A population database analysis to estimate the varicella vaccine effectiveness in children < 14 years in a high vaccination coverage area from 2004 to 2022

Introduction: In the Veneto Region of Italy, universal varicella vaccination (VV) started in 2007 with a two-dose schedule at 12-15 months and 5-6 years of age achieving 90 % coverage in 2019. The study aimed at evaluating the vaccine effectiveness (VE) in children using a primary-care database METHODS: This retrospective analysis used Pedianet, a comprehensive database of 73 family paediatricians in the Veneto Region. Incidence rates (IR) of varicella were evaluated in children aged <14 years enrolled since birth, between January 2004 to April 2022. Cases were classified as breakthrough if happening beyond 42 days post-VV. Complications and prescription were evaluated. Subject were followed up from 2004 or the enrollment date, until the end of assistance/study or the first or second VV dose. Kaplan-Meier curves and log-rank tests were used to compare the varicella incidence by vaccination status. Hazard ratios of varicella infection, adjusted (aHRs) for sex, vaccinal status, age group, prematurity and socioeconomic status were estimated with Cox's regression. VE for one and two VV doses was defined as 1-aHR*. Results: 36,498 children, followed for 233,508 person-years from 2004 to 2022 experienced 1006 cases of varicella (13 complicated and 35 breakthrough). Younger children had a higher risk of experiencing varicella compared to children aged >7 years, irrespective of their vaccination status. Indeed, the IR increased from 5.5 to 19.5 × 1000 person-years and from 1.1 to 5.4 × 1000 person-years in unvaccinated and vaccinated children aged <12 months versus those aged 5-6 years, respectively. Varicella VE was 83.4 % and 94.7 % in those vaccinated with one and two doses. After six years, the cumulative probability of experiencing varicella was 10.7 % for unvaccinated subjects, and 2.5 % and 0.4 % for those vaccinated with one and two-doses (log-rank test, p < 0.001). Conclusions: Two-dose schedule VV is effective in drastically reduce varicella episodes. Breakthrough varicella episodes remain rare events.