A healthy one-year-old girl presents in the fall for well-child care and an immunization update. The girl’s mother asks you whether her child should have an influenza vaccination.
Would an influenza vaccination prevent illness in this patient, and would it be safe?
Influenza vaccines have good efficacy (i.e., prevention of influenza) in children older than two years, and live, attenuated vaccine is more efficacious than trivalent, inactivated vaccine. Effectiveness (i.e., prevention of influenza-like illness, perhaps a clinically more important measure) is poor for all influenza vaccines in healthy children. Safety outcomes have not been analyzed. In children younger than two years, trivalent inactivated vaccine is no better than placebo and there are no good-quality safety data. There is some evidence that vaccines are effective in reducing school absence.1
Background: In children and adults, the consequences of influenza mainly are absences from school and work; however, the risk of complications is greatest in children and in persons older than 65 years.
Objectives: To appraise all comparative studies evaluating the effects of influenza vaccines in healthy children, to assess vaccine efficacy (i.e., prevention of confirmed influenza) and effectiveness (i.e., prevention of influenza-like illness), and to document adverse events associated with receiving influenza vaccines.
Search Strategy: The reviewers1 searched the Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane Library Issue 1, 2005), OLD MEDLINE (1966 to 1969), MEDLINE (1969 to December 2004), EMBASE (1974 to December 2004), Biological Abstracts (1969 to December 2004), and Science Citation Index (1974 to December 2004). They wrote to vaccine manufacturers and a number of corresponding authors of studies in the review.
Selection Criteria: Any randomized controlled trials (RCTs) and cohort or case-control studies of any influenza vaccine in healthy children younger than 16 years.
Data Collection and Analysis: Two authors independently assessed trial quality and extracted data.
Primary Results: Fifty-one studies involving a total of 263,987 children were included. Seventeen papers were translated from Russian. Fourteen RCTs and 11 cohort studies were included in the analysis of vaccine efficacy and effectiveness. From RCTs, live vaccines showed an efficacy of 79 percent (95% confidence interval [CI], 48 to 92) and an effectiveness of 33 percent (95% CI, 28 to 38) in children older than two years compared with placebo or no intervention. Inactivated vaccines had a lower efficacy (59 percent; 95% CI, 41 to 71) than live vaccines but similar effectiveness (36 percent; 95% CI, 24 to 46). In children younger than two years, the efficacy of inactivated vaccine was similar to placebo. Thirty-four reports containing safety outcomes were included: 22 of live vaccines, eight of inactivated vaccines, and four of both types. The most commonly presented short-term outcomes were temperature and local reactions. The variability in design of studies and presentation of data was such that meta-analysis of safety outcome data was not feasible.
Reviewers’ Conclusions: Influenza vaccines are efficacious in children older than two years, but little evidence is available for children younger than two years. There was a marked difference between vaccine efficacy and effectiveness. That no safety comparisons could be carried out emphasizes the need for standardization of methods and presentation of vaccine safety data in future studies. It was surprising to find only one study of inactivated vaccine in children younger than two years given recent recommendations to vaccinate healthy children from six months of age in the United States and Canada. If immunization in children is to be recommended as public health policy, large-scale studies assessing important outcomes and directly comparing vaccine types are urgently required.
These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the originalreviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minorediting changes have been made to the text (http://www.cochrane.org).
Influenza in otherwise healthy children most commonly causes a febrile respiratory illness that leads to school (and, for their parents, work) absenteeism; however, it can result in hospitalization and, rarely, death. Hospitalization rates for influenza in children up to one year of age are comparable with those reported for 65-year-old adults. Influenza was responsible for an estimated 92 deaths per year in the 1990s among children younger than five years. One study revealed that 70 percent of deaths caused by influenza in children two to 17 years of age were in patients without an underlying medical condition.2
In 2002, the vaccination for influenza of all children six to 23 months of age was encouraged by the universal recommendations of the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention,3 which is endorsed by the American Academy of Family Physicians. The vaccine was included in the Vaccines for Children program in 2003.4 Recommendations for the 2005–2006 influenza season included administration of influenza vaccine to all children six to 23 months of age and any persons wishing to reduce the likelihood of becoming ill with influenza or of transmitting influenza to others.2 Support for extending vaccination to healthy younger children is provided largely by a two-year randomized study involving children six to 24 months of age.5 In this study, a high rate of seroconversion was found among children given the influenza vaccine, but there was only a small decrease in the rate of influenza during year 1 (culture-proven influenza was identified in 5.5 percent of children in the vaccination group versus 15.9 percent of those in the placebo group) and no difference in rates during year 2.5 Influenza vaccination did not reduce the likelihood of otitis media.5
Two influenza vaccines are available for use in children. The trivalent, inactivated vaccine is given by intramuscular injection and is approved for children six months of age. It is given annually, except in previously unvaccinated children younger than nine years, for whom two doses are recommended, one month apart, with the second dose given before December. The live, attenuated vaccine is given by intranasal spray and is approved for healthy patients five to 49 years of age. It also is given annually, except in previously unvaccinated children five to nine years of age, who should receive two doses separated by six to 10 weeks.2
The Cochrane authors reviewed the literature and included randomized controlled trials (RCTs) and cohort and case-control studies.1 Efficacy and effectiveness results were taken mainly from 14 RCTs. Safety outcomes could not be combined for analysis because of the variability in study design and the diversity of safety outcomes reported, as well as the variable presentation of data. There are some lower-quality safety data available for trivalent, inactivated vaccine and live, attenuated vaccine in children, including those six to 23 months of age, from event-reporting networks and population-based studies.2 The most commonly reported adverse events from reporting networks and observational studies were fever, rash, injection-site reactions, irritability, insomnia, and seizures. Causality could not be proved, and in some studies the seizures were thought to be febrile seizures. One placebo-controlled study and one population-based study showed no increase in significant adverse events, but neither met criteria for inclusion in the Cochrane review.
Family physicians should present parents with the ACIP recommendations, explain that there is limited evidence that the vaccine is effective for children younger than two years, advise that the vaccine may reduce school absence in school-age children, and let parents decide. Future research is needed to clarify the benefit and safety of influenza vaccines in healthy children.