Analysis on the epidemiological characteristics of varicella and breakthrough case from 2014 to 2022 in Qingyang City

ABSTRACT

We analyze the epidemiological characteristics of varicella and breakthrough cases in Qing Yang City, Gansu Province, and provide a basis for the formulation of varicella prevention and control policies. Varicella and breakthrough cases, public health emergency events in Qing Yang City during 2014–2022 were obtained from the China Disease Prevention and Control information System, and the immunization history of the cases were collected from the Gansu Provincial Immunization Planning Information System, descriptive epidemiological analysis of the obtained information was then performed. A total of 6961 cases of varicella were reported in Qing Yang City from 2014 to 2022, yielding an annual incidence of 36.99 cases per 100 000 population. The incidence increased from 19.74/100,000 in 2014 to 35.97/100,000 in 2022; the incidence peaks were observed from May to July and from November to January of the next year. The reported incidence is higher in males (37.70/100,000) than in females (31.54/100,000), and the main age groups were 4 ~ 6 years old (241.98/100,000), 7 ~ 9 years old (142.39/100,000), 10 ~ 14 years old (101.99/100,000). There were 1975 breakthrough cases, accounting for 28.4% of the total reported cases; the majority of patients were students, children in nursery care and scattered children; a total of 10 outbreaks of varicella were reported in primary schools (40.0%), secondary schools (30.0%), kindergartens (20.0%) and high schools (10.0%). The incidence of varicella showed an increasing trend, children and students are high-risk population. It is suggested that varicella vaccine should be included into the immunization program, and the vaccination rate of two-dose of varicella vaccine should be increased for age-eligible children, and varicella surveillance should be strengthened.

Varicella is an acute self-limiting respiratory infectious disease caused by the primary infection of varicella-zoster virus (VZV). The main clinical features are fever and pruritic rash, maculopapule and hyaline herpes on the skin and mucosa of the whole body,¹ severe symptoms can be combined with complications (pneumonia, encephalitis, etc.) and even death.² According to the conservative estimates in developed countries, varicella has caused 4.2 million serious complications, resulting in hospitalization and about 4200 deaths.³ The transmission speed is very fast and the infectivity is extremely strong. The average incubation period is about 14 ~ 16 days. It is infectious from 2 days before the rash to the complete scabbing period of the herpes. Children are the mainly affected population. Transmission can be caused by exposure to air droplets from infected individuals.⁴ The disease can occur in all seasons of the year, and the peak season is generally winter and spring,^5,6 which can easily cause clustered epidemics in schools and kindergartens.⁷ Unbridled circulation of varicella in the population can also cause reactivation of latent VZV in older and immunocompromised individuals, in the form of shingles (herpes zoster), with its feared complication, post-herpetic neuralgia, both of which represent a significant public health burden. Reduced circulation of varicella through population-level vaccination would also reduce opportunities for older individuals to be exposed to VZV, thereby reducing the risk of shingles. In addition, reducing the incidence of varicella and varicella vaccination can also decrease the incidence of varicella, reduce the clinical symptoms, and severe and hospitalized cases of varicella cases.^8–10 Varicella attenuated live vaccine (Var V) is not free of charge in China.¹¹ Although two doses of varicella vaccine have been used in some provinces,¹² varicella attenuated live vaccine (Var V) has not been included in the children ‘s immunization program in Gansu Province, and only one dose of Var V is recommended for children over 1-year old at their own expense. Therefore, we conducted an epidemiological analysis of varicella surveillance data and antibody levels of breakthrough cases during 2014 to 2022 in Qing Yang City, Gansu Province, providing a theoretical basis for formulating varicella prevention and control strategies.

Information and methodology

Data source

The data of varicella and breakthrough cases and public health emergency events (PHEEs) in Qing Yang City, Gansu Province from 2014 to 2022were obtained from the China Disease Prevention and Control information System according to the current address and date of onset, the immunization history of the cases were collected from the Gansu Provincial Immunization Planning Information System, and the population data were from the yearbook of Qing Yang Statistical Bureau of Gansu Province.

Case definition

Varicella cases

It refers to the clinical diagnosis of varicella cases diagnosed by medical institutions or laboratory confirmed varicella cases: (1) A clear contact history of varicella or herpes zoster cases within 14 days; (2) The main symptoms were mixed macules, maculopapules, transparent blisters with itching in batches, and generally no pigmentation after scabbing. (3) laboratory test: the serum VZV-IgM antibody was positive in the acute phase of varicella cases by enzyme-linked immunosorbent assay, or the serum VZV-IgG antibody titer was ≥4 times higher than that in the acute phase, or the IgG antibody was negative in the acute phase and positive in the recovery phase.

Breakthrough cases

According to the US Centers for Disease Control and Prevention “Vaccine Preventable Disease Guidance Manual,” varicella breakthrough cases are defined as cases of varicella infection 42 days after vaccination.

Outbreak of varicella

Outbreak of varicella is 10 or more varicella cases occurred within 7 days in a collective unit such as a school or kindergarten.

Statistical analysis

Excel 2010 was used to establish a database. Descriptive epidemiological methods were used to analyze the epidemiological characteristics of varicella cases and the history of varicella vaccine immunization. SPSS18.0 was used to analyze the data, the County distribution、 gender、occupation etc. Categorical variables were expressed by rate or composition ratio. Trend chi-square test was used to assess the statistical significance of differences in annual reported incidence rate, and chi-square test was used to assess the statistical difference between categorical values. The results were considered statistically significant if the two-tailed P value was <.05.

Results

Pathogenesis profile

A total of 6961 varicella cases were reported between 2014 and 2022 in Qing Yang City, Gansu Province, yielding an annual incidence of 36.99/100000 and no deaths. The reported incidence rate increased from 19.74/100,000 in 2014 to 35.97/100,000 in 2022, showing an increasing trend (χ² = 1078.409,P < .05). The growth rate of reported incidence was 59.16% during the 8 years. However, the peak incidence in 2020 (38.00/100,000), 2021 (46.29/100,000) and 2022 (35.97/100,000) was lower than that in 2019 (57.09/100,000), and the difference was statistically significant (χ² = 172.259, P < .05), it can be seen in Figure 1.

Figure 1.

Reported incidence of varicella during 2014 to 2022 in Qingyang City, Gansu Province.

Spatial distribution

Reported number of varicella cases from 2014 to 2022 in Qing Yang City, Gansu Province, the top four counties (districts) were Xi feng Qu (6.8%,1863/6961), Qingcheng Xian (22.4%,1562/6961), Zhen Yuan Xian (15.2%,1061/6961), and Huan Xian (10.1%,702/6961). Hua chi Xian reported the least number of cases (136 cases), accounting for 2.0% of the total reported cases. There were significant differences in the reported incidence rates per 100,000 among counties (districts) (χ² = 1126.343, P < .05), the top four counties were Qing cheng Xian (60.40/100,000), He shui Xian (40.04/100,000), Xi feng Qu (34.01/100,000) and Zheng ning Xian (29.72/100,000), the lowest reported incidence rate was 10.27/100,000 in Hua chi Xian. The annual incidence trend of each county is shown in Figure 2.

Figure 2.

Spatial distribution of varicella incidence during 2014 to 2022 in Qingyang City, Gansu Province.

Temporal distribution

Varicella cases were reported throughout the year between 2014 and 2022 in Qing Yang City, Gansu Province, but there were two peaks of incidence in May and July (40.6%,2828/6961) and November to January of the following year (36.8%, 2559/6961). The lowest incidence was in February and August, as shown in Figure 3.

Figure 3.

Monthly distribution of varicella reported cases during 2014 to 2022 in Qingyang City, Gansu Province.

Population distribution

Sex distribution

A total of 3848 male cases and 3113 female cases were reported between 2014 and 2022 in Qing Yang City, with male-to-female ratio of 1.24:1. The reported incidence rate per 100,000 of males 37.70 was higher than that of females 31.54, and the difference was statistically significant (χ² = 54.959, P < .05), as shown in Figure 4 and Table 1.

Figure 4.

Sex distribution of varicella cases reported during 2014 to 2022 in Qingyang City, Gansu Province.

Table 1.

Sex and age distribution of varicella cases reported between 2014 and 2022 in Qingyang City, Gansu Province.

Age group	Number of male reported cases	Male reported incidence(/100000)	Number of female reported cases	Female reported incidence(/100000)
0~	102	70.36	80	67.36
1~	468	94.42	391	97.39
4~	994	245.39	803	238.47
7~	866	154.69	643	129.53
10~	622	104.21	481	100.07
15~	348	45.95	251	38.84
20~	114	12.85	116	13.00
25~	137	18.70	168	23.28
30~	133	12.36	139	8.41
40~	34	1.94	19	1.19
50~	13	1.03	8	0.90
60~	10	1.12	9	0.95
70~	7	1.08	5	0.73
aggregate	3848	37.70	3113	31.54

Age distribution

The age groups with a relatively high proportion of reported cases were 4 ~ 6 years old (25.8%), 7 ~ 9 years old (21.6%), 10 ~ 14 years old (15.8%), 1 ~ 3 years old (12.3%) and 15 ~ 19 years old (8.6%). The age group with the highest reported incidence per 100,000 was 4 ~ 6 years old (241.98), followed by 7 ~ 9 years old (142.39), 10 ~ 14 years old (101.99), 1 ~ 3 years old (95.75), less than 1-year old (69.01) and 15 ~ 19 years old (42.54). The lowest incidence rate per 100,000 was in the group over 20 years old (6.28), as shown in Figure 5.

Figure 5.

Age distribution of varicella cases reported during 2014 to 2022 in Qingyang City, Gansu Province.

Occupational distribution

There were 3517 students (50.5%), 1436 kindergarten children (20.6%), 1093 children living at home (15.7%), 633 farmers (9.1%), 62 household and unemployment personnel (0.9%), 54 cadre and staff (0.8%), 47 teachers (0.68%), 41 workers (0.6%), and fewer cases of other personnel, accounting for 1.1% (78/6961) of the total cases as shown in Figure 6.

Figure 6.

Occupational distribution of varicella cases reported during 2014 to 2022 in Qingyang City, Gansu Province.

Varicella epidemic outbreaks

A total of 456 cases of varicella outbreak were reported during 2014 to 2022 in Qing Yang City, of which 10 were varicella outbreaks, accounting for 6.6% of the total reported cases (6961); two varicella outbreaks were reported in 2016 and 2018, with 98 and 121 reported cases, accounting for 22.5% and 15.3% of the total number of reported cases in the same year, respectively. One outbreak of varicella was reported in 2014, 2015, 2017, 2019 and 2022, the number of reported cases was 35,39,42,38 and 83, accounting for 8.0%, 8.0%, 4.9%, 2.9% and 10.6% of the total number of reported cases in the same year, respectively. All varicella outbreaks were mainly in primary schools (40.0%), middle schools (30.0%), kindergartens (20.0%) and high schools (10.0%).

Breakthrough cases

Among the 6961 varicella cases reported between 2014 and 2022, 4986 (71.6%) cases without varicella vaccination history and 1975 (28.4%) cases had one dose of varicella vaccination history. The longest interval between vaccination and the onset of 1975 varicella breakthrough cases was 9 years, the shortest was 1.5 years, and the median time was 7 years. The age group distribution of 10 ~ 14 years old accounted for the highest proportion of 29.2%(576/1975), followed by 7 ~ 9 years old 25.2% (498/1975), 4 ~ 6 years old 21.5% (425/1975), 15 ~ 19 years old 18.5% (365/1975), and other age groups accounted for 5.6%. The population distribution was dominated by primary and secondary school students, accounting for 54.1% (1068/1975) of the total number of breakthrough cases, followed by kindergarten children 21.2% (418/1975), high-school students 18.1% (357/1975), and other populations 6.7% (132/1975).

Discussion

The annual incidence of varicella cases was 36.99/100,000 from 2014 to 2022 in Qing Yang City, which was much higher than that from 2007 to 2012 (9.57/100,000).¹³ The reported incidence rate showed an increasing trend year by year, which was consistent with the reported incidence trend of varicella cases in China.^14,15 The occurrence of this phenomenon may be the result of low vaccination rate of varicella vaccine, low serum antibody concentration, aggregation of susceptible population, continuous occurrence of breakthrough cases^16,17 and improved sensitivity to monitoring. After the outbreak of COVID−19 in Wuhan City, Hubei Province at the end of 2019, Qing Yang City took a series of measures to prevent and control the spread of COVID−19, such as not gathering in public places, wearing masks when traveling, washing hands frequently, strengthening disinfection in childcare institutions and schools, strengthening morning and afternoon inspection, and opening windows and ventilation regularly. At the same time, it also reduced the risk of varicella epidemic transmission. The reported incidence of varicella in 2019 was 57.09/100,000, dropping significantly to 38.00/100,000 in 2020. The first epidemic peak basically disappeared, and it was 35.97/100,000 in 2022.

The average annual reported incidence per 100,000 of varicella cases in different counties (districts) varied greatly. Qingcheng County had the highest reported incidence (60.40), followed by He shui Xian (40.04), Xi feng Qu (34.01), and Hua chi Xian had the lowest reported incidence (10.27), which was one-sixth of the reported incidence in Qingcheng Xian. This difference may be related to the outbreak, monitoring sensitivity of varicella in Qingcheng Xian and the vaccination rate of varicella vaccine.

The incidence season showed two peaks from May to July and November to January of the following year, and two troughs in February and August, which were consistent with the relevant literature reports.^18,19 This is generally consistent with the students learning time in school and the vacation time in the winter and summer, which may be related to the clustering characteristics of susceptible population. In addition, related research shows^20,21that meteorological are also one of the factors affecting the incidence of varicella cases, high temperature and low temperature can cause the risk of varicella to rise, and the low-temperature effect is greater than the high temperature.

The incidence of males is higher than that of females, which is inconsistent with the results reported in the previous study.²² Men may have more opportunities for exposure. Studies have shown that²³ treatment bias and sample collection also contribute to gender differences between male and female, and varicella zoster virus24 is a non-gender-specific disease. The age distribution of varicella was mainly in the 4 ~ 6 age group with the highest proportion and incidence, followed by the 7 ~ 9 age group and the 10 ~ 14 age group. The age distribution of breakthrough cases was the highest in the 10 ~ 14 age group, followed by the 7 ~ 9 age group. It may be because the varicella vaccine is self-funded, basic immunization can be achieved with one dose inoculation, the number of receiving booster immunization is small, the vaccination rate is low, and there are some breakthrough cases; thus, the immune barrier is weak. Study has shown that²⁵ the efficacy of single-dose vaccine was moderate, and the protective efficacy decreased with the prolongation of vaccination time. It is also the cause of breakthrough cases. The Shu study showed that26 the age at the second vaccination and the interval between two doses affected the VE of 2-dose vaccine, and the shorter the two doses intervals, the better the effect of the vaccine, and could reduce breakthrough varicella and outbreaks in preschool. In other words, the VE of two doses of varicella in vaccine recipients receiving vaccines at <4 years of age was higher than that of vaccine recipients injecting vaccines at ≥4 years of age, whether the interval between the two vaccine doses was >24 months, suggesting that the second dose of varicella could be given as soon as possible when the vaccination interval meets the basic requirements of the interval was more than 3 months. Therefore, on the one hand, according to the degree of harm of varicella disease, varicella is included in the statutory infectious disease to improve the monitoring sensitivity; on the other hand, considering the effectiveness and accessibility of VarV and referring to the experience and remarkable effect of incorporating Var V into immunization programs in the United States, EU countries^27–30 and Beijing, Shanghai, and other regions of China, integrating varicella vaccine into routine childhood immunization programs, increasing the basic immunization rate of VarV in improving in age-eligible children and Strengthen the second dose of varicella vaccine immunization; these two measures are the key factors to reduce the incidence of varicella in young age groups, and that would surely lessen the burden of breakthrough cases, and reduce overall incidence. This study shows that students, kindergarten children and children living at home are the main population of varicella, accounting for 86.86% of the total number of reported cases, and adult varicella such as farmers accounts for 13.14%. The risk of severe pneumonia in adult varicella is high.³¹ It is recommended that adults without varicella disease and immunization history should be timely immunized with Var V after exposure to varicella cases to reduce the harm of varicella.

Varicella outbreaks have a higher incidence in schools and childcare institutions. Varicella outbreaks reported are mainly concentrated in primary schools, secondary schools, and kindergartens (90%) between 2014 and 2022 in Qing Yang City, and fewer in high schools (10%). Therefore, when varicella clusters appear in school collective units, Var V should be given to susceptible people exposed to varicella cases within 3–5 days in accordance with the World Health Organization recommendations³²to control the further spread of the epidemic. Studies have shown that,³³ the first dose of Var V immunization for students without Var V immunization history is an effective measure to control the outbreak. The implementation of two doses of Var V strategy is expected to reduce the outbreak of varicella and protect the health of children. Based on these studies, we recommend that two doses of varicella vaccination should be included in the national childhood immunization program.

In summary, the reported incidence of varicella showed an increasing trend year by year from 2014 to 2022 in Qing yang City, Gansu Province. The cases were mostly concentrated in people under 15 years old, and the outbreak occurred mainly in primary and secondary schools and childcare institutions. It is recommended to incorporate varicella vaccine into the national immunization program vaccine management, increase two-dose Var V vaccination rate for age-eligible children, conduct emergency vaccination for children and adults who have close contact without varicella disease and immunization history, incorporate varicella into statutory infectious disease reporting, strengthen monitoring and increase the sensitivity of varicella case reporting.

Funding Statement

The author(s) reported that there is no funding associated with the work featured in this article.

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.