether the protection of influenza vaccine decreases when vaccination is repeated annually.

Methods  Articles published between 1966 and 1997 were selected from MEDLINE. The end point for field studies was the influenza-related morbidity or mortality during influenza outbreaks (resulting in field protection rates). The end point for serologic studies was exceeding a protective postvaccination hemagglutination-inhibition titer (serologic protection rates). Protection rate differences between groups with single and multiple vaccinations were subjected to meta-analysis.

Results  Seven field studies (including 13 trials) supported the hypothesis that protection in multiple-vaccination groups is at least as good as that in single-vaccination groups. Ten trials with 5117 observations could be subjected to meta-analysis. The pooled protection-rate difference was close to 0 (1.1%; 95% confidence interval, -0.2% to 2.4%), thus detecting no difference between single or multiple vaccination. Twelve serologic studies (including 53 trials) showed heterogeneous results: 9 trials were significantly in favor of single vaccination, and 7 were in favor of multiple vaccination, but in most cases, there was no significant difference between the 2 vaccination groups. The pooled serologic protection-rate difference from 52 trials (12,341 observations) was again close to 0 (1.7%; 95% confidence interval, -1.3% to 4.8%).

Conclusions  We did not detect any evidence for a decreasing protection with annually repeated influenza vaccination. Annual vaccination should not be discouraged in populations at risk.

From the World Health Organization National Influenza Centre, Institute of Virology, Erasmus University, Rotterdam (Drs Beyer, Palache, and Osterhaus); and the Section of Gerontology, University Hospital, Leiden (Ms de Bruijn and Dr Westendorp), the Netherlands.

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