2.6. Cost-effectiveness of the VarV in relation to ED visits
The medical fee for visiting our center for varicella depends on age. However, the average fee per patient at our hospital is approximately JPY15,000 (US$143) for the medical examination, acyclovir, and ointment. The cost of one dose of VarV is approximately JPY 5,000 in Japan; thus, the cost of two doses is approximately JPY10,000. Our data showed that the annual number of varicella patients was approximately 500 before 2014; however, after 2014, the annual number was approximately 200. Therefore, an approximate calculation (300 × [JPY15,000 minus JPY10,000]) indicated that JPY1.5 million (US$14,300) was saved annually by our center. Additionally, considering the risk of infection to other people in hospitals, schools, and communities, the loss associated with being unable to attend school, and the loss associated with parents having to miss work to care for their children, the benefits of universal VarV are expected to outweigh the cost.
We conducted a retrospective observational study of the effectiveness and cost-effectiveness of the universal VarV by analyzing consecutive patients who visited our primary ED center. We showed that after the implementation of the universal VarV in 2014, the number of children with varicella who presented to our ED dramatically decreased and JPY1.5 million (US$14,300) was saved annually by our center alone.
Currently, 33 countries and regions have introduced the universal VarV since 2014 . The effectiveness of the VarV was proven in many countries, and a dramatic decline in the incidence of varicella has been reported [5–8, 20]. Although one dose of the VarV is highly protective against severe varicella, two doses of the VarV further improved the rates of protection from varicella [5, 8]. In the United States, the one-dose VarV program was implemented in 1996, and the two-dose VarV program was started in 2007. An 87% reduction in varicella deaths occurred during 2008–2011 compared with the pre-vaccine period (1990–1994) . A meta-analysis of the effectiveness of the VarV revealed the superiority of the two-dose VarV (estimated at 81% for one dose and 92% for two doses) . Immediately after the introduction of the universal VarV in Japan, Hattori et al. reported the effectiveness of the VarV (Oka/Biken) using a case-control study; they showed that the VarV effectiveness rates were 76.9% and 94.7% for one dose and two doses, respectively . These data showed the superiority of the routine two-dose VarV. The data obtained in the ED setting also showed a dramatic decline in the number of varicella patients after implementation of the universal two-dose VarV. Additionally, we showed that a decline occurred among children younger than 1 year who were not yet eligible for the vaccination. These effects of the VarV are considered important from the viewpoint of not infecting other patients in the ED.
Cost-effectiveness is an important issue that should be addressed. In the present study, we reported that the average fee per patient at our center is approximately JPY15,000 (US$143), and that JPY1.5 million (US$14,300) was saved annually by our center. Before the universal VarV program was initiated, according to the report by the Varicella Vaccination Working Team, Infectious Diseases Subcommittee, and Health Science Council, it was estimated that the universal two-dose VarV could be expected to reduce costs by approximately JPY36.23 billion (US$348 million) per year in Japan ( http://www.mhlw.go.jp/stf/shingi/2r98520000014wdd-att/2r98520000016rqn.pdf ).
A sensitivity analysis of the cost-effectiveness of VarV showed apparent cost-savings from the perspectives of society and the health system in European countries . In the United States, before the availability of the VarV, 4 million cases of varicella occurred each year; of these, more than approximately 10,000 required hospitalization and more than 100 resulted in death . Previous studies estimated that the universal VarV during childhood is beneficial, but there is a debate regarding whether it is more cost-effective to administer one dose or two doses [23, 24]. Thus, several previous studies as well as our data revealed the cost-effectiveness of two-dose VarV.
Our data showed that the current VarV program in Kobe City is not sufficiently widespread. The present study clearly showed that the age of varicella patients who presented to our ED has increased since the implementation of the universal two-dose VarV. Previous studies also reported that the occurrence of varicella has shifted to older children [9, 20]. Qin et al. reported the shift of varicella to older children after the implementation of one-dose VarV in Lu’an, China . They mentioned that this was attributable to the one-dose voluntary vaccination policy. The World Health Organization position is that the VarV administration rate, which has been less than 80%, is expected to shift varicella to older children . However, in the present study, although the two-dose VarV was implemented, approximately more than 95% of children have received a single dose and approximately more than 85% of children have received two doses; therefore, a shift of varicella to older children has been observed. Based on national surveillance data from 2000 to 2017, Morino et al. also reported the shift of varicella to older children in Japan after the introduction of the VarV in the routine vaccination program . Although they showed that the incidence of varicella in 1- to 4-year-olds declined to 34.8% in 2017, the incidence in 5- to 9-year-olds relatively increased from 20.5% during 2000–2011 to 51.6% in 2017, even though the number of cases occurring in 5- to 9-year-olds had decreased. In the present study, it was found that the number of varicella cases in children older than 5 years increased in 2019. Therefore, to prevent any potential shift to older children, it may be necessary to introduce the VarV not only to the non-vaccinated target age group but also to unvaccinated and single-vaccinated children. In 2012, before the universal VarV program started, the Japan Pediatric Society recommended the VarV and stated that the two-dose VarV was required to ensure its preventive effects. However, our study clearly showed that these recommendations were insufficiently supported based on the increased number of varicella patients 1–2 years of age between 2012 and 2013. Therefore, national support is needed to increase the VarV administration rate and decrease the number varicella cases. In the present study, the number of varicella patients younger than 1 year (who were not the target age for VarV) presenting to the ED also declined. This result suggests the herd protection effect of the VarV, and the same effect was observed in other countries . Our data revealed that many unvaccinated children were diagnosed with varicella at our center (59.0%). Because the proportion of unvaccinated individuals is 5% in Kobe City, 1,805 children in Kobe City are estimated to be unvaccinated. If that 1,805 were reduced to 66, then the reduction rate would be approximately 96.3%. Although that reduction rate seems high, our data showed that the number of unvaccinated patients with varicella presenting to our center was relatively high (53.7%-64.5%). Therefore, the VarV administration rate for children in the current target age group must be increased to reduce the number of varicella patients.
Our study had many strengths. Because a relatively large number of consecutive patients were included, we were able to analyze the effectiveness of the VarV for each age in detail at the ED. The secondary effect of the vaccine for those younger than 1 year who are not eligible for the VarV could be proven more strongly because the total number of consecutive patients with VZV infection was large. Our observational study period was relatively long (9 years). Finally, we obtained the VarV history of most patients. However, our study also had some limitations. First, this study was conducted at a single center. Therefore, it is unknown whether our results can be applied to other areas. Second, detailed patient backgrounds were unavailable in our database. Third, there was a possible misclassification bias during the study of confirmed cases because a clinical sample could not be extracted and the diagnosis was clinically determined. Regardless of these limitations, our data clearly showed the excellent effectiveness and cost-effectiveness of the VarV in the ED setting.
In conclusion, our data showed a dramatic decline in the number of varicella patients who presented to the ED after the implementation of the universal two-dose VarV. These data also showed that the benefits of the VarV outweigh its cost. Currently, the VarV program in Japan is insufficiently implemented. Our data suggest that we need to increase the VarV administration rate for children in the target age group, and that public assistance is required to expand VarV administration to older children.