Intranasal influenza vaccine may be a safe, effective option for many children

Article Outline

• Belshe RB, Edwards KM, Vesikari T, Black SV, Walker RE, Hultquist M, et al. for the CAIV-T Comparative Efficacy Study Group. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med 2007;356:685-96
• Copyright

Back to Article Outline

Belshe RB, Edwards KM, Vesikari T, Black SV, Walker RE, Hultquist M, et al. for the CAIV-T Comparative Efficacy Study Group. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med 2007;356:685-96 

Question Among children 6 to 59 months of age, is live attenuated influenza vaccine safe and effective?

Design Randomized, controlled trial.

Setting Physician’s offices and primary care clinics in 16 countries (United States, Europe, Middle East, Asia).

Participants Children 6 to 59 months of age.

Intervention Live attenuated (intranasal) influenza vaccine was compared with inactivated (intramuscular) influenza vaccine.

Outcomes Number of culture-confirmed cases of influenza-like illness, medically significant wheezing, and other serious adverse events.

Main Results Live attenuated vaccine was more effective than inactivated vaccine in preventing influenza (153 vs 338 cases, p<0.001). The superior efficacy of live attenuated vaccine, as compared with inactivated vaccine, was observed for both antigenically well-matched and drifted viruses. Overall, there was no significant difference in medically significant wheezing between the two groups. However, several subgroups of children who had not previously received vaccine in the live attenuated group had more wheezing after the first dose. This trend was notable in previously unvaccinated children 6-11 months old (3.8% vs 2.1%, p=0.076). With respect to hospitalization for any cause, rates were higher in recipients of live attenuated vaccine who were 6-11 months old (6.1% vs 2.6%, p=0.002). There was a trend towards more hospitalizations in children 6-47 months old with a prior history of wheezing who received live attenuated vaccine. Conversely, in children 12-59 months old with no prior history of wheezing who received live attenuated vaccine, there was a trend towards fewer hospitalizations.

Conclusions In children over one year of age without a prior history of wheezing, live attenuated influenza vaccine was a safe and more effective alternative to inactivated vaccine.

Commentary The option of an intranasal influenza vaccine is quite attractive in light of patient aversion to shots and the often limited availability of inactivated influenza vaccine doses. However, concern about the safety of live attenuated influenza vaccine has thus far prevented its widespread use in children. This multicenter study reports efficacy and safety data on a large number of children, including a subpopulation of children with a previous history of wheezing. The broad scope of this study allows it to address the concern over whether live attenuated vaccine is associated with wheezing in previously healthy children. The answer appears to be “no,” except perhaps in 6-11 month olds. However, it also reveals more questions about safety in children less than 12 months of age, and in children with a past history of wheezing. The overall incidence of adverse events was not significantly different between the two groups in this study; it was only in post-hoc secondary analysis that a few differences emerged. Further studies are needed to determine the true risk of live attenuated vaccine in children 6-11 months of age and children with a past history of wheezing. For those children 12-59 months of age without a past history of wheezing, this study adds convincing efficacy and safety data in support of offering the live attenuated vaccine.

Should clinics stock the intranasal vaccine during the upcoming influenza season? In light of data from this study, live attenuated influenza vaccine would be a good option for children 12-59 months of age without a past history of wheezing. Perhaps the more practical answer to this question lies in whether insurance companies are willing to cover the intranasal form. Some parents may also be willing to pay for the intranasal vaccine in order to spare their child another intramuscular injection. The authors suggest that live attenuated vaccine may also be a reasonable option in children 6-11 months of age after they have received a first dose of inactivated vaccine, because increased wheezing in this age group was only seen after the first dose of live attenuated vaccine.