Because viruses are often the etiologic agent in acute otitis media (AOM), it stands to reason that influenza vaccines might help prevent some cases of AOM. Previous studies of AOM prevention with influenza vaccines have been limited by small sample size and flaws in study design. Hoberman and colleagues studied the preventive effect of influenza vaccine on AOM in children aged six to 24 months. Studying the vaccine's safety, immunogenicity, and efficacy against influenza were secondary aims of the study.

Enrollees were stratified according to whether they were otitis-prone and whether they attended day care. In one cohort, children also were stratified according to whether they had received at least one dose of the newly available pneumococcal vaccine. Within each of these strata, children were randomized to influenza vaccine or placebo, given in two doses, four weeks apart. Office visits were arranged if patients developed any sign or symptom of AOM or upper respiratory infection. Throats were cultured for influenza virus if patients had signs or symptoms of upper respiratory infection accompanied by fever. Immunogenicity was assessed by blood samples, and safety by reporting of adverse events.

A first cohort of 411 children and a second of 375 children were studied, with 373 and 346 completing the study, respectively. Sero-conversion occurred in 88.6 percent to 96.8 percent of a representative subset. In the first cohort, culture-proven influenza was identified in 15 (5.5 percent) of the 273 children in the vaccine group and 22 (15.9 percent) of the 138 children in the placebo group. In the second cohort, the number of positive cultures was nine (3.6 percent) of the 252 children in the vaccine group and four (3.3 percent) of the 123 children in the placebo group. Efficacy rates were 66 percent in the first cohort and −7 percent in the second. In the first cohort, no differences were seen in the rate of upper respiratory infections between vaccinated and placebo groups, but in the second cohort, upper respiratory infection rates were actually higher in the vaccine group than in the placebo group during the influenza season and the respiratory season. In the first cohort, there were no differences between the vaccine group and the placebo group in the proportion of children who had at least one episode of AOM. However, in a subgroup of patients aged 19 to 24 months, the proportion of patients with one episode of AOM was lower in the vaccine group than in the placebo group. In the second cohort, there were no significant differences between groups in the proportion of those with at least one episode of AOM. There were no statistically significant differences in health care utilization between groups. The placement of tympanostomy tubes over the two-year study period occurred in 39 children in the vaccine group and 12 children in the placebo group. Adverse events possibly related to the vaccine included one episode of unexplained staring, one child with mild wheezing, and one child with gastroenteritis.

In this study, influenza vaccine did not appear to reduce episodes of AOM, although a subset of children aged 19 to 24 months may have benefited. Influenza may be a less common cause of upper respiratory infection in younger children. In addition, influenza vaccine may be less effective in preventing influenza and its complications in younger children. Nonetheless, the vaccine did appear to provide limited protection against influenza, and this reduction may justify giving the vaccine to infants and healthy young children, in accordance with the recommendations of the Advisory Committee on Immunization Practices.