VARICELLA-ZOSTER VIRUS VACCINE

5 Jun

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.

Adverse Effects

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.

Special Considerations

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).

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