 Non-government and government organizations involved

The first varicella vaccine was developed in Japan in 1974 by Takahashi et al. [1] and was subsequently approved for use
in high-risk children in Europe in 1984. In Japan, it was approved in 1986 and became commercially available in 1987. In
the United States, the US Food and Drug Administration (FDA) approved the first varicella vaccine in 1995 [2]. Varicella
vaccines have subsequently become part of routine immunization programs in several countries

In Japan, as the varicella vaccine was not used for routine immunization after its approval in 1986, the incidence of
varicella was approximately 1,000,000 cases annually, with most cases occurring in children [17,18]. Routine
immunization with two doses of the vaccine was introduced in 2014. It is recommended that the second dose should be
administered at least 3 months after the first dose, at the age of 12–36 months
 Sustainable development goals achieved
 Results/ Conclusions
Conclusions In the United States, many states and jurisdictions have achieved high immunization rates and require
children to receive vaccinations for vaccine-preventable diseases before they start school [50,51]. In Japan, the varicella
vaccine became part of routine immunization programs in 2014 [52]. However, routine immunization is not a requirement
before starting school, and as a result, the immunization rate remains lower in Japan than in the United States. The basic
reproduction number of varicella is thought to range from 8 to 10 [53], indicating that the current immunization coverage
in Japan is insufficient to prevent varicella, and that additional efforts are needed to promote vaccination against varicella.
In addition, while the incidence of herpes zoster is higher in individuals over the age of 50 years [3], the incidence will
likely increase in younger individuals as the incidence of varicella decreases. Thus, vaccination against herpes zoster is
needed for individuals with decreased CMI against VZV. In order to identify vulnerable individuals, it is important to
develop a method to assess the activity of CMI.

 Measures taken to prevent the disease. Eg: vaccines, immunization programs, etc.
Prevention and Therapy
- Varicella vaccine is the best for prevention of chickenpox.  When a person without immunization or infection
history is exposed to varicella, immediate vaccination within 3 days after exposure can prevent disease onset or
aggravation of symptoms.  As a post-exposure treatment, anti-herpes drugs, such as, acyclovir (ACV) and
valacyclovir (VCV), or anti-chickenpox/varicella zoster immunoglobulin (VZIG) is administered.  ACV and
VCV are not covered by the health insurance in Japan, and VZIG is primarily used abroad.  As treatment of
infants at high risk needs VZIG, clinicians request its approval and supply in Japan.

- Varicella vaccine:  The Oka strain varicella live vaccine is recognized by WHO as the most desirable varicella
vaccine.  In Japan, vaccination targets are people older than 12 months who have no history of chickenpox, people
having risk of developing severe form of chickenpox, people having risk individuals in their family, or health care
providers.  As the vaccination has been conducted on the voluntary basis, exact coverage rate is unknown; so far,
coverage rate has been calculated on the basis of number of shipped lots and number of births, which was 30-
40%.  From 2009 to 2012, the vaccine production doubled probably thanks to increased public recognition and
local governments’ expanded subsidy to vaccination (Fig. 3).  The vaccination dose, which used to be one dose, is
now becoming two doses under the influence of the world trend.  Therefore, the increased shipment can’t be
translated directly into increased number of children receiving the vaccine.  A system of more precise estimation
of vaccine coverage is needed.  The amount of the vaccine shipped dose 1-year-old children population is quite
variable among prefectures in Japan 
 Statistics on how effective this program is. Eg: The disease is 78% eradicate
Following the introduction of routine varicella immunization in 2014, the incidence rate of varicella decreased
substantially in 2015 [19] and decreased by 78% in 2019 compared with the 2000–2011 average annual incidence rate
[20]. There was a substantial decrease in the incidence of varicella in children, with those under the age of 4 years
representing approximately 80% of all cases prior to the introduction of the routine immunization program and only 40%
of all cases in 2017 [19]. The decrease in the incidence rate plateaued in 2018 and 2019 [21]. Data from sentinel
surveillance sites (approximately 3000) showed that the incidence rate of varicella decreased from 81.4 cases/year in 2000
to 18 cases/year in 2019 [21]. The vaccination coverage in 2018 was reported to be approximately 70.3% [22]. The
incidence rate decreased in 2020 and 2021, probably because of the effect of droplet infection control measures to prevent
the spread of COVID-19, in addition to the effect of vaccination [23].

 Rate of incidence
- Number of cases increases from winter to spring, and then gradually decreases towards the autumn.  Estimatedly
about 1,000,000 chickenpox patients, mostly infants, occur every year, though the overall incidence is decreasing
(though slightly) in the recent three years (Fig. 1).  While 80% of the patients used to be under 4 years of age, since
2010 the percentage of this age group has been decreasing possibly owing to the increased vaccination coverage of
this age group (Fig. 2).  When chickenpox and rubella, both sentinel reportable infectious diseases, are compared,
however, while rubella decreased dramatically after starting of rubella routine vaccination to infants of the both
genders in 1995, the incidence of chickenpox, to which immunization has been conducted on voluntary basis,
remained continuously high. 

- Severe cases: Transmissibility of VZV is strong.  It spreads by the air-borne infection, and subclinical infection is
very rare.  On estimation, one in 400 natural chickenpox infections among unvaccinated children require
hospitalization, and nearly 20 in 1,000,000 infections are fatal (Chickenpox fact sheet, National Institute of Infectious
Diseases).  The incidence of deaths due to chickenpox is the highest among all the deaths caused by vaccine
preventable diseases including measles, rubella, mumps and chickenpox that have been reported since 2004.

Methodology for Assessing Immunity

- Immunity against varicella is evaluated based on humoral immunity (antibody testing). Methods to evaluate the level
of humoral immunity include the fluorescent-antibody-tomembrane-antigen (FAMA) test, immune adherence
hemagglutination assay (IAHA), and enzyme-linked immunosorbent assay (ELISA). Among them, FAMA and
glycoproteinbased ELISA (gpELISA) are preferred for evaluating vaccine-induced immunity because of their high
sensitivity [45]. A World Health Organization position paper [46] also endorses the use of gpELISA for assessing the
protective antibody level. While gpELISA kits are commercially available, they are not widely used in Japan, and a
standard ELISA (Denka Seiken Co., Tokyo, Japan) is often used. The gpELISA and the Denka Seiken ELISA have
been shown to have equivalent sensitivity to the FAMA test [47]. Thus, ELISAs are effective tools for evaluating the
level of humoral immunity against VZV.

Conclusion
- As Japan’s VZV vaccine for routine immunization has titer comparable to that of the United States’ VZ vaccine, since
2004 the VZV vaccines sold in Japan have been attached with a package insert informing that, under “pharmacology”,
the vaccine can enhance cellular immunity to VZ when applied to persons with decreased immunity due to aging and
other reasons.
- In the United States, many states and jurisdictions have achieved high immunization rates and require children to
receive vaccinations for vaccine-preventable diseases before they start school [50,51]. In Japan, the varicella vaccine
became part of routine immunization programs in 2014 [52]. However, routine immunization is not a requirement
before starting school, and as a result, the immunization rate remains lower in Japan than in the United States. The
basic reproduction number of varicella is thought to range from 8 to 10 [53], indicating that the current immunization
 coverage in Japan is insufficient to prevent varicella, and that additional efforts are needed to promote vaccination
against varicella. In addition, while the incidence of herpes zoster is higher in individuals over the age of 50 years [3],
the incidence will likely increase in younger individuals as the incidence of varicella decreases. Thus, vaccination
against herpes zoster is needed for individuals with decreased CMI against VZV. In order to identify vulnerable
individuals, it is important to develop a method to assess the activity of CMI.

References
https://www.niid.go.jp/niid/en/iasr-vol39-e/865-iasr/4046-tpc404.html#:~:text=Prevention%20and%20therapy%3A
%20Varicella%20vaccine,onset%20or%20aggravation%20of%20symptoms.
https://www.mdpi.com/1999-4915/14/3/588/pdf?version=1647240969