Reply letter: trends in varicella and herpes zoster epidemiology before and after the implementation of universal one-dose varicella vaccination over one decade in South Korea, 2003-2015

ABSTRACT

In the letter, Lai SW suggested that the cost-benefit of two-dose varicella vaccines should be considered since universal one-dose vaccination effectively reduced varicella incidence in Taiwan. However, the vaccination impact was different between South Korea and Taiwan. In South Korea, only a moderate reduction in varicella incidence was observed after implementing universal one-dose vaccination. Such difference possibly reflects the relatively high background varicella incidence in South Korea. As substantial variability in varicella epidemiology exists across countries, an optimal vaccination strategy may differ in each country. Despite the effectiveness of one-dose vaccine being moderate, primary vaccine failure and rapidly waning immunity are major concerns. Therefore, two-dose vaccination would be a reasonable choice for effectively preventing virus transmission in South Korea.

KEYWORDS:

• Varicella
• vaccination

Reply letter

We appreciate the opportunity to reply to the Letter to the Editor from Lai SW¹ regarding our manuscript which examined the impact of universal one-dose varicella vaccination on epidemiology of varicella and herpes zoster in South Korea.²

We would like to thank Lai SW for his appreciation of our work and for emphasizing the need for universal varicella vaccination. Lai SW also raised an issue regarding the national vaccination policy from an economic perspective in that the one-dose varicella vaccination effectively reduced the varicella incidence in Taiwan.³

Cheng et al. demonstrated an 82.8% reduction in varicella incidence and a decline in breakthrough varicella in Taiwan over 11 y after universal one-dose varicella vaccination was implemented.³ In that study, the effectiveness of one-dose varicella vaccine ranged from 82% to 93%. In contrast, our study showed that the varicella incidence rate was moderately reduced by 67% in South Korea over more than 10 y after the universal one-dose varicella vaccination was introduced.² Considering the similar vaccination policy, high vaccine coverage (>95%), and long study period (>10 y) in both countries, such a substantial difference is puzzling.

The difference in the impact of universal varicella vaccination possibly reflects the differences in background varicella incidence and the level of population immunity in the two countries prior to implementation of the universal varicella vaccination program. In settings with high background incidence rates, the impact of vaccination on reducing the incidence of vaccine-preventable diseases could be slower and less prominent than in settings with low background incidence rates.⁴ Because varicella-zoster virus (VZV) transmissibility can be influenced by multiple factors other than the virus itself, such as contact patterns, social behavior and structure, and environment, VZV epidemiology may vary across countries. A comparative seroepidemiological study revealed a substantial variation in VZV transmissibility in European countries, with the basic reproductive number (R₀) ranging from 3.8 to 16.9.⁵ This implies that the target vaccine coverage required to reach the herd immunity threshold can differ across countries as the herd immunity threshold is calculated as 1-(1/R₀).

Background varicella incidence seems to be relatively higher in South Korea than in Taiwan. Despite the study periods being different, the seroepidemiologic study showed that 90% of children were seropositive by 8–9 y of age in South Korea,⁶ while 80% were seropositive in Taiwan in the same age group.⁷ When the universal varicella vaccination was initiated, the varicella incidence rate was 28% higher in South Korea (5.75 per 1,000 person years)² than that in Taiwan (4.17 per 1,000 person years).³ These findings suggest that VZV transmission and force of infection might be higher in South Korea, requiring a longer time for maturation of the vaccination program and for reaching population immunity with vaccination. In our study, in contrast to the rapid decline in varicella incidence reported in Cheng’s study, the varicella incidence rate slowly declined, and a significant decline was only observed since 2012 when 90% of children aged ≤ 9 years were comprised of the birth cohorts targeted for universal varicella vaccination with high vaccination coverage.² Accordingly, the vaccination impact could be different between South Korea and Taiwan despite the similar varicella vaccine schedule being implemented. Therefore, such differences in background varicella incidence should be considered for understanding the impact of vaccination in each country.

In Letter to the Editor, Lai SW mentioned that a second dose of varicella vaccine can provide only an additional 10% protection. However, although two-dose vaccination may provide 10% or more protection than one-dose vaccination per se, a 10% improvement in vaccine effectiveness can be critical for achieving herd immunity in countries with a high background varicella incidence. As vaccination does not always confer perfect immunity against infection to all recipients, the threshold level of vaccine coverage required to protect a population increases. Assuming that the R₀ in South Korea is 8, with a perfect vaccine, 87.5% vaccine coverage is required to achieve herd immunity. However, with an 85% effective vaccine, the herd immunity cannot be achieved even at 100% coverage. Although the effectiveness of varicella vaccine was estimated to differ according to vaccine types, the pooled one-dose vaccine effectiveness was approximately 80% against all varicella,⁸ indicating that 20% of vaccinees are not protected against varicella. Primary vaccine failure was reported to be as high as 24%;⁹ furthermore, one-dose varicella vaccination is known to confer short-lived protection against varicella,^10,11 leading to accumulation of susceptible individuals, thereby increasing the possibility of outbreaks in the future. To overcome these limitations, adopting the two-dose varicella vaccine schedule would be a reasonable choice for preventing virus circulation and outbreaks. Mathematical modeling also showed a substantial reduction in varicella incidence with the two-dose vaccination schedule.^12,13

We agree with Lai SW’s opinion in that vaccination policy should be cautiously implemented balancing the cost-benefit of using two-dose varicella vaccines. However, in the era of controlling infectious diseases through vaccination, a social consensus has been reached that vaccination schedules for controlling vaccine-preventable diseases should be developed in the most effective way and that the associated decisions be made from the perspective of improving public health rather than that of cost benefits. The social environment cannot be the same in each country, and thus, implementation of a one- or two-dose varicella vaccination strategy depends on the goal of the vaccination program and allocation priority of health-care budgets in each country.¹⁴ Two-dose vaccination is recommended in countries where the program goal is to further reduce varicella incidence and outbreaks, in addition to decreasing severe morbidity and mortality.¹⁴ In South Korea, a large number of varicella cases still occur (approximately 90,000 cases in 2015), and the societal and economic benefits of a two-dose vaccine schedule may outweigh those of a one-dose vaccine schedule. Further studies are required on the changing epidemiology and economic analysis to develop a varicella vaccination policy that is optimally tailored for South Korea.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.