Level 2: Mid-level evidence
The live attenuated flu vaccine (FluMist intranasally) appears more effective than the inactivated vaccine (Fluzone IM), based on a randomized trial of 8,352 immunocompetent children aged 6-59 months in 16 countries (N Engl J Med. 2007;356:685-696). Participants also received intranasal saline mist and IM saline injections as placebos to maintain blinding; a second treatment dose was given 28-42 days later if there was no history of previous vaccination.
Influenzalike illness was defined using a modified CDC definition: oral temperature ≥37.8°C (100°F) plus cough, sore throat, runny nose, or nasal congestion on the same or consecutive days.
In an “according-to-protocol population” analysis of 7,852 children (94%), live attenuated vaccine was associated with reduced rates of culture-confirmed symptomatic influenza (3.9% vs. 8.6%, NNT 22), symptomatic influenza well-matched to vaccine strains (1.4% vs. 2.4%, NNT 100), and symptomatic influenza not well-matched to vaccine strains (2.6% vs. 6.2%, NNT 28).
On follow-up for 180 days after the last vaccine dose, there were no significant differences in adverse events in an overall analysis and analyses stratified by age group. Comparing live attenuated vs. inactivated vaccine in all 8,352 children aged 6-59 months, 8.7% vs. 7.8% had medically significant wheezing, 3.3% vs. 3.1% had any serious adverse event, and 3.1% vs. 2.9% required hospitalization for any reason. In an analysis of 6,985 children aged 6-11 months, 13.6% vs. 10.4% had medically significant wheezing, 6.4% vs. 3.4% had any serious adverse event, and 6.1% vs. 2.6% required hospitalization for any reason. Evaluating 1,367 children aged 12-59 months, 7.8% vs. 7.3% had medically significant wheezing, 2.6% vs. 3% had any serious adverse event, and 2.5% vs. 2.9% required hospitalization for any reason.