(329) A Population Database Analysis To Estimate The Varicella Vaccine Effectiveness In Children <14 Years In A High Vaccination Coverage Area From 2004 To 2022

Background: Routine childhood immunization has dramatically reduced varicella incidence. 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.

Objectives: To overcome surveillance database limitations in capturing varicella episodes, the study aimed at assessing the varicella vaccine effectiveness (VE) and the disease residual burden in the pediatric population using a primary-care database.

Methods: This retrospective analysis used data from Pedianet, a comprehensive database of 73 family paediatricians in the Veneto Region. Incidence rates (IR) of varicella, primary outcome, (ICD-9-CM code 052.0–052.9) were evaluated in children < 14 years of age enrolled since birth, between January 2004 to April 2022. A case was classified as break-through if happening beyond 42 days post-VV. Complications associated to the varicella episode were evaluated. Subject were followed up from 2004 or the enrollment date, until the end of assistance or the first or second VV dose (exposures of interest) or the end of study period. 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, VV 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: Overall, 36,498 children, followed for 233,508 person-years from 2004 to 2022 experienced 1,006 cases of varicella, 13 of which complicated and 35 of which breakthrough. At the end of the observation period, 42.5% were fully vaccinated (two doses), 38.2% received one dose, and 19.3% were unvaccinated. Among the unvaccinated, the IR increased from 5.5 to 19.5 cases x 1,000 person-years in children < 12months versus those aged 5-6 years, respectively. Among the vaccinated population, the IR increased up to 6 years of age from 1.1 to 5.4 cases x 1,000 patient-years in children aged 12-15 months to those aged 5-6 years. Younger children had a higher risk of experiencing varicella compared to children >7 years of age, irrespective of their vaccination status. Varicella VE was 83.4% in those vaccinated with one dose (aHR [95%CI]: 0.17 [0.14-0.19], p< 0.001] and 94.7% in those with two doses (aHR [95%CI]:0.05 [0.04-0.08], p< 0.001). After six years of follow-up, the cumulative probability of experiencing varicella was 10.7% for unvaccinated subjects, 2.5% for those vaccinated with one dose and 0.4% for those vaccinated with 2 doses with significative difference (log-rank test, p < 0.001).

Conclusions: Two-schedule VV is effective in drastically reduce varicella episodes. Breakthrough varicella episodes remain rare events.