Impact of Immunisation Strategies and Public Health and Social Measures on Varicella Incidence: An Analysis of Surveillance Data from Quzhou City, 2006–2022

Impact of Immunisation Strategies and Public Health and Social Measures on Varicella Incidence: An Analysis of Surveillance Data from Quzhou City, 2006–2022 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of Immunisation Strategies and Public Health and Social Measures on Varicella Incidence: An Analysis of Surveillance Data from Quzhou City, 2006–2022 Quanjun Fang, Hui yang, Shuangqing wang, Xiaoying Gong, Canjie Zheng, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7331077/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background. To assess the impact of different immunisation strategies and public health and social measures (PHSMs) on the incidence of varicella in Quzhou. Methods. We collected data on varicella cases reported in Quzhou City from 2006 to 2022, constructed an interrupted time-series (ITS) regression model, and evaluated changes in monthly varicella incidence during three periods: the single-dose varicella vaccine (VarV) immunisation strategy period, the two-dose VarV immunisation strategy period, and the PHSMs implementation period. Results. ITS analysis indicated that, during the single-dose VarV immunisation strategy period, the incidence of varicella exhibited a significant upward trend (p < 0.001). Following the introduction of the two-dose VarV immunisation strategy, the monthly incidence decreased immediately by .848 per 100,000 population (p = 0.057), representing a marginally significant change. Immediately following the implementation of PHSMs, the monthly incidence of varicella declined by 2.960 cases per 100,000 population ( p = 0.034), a statistically significant reduction. In the longer term, the monthly incidence of varicella increased by 0.032 cases per 100,000 population following the introduction of the two-dose VarV immunisation strategy ( p = 0.367), while a decline of 0.043 cases per 100,000 population was observed after the implementation of PHSMs( p = 0.370), although neither change was statistically significant. Conclusions. This study suggests that the low coverage of the two-dose VarV vaccination in Quzhou has contributed to its limited effectiveness in curbing the long-term upward trend in varicella incidence. Furthermore, while the implementation of PHSMs can serve as a useful complementary strategy to help prevent varicella, their impact on the transmission dynamics of the disease appears relatively limited. PHSMs varicella interrupted time series analysis incidence vaccination coverage Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Varicella is an acute respiratory illness caused by the varicella-zoster virus (VZV). Varicella is highly contagious, with secondary attack rates ranging from 61–100% among susceptible contacts. 1 , 2 The majority of otherwise healthy children experience mild symptoms and a favourable prognosis following primary VZV infection; however, serious complications such as pneumonia, encephalopathy, and, in rare cases, death may occur. 3 , 4 The World Health Organization recently estimated that varicella affects at least 140 million individuals globally each year, leading to approximately 4.2 million cases with serious complications and 4,200 associated deaths. 5 In China, varicella is the third most commonly reported vaccine-preventable infectious disease, with approximately one million cases notified annually. 6 Between 2006 and 2022, a total of 11,990 outbreaks comprising 354,082 cases were reported. 7 As varicella is not officially classified as a notifiable infectious disease in China, its true burden is likely to be underestimated. This highlights the urgent need for effective preventive strategies to mitigate its substantial public health impact. Vaccination with the live attenuated varicella vaccine (VarV) remains the most cost-effective strategy for the prevention and control of varicella. The United States began promoting the use of VarV in March 1995, and with the subsequent increase in vaccination coverage, varicella morbidity and mortality have shown a declining trend. 8 Breakthrough infections can still occur in vaccinated populations, despite the reported high efficacy of the single-dose VarV. 9 In contrast, a two-dose VarV vaccination programme confers nearly 95% protection against varicella of all severities and significantly reduces the incidence of breakthrough infections. 5 Despite substantial scientific evidence supporting the benefits of VarV vaccination, the vaccine has not been incorporated into routine immunisation programmes across most regions of China. 7 VarV was introduced in Quzhou in 2002, with a single dose recommended at 12 months of age. A two-dose immunisation strategy was implemented in July 2014. It is advised that varicella-susceptible children receive the first dose of VarV between 12 and 18 months of age, followed by a second dose at 3 to 4 years, with an interval of at least three months between doses. In Quzhou, VarV is not included in the National Immunisation Programme (NIP) and is therefore available only through voluntary, self-funded vaccination. Given the rising incidence of varicella in China between 2016 and 2019, 10 it remains unclear whether the two-dose VarV immunisation strategy has effectively reduced varicella incidence in the Quzhou region. During the COVID-19 pandemic, public health and social measures (PHSMs) demonstrated significant efficacy in controlling varicella outbreaks. 11 , 12 Although these interventions were initially implemented to contain COVID-19, their application has inadvertently reduced the incidence of other respiratory infections, including varicella, owing to the shared transmission routes. 12 Measures such as increased social distancing, mask-wearing, and enhanced hygiene practices have led to a significant reduction in varicella cases, emphasising their effectiveness in managing respiratory infections. In Xi'an, China, the incidence of varicella declined by 43.18% in 2020 compared to 2019, attributable to the implementation of PHSMs aimed at containing COVID-19. 13 A European study suggests that infection control measures implemented during the COVID-19 pandemic may have curtailed the spread of varicella. 14 The interrupted time series (ITS) design is a quasi-experimental approach that employs segmented linear regression models to analyse changes in both levels and slopes of outcome measures, thereby assessing the longitudinal effects of interventions. It has been widely used to evaluate diverse public health interventions. Previous studies on VarV effectiveness have primarily focused on changes in serum antibodies to VZV 15 , 16 or on assessing vaccine efficacy within specific populations. 17 Fewer investigations have addressed the impact of alterations in vaccination strategies and the implementation of PHSMs on population-level morbidity. Since PHSMs were implemented to control the COVID-19 pandemic from 2020 to 2022 and discontinued thereafter, the cut-off date for this study was December 2022. In this study, we employed the ITS method to compare changes in varicella incidence before and after adjustments to vaccination strategies, as well as before and after the implementation of PHSMs. This approach enabled us to investigate the effects of different vaccination strategies and PHSMs implementation on population-level varicella incidence. Methods Study design Quzhou is a prefecture-level city located in Zhejiang Province, eastern China, covering an area of 8,844 square kilometres with a resident population of approximately 2.2 million. Situated at the intersection of four provinces—Fujian, Zhejiang, Jiangxi, and Anhui—Quzhou serves as a significant transport hub. Its extensive transport network facilitates the rapid spread of infectious diseases. Three distinct periods were defined according to the differing VarV immunisation strategies and the implementation of PHSMs. Period A (January 2006 to June 2014) corresponds to the one-dose VarV immunisation strategy; Period B (July 2014 to December 2019) corresponds to the two-dose VarV immunisation strategy; and Period C (January 2020 to December 2022) corresponds to the implementation of PHSMs aimed at curbing the spread of COVID-19. In 2010, the Quzhou Municipal Health Bureau mandated that all medical institutions report varicella cases, including both laboratory-confirmed and clinically diagnosed cases, to the China Information System for Disease Control and Prevention (CISDCP) within 24 hours. Epidemiological data collected for each reported case include age, sex, current residential address, household registration status, date of symptom onset, date of diagnosis, vaccination history, and other pertinent details. Public health physicians within the surveillance area are also tasked with actively identifying varicella cases on a weekly basis across hospitals, community health centres, schools, and kindergartens. Any unreported cases detected through this active surveillance are subsequently reported to the China Information System for Disease Control and Prevention (CISDCP). Data sources Data on varicella cases in Quzhou City from 2006 to 2022 were obtained from CISDCP. Population data were obtained from the Statistical Bulletin of the Quzhou Municipal Bureau of Statistics. Data on VarV vaccination coverage were obtained from the Zhejiang Provincial Immunisation Information System, which has recorded demographic and vaccination data for all children under 15 years of age residing in Zhejiang Province since 2006. This study presents birth cohort-based vaccination coverage. VarV coverage was calculated as the cumulative number of children vaccinated with VarV by the time of enumeration (December 2022), divided by the total number of children in the corresponding birth cohort. Seasonal distribution-M value The concentration M-value quantifies the intensity of seasonal variation in disease occurrence and is calculated using the following formula: 18 \(\:{R}_{x}=\frac{{r}_{2}+{r}_{6}-{r}_{8}-{r}_{12}}{2}+\frac{\sqrt{3}}{2}\left({r}_{3}+{r}_{5}-{r}_{9}-{r}_{11}\right)+\left({r}_{4}-{r}_{10}\right);{R}_{y}=\frac{{r}_{3}-{r}_{5}-{r}_{9}+{r}_{11}}{2}+\frac{\sqrt{3}}{2}\left({r}_{2}-{r}_{6}-{r}_{8}+{r}_{12}\right)+\left({r}_{1}-{r}_{7}\right);M=\sqrt{\left({R}_{x}^{2}+{R}_{y}^{2}\right)}\) ; where R represents the degree of dispersion, and r denotes the ratio of the number of cases in a given month to the total number of cases in the year. An M-value of 0 indicates that cases are evenly distributed across all 12 months of the year. A value below 0.3 suggests a relatively uniform distribution of disease onset over time. An M-value between 0.3 and < 0.5 indicates moderate seasonality; between 0.5 and < 0.7 or 0.7 and < 0.9 reflects strong seasonality; and between 0.9 and < 1 denotes strict seasonality. An M-value of 1 indicates that cases are concentrated within a single month. Interrupt time series design ITS analysis is a statistical modelling method used to evaluate the effects of interventions by analysing changes in levels and trends before and after the intervention point. This approach involves collecting outcome data at multiple time points surrounding the intervention, while controlling for pre-existing upward or downward trends. ITS analyses constitute a quasi-experimental design that, through fitting segmented multiple linear regressions, can provide robust estimates even in the absence of valid control groups. 19 The segmented linear regression equations were established as follows: $$\:\begin{array}{ll}{Y}_{t}&\:={\beta\:}_{0}+{\beta\:}_{1}\times\:Time+{\beta\:}_{2}\times\:Intervention\hspace{0.17em}1+{\beta\:}_{3}\times\:Postslope\hspace{0.17em}1\\\:&\:+{\beta\:}_{4}\times\:\text{I}\text{n}\text{t}\text{e}\text{r}\text{v}\text{e}\text{n}\text{t}\text{i}\text{o}\text{n}2+{\beta\:}_{5}\times\:\text{P}\text{o}\text{s}\text{t}\text{s}\text{l}\text{o}\text{p}\text{e}2+{\epsilon\:}_{t}\end{array}$$ where the dependent variable, Yₜ, represents the monthly incidence of varicella; Time is a continuous variable with values ranging from 0 to 204; β₀ represents the incidence of varicella in January 2006, the start of the study period; β₁ denotes the slope of the first segment of the regression equation, representing the trend in monthly varicella incidence during the one-dose immunisation strategy. β₂ indicates the change in level, reflecting the immediate effect of the two-dose immunisation strategy; β₃ represents the change in slope of the second segment of the regression equation, reflecting the long-term effect following implementation of the two-dose immunisation strategy, while β₄ denotes the change in level corresponding to the short-term effect during the period of PHSMs implementation; β₅ represents the change in slope of the third segment of the regression equation, indicating the long-term effect of PHSMs implementation on the monthly incidence of varicella. Intervention is a binary variable coded as 0 for pre-intervention observations and 1 for post-intervention observations; posterior slope is a continuous variable coded as 0 for pre-intervention observations, 1 for the first post-intervention observation, 2 for the second, and so forth; and εₜ represents the random error, denoting the portion of variance unexplained by the regression model. 20 Statistical analysis Microsoft Excel 2019 was used to establish a database of the Varicella incidence and to calculate the M value. Statistical analyses were conducted using R version 4.4.2. ITS analysis required time series to be free of autocorrelation, and the Breusch–Godfrey test was used to assess whether autocorrelation was present. For time series without autocorrelation, analysis was conducted using ordinary least squares (OLS); For time series exhibiting first-order autocorrelation, generalised least squares (GLS) was used, implemented via the Prais–Winsten method; the Newey-West method was used for analysis when time series with higherorder autocorrelation. 21 A two-sided t-test was used to assess statistical differences in regression coefficients, with a significance level set at p < 0.05. Results with p-values between 0.05 and 0.10 were considered borderline significant, suggesting a potential effect that should be interpreted cautiously in light of the effect size and biological plausibility. Results Epidemiological Characteristics A total of 13,170 cases of varicella were reported in Quzhou between 2006 and 2022, with an average annual reported incidence of 35.09 per 100,000 population. The yearly incidence ranged from 9.32 per 100,000 (208 cases) in 2006 to 65.55 per 100,000 (1,448 cases) in 2019 (Fig. 1 ). The mean annual reported incidence rates during the one-dose VarV immunisation strategy period, the two-dose VarV immunisation strategy period, and the period of PHSMs implementation were 27.38, 47.51, and 37.95 per 100,000 population, corresponding to 5,457, 5,139, and 2,574 cases, respectively. The average reported incidence rates of varicella among individuals aged 0–4, 5–9, 10–14, and ≥ 15 years from 2006 to 2022 were 64.55, 156.40, 212.75, and 14.32 per 100,000 population, respectively. Statistically significant differences were observed in the average incidence rates across age groups (χ² = 30,942.075, p < 0.001); The average reported incidence rates of varicella were 37.25 and 32.84 per 100,000 population for males and females, respectively. A statistically significant difference was observed between the sexes (χ 2 = 51.902, p < 0.001) (Table 1 ). Table 1 Distribution of reported varicella incidence by age group and sex in Quzhou, 2006–2022 Characteristic One-dose VarV immunisation strategy period Two-dose VarV immunisation strategy period The period of PHSMs implementation Total Cases Incidence(1/100,000) Cases Incidence(1/100,000) Cases Incidence(1/100,000) Cases Incidence(1/100,000) Age group(years) 0–4 682 68.91 406 70.29 135 41.23 1223 64.55 5–9 1962 178.64 948 167.69 190 59.67 3100 156.40 10–14 1367 119.13 1980 370.42 973 279.20 4320 212.75 ≥ 15 1446 8.66 1805 19.75 1276 22.05 4527 14.32 Gender Male 2939 28.74 2816 51.10 1395 40.32 7150 37.25 Female 2518 25.95 2323 43.79 1179 35.49 6020 32.84 Peak incidence was observed annually during May–June and November–January throughout the period 2006–2022, with a consistent temporal distribution evident across the subperiods 2006–2014, 2015–2019, and 2020–2022 (Fig. 2 ). The overall M-value for the average monthly reported incidence of varicella from 2006 to 2022 was 0.25, with corresponding M-values of 0.22, 0.29, and 0.27 for the periods 2006–2014, 2015–2019, and 2020–2022, respectively. These findings suggest that varicella incidence does not exhibit a strong seasonal pattern; therefore, seasonal control variables were not included in the interrupted time series model. VarV vaccination status Vaccination coverage for different doses of VarV among birth cohorts from 2006 to 2021 was queried from the Zhejiang Province Immunisation Planning Information System, with coverage rates as of the end of 2022 presented in Fig. 3 . Coverage of one-dose and two-dose VarV vaccinations increased progressively with each successive birth cohort. Following the introduction of the two-dose VarV immunisation strategy in July 2014, a marked increase in two-dose VarV coverage was observed beginning with the 2010 birth cohort. During the period in which the two-dose strategy was implemented, full VarV coverage ranged from 46.35–60.65% across different birth cohorts in Quzhou. In Quzhou City, the recommended schedule for the second dose of VarV vaccination is at 3 to 4 years of age. Accordingly, the cohort born between 2006 and 2010 corresponds to the single-dose VarV immunisation strategy period, while those born between 2011 and 2019 correspond to the two-dose strategy period. As the data cutoff was at the end of 2022, children born in 2020 were under three years old and had not yet reached the recommended age for the second dose. Interrupt time series analysis The Breusch–Godfrey test indicated the presence of autocorrelation in the series of monthly varicella incidence rates (Lagrange multiplier value = 123.00, p < 0.001). Consequently, the Newey–West method was employed to adjust the standard errors of the parameters. The equation for the interrupted time series regression model of the monthly incidence of Varicella in Quzhou City from 2006 to 2022 was: $$\:\begin{array}{ll}{Y}_{t}&\:=0.686+0.030\times\:Time-1.848\times\:Intervention\hspace{0.17em}1+0.032\times\:Postslope\hspace{0.17em}1\\\:&\:-2.960\times\:\text{I}\text{n}\text{t}\text{e}\text{r}\text{v}\text{e}\text{n}\text{t}\text{i}\text{o}\text{n}2-0.043\times\:\text{P}\text{o}\text{s}\text{t}\text{s}\text{l}\text{o}\text{p}\text{e}2+{\epsilon\:}_{t}\end{array}$$ At the start of the time series, the monthly incidence of varicella was 0.686 cases per 100,000 population (β₀ = 0.686; 95% CI: 0.061 to 1.311; p = 0.032), followed by a statistically significant average monthly increase of 0.030 cases per 100,000 (β₁ = 0.030; 95% CI: 0.015 to 0.045; p < 0.001). The first intervention time point was July 2014, marking the introduction of the two-dose VarV immunisation strategy. This was associated with an immediate reduction of 1.848 cases per 100,000 population in the monthly incidence of varicella (β₂ = − 1.848; 95% CI: − 3.748 to 0.052; p = 0.057), representing a marginally significant effect. During this period, the monthly incidence of varicella exhibited a long-term increasing trend, with a combined slope of β₁ + β₃ = 0.062 (95% CI: − 0.023 to 0.147). The change in slope attributed to the intervention (β₃ = 0.032) was not statistically significant (p = 0.367). The second intervention time point was January 2020, coinciding with the implementation of PHSMs. This was associated with an immediate decrease of 2.960 cases per 100,000 population in the monthly incidence of varicella, representing a statistically significant difference (p = 0.034). The monthly incidence of varicella demonstrated a declining trend, with a change in slope of β₅ = − 0.043, which was not statistically significant (p = 0.370). The results of the t-tests for the regression coefficients are presented in Table 2 , and the segmented linear regression is illustrated in Fig. 4 . ITS modelling of varicella incidence by age group showed that the implementation of the two-dose VarV immunisation strategy resulted in immediate reductions in monthly varicella incidence rates of 3.572, 9.664, and 10.426 cases per 100,000 population for the 0–4, 5–9, and 10–14 year age groups, respectively. All these reductions were marginally significant (p 0.10). Following the implementation of PHSMs, immediate reductions in monthly varicella incidence were observed in the 0–4 and 5–9 year age groups, with decreases of 3.051 and 8.490 cases per 100,000 population, respectively (p = 0.079 and 0.052), both reaching marginal significance (p < 0.10). In the 10–14 year olds, the immediate decrease was more pronounced at 30.058 cases per 100,000 (p = 0.003), representing a statistically significant effect. However, during this period, no statistically significant long-term effects were observed across any age group (p > 0.10) (Table 3 ). Table 3 Parameter estimates from the interrupted time-series regression model for monthly reported varicella incidence rates by age group in Quzhou City, 2006–2022 Variable 0–4 5–9 10–14 ≥ 15 Coefficient (95%CI) t-value P-value Coefficient (95%CI) t-value P-value Coefficient (95%CI) t-value P-value Coefficient (95%CI) t-value P-value β 0 2.892 (0.283 to 5.501) 2.19 0.030 6.174 (2.312 to 10.037) 3.15 0.002 −1.367 (−5.244 to 2.510) −0.70 0.488 0.248 (−0.003 to 0.498) 1.95 0.053 † β1 0.053 (0.010 to 0.097) 2.40 0.017 0.163 (0.066 to 0.259) 3.31 0.001 0.224 (0.137 to 0.310) 5.11 <0.001 0.009 (0.004 to 0.014) 3.38 <0.001 β2 −3.572 (−7.170 to 0.026) −1.96 0.052 † −9.664 (−19.541 to 0.212) −1.93 0.055 † −10.426 (−21.164 to 0.312) −1.91 0.057 † −0.658 (−1.495 to 0.180) −1.55 0.123 β3 −0.027 (−0.133 to 0.079) −0.50 0.617 −0.162 (−17.072 to 0.091) −1.25 0.211 0.375 (−50.021 to−10.096) 1.68 0.101 0.027 (−0.006 to 0.059) 1.62 0.106 β 4 −3.051 (−6.462 to 0.360) −1.76 0.079 † −8.490 (−0.418 to 0.093) −1.95 0.052 † −30.058 (−0.066 to 0.817) −2.97 0.003 −1.020 (−2.432 to 0.393) −1.42 0.156 β 5 −0.035 (−0.158 to 0.089) −0.56 0.578 −0.029 (−0.325 to 0.266) −0.20 0.845 −0.340 (−1.011 to 0.330) −1.00 0.318 −0.027 (−0.078 to 0.024) −1.04 0.300 † 0.05 ≤ p < 0.10, marginally significant The differently coloured dots represent the monthly reported incidence of varicella in Quzhou from 2006 to 2022. The solid red line indicates the trend in incidence rates estimated using segmented regression. The reddish shaded areas represent the 95% confidence intervals estimated using segmented regression. The dashed vertical lines indicate the introduction of the two-dose VarV strategy into the local immunisation programme (July 2014) and the implementation of PHSMs to curb the spread of novel coronaviruses (January 2020). PHSMs: public health and social measures; VarV: varicella vaccine. Table 2 Parameter estimates from the interrupted time series regression model for monthly reported varicella incidence in the total population of Quzhou City, 2006–2022 Variable Coefficient (95%CI) t-value P-value β 0 0.686 (0.061 to 1.311) 2.16 0.032 β1 0.030 (0.015 to 0.045) 3.90 <0.001 β2 -1.848 (−3.748 to 0.052) −1.92 0.057 † β3 0.032 (−0.038 to 0.102) 0.90 0.367 β 4 -2.960 (−5.695 to−0.225) −2.13 0.034 β 5 -0.043 (−0.137 to 0.051) −0.90 0.370 † 0.05 ≤ p < 0.10, marginally significant Discussion Between January 2006 to June 2014, Quzhou City implemented a one-dose VarV immunisation strategy, during which the average annual reported incidence rate was 27.38 per 100,000 population—slightly higher than the national average observed in China between 2005 and 2015. 22 Following the introduction of the two-dose VarV immunisation strategy in Quzhou City in July 2014, the vaccination coverage among school-age children ranged from 46.35–60.65%. Despite this, the incidence of varicella did not exhibit a declining trend between August 2014 to December 2019, with an average annual reported incidence rate of 47.51 per 100,000 population—lower than the national average observed in China during 2016–2019. 10 China experienced an outbreak of novel coronavirus pneumonia in early 2020. During the implementation of PHSMs to contain the spread of COVID-19, the incidence of varicella exhibited a declining trend, with an average annual reported incidence of 37.95 per 100,000 population—lower than that reported in Ningbo City 23 and Anhui Province 24 over the same period. Overall, the incidence of varicella exhibited an initial increase followed by a decline between 2006 and 2022, mirroring the epidemiological trends observed in Ningbo City and Anhui Province. In the present study, prevalence was higher in males than in females, which may be attributable to poorer hygiene practices and greater socialisation among males, resulting in increased exposure to disease-causing agents. 25 With respect to age of onset, the highest incidence was observed primarily among children aged 5–9 and 10–14 years. This finding is consistent with other regional studies 10 and indicates that children aged 5–14 years remain a priority population for varicella prevention and control. In this study, we observed a bimodal seasonal distribution of varicella incidence across three distinct periods, consistent with the national varicella epidemiological characteristics 10 and aligning with the typical high incidence of respiratory-transmitted diseases during winter and spring. The seasonal increase in varicella incidence largely coincides with the period when students congregate in schools, highlighting the need for improved prevention and control of varicella outbreaks within educational settings. The seasonality of varicella incidence during both the implementation of the two-dose VarV immunisation strategy and the period of PHSMs continued to exhibit a bimodal distribution, with no significant change observed—differing from the findings of other studies 14 . This may be attributable to the relatively low two-dose VarV vaccination coverage among school-age children in the Quzhou area, and suggests that the implementation of PHSMs alone may be insufficient to alter the transmission dynamics of varicella. Previous studies have demonstrated a declining trend in varicella incidence following the introduction of the VarV. 26 However, the findings of the present study contrast with those of previous reports. During the period from 2006 to 2014, when the one-dose VarV immunisation strategy was implemented in Quzhou City, the incidence of varicella exhibited an increasing trend. Wang Y et al. conducted a case–control study to evaluate vaccine effectiveness and failure rates during a varicella outbreak in Jiangsu Province. 27 Their findings similarly indicated that a single dose of VarV was insufficient to effectively control varicella transmission. Studies have shown that the protective effect of a single dose of VarV wanes over time, with effectiveness dropping to approximately 50% three years post-vaccination. 15 This suggests that a single dose does not confer sufficient population-level immunity to reduce the incidence of varicella. In some schools in China, multiple varicella outbreaks have occurred despite high coverage with a single dose of VarV. 28 ITS analysis showed an immediate decrease of 1.848 cases per 100,000 population in the monthly incidence of varicella following the implementation of the two-dose VarV immunisation strategy, with a marginally significant difference (p = 0.057). However, the long-term effect was not statistically significant (p = 0.367). By age group, a marginally significant decrease in the immediate effect at the time of intervention was observed among children aged 0–4, 5–9, and 10–14 years (0.05 ≤ p < 0.10). However, none of the long-term effects were statistically significant (p = 0.370), indicating that the two-dose strategy did not significantly modify the original upward trend in varicella morbidity over time. This is likely attributable to the two-dose VarV vaccination coverage among school-age children during this period (46.35–60.65%) being well below the WHO-recommended threshold of 80%, 5 suggesting that suboptimal coverage represents a major limitation to the population-level protective effect of the two-dose strategy. The voluntary, self-funded nature of the VarV vaccination policy limits coverage expansion, resulting in the accumulation of susceptible individuals among school-aged children and thereby diminishing the overall protective effect of the vaccine. Although our data did not demonstrate a decline in varicella incidence following the implementation of the two-dose immunisation strategy, we observed a shift in the age group with the highest incidence from 5–9 to 10–14 years compared to the one-dose VarV immunisation period. The incidence rate in this age group reached 370.42 per 100,000 during the two-dose strategy period, and its long-term trend showed a non-significant increase following the intervention, underscoring the challenges of prevention and control within this cohort and suggesting a possible “age shift” phenomenon. This observation of age shift aligns with findings from the Ningbo region 23 and supports the effectiveness of vaccination in younger age groups. China initiated direct network reporting of varicella through the IDRMS in 2005. Notably, in 2006, varicella outbreak cases were incorporated into the management of public health emergencies, leading to a continuous improvement in reporting sensitivity. 10 This may also be a key factor contributing to the absence of a downward trend in the reported incidence of varicella in Quzhou during the two-dose immunisation strategy period. From 2020 to 2022, China experienced the COVID-19 pandemic, during which the government implemented a series of PHSMs aimed at curbing the spread of the virus. 29 , 30 Studies have demonstrated a decline in respiratory infection cases during the prevention and control of novel coronavirus outbreaks. 31 The findings of this study demonstrated a significant and substantial immediate reduction in varicella incidence among children aged 10–14 years following the implementation of PHSMs. Marginally significant immediate decreases were also observed in the 0–4 and 5–9 year age groups. These results support the immediate effectiveness of school-based PHSMs in interrupting the transmission of respiratory infectious diseases such as varicella. However, the results of this study indicate that PHSMs did not induce a fundamental long-term decline in varicella incidence, with its impact on transmission dynamics being relatively limited—findings consistent with those of previous studies. 26 , 32 In 2020, during the period of local transmission of coronavirus, approximately 80% of vaccination clinics in China suspended all services except for the administration of hepatitis B, BCG, rabies, and tetanus antitoxin vaccines. Such disruptions to immunisation services may result in reduced coverage and could precipitate outbreaks of measles, poliomyelitis, and other vaccine-preventable diseases. 33 In February 2020, Quzhou City suspended vaccination clinic services, resuming them in March of the same year. Thereafter, an online appointment system was introduced to limit the number of clinic visits, which reduced the accessibility of childhood immunisation services. Data from the Zhejiang Province Immunisation Information System indicated that, in 2020, the timely VarV vaccination rate among eligible children in the locality was only 47.62%. Concurrently, as epidemic prevention and control entered a ‘normalised’ phase and social contact resumed—particularly following the reopening of schools—the incidence of varicella rebounded rapidly, leading to the absence of a sustained downward trend in the long-term effectiveness of PHSMs. These findings indicate that reliance on PHSMs alone is insufficient to alter the long-term incidence patterns of respiratory infectious diseases, and that increasing varicella vaccination coverage within the population is essential for effective control. 34 This finding underscores the limitations of relying solely on ad hoc PHSMs and emphasises the importance of establishing sustainable prevention and control strategies grounded in high vaccination coverage. In this study, ITS analysis employing segmented linear regression models was used to evaluate the impact of different immunisation strategies and the implementation of PHSMs on varicella incidence. Compared to traditional epidemiological study designs such as cohort studies, case–control studies, and randomised controlled trials, ITS analysis offers the advantage of quantifying the effect of an intervention in situations where identifying a suitable control group is challenging. 35 – 37 This provides a foundation for refining the VarV vaccination strategy and the effective implementation of PHSMs in varicella outbreak management. Future research could integrate monthly vaccination rates with socioeconomic variables to optimise the ITS model. Nevertheless, this study has several limitations. First, varicella is not a statutorily notifiable infectious disease in China. The data used in this study were derived from passive surveillance at healthcare facilities, where data quality may be influenced by the level of clinical care and the attending physicians’ awareness of infectious disease reporting requirements, potentially leading to underestimation of disease incidence. Secondly, this study did not sufficiently account for the potential influence of variables such as socioeconomic factors and population migration on varicella incidence. In addition, owing to difficulties in obtaining monthly varicella vaccination rate data, this study utilised only annual vaccination rates for different VarV doses, without incorporating vaccine coverage into the ITS model. This limitation may have affected the accuracy of assessing the effectiveness of vaccination campaigns to some extent. Conclusion In summary, although the two-dose VarV strategy is theoretically superior to the one-dose approach, the relatively low two-dose vaccination coverage in Quzhou has rendered it ineffective in curbing the long-term rising trend of varicella incidence; The implementation of PHSMs can serve as an effective complementary measure in preventing varicella; however, its impact on transmission dynamics remains relatively limited. A key priority for future varicella prevention and control is to substantially increase coverage with the two-dose VarV schedule. Inclusion of VarV in the national immunisation programme is therefore strongly recommended. Abbreviations PHSMs public health and social measures Declarations Ethics approval and consent to participate The study was approved by the Research Ethics Committee of the Centre for Disease Control and Prevention of Quzhou City (approval number: 2025-015-01) and was conducted in accordance with the principles of the Declaration of Helsinki. The Ethics Committee waived individual informed consent for the following reasons: Consent for publication Not applicable as all data are presented in the aggregate. Competing interests The authors declare no competing interests. Author details Quzhou Center for Disease Control and Prevention, Quzhou 324000, China Funding This study was funded by the Guiding projects for science and technology plans of Quzhou, Zhejiang Province, China [2023ZD080]. Author Contribution Quanjun Fang wrote the article and Zhiying Yin critically reviewed the article; Huiyang, Shuangqing wang, Xiaoying Gong, and Canjie Zheng were involved in the investigation and data analysis. All authors have agreed on the journal to which the article will be submitted and all agree to take responsibility for all aspects of the work. Acknowledgement The authors would like to sincerely thank Quzhou Center for Disease Control and Prevention for the support of this study, and most importantly, the participants of the study and the members of the survey team. Data availability All data can be available upon request from the corresponding author. References ROSS AH. Modification of chicken pox in family contacts by administration of gamma globulin. N Engl J Med. 1962;267:369–76. 10.1056/NEJM196208232670801 . Seward JF, Zhang JX, Maupin TJ, Mascola L, Jumaan AO. Contagiousness of varicella in vaccinated cases: a household contact study. 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Interrupted time-series analysis and its application in public health[J]. Chin J Epidemiol 2015,36(9):1015–7. 10.3760/cma.j.issn.0254-6450.2015.09.023 Shi T, Meng L, Li D, Jin N, Zhao X, Zhang X, Liu Y, Zheng H, Zhao X, Li J, et al. Impact of the expanded program on immunization on the incidence of Japanese encephalitis in different regions of Mainland China: An interrupt time series analysis. Acta Trop. 2022;233:106575. 10.1016/j.actatropica.2022.106575 . Turner SL, Karahalios A, Forbes AB, Taljaard M, Grimshaw JM, McKenzie JE. Comparison of six statistical methods for interrupted time series studies: empirical evaluation of 190 published series. BMC Med Res Methodol. 2021;21(1):134. 10.1186/s12874-021-01306-w . Haitian S, Jingcheng L, Miao W et al. Varicella epidemiology in China, 2005–2015[J].Chinese Journal of Vaccines and Immunization,2019,25(02):155–9. 10.19914/j.cjvi.2019.02.009 Pan X, Zhang Y, Zhao X, Zhang D. Changes in Epidemiological Characteristics of Varicella and Breakthrough Cases in Ningbo, China, From 2010 to 2023: Surveillance Study. JMIR Public Health Surveill. 2025;11:e71691. 10.2196/71691 . Xuan K, Zhang N, Li T, Pang X, Li Q, Zhao T, Wang B, Zha Z, Tang J. Epidemiological Characteristics of Varicella in Anhui Province, China, 2012–2021: Surveillance Study. JMIR Public Health Surveill. 2024;10:e50673. 10.2196/50673 . van Lunzen J, Altfeld M. Sex differences in infectious diseases-common but neglected. J Infect Dis. 2014;209(Suppl 3):S79–80. 10.1093/infdis/jiu159 . Shi L, Lu J, Sun X, Li Z, Zhang L, Lu Y, Yao Y. Impact of Varicella Immunization and Public Health and Social Measures on Varicella Incidence: Insights from Surveillance Data in Shanghai, 2013–2022. Vaccines (Basel). 2023;11(11):1674. 10.3390/vaccines11111674 . Wang Y, Zhang L, Sun X, Cao Y, Wang Z, Liu L, Xu Y, Zhou M, Liu Y. Effectiveness and failure rate of the varicella vaccine in an outbreak in Jiangsu, China: a 1:2 matched case-control study. Hum Vaccin Immunother. 2020;16(3):506–12. 10.1080/21645515.2019.1665959 . Qin W, Xu XK, Wang Y, Meng XM, Yang CW, Xia F, Su H. Clinical characteristics and risk factors associated with breakthrough varicella during varicella outbreaks. Hum Vaccin Immunother. 2020;16(8):1851–6. 10.1080/21645515.2019.1704574 . Sullivan SG, Carlson S, Cheng AC, Chilver MB, Dwyer DE, Irwin M, Kok J, Macartney K, MacLachlan J, Minney-Smith C, et al. Where has all the influenza gone? The impact of COVID-19 on the circulation of influenza and other respiratory viruses, Australia, March to September 2020. Euro Surveill. 2020;25(47):2001847. 10.2807/1560-7917.ES.2020.25.47.2001847 . Cowling BJ, Ali ST, Ng T, Tsang TK, Li J, Fong MW, Liao Q, Kwan MY, Lee SL, Chiu SS, et al. Impact assessment of non-pharmaceutical interventions against coronavirus disease 2019 and influenza in Hong Kong: an observational study. Lancet Public Health. 2020;5(5):e279–279288. 10.1016/S2468-2667(20)30090-6 . Cheng VC, Wong SC, Chuang VW, et al. The role of community-wide wearing of face mask for control of coronavirus disease 2019 (COVID-19) epidemic due to SARS-CoV-2. J Infect. 2020;81(1):107–14. Suzuki A, Nishiura H. Transmission dynamics of varicella before, during and after the COVID-19 pandemic in Japan: a modelling study. Math Biosci Eng. 2022;19(6):5998–6012. Wu J, Yu W, Cao L, Cao L, Rodewald L, Ye J, Song Y, Li L, Liu X, Wen N, et al. Effectiveness of Catch-Up Vaccinations after COVID-19 Containment - China, 2020. China CDC Wkly. 2020;2(50):968–74. 10.46234/ccdcw2020.262 . Elam-Evans LD, Valier MR, Fredua B, Zell E, Murthy BP, Sterrett N, Harris LQ, Leung J, Singleton JA, Marin M. Celebrating 25 Years of Varicella Vaccination Coverage for Children and Adolescents in the United States: A Success Story. J Infect Dis. 2022;226(Suppl 4):S416–416424. 10.1093/infdis/jiac337 . Bernal JL, Cummins S, Gasparrini A. Interrupted time series regression for the evaluation of public health interventions: a tutorial. Int J Epidemiol. 2017;46(1):348–55. Bonell CP, Hargreaves J, Cousens S, et al. Alternatives to randomisation in the evaluation of public health interventions: design challenges and solutions. J Epidemiol Community Health. 2011;65(7):582–7. Victora CG, Habicht JP, Bryce J. Evidence-based public health: moving beyond randomized trials. Am J Public Health. 2004;94(3):400–5. Additional Declarations No competing interests reported. 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03:53:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7331077/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7331077/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91072315,"identity":"e5d55631-f2f6-41ac-952a-f63a7e069a97","added_by":"auto","created_at":"2025-09-11 10:54:02","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":82851,"visible":true,"origin":"","legend":"\u003cp\u003eReported cases and incidence rate of varicella in Quzhou, 2006–2022\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7331077/v1/a8333d585df08d2f7ceb0038.jpg"},{"id":91072310,"identity":"685ec20e-719f-4256-91f7-db0256b8c7b3","added_by":"auto","created_at":"2025-09-11 10:54:02","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":58409,"visible":true,"origin":"","legend":"\u003cp\u003eComposition ratio of monthly reported cases of varicella in Quzhou, 2006-2022.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7331077/v1/d5454b2f0d8ff40d02cccc64.jpg"},{"id":91072327,"identity":"d414e5f0-4190-4abe-a2fb-d31be8b2e18c","added_by":"auto","created_at":"2025-09-11 10:54:04","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":111125,"visible":true,"origin":"","legend":"\u003cp\u003eVarV vaccination coverage in the 2006–2021 birth cohort population in Quzhou City\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7331077/v1/e654828872b34ccbb6872d29.jpg"},{"id":91072286,"identity":"af464c6f-94e2-456c-8b2a-654e491bee76","added_by":"auto","created_at":"2025-09-11 10:53:58","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":117977,"visible":true,"origin":"","legend":"\u003cp\u003eInterrupted time series of monthly reported varicella incidence rates in Quzhou, 2006–2022.\u003c/p\u003e","description":"","filename":"Picture4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7331077/v1/9133a419bd45b1b444de387f.jpg"},{"id":97958292,"identity":"e81d5fd5-ac78-4941-9c71-fba3cf3d03d0","added_by":"auto","created_at":"2025-12-11 08:24:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1303066,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7331077/v1/10b513eb-58ab-4313-915b-3b51d90b1120.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of Immunisation Strategies and Public Health and Social Measures on Varicella Incidence: An Analysis of Surveillance Data from Quzhou City, 2006–2022","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVaricella is an acute respiratory illness caused by the varicella-zoster virus (VZV). Varicella is highly contagious, with secondary attack rates ranging from 61\u0026ndash;100% among susceptible contacts.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e The majority of otherwise healthy children experience mild symptoms and a favourable prognosis following primary VZV infection; however, serious complications such as pneumonia, encephalopathy, and, in rare cases, death may occur.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e The World Health Organization recently estimated that varicella affects at least 140\u0026nbsp;million individuals globally each year, leading to approximately 4.2\u0026nbsp;million cases with serious complications and 4,200 associated deaths.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e In China, varicella is the third most commonly reported vaccine-preventable infectious disease, with approximately one million cases notified annually.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Between 2006 and 2022, a total of 11,990 outbreaks comprising 354,082 cases were reported.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e As varicella is not officially classified as a notifiable infectious disease in China, its true burden is likely to be underestimated. This highlights the urgent need for effective preventive strategies to mitigate its substantial public health impact.\u003c/p\u003e\u003cp\u003eVaccination with the live attenuated varicella vaccine (VarV) remains the most cost-effective strategy for the prevention and control of varicella. The United States began promoting the use of VarV in March 1995, and with the subsequent increase in vaccination coverage, varicella morbidity and mortality have shown a declining trend.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Breakthrough infections can still occur in vaccinated populations, despite the reported high efficacy of the single-dose VarV.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e In contrast, a two-dose VarV vaccination programme confers nearly 95% protection against varicella of all severities and significantly reduces the incidence of breakthrough infections.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Despite substantial scientific evidence supporting the benefits of VarV vaccination, the vaccine has not been incorporated into routine immunisation programmes across most regions of China.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e VarV was introduced in Quzhou in 2002, with a single dose recommended at 12 months of age. A two-dose immunisation strategy was implemented in July 2014. It is advised that varicella-susceptible children receive the first dose of VarV between 12 and 18 months of age, followed by a second dose at 3 to 4 years, with an interval of at least three months between doses. In Quzhou, VarV is not included in the National Immunisation Programme (NIP) and is therefore available only through voluntary, self-funded vaccination. Given the rising incidence of varicella in China between 2016 and 2019,\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e it remains unclear whether the two-dose VarV immunisation strategy has effectively reduced varicella incidence in the Quzhou region.\u003c/p\u003e\u003cp\u003eDuring the COVID-19 pandemic, public health and social measures (PHSMs) demonstrated significant efficacy in controlling varicella outbreaks.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Although these interventions were initially implemented to contain COVID-19, their application has inadvertently reduced the incidence of other respiratory infections, including varicella, owing to the shared transmission routes.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Measures such as increased social distancing, mask-wearing, and enhanced hygiene practices have led to a significant reduction in varicella cases, emphasising their effectiveness in managing respiratory infections. In Xi'an, China, the incidence of varicella declined by 43.18% in 2020 compared to 2019, attributable to the implementation of PHSMs aimed at containing COVID-19.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e A European study suggests that infection control measures implemented during the COVID-19 pandemic may have curtailed the spread of varicella.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe interrupted time series (ITS) design is a quasi-experimental approach that employs segmented linear regression models to analyse changes in both levels and slopes of outcome measures, thereby assessing the longitudinal effects of interventions. It has been widely used to evaluate diverse public health interventions. Previous studies on VarV effectiveness have primarily focused on changes in serum antibodies to VZV\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e or on assessing vaccine efficacy within specific populations.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e Fewer investigations have addressed the impact of alterations in vaccination strategies and the implementation of PHSMs on population-level morbidity. Since PHSMs were implemented to control the COVID-19 pandemic from 2020 to 2022 and discontinued thereafter, the cut-off date for this study was December 2022. In this study, we employed the ITS method to compare changes in varicella incidence before and after adjustments to vaccination strategies, as well as before and after the implementation of PHSMs. This approach enabled us to investigate the effects of different vaccination strategies and PHSMs implementation on population-level varicella incidence.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design\u003c/h2\u003e\u003cp\u003eQuzhou is a prefecture-level city located in Zhejiang Province, eastern China, covering an area of 8,844 square kilometres with a resident population of approximately 2.2\u0026nbsp;million. Situated at the intersection of four provinces\u0026mdash;Fujian, Zhejiang, Jiangxi, and Anhui\u0026mdash;Quzhou serves as a significant transport hub. Its extensive transport network facilitates the rapid spread of infectious diseases.\u003c/p\u003e\u003cp\u003eThree distinct periods were defined according to the differing VarV immunisation strategies and the implementation of PHSMs. Period A (January 2006 to June 2014) corresponds to the one-dose VarV immunisation strategy; Period B (July 2014 to December 2019) corresponds to the two-dose VarV immunisation strategy; and Period C (January 2020 to December 2022) corresponds to the implementation of PHSMs aimed at curbing the spread of COVID-19.\u003c/p\u003e\u003cp\u003eIn 2010, the Quzhou Municipal Health Bureau mandated that all medical institutions report varicella cases, including both laboratory-confirmed and clinically diagnosed cases, to the China Information System for Disease Control and Prevention (CISDCP) within 24 hours. Epidemiological data collected for each reported case include age, sex, current residential address, household registration status, date of symptom onset, date of diagnosis, vaccination history, and other pertinent details. Public health physicians within the surveillance area are also tasked with actively identifying varicella cases on a weekly basis across hospitals, community health centres, schools, and kindergartens. Any unreported cases detected through this active surveillance are subsequently reported to the China Information System for Disease Control and Prevention (CISDCP).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eData sources\u003c/h3\u003e\n\u003cp\u003eData on varicella cases in Quzhou City from 2006 to 2022 were obtained from CISDCP. Population data were obtained from the Statistical Bulletin of the Quzhou Municipal Bureau of Statistics.\u003c/p\u003e\u003cp\u003eData on VarV vaccination coverage were obtained from the Zhejiang Provincial Immunisation Information System, which has recorded demographic and vaccination data for all children under 15 years of age residing in Zhejiang Province since 2006. This study presents birth cohort-based vaccination coverage. VarV coverage was calculated as the cumulative number of children vaccinated with VarV by the time of enumeration (December 2022), divided by the total number of children in the corresponding birth cohort.\u003c/p\u003e\n\u003ch3\u003eSeasonal distribution-M value\u003c/h3\u003e\n\u003cp\u003eThe concentration M-value quantifies the intensity of seasonal variation in disease occurrence and is calculated using the following formula:\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{R}_{x}=\\frac{{r}_{2}+{r}_{6}-{r}_{8}-{r}_{12}}{2}+\\frac{\\sqrt{3}}{2}\\left({r}_{3}+{r}_{5}-{r}_{9}-{r}_{11}\\right)+\\left({r}_{4}-{r}_{10}\\right);{R}_{y}=\\frac{{r}_{3}-{r}_{5}-{r}_{9}+{r}_{11}}{2}+\\frac{\\sqrt{3}}{2}\\left({r}_{2}-{r}_{6}-{r}_{8}+{r}_{12}\\right)+\\left({r}_{1}-{r}_{7}\\right);M=\\sqrt{\\left({R}_{x}^{2}+{R}_{y}^{2}\\right)}\\)\u003c/span\u003e\u003c/span\u003e; where R represents the degree of dispersion, and r denotes the ratio of the number of cases in a given month to the total number of cases in the year. An M-value of 0 indicates that cases are evenly distributed across all 12 months of the year. A value below 0.3 suggests a relatively uniform distribution of disease onset over time. An M-value between 0.3 and \u0026lt;\u0026thinsp;0.5 indicates moderate seasonality; between 0.5 and \u0026lt;\u0026thinsp;0.7 or 0.7 and \u0026lt;\u0026thinsp;0.9 reflects strong seasonality; and between 0.9 and \u0026lt;\u0026thinsp;1 denotes strict seasonality. An M-value of 1 indicates that cases are concentrated within a single month.\u003c/p\u003e\n\u003ch3\u003eInterrupt time series design\u003c/h3\u003e\n\u003cp\u003eITS analysis is a statistical modelling method used to evaluate the effects of interventions by analysing changes in levels and trends before and after the intervention point. This approach involves collecting outcome data at multiple time points surrounding the intervention, while controlling for pre-existing upward or downward trends. ITS analyses constitute a quasi-experimental design that, through fitting segmented multiple linear regressions, can provide robust estimates even in the absence of valid control groups.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e The segmented linear regression equations were established as follows:\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:\\begin{array}{ll}{Y}_{t}\u0026amp;\\:={\\beta\\:}_{0}+{\\beta\\:}_{1}\\times\\:Time+{\\beta\\:}_{2}\\times\\:Intervention\\hspace{0.17em}1+{\\beta\\:}_{3}\\times\\:Postslope\\hspace{0.17em}1\\\\\\:\u0026amp;\\:+{\\beta\\:}_{4}\\times\\:\\text{I}\\text{n}\\text{t}\\text{e}\\text{r}\\text{v}\\text{e}\\text{n}\\text{t}\\text{i}\\text{o}\\text{n}2+{\\beta\\:}_{5}\\times\\:\\text{P}\\text{o}\\text{s}\\text{t}\\text{s}\\text{l}\\text{o}\\text{p}\\text{e}2+{\\epsilon\\:}_{t}\\end{array}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ewhere the dependent variable, Yₜ, represents the monthly incidence of varicella; Time is a continuous variable with values ranging from 0 to 204; β₀ represents the incidence of varicella in January 2006, the start of the study period; β₁ denotes the slope of the first segment of the regression equation, representing the trend in monthly varicella incidence during the one-dose immunisation strategy. β₂ indicates the change in level, reflecting the immediate effect of the two-dose immunisation strategy; β₃ represents the change in slope of the second segment of the regression equation, reflecting the long-term effect following implementation of the two-dose immunisation strategy, while β₄ denotes the change in level corresponding to the short-term effect during the period of PHSMs implementation; β₅ represents the change in slope of the third segment of the regression equation, indicating the long-term effect of PHSMs implementation on the monthly incidence of varicella. Intervention is a binary variable coded as 0 for pre-intervention observations and 1 for post-intervention observations; posterior slope is a continuous variable coded as 0 for pre-intervention observations, 1 for the first post-intervention observation, 2 for the second, and so forth; and εₜ represents the random error, denoting the portion of variance unexplained by the regression model.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eMicrosoft Excel 2019 was used to establish a database of the Varicella incidence and to calculate the M value. Statistical analyses were conducted using R version 4.4.2. ITS analysis required time series to be free of autocorrelation, and the Breusch\u0026ndash;Godfrey test was used to assess whether autocorrelation was present. For time series without autocorrelation, analysis was conducted using ordinary least squares (OLS); For time series exhibiting first-order autocorrelation, generalised least squares (GLS) was used, implemented via the Prais\u0026ndash;Winsten method; the Newey-West method was used for analysis when time series with higherorder autocorrelation.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e A two-sided t-test was used to assess statistical differences in regression coefficients, with a significance level set at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Results with p-values between 0.05 and 0.10 were considered borderline significant, suggesting a potential effect that should be interpreted cautiously in light of the effect size and biological plausibility.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003eEpidemiological Characteristics\u003c/h2\u003e\u003cp\u003eA total of 13,170 cases of varicella were reported in Quzhou between 2006 and 2022, with an average annual reported incidence of 35.09 per 100,000 population. The yearly incidence ranged from 9.32 per 100,000 (208 cases) in 2006 to 65.55 per 100,000 (1,448 cases) in 2019 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The mean annual reported incidence rates during the one-dose VarV immunisation strategy period, the two-dose VarV immunisation strategy period, and the period of PHSMs implementation were 27.38, 47.51, and 37.95 per 100,000 population, corresponding to 5,457, 5,139, and 2,574 cases, respectively.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe average reported incidence rates of varicella among individuals aged 0\u0026ndash;4, 5\u0026ndash;9, 10\u0026ndash;14, and \u0026ge;\u0026thinsp;15 years from 2006 to 2022 were 64.55, 156.40, 212.75, and 14.32 per 100,000 population, respectively. Statistically significant differences were observed in the average incidence rates across age groups (χ\u0026sup2; = 30,942.075, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001); The average reported incidence rates of varicella were 37.25 and 32.84 per 100,000 population for males and females, respectively. A statistically significant difference was observed between the sexes (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;51.902, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDistribution of reported varicella incidence by age group and sex in Quzhou, 2006\u0026ndash;2022\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"10\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eOne-dose VarV immunisation strategy period\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eTwo-dose VarV immunisation strategy period\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u003cp\u003eThe period of PHSMs implementation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCases\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIncidence(1/100,000)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCases\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eIncidence(1/100,000)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eCases\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eIncidence(1/100,000)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eCases\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eIncidence(1/100,000)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"10\" nameend=\"c10\" namest=\"c1\"\u003e\u003cp\u003eAge group(years)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u0026ndash;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e682\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e68.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e406\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e70.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e135\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e41.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1223\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e64.55\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u0026ndash;9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1962\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e178.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e948\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e167.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e190\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e59.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e3100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e156.40\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e10\u0026ndash;14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1367\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e119.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1980\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e370.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e973\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e279.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e4320\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e212.75\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1446\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1805\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e19.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1276\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e22.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e4527\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e14.32\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"10\" nameend=\"c10\" namest=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2939\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2816\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e51.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1395\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e40.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e7150\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e37.25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2518\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25.95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2323\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003e43.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1179\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e35.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e6020\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e32.84\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePeak incidence was observed annually during May\u0026ndash;June and November\u0026ndash;January throughout the period 2006\u0026ndash;2022, with a consistent temporal distribution evident across the subperiods 2006\u0026ndash;2014, 2015\u0026ndash;2019, and 2020\u0026ndash;2022 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The overall M-value for the average monthly reported incidence of varicella from 2006 to 2022 was 0.25, with corresponding M-values of 0.22, 0.29, and 0.27 for the periods 2006\u0026ndash;2014, 2015\u0026ndash;2019, and 2020\u0026ndash;2022, respectively. These findings suggest that varicella incidence does not exhibit a strong seasonal pattern; therefore, seasonal control variables were not included in the interrupted time series model.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eVarV vaccination status\u003c/h3\u003e\n\u003cp\u003eVaccination coverage for different doses of VarV among birth cohorts from 2006 to 2021 was queried from the Zhejiang Province Immunisation Planning Information System, with coverage rates as of the end of 2022 presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Coverage of one-dose and two-dose VarV vaccinations increased progressively with each successive birth cohort. Following the introduction of the two-dose VarV immunisation strategy in July 2014, a marked increase in two-dose VarV coverage was observed beginning with the 2010 birth cohort. During the period in which the two-dose strategy was implemented, full VarV coverage ranged from 46.35\u0026ndash;60.65% across different birth cohorts in Quzhou.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eIn Quzhou City, the recommended schedule for the second dose of VarV vaccination is at 3 to 4 years of age. Accordingly, the cohort born between 2006 and 2010 corresponds to the single-dose VarV immunisation strategy period, while those born between 2011 and 2019 correspond to the two-dose strategy period. As the data cutoff was at the end of 2022, children born in 2020 were under three years old and had not yet reached the recommended age for the second dose.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eInterrupt time series analysis\u003c/h2\u003e\u003cp\u003eThe Breusch\u0026ndash;Godfrey test indicated the presence of autocorrelation in the series of monthly varicella incidence rates (Lagrange multiplier value\u0026thinsp;=\u0026thinsp;123.00, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Consequently, the Newey\u0026ndash;West method was employed to adjust the standard errors of the parameters. The equation for the interrupted time series regression model of the monthly incidence of Varicella in Quzhou City from 2006 to 2022 was:\u003cdiv id=\"Equb\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equb\" name=\"EquationSource\"\u003e\n$$\\:\\begin{array}{ll}{Y}_{t}\u0026amp;\\:=0.686+0.030\\times\\:Time-1.848\\times\\:Intervention\\hspace{0.17em}1+0.032\\times\\:Postslope\\hspace{0.17em}1\\\\\\:\u0026amp;\\:-2.960\\times\\:\\text{I}\\text{n}\\text{t}\\text{e}\\text{r}\\text{v}\\text{e}\\text{n}\\text{t}\\text{i}\\text{o}\\text{n}2-0.043\\times\\:\\text{P}\\text{o}\\text{s}\\text{t}\\text{s}\\text{l}\\text{o}\\text{p}\\text{e}2+{\\epsilon\\:}_{t}\\end{array}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAt the start of the time series, the monthly incidence of varicella was 0.686 cases per 100,000 population (β₀ = 0.686; 95% CI: 0.061 to 1.311; p\u0026thinsp;=\u0026thinsp;0.032), followed by a statistically significant average monthly increase of 0.030 cases per 100,000 (β₁ = 0.030; 95% CI: 0.015 to 0.045; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The first intervention time point was July 2014, marking the introduction of the two-dose VarV immunisation strategy. This was associated with an immediate reduction of 1.848 cases per 100,000 population in the monthly incidence of varicella (β₂ = \u0026minus;\u0026thinsp;1.848; 95% CI: \u0026minus;\u0026thinsp;3.748 to 0.052; p\u0026thinsp;=\u0026thinsp;0.057), representing a marginally significant effect. During this period, the monthly incidence of varicella exhibited a long-term increasing trend, with a combined slope of β₁ + β₃ = 0.062 (95% CI: \u0026minus;\u0026thinsp;0.023 to 0.147). The change in slope attributed to the intervention (β₃ = 0.032) was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.367). The second intervention time point was January 2020, coinciding with the implementation of PHSMs. This was associated with an immediate decrease of 2.960 cases per 100,000 population in the monthly incidence of varicella, representing a statistically significant difference (p\u0026thinsp;=\u0026thinsp;0.034). The monthly incidence of varicella demonstrated a declining trend, with a change in slope of β₅ = \u0026minus;\u0026thinsp;0.043, which was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.370). The results of the t-tests for the regression coefficients are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e2\u003c/span\u003e, and the segmented linear regression is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eITS modelling of varicella incidence by age group showed that the implementation of the two-dose VarV immunisation strategy resulted in immediate reductions in monthly varicella incidence rates of 3.572, 9.664, and 10.426 cases per 100,000 population for the 0\u0026ndash;4, 5\u0026ndash;9, and 10\u0026ndash;14 year age groups, respectively. All these reductions were marginally significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.10). During this period, no statistically significant long-term effects were observed across all age groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.10). Following the implementation of PHSMs, immediate reductions in monthly varicella incidence were observed in the 0\u0026ndash;4 and 5\u0026ndash;9 year age groups, with decreases of 3.051 and 8.490 cases per 100,000 population, respectively (p\u0026thinsp;=\u0026thinsp;0.079 and 0.052), both reaching marginal significance (p\u0026thinsp;\u0026lt;\u0026thinsp;0.10). In the 10\u0026ndash;14 year olds, the immediate decrease was more pronounced at 30.058 cases per 100,000 (p\u0026thinsp;=\u0026thinsp;0.003), representing a statistically significant effect. However, during this period, no statistically significant long-term effects were observed across any age group (p\u0026thinsp;\u0026gt;\u0026thinsp;0.10) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eParameter estimates from the interrupted time-series regression model for monthly reported varicella incidence rates by age group in Quzhou City, 2006\u0026ndash;2022\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"13\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003e0\u0026ndash;4\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e5\u0026ndash;9\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e\u003cp\u003e10\u0026ndash;14\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c13\" namest=\"c11\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;15\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCoefficient (95%CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003et-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCoefficient (95%CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003et-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCoefficient\u003c/p\u003e\u003cp\u003e(95%CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003et-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eCoefficient\u003c/p\u003e\u003cp\u003e(95%CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003et-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eβ\u003csub\u003e0\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.892\u003c/p\u003e\u003cp\u003e(0.283 to 5.501)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.030\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6.174\u003c/p\u003e\u003cp\u003e(2.312 to 10.037)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026minus;1.367\u003c/p\u003e\u003cp\u003e(\u0026minus;5.244 to 2.510)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u0026minus;0.70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.488\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.248\u003c/p\u003e\u003cp\u003e(\u0026minus;0.003 to 0.498)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e1.95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.053\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eβ1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.053\u003c/p\u003e\u003cp\u003e(0.010 to 0.097)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.017\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.163\u003c/p\u003e\u003cp\u003e(0.066 to 0.259)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.224\u003c/p\u003e\u003cp\u003e(0.137 to 0.310)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e5.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.009\u003c/p\u003e\u003cp\u003e(0.004 to 0.014)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e3.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eβ2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026minus;3.572\u003c/p\u003e\u003cp\u003e(\u0026minus;7.170 to 0.026)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026minus;1.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.052\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026minus;9.664\u003c/p\u003e \u003cp\u003e(\u0026minus;19.541 to 0.212)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026minus;1.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.055\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026minus;10.426\u003c/p\u003e\u003cp\u003e(\u0026minus;21.164 to 0.312)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u0026minus;1.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.057\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u0026minus;0.658\u003c/p\u003e\u003cp\u003e(\u0026minus;1.495 to 0.180)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e\u0026minus;1.55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.123\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eβ3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026minus;0.027\u003c/p\u003e\u003cp\u003e(\u0026minus;0.133 to 0.079)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026minus;0.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.617\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026minus;0.162\u003c/p\u003e \u003cp\u003e(\u0026minus;17.072 to 0.091)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026minus;1.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.211\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.375\u003c/p\u003e\u003cp\u003e(\u0026minus;50.021 to\u0026minus;10.096)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.101\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0.027\u003c/p\u003e\u003cp\u003e(\u0026minus;0.006 to 0.059)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e1.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.106\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eβ\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026minus;3.051\u003c/p\u003e\u003cp\u003e(\u0026minus;6.462 to 0.360)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026minus;1.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.079\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026minus;8.490\u003c/p\u003e \u003cp\u003e(\u0026minus;0.418 to 0.093)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026minus;1.95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.052\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026minus;30.058\u003c/p\u003e\u003cp\u003e(\u0026minus;0.066 to 0.817)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u0026minus;2.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u0026minus;1.020\u003c/p\u003e\u003cp\u003e(\u0026minus;2.432 to 0.393)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e\u0026minus;1.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.156\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eβ\u003csub\u003e5\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026minus;0.035\u003c/p\u003e\u003cp\u003e(\u0026minus;0.158 to 0.089)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026minus;0.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.578\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026minus;0.029\u003c/p\u003e \u003cp\u003e(\u0026minus;0.325 to 0.266)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026minus;0.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.845\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026minus;0.340\u003c/p\u003e\u003cp\u003e(\u0026minus;1.011 to 0.330)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u0026minus;1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.318\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u0026minus;0.027\u003c/p\u003e\u003cp\u003e(\u0026minus;0.078 to 0.024)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e\u0026minus;1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.300\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"13\"\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e0.05\u0026thinsp;\u0026le;\u0026thinsp;p\u0026thinsp;\u0026lt;\u0026thinsp;0.10, marginally significant\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe differently coloured dots represent the monthly reported incidence of varicella in Quzhou from 2006 to 2022. The solid red line indicates the trend in incidence rates estimated using segmented regression. The reddish shaded areas represent the 95% confidence intervals estimated using segmented regression. The dashed vertical lines indicate the introduction of the two-dose VarV strategy into the local immunisation programme (July 2014) and the implementation of PHSMs to curb the spread of novel coronaviruses (January 2020). PHSMs: public health and social measures; VarV: varicella vaccine.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eParameter estimates from the interrupted time series regression model for monthly reported varicella incidence in the total population of Quzhou City, 2006\u0026ndash;2022\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCoefficient\u003c/p\u003e\u003cp\u003e(95%CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003et-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eβ\u003csub\u003e0\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.686\u003c/p\u003e\u003cp\u003e(0.061 to 1.311)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.032\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eβ1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.030\u003c/p\u003e\u003cp\u003e(0.015 to 0.045)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eβ2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-1.848\u003c/p\u003e\u003cp\u003e(\u0026minus;3.748 to 0.052)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026minus;1.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.057\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eβ3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.032\u003c/p\u003e\u003cp\u003e(\u0026minus;0.038 to 0.102)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.367\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eβ\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-2.960\u003c/p\u003e\u003cp\u003e(\u0026minus;5.695 to\u0026minus;0.225)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026minus;2.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.034\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eβ\u003csub\u003e5\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.043\u003c/p\u003e\u003cp\u003e(\u0026minus;0.137 to 0.051)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026minus;0.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.370\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e0.05\u0026thinsp;\u0026le;\u0026thinsp;p\u0026thinsp;\u0026lt;\u0026thinsp;0.10, marginally significant\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eBetween January 2006 to June 2014, Quzhou City implemented a one-dose VarV immunisation strategy, during which the average annual reported incidence rate was 27.38 per 100,000 population\u0026mdash;slightly higher than the national average observed in China between 2005 and 2015.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Following the introduction of the two-dose VarV immunisation strategy in Quzhou City in July 2014, the vaccination coverage among school-age children ranged from 46.35\u0026ndash;60.65%. Despite this, the incidence of varicella did not exhibit a declining trend between August 2014 to December 2019, with an average annual reported incidence rate of 47.51 per 100,000 population\u0026mdash;lower than the national average observed in China during 2016\u0026ndash;2019.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e China experienced an outbreak of novel coronavirus pneumonia in early 2020. During the implementation of PHSMs to contain the spread of COVID-19, the incidence of varicella exhibited a declining trend, with an average annual reported incidence of 37.95 per 100,000 population\u0026mdash;lower than that reported in Ningbo City\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e and Anhui Province\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e over the same period. Overall, the incidence of varicella exhibited an initial increase followed by a decline between 2006 and 2022, mirroring the epidemiological trends observed in Ningbo City and Anhui Province.\u003c/p\u003e\u003cp\u003eIn the present study, prevalence was higher in males than in females, which may be attributable to poorer hygiene practices and greater socialisation among males, resulting in increased exposure to disease-causing agents.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e With respect to age of onset, the highest incidence was observed primarily among children aged 5\u0026ndash;9 and 10\u0026ndash;14 years. This finding is consistent with other regional studies\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e and indicates that children aged 5\u0026ndash;14 years remain a priority population for varicella prevention and control. In this study, we observed a bimodal seasonal distribution of varicella incidence across three distinct periods, consistent with the national varicella epidemiological characteristics\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e and aligning with the typical high incidence of respiratory-transmitted diseases during winter and spring. The seasonal increase in varicella incidence largely coincides with the period when students congregate in schools, highlighting the need for improved prevention and control of varicella outbreaks within educational settings. The seasonality of varicella incidence during both the implementation of the two-dose VarV immunisation strategy and the period of PHSMs continued to exhibit a bimodal distribution, with no significant change observed\u0026mdash;differing from the findings of other studies\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. This may be attributable to the relatively low two-dose VarV vaccination coverage among school-age children in the Quzhou area, and suggests that the implementation of PHSMs alone may be insufficient to alter the transmission dynamics of varicella.\u003c/p\u003e\u003cp\u003ePrevious studies have demonstrated a declining trend in varicella incidence following the introduction of the VarV.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e However, the findings of the present study contrast with those of previous reports. During the period from 2006 to 2014, when the one-dose VarV immunisation strategy was implemented in Quzhou City, the incidence of varicella exhibited an increasing trend. Wang Y et al. conducted a case\u0026ndash;control study to evaluate vaccine effectiveness and failure rates during a varicella outbreak in Jiangsu Province.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Their findings similarly indicated that a single dose of VarV was insufficient to effectively control varicella transmission. Studies have shown that the protective effect of a single dose of VarV wanes over time, with effectiveness dropping to approximately 50% three years post-vaccination.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e This suggests that a single dose does not confer sufficient population-level immunity to reduce the incidence of varicella. In some schools in China, multiple varicella outbreaks have occurred despite high coverage with a single dose of VarV.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eITS analysis showed an immediate decrease of 1.848 cases per 100,000 population in the monthly incidence of varicella following the implementation of the two-dose VarV immunisation strategy, with a marginally significant difference (p\u0026thinsp;=\u0026thinsp;0.057). However, the long-term effect was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.367). By age group, a marginally significant decrease in the immediate effect at the time of intervention was observed among children aged 0\u0026ndash;4, 5\u0026ndash;9, and 10\u0026ndash;14 years (0.05\u0026thinsp;\u0026le;\u0026thinsp;p\u0026thinsp;\u0026lt;\u0026thinsp;0.10). However, none of the long-term effects were statistically significant (p\u0026thinsp;=\u0026thinsp;0.370), indicating that the two-dose strategy did not significantly modify the original upward trend in varicella morbidity over time. This is likely attributable to the two-dose VarV vaccination coverage among school-age children during this period (46.35\u0026ndash;60.65%) being well below the WHO-recommended threshold of 80%,\u003csup\u003e5\u003c/sup\u003e suggesting that suboptimal coverage represents a major limitation to the population-level protective effect of the two-dose strategy. The voluntary, self-funded nature of the VarV vaccination policy limits coverage expansion, resulting in the accumulation of susceptible individuals among school-aged children and thereby diminishing the overall protective effect of the vaccine. Although our data did not demonstrate a decline in varicella incidence following the implementation of the two-dose immunisation strategy, we observed a shift in the age group with the highest incidence from 5\u0026ndash;9 to 10\u0026ndash;14 years compared to the one-dose VarV immunisation period. The incidence rate in this age group reached 370.42 per 100,000 during the two-dose strategy period, and its long-term trend showed a non-significant increase following the intervention, underscoring the challenges of prevention and control within this cohort and suggesting a possible \u0026ldquo;age shift\u0026rdquo; phenomenon. This observation of age shift aligns with findings from the Ningbo region\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e and supports the effectiveness of vaccination in younger age groups. China initiated direct network reporting of varicella through the IDRMS in 2005. Notably, in 2006, varicella outbreak cases were incorporated into the management of public health emergencies, leading to a continuous improvement in reporting sensitivity.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e This may also be a key factor contributing to the absence of a downward trend in the reported incidence of varicella in Quzhou during the two-dose immunisation strategy period.\u003c/p\u003e\u003cp\u003eFrom 2020 to 2022, China experienced the COVID-19 pandemic, during which the government implemented a series of PHSMs aimed at curbing the spread of the virus.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e Studies have demonstrated a decline in respiratory infection cases during the prevention and control of novel coronavirus outbreaks.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e The findings of this study demonstrated a significant and substantial immediate reduction in varicella incidence among children aged 10\u0026ndash;14 years following the implementation of PHSMs. Marginally significant immediate decreases were also observed in the 0\u0026ndash;4 and 5\u0026ndash;9 year age groups. These results support the immediate effectiveness of school-based PHSMs in interrupting the transmission of respiratory infectious diseases such as varicella. However, the results of this study indicate that PHSMs did not induce a fundamental long-term decline in varicella incidence, with its impact on transmission dynamics being relatively limited\u0026mdash;findings consistent with those of previous studies.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e In 2020, during the period of local transmission of coronavirus, approximately 80% of vaccination clinics in China suspended all services except for the administration of hepatitis B, BCG, rabies, and tetanus antitoxin vaccines. Such disruptions to immunisation services may result in reduced coverage and could precipitate outbreaks of measles, poliomyelitis, and other vaccine-preventable diseases.\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e In February 2020, Quzhou City suspended vaccination clinic services, resuming them in March of the same year. Thereafter, an online appointment system was introduced to limit the number of clinic visits, which reduced the accessibility of childhood immunisation services. Data from the Zhejiang Province Immunisation Information System indicated that, in 2020, the timely VarV vaccination rate among eligible children in the locality was only 47.62%. Concurrently, as epidemic prevention and control entered a \u0026lsquo;normalised\u0026rsquo; phase and social contact resumed\u0026mdash;particularly following the reopening of schools\u0026mdash;the incidence of varicella rebounded rapidly, leading to the absence of a sustained downward trend in the long-term effectiveness of PHSMs. These findings indicate that reliance on PHSMs alone is insufficient to alter the long-term incidence patterns of respiratory infectious diseases, and that increasing varicella vaccination coverage within the population is essential for effective control.\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThis finding underscores the limitations of relying solely on ad hoc PHSMs and emphasises the importance of establishing sustainable prevention and control strategies grounded in high vaccination coverage.\u003c/p\u003e\u003cp\u003eIn this study, ITS analysis employing segmented linear regression models was used to evaluate the impact of different immunisation strategies and the implementation of PHSMs on varicella incidence. Compared to traditional epidemiological study designs such as cohort studies, case\u0026ndash;control studies, and randomised controlled trials, ITS analysis offers the advantage of quantifying the effect of an intervention in situations where identifying a suitable control group is challenging.\u003csup\u003e\u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e This provides a foundation for refining the VarV vaccination strategy and the effective implementation of PHSMs in varicella outbreak management. Future research could integrate monthly vaccination rates with socioeconomic variables to optimise the ITS model.\u003c/p\u003e\u003cp\u003eNevertheless, this study has several limitations. First, varicella is not a statutorily notifiable infectious disease in China. The data used in this study were derived from passive surveillance at healthcare facilities, where data quality may be influenced by the level of clinical care and the attending physicians\u0026rsquo; awareness of infectious disease reporting requirements, potentially leading to underestimation of disease incidence. Secondly, this study did not sufficiently account for the potential influence of variables such as socioeconomic factors and population migration on varicella incidence. In addition, owing to difficulties in obtaining monthly varicella vaccination rate data, this study utilised only annual vaccination rates for different VarV doses, without incorporating vaccine coverage into the ITS model. This limitation may have affected the accuracy of assessing the effectiveness of vaccination campaigns to some extent.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, although the two-dose VarV strategy is theoretically superior to the one-dose approach, the relatively low two-dose vaccination coverage in Quzhou has rendered it ineffective in curbing the long-term rising trend of varicella incidence; The implementation of PHSMs can serve as an effective complementary measure in preventing varicella; however, its impact on transmission dynamics remains relatively limited. A key priority for future varicella prevention and control is to substantially increase coverage with the two-dose VarV schedule. Inclusion of VarV in the national immunisation programme is therefore strongly recommended.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePHSMs public health and social measures\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cp\u003eThe study was approved by the Research Ethics Committee of the Centre for Disease Control and Prevention of Quzhou City (approval number: 2025-015-01) and was conducted in accordance with the principles of the Declaration of Helsinki. The Ethics Committee waived individual informed consent for the following reasons:\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eConsent for publication\u003c/h2\u003e\u003cp\u003eNot applicable as all data are presented in the aggregate.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eAuthor details\u003c/h2\u003e\u003cp\u003eQuzhou Center for Disease Control and Prevention, Quzhou 324000, China\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis study was funded by the Guiding projects for science and technology plans of Quzhou, Zhejiang Province, China [2023ZD080].\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eQuanjun Fang wrote the article and Zhiying Yin critically reviewed the article; Huiyang, Shuangqing wang, Xiaoying Gong, and Canjie Zheng were involved in the investigation and data analysis. All authors have agreed on the journal to which the article will be submitted and all agree to take responsibility for all aspects of the work.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors would like to sincerely thank Quzhou Center for Disease Control and Prevention for the support of this study, and most importantly, the participants of the study and the members of the survey team.\u003c/p\u003e\u003ch2\u003eData availability\u003c/h2\u003e\u003cp\u003eAll data can be available upon request from the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eROSS AH. Modification of chicken pox in family contacts by administration of gamma globulin. 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Am J Public Health. 2004;94(3):400\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"PHSMs, varicella, interrupted time series analysis, incidence, vaccination coverage","lastPublishedDoi":"10.21203/rs.3.rs-7331077/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7331077/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground.\u003c/b\u003e To assess the impact of different immunisation strategies and public health and social measures (PHSMs) on the incidence of varicella in Quzhou.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods.\u003c/b\u003e We collected data on varicella cases reported in Quzhou City from 2006 to 2022, constructed an interrupted time-series (ITS) regression model, and evaluated changes in monthly varicella incidence during three periods: the single-dose varicella vaccine (VarV) immunisation strategy period, the two-dose VarV immunisation strategy period, and the PHSMs implementation period.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults.\u003c/b\u003e ITS analysis indicated that, during the single-dose VarV immunisation strategy period, the incidence of varicella exhibited a significant upward trend (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Following the introduction of the two-dose VarV immunisation strategy, the monthly incidence decreased immediately by \u003ca class=\"FNLink\" href=\"#Fn1\" id=\"#FNLinkFn1\"\u003e\u003c/a\u003e.848 per 100,000 population (p\u0026thinsp;=\u0026thinsp;0.057), representing a marginally significant change. Immediately following the implementation of PHSMs, the monthly incidence of varicella declined by 2.960 cases per 100,000 population (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.034), a statistically significant reduction. In the longer term, the monthly incidence of varicella increased by 0.032 cases per 100,000 population following the introduction of the two-dose VarV immunisation strategy (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.367), while a decline of 0.043 cases per 100,000 population was observed after the implementation of PHSMs(\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.370), although neither change was statistically significant.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions.\u003c/b\u003e This study suggests that the low coverage of the two-dose VarV vaccination in Quzhou has contributed to its limited effectiveness in curbing the long-term upward trend in varicella incidence. Furthermore, while the implementation of PHSMs can serve as a useful complementary strategy to help prevent varicella, their impact on the transmission dynamics of the disease appears relatively limited.\u003c/p\u003e","manuscriptTitle":"Impact of Immunisation Strategies and Public Health and Social Measures on Varicella Incidence: An Analysis of Surveillance Data from Quzhou City, 2006–2022","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-11 10:53:31","doi":"10.21203/rs.3.rs-7331077/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2545023f-dcd5-46f8-8250-2ddfd81b2e56","owner":[],"postedDate":"September 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-11T08:23:42+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-11 10:53:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7331077","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7331077","identity":"rs-7331077","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}