Incidence rate of breakthrough varicella observed in healthy children after 1 or 2 doses of varicella vaccine: Results from a meta-analysis

•Average breakthrough varicella incidence rate varied in different study designs and types of vaccine.•Second dose of varicella vaccine may achieve higher efficacy than that achieved with only a single dose in healthy children.•Three to four years apart after the first vaccination may provide more vaccine effectiveness. Although extensive varicella vaccination coverage has been reported in many countries, breakthrough varicella (BV) still occurs in healthy children. We performed a meta-analysis to understand whether 2 varicella vaccine doses are needed in children and, if so, to determine the best time to vaccinate. The BV incidence rates after 1 or 2 doses of varicella vaccine were pooled using random effects, and 95% confidence intervals (CI) were used to estimate the risk factors after vaccination. A total of 27 original articles were included in this meta-analysis. The pooled average BV incidence rate in children vaccinated with 1 dose was 8.5 cases per 1,000 person years (PY) (95% confidence interval [CI], 5.3-13.7; random effects model) and 2.2 cases per 1,000 PY (95% CI, 0.5-9.3; random effects model) in children vaccinated with 2 doses. The pooled trend of the annual BV incidence rate from the first to eighth year fluctuated, with a peak annual incidence rate of 35.3 cases per 1,000 population in the fourth year. The meta-regression showed that design type, type of vaccine, and their interaction accounted for approximately 71.74% of the heterogeneity in the average BV incidence rate after 1 vaccine dose. Two doses of varicella vaccine are more effective than a single dose, and 3-4 years between the first and second vaccinations may achieve higher efficacy.