In this study, we found a temporal uptrend in the incidence of varicella in Korea from 2006 to 2017 in the setting of positive spatial associations confined to the northeast (Gangwon-do) that gradually spread and faded over time, which led to an overall increase in varicella incidence across the country. The upward trend in varicella in Korea despite the adoption of universal one-dose vaccination is consistent with previous studies, which have suggested insufficient effectiveness of the vaccine. In a population-based study, the effectiveness of the varicella vaccine was 13% (95% CI: − 17.3 to 35.6), and the immunity waned rapidly 3 years after vaccination . Furthermore, a population-based study of the effectiveness of one-dose varicella vaccination on disease severity suggested that one-dose varicella vaccination resulted in milder symptoms, resulting in failure to isolate patients, leading in turn to outbreaks among those in close contact, such as children in kindergarten or elementary school .
This is the first study to investigate the spatial epidemic characteristics of varicella on a nation-wide scale. Nevertheless, the occurrence of local ‘hot-spots’ in remote areas, such as Gangwon-do, may be similar to the results of studies on a province scale or of other respiratory diseases, such as mumps and measles. A spatiotemporal analysis of varicella in Valencia, Spain from 2008 to 2012 identified spatiotemporal clusters where the population was economically disadvantaged or perhaps less educated and less aware of vaccination schedules . In spatio-temporal analysis of measles  and mumps  in China, high-risk clusters were mainly distributed in the urban-rural transition zones or semi-urban areas because, with parents migrating to urban areas for employment opportunities, children were left in impoverished and remote area from vaccination clinics and become susceptible to disease.
We also found that the childhood percentage had a positive effect on the incidence of varicella at the district level, whereas population density and number of hospitals per 1,000 persons had negative effects. The spatial regression revealed that childhood percentage, a high-risk population, influenced the incidence of varicella. In our study, childhood percentage showed vulnerability to varicella outbreaks. This concurs with a previous study conducted APC analysis of varicella incidence in Korea , in which the peak incidence was 4–6 years of age. In a spatial analysis of mumps in Korea, childhood percentage was a significant risk factor for mumps because children are more susceptible than other age groups .
The number of hospitals per 1,000 persons in a district, which we used to indicate the health infrastructure, also had affected the incidence of varicella, albeit not significantly (p-value = 0.0693). The fewer healthcare providers in a district, the higher the varicella incidence. This may be associated with the low economic status of a district, in accordance with the results of the spatial analysis mentioned above.
The lack of a relationship between the vaccine coverage rate and incidence of varicella may be explained by the high level of coverage, ranging from 92.3–100%. Given the high vaccination coverage in Koreans before the introduction of a universal one-dose varicella vaccination in 2005, the vaccine may not have affected the incidence of varicella greatly.
Our study had several limitations. First, given the data was obtained from passive collected surveillance system, there may be underreported cases especially those with mild breakthrough infections. Second, varicella cases were obtained from aggregate data at the district level, and not from individuals because of the inaccessibility of personal information. Factors such as vaccination coverage, disease severity, and socioeconomic status at the individual level, which may drive a varicella epidemic were not included in the spatial regression model and have yet to be examined in detail. Finally, there might be multicollinearity among the predictors of varicella incidence. Despite these limitations, this study is the first to describe the spatial epidemiological characteristics of varicella using spatial analysis at the district level in Korea, and it identified high-risk clusters and risk factors.