Influenza vaccine for preventing acute otitis media (middle ear infection)

Review question
We reviewed the effect of influenza vaccine on preventing acute otitis media (AOM) in infants and children. We identified 10 randomised controlled trials (RCTs) involving 16,707 children aged six months to six years, of either sex and of any ethnicity, with or without a history of recurrent AOM.

AOM is one of the most common infectious diseases in infants and preschool children. Symptoms include ear pain and fever, but it may cause hearing loss due to ear drum perforation or fluid accumulation in the middle ear. AOM is usually bacterial in origin and antibiotics are often used to treat it, but they carry their own side effects and the risk of antibiotic resistance. Even so, AOM is often preceded by viral infection such as influenza. Preventing viral infections might prevent AOM. Therefore, we investigated whether influenza vaccines might reduce the occurrence of AOM in infants and children.

Study characteristics
The evidence is current to July 2014. We selected randomised controlled trials (RCTs) comparing influenza vaccine with placebo or no treatment in infants and children younger than six years old of either sex and any ethnicity, with or without a history of previous episodes of AOM. Nine out of 10 studies (and all five studies that contributed to the primary outcome) were funded by the vaccine manufacturers.

Key results
The review found a 4% (this could be between 2% and 7%) reduction in AOM. It also found about a 15% (this could be between 0% to 30%) reduction in the number of antibiotic prescriptions. There was no difference in the number of doses, courses, settings, seasons or types of vaccine administered between those vaccinated and unvaccinated. Influenza vaccine side effects included an increase in fever and runny nose. It remains uncertain whether it reduced visits to healthcare facilities or hospital admissions. Data were also insufficient to show that this benefit might be traded off against more serious or rarer side effects from the vaccine.

The review has included subgroup analyses for AOM episodes by season, which we did not include in our protocol (plan for the review). The 'respiratory season' is when viruses that cause the common cold and other respiratory conditions occur more frequently and AOM generally occurs in the respiratory season. In temperate climates, the respiratory season occurs in the autumn and winter and in tropical climates, during the rainy season. In the equatorial belt, the respiratory season may occur throughout the year. The respiratory season may not coincide with the influenza season, which may occur in the winter and spring. However, it can vary depending on the presence of influenza virus epidemics.

Although we observed a reduction in antibiotic usage, this impact is uncertain because the current practice is to avoid overuse of antibiotics. Coupled with other vaccine safety concerns, the use of influenza vaccine to reduce AOM is not yet justified and additional research is needed.

Quality of evidence
The overall quality of the evidence was high to moderate.

Authors' conclusions: 

Influenza vaccine results in a small reduction in AOM. The observed reduction with the use of antibiotics needs to be considered in the light of current recommended practices aimed at avoiding antibiotic overuse. Safety data from these trials are limited. The benefits may not justify the use of influenza vaccine without taking into account the vaccine efficacy in reducing influenza and safety data. The quality of the evidence was high to moderate. Additional research is needed.

Read the full abstract...

Acute otitis media (AOM) is one of the most common infectious diseases in children. It has been reported that 64% of infants have an episode of AOM by the age of six months and 86% by one year. Although most cases of AOM are due to bacterial infection, it is commonly triggered by a viral infection. In most children it is self limiting, but it does carry a risk of complications. Since antibiotic treatment increases the risk of antibiotic resistance, influenza vaccines might be an effective way of reducing this risk by preventing the development of AOM.


To assess the effectiveness of influenza vaccine in reducing the occurrence of acute otitis media (AOM) in infants and children.

Search strategy: 

We searched CENTRAL (2014, Issue 6), MEDLINE (1946 to July week 1, 2014), EMBASE (2010 to July 2014), CINAHL (1981 to July 2014), LILACS (1982 to July 2014), Web of Science (1955 to July 2014) and reference lists of articles to July 2014.

Selection criteria: 

Randomised controlled trials (RCTs) comparing influenza vaccine with placebo or no treatment in infants and children aged younger than six years old. We included children of either sex and of any ethnicity, with or without a history of recurrent AOM.

Data collection and analysis: 

Two review authors independently screened studies, assessed trial quality and extracted data. We performed statistical analyses using the random-effects and fixed-effect models and expressed the results as risk ratio (RR), risk difference (RD) and number needed to treat to benefit (NNTB) for dichotomous outcomes, with 95% confidence intervals (CI).

Main results: 

We included 10 trials (six trials in high-income countries and four multicentre trials in high-, middle- and low-income countries) involving 16,707 children aged six months to six years. Eight trials recruited participants from a healthcare setting. Nine trials (and all five trials that contributed to the primary outcome) declared funding from vaccine manufacturers. Four trials reported adequate allocation concealment and nine trials reported adequate blinding of participants and personnel. Attrition was low for all trials included in the analysis.

The primary outcome showed a small reduction in at least one episode of AOM over at least six months of follow-up (five trials, 4736 participants: RR 0.80, 95% CI 0.67 to 0.96; RD -0.04, 95% CI -0.07 to -0.02; NNTB 25, 95% CI 15 to 50).

The subgroup analyses (i.e. number of courses, settings, seasons or types of vaccine administered) showed no differences.

There was a reduction in the use of antibiotics in vaccinated children (two trials, 1223 participants: RR 0.70, 95% CI 0.59 to 0.83; RD -0.15, 95% CI -0.30 to -0.00).

There was no significant difference in the utilisation of health care for the one trial that provided sufficient information to be included. The use of influenza vaccine resulted in a significant increase in fever (six trials, 10,199 participants: RR 1.15, 95% CI 1.06 to 1.24; RD 0.02, 95% CI -0.00 to 0.05) and rhinorrhoea (six trials, 10,563 children: RR 1.17, 95% CI 1.07 to 1.29; RD 0.09, 95% CI 0.01 to 0.16) but no difference in pharyngitis. No major adverse events were reported.

Compared to the protocol, the review included a subgroup analysis of AOM episodes by season, and changed the types of influenza vaccine from a secondary outcome to a subgroup analysis.