Characteristics of Varicella Breakthrough Cases in Jinhua City, 2016-2024

Abstract

Background: Varicella remains a prevalent vaccine-preventable disease, but breakthrough infections are increasingly reported. However, long-term, population-based studies investigating the temporal and demographic characteristics of breakthrough varicella remain limited. Methods: This retrospective study analyzed surveillance data from Jinhua City, China, from 2016 to 2024. Varicella case records were obtained from the China Information System for Disease Control and Prevention (CISDCP), while vaccination data were retrieved from the Zhejiang Provincial Immunization Program Information System (ISIS). Breakthrough cases were defined as infections occurring more than 42 days after administration of the varicella vaccine. Differences in breakthrough interval were analyzed across subgroups defined by dose, sex, age, population category, and vaccination type. A bivariate cubic regression model was used to assess the combined effect of initial vaccination age and dose interval on the breakthrough interval. Results: Among 28,778 reported varicella cases, 7373 (25.62%) were classified as breakthrough infections, with a significant upward trend over the 9-year period (p < 0.001). Most cases occurred in school-aged children, especially those aged 6-15 years. One-dose recipients consistently showed shorter breakthrough intervals than two-dose recipients (M = 62.10 vs. 120.10 months, p < 0.001). Breakthrough intervals also differed significantly by sex, age group, population category, and vaccination type (p < 0.05). Regression analysis revealed a negative correlation between the initial vaccination age, the dose interval, and the breakthrough interval (R² = 0.964, p < 0.001), with earlier and closely spaced vaccinations associated with longer protection. Conclusions: The present study demonstrates that a two-dose varicella vaccination schedule, when initiated at an earlier age and administered with a shorter interval between doses, provides more robust and longer-lasting protection. These results offer strong support for incorporating varicella vaccination into China's National Immunization Program to enhance vaccine coverage and reduce the public health burden associated with breakthrough infections.

Keywords: breakthrough cases; breakthrough intervals; dose intervals; varicella.

Figure 1

Epidemiological distribution of varicella and breakthrough cases in Jinhua City from 2016 to 2024. (A) Annual distribution of total varicella and breakthrough cases, along with annual incidence rate of varicella. (B) Annual proportion of breakthrough cases among all reported varicella cases. (C) Monthly distribution of reported varicella and breakthrough cases, and average monthly incidence rate of varicella. (D) Monthly proportion of breakthrough cases among total reported cases.

Figure 2

Group-wise comparison of breakthrough intervals. (A) Comparison of breakthrough intervals by sex. (B) Comparison of breakthrough intervals by age group. (C) Comparison of breakthrough intervals by population category. (D) Comparison of breakthrough intervals by vaccination type. NS: not statistically significant. * p < 0.05, ** p < 0.01, and *** p < 0.001 indicate statistically significant differences between groups.

Figure 3

The effect of the initial vaccination age and the dose interval on the breakthrough interval. (A) A heatmap showing the combined effect of the initial vaccination age and the dose interval on the breakthrough interval. (B) A fitted surface plot based on a bivariate cubic regression model illustrating the relationship among the initial vaccination age, the dose interval, and the breakthrough interval.