Real-world effectiveness of influenza vaccination in preventing influenza and influenza-like illness in children

Background and objectives: Quadrivalent live attenuated influenza vaccines (LAIV-4) offer an alternative to inactivated influenza vaccines (IIV) for children aged 2–17 years, but data on their comparative effectiveness are limited. This study assessed vaccination rates and real-world effectiveness of LAIV-4 and IIV in preventing influenza and influenza-like illness (ILI) in Italian children during the 2022–2023 and 2023–2024 seasons. Methods: We conducted a population-based cohort study of children aged 2–14 years from September 2022 to April 2024, using data from Pedianet, a pediatric primary care database of anonymized records from family pediatricians. Children vaccinated with LAIV-4 or IIV were compared to unvaccinated children. The primary outcome was any first influenza or ILI episode. Monthly vaccination incidence rates per 1000 person-months were calculated for each vaccine type. Hazard ratios (HRs) and their 95 % confidence intervals (CIs) for vaccine effectiveness (VE) were estimated using adjusted mixed-effects Cox models. Results: A total of 65,545 (472,173 person-months) and 72,377 (527,348 person-months) children were included for the 2022–2023 and 2023–2024 seasons, respectively. Vaccination rates were 12.71 and 12.85 per 1000 person-months, respectively. Compared to unvaccinated children, LAIV-4 had an overall effectiveness of 43 % (95 % CI, 32 %–53 %), while IIV effectiveness was 54 % (95 % CI, 46 %–61 %). In 2022–2023, LAIV-4 (38 % [95 % CI, 12 %–56 %]) and IIV (49 % [95 % CI, 37 %–58 %]) had comparable effectiveness. In 2023–2024, LAIV-4 (40 % [95 % CI, 25 %–52 %]) was slightly less effective than IIV (58 % [95 % CI, 44 %–68 %])(p = 0.048). Conclusions: An overall moderate, comparable effectiveness of LAIV-4 and IIV in preventing influenza/ILI among Italian children was observed.