Prior to the widespread availability of varicella vaccine, yearly U.S. ﬁgures for varicella disease included approximately 4 million cases, 11,000 hospitalizations, and 100 deaths (70). The currently available varicella vaccine in the United States is a live-attenuated Oka strain vaccine approved in 1995. The vaccine is very safe and effective (71–73). Clinical trials began over 20 years earlier in Japan after the vaccine was developed by attenuation of virus isolated from the vesicular ﬂuid of a healthy boy (with the surname Oka) with natural vari- cella infection (74). These initial studies showed a 90% serocon- version rate 4 weeks after vaccination with few clinical reactions (75). Follow-up studies showed that the vaccine pro- tected against chickenpox for at least 17–19 years, and all of the subjects had persistent antibodies and delayed-type skin reactions to the varicella-zoster antigen (76). In the United States, a double-blind, placebo-controlled study of the Oka vaccine in 914 children revealed an efﬁcacy of 100% at 9 months (77). After a seven-year follow-up, 95% of the subjects remained free of clinical disease with chickenpox (78). Compared with the disease rates of unvaccinated children in the United States, it appears that the Oka vaccine reduces the rate of varicella in children participating in the clinical trials by 65–90% (74). Additional studies in the United States have shown that the Oka vaccine induces humoral and cell-mediated immunity in healthy children (79–81), both of which have been demonstrated to persist for at least 8 years (82). Delayed- type hypersensitivity skin reactions to varicella-zoster virus antigens have also been shown to occur for at least 10 years after vaccination (83).
Studies of adolescents and adults have demonstrated that 2 doses 4–8 weeks apart were necessary to produce sero- conversion rates and antibody responses similar to those obtained in healthy children (84). Vaccination is recommended for susceptible adults, particularly those in high-risk situa- tions (health-care personnel, etc.). The vaccine is recom- mended for all children who have no history of chickenpox and is required to attend school in most states. Clinical studies have also evaluated the use of vaccination in immunosup- pressed children and adolescents, particularly in those with acute lymphocytic leukemia (85–87). Results indicated that vaccination is safe for those who are at least 1 year away from induction chemotherapy if the current chemotherapy is halted around the time of vaccination and the patient’s lymphocyte counts are >700/mm3. The immune response in these individ- uals is lower than that of healthy recipients, thus requiring 2 doses separated by 3 months. Transmission of varicella from these vaccinees may occur if a vaccine-associated rash develops, although the risk of transmission is about one-fourth that of natural varicella (20–25% vs 87%) (88). The Oka vaccine should be given as a single dose to children 12 months to 12 years of age. Individuals over the age of 13 should receive 2 doses, 4–8 weeks apart. The duration of protection is unknown at this time, and the need for a booster immunization is uncer- tain. It has been observed that vaccinees who are exposed to natural varicella have a boost in antibody levels. However, it is postulated that in a highly vaccinated population, a lack of exposure to natural varicella may result in waning immunity for some.
Modiﬁed varicella-like syndrome. Multiple studies have reported a modiﬁed varicella-like syndrome (MV- LS) in some vaccinated children after exposure to the natural wild-type varicella virus (78,89,90). The aver- age rate of MVLS varies from 0.00–2.72% of vaccinat- ed children each year after vaccination with the U.S. licensed Oka strain vaccine. These children typically de- velop a milder form of disease with less than 50 lesions. Most children do not have associated fever, and only 50% of them develop vesicular lesions (91). None of the cases have been associated with systemic or serious disease. It has been noted that more complete and long-lasting protection from varicella is associated with a stronger antibody response to vaccination (89).
Latent infection. Herpes zoster can later develop either from the Oka strain vaccine-type virus or from natural wild-type varicella-zoster virus (92,93). There have been several reports of mild herpes zoster in healthy children who had previously received the varicella vac- cine. The incidence is less than that seen in children with prior chickenpox (94), such that vaccinated per- sons may have a decreased risk for herpes zoster.
Tenderness, erythema, or induration at the injec- tion site. This most common side effect occurs in 19.3–24.4% of injection sites.
Fever. Fever occurred in 10.2–14.7% of clinical trial sub- jects and a generalized varicella-like rash developed in 3.8–5.5% of subjects.
Rash. A generalized varicella-like rash developed in 3.8–5.5% of cases. A localized varicella-like rash at the injection site may also occur.
Exposure to high-risk patients. The likelihood of transmission of the vaccine virus from a healthy vac- cinee is low, but may be more likely if a rash develops after vaccination. One case of transmission from a vac- cinated child to a susceptible mother has been reported in the United States, but it is suspected that the child may have been concurrently infected with natural wild-type varicella. Individuals receiving vaccination should avoid close association with susceptible high- risk individuals for up to 6 weeks, if possible.
Pregnancy. This vaccination is also contraindicated in pregnancy or any women planning to become pregnant within 3 months, since this is a live attenuated virus and natural varicella is known to cause fetal harm.
Susceptible contact exposure. Recent data indicates that the varicella vaccine is highly effective in prevent- ing disease in susceptible contacts when given within 36 hours of exposure (95).