Piedra PA, Yan L, Kotloff K, et al. Pediatrics. 2002;110:662–672
Purpose of the Study.
Influenza is a major cause of morbidity in all age groups. The study objective was to provide safety data for the intranasally administered, trivalent, cold-adapted influenza vaccine (CAIV-T) in young children using a multicenter, prospective, randomized, double-blind, placebo-controlled study.
Healthy children 15 to 71 months old were enrolled. Exclusion criteria included history of significant hypersensitivity to eggs or a chronic illness for which trivalent inactivated influenza virus (IIV-T) would be recommended. Inclusion in years 2 to 4 of the study required inclusion in all of the previous consecutive years beginning in 1996.
Each year CAIV-T provided by Aviron (Mountain View, CA) contained vaccine strains that matched antigens consistent with the licensed US Food and Drug Administration IIV-T product. In year 1, 1314 children were enrolled in the 2-dose cohort (either active CAIV-T or placebo) and 288 were enrolled in the 1-dose cohort. In year 2, 1358 original participants received 1 dose of CAIV-T or placebo to match their original treatment. In years 3 and 4, 642 and 549 children, respectively, received their third and fourth doses of CAIV-T in an open-label extension. Safety was evaluated by measuring the occurrence of specific or unexpected symptoms within 10 days of vaccination, incidence of an acute illness and use of medication within 11 to 42 days of vaccination, and occurrence of a serious adverse event within 42 days of vaccination.
In the first year, runny nose or nasal congestion, vomiting, muscle aches, and fever were significantly associated with the first dose of CAIV-T. Runny nose was the only symptom associated with CAIV-T after the second dose. In years 2 to 4 specific symptoms were not associated with CAIV-T. The symptoms associated with CAIV-T were most likely to occur on day 2, after the first dose of vaccine. Vomiting, abdominal pain, and muscle aches were associated with the first dose of vaccine. Unexpected symptoms most commonly involved the gastrointestinal system. A significant increase in the use of analgesics/antipyretics was observed with the first dose of CAIV-T compared with placebo (23.5% vs 16.6%). CAIV-T was not associated with illness or medication use on days 11 to 42 or serious adverse events.
CAIV-T was deemed safe in preschool-aged children. Mild respiratory, gastrointestinal, and systemic symptoms were observed primarily with the first dose of vaccine and occurred in a minority of children. Subsequent consecutive annual doses of CAIV-T were tolerated without significant effects.
Influenza remains a significant cause of morbidity in children. The American Academy of Pediatrics (AAP) has recommended vaccinating all children between 6 and 23 months of age using the IIV-T product, especially those at high-risk of hospitalization. Nonetheless, most children are still not immunized, perhaps because of a lack of desire to use the injectable product. This study demonstrates that the CAIV-T is safe with minimal side effects in healthy children. Hopefully, we will see this vaccine come to market in the near future.