Special Feature

Updated Varicella Vaccine Recommendations

By Hal B. Jenson, MD, FAAP

The advisory committee on immunization practices (ACIP) of the Centers for Disease Control and Prevention (CDC) has issued updated varicella vaccine recommendations1 of the original CDC recommendations published in 1996.2 These expanded recommendations include: 1) establishing requirements for child daycare and school entry; 2) vaccination following exposure of susceptible persons to varicella, and for outbreak control; 3) expanded recommendations for vaccination of susceptible adolescents and adults at high risk for exposure or transmission; and 4) vaccination for persons with humoral immune deficiencies, and for some children infected with human immunodeficiency virus (HIV). The ACIP also reviewed postlicensure adverse events reportedly associated with the varicella vaccine.

Updated Varicella Vaccine Recommendations

Daycare and School Entry Requirements. Because the incidence of varicella is highest among children 1-6 years of age, vaccination during early childhood will have the greatest effect on reducing the incidence of disease. The ACIP now recommends that all states require that children entering child daycare facilities and elementary schools either have received varicella vaccine or have other evidence of immunity to varicella. Because school vaccine requirements are set at the state level, there will likely be some disparity across the United States in actual requirements. Already, 10 states have enacted requirements for varicella vaccination, and additional requirements are pending in many other states. Evidence of immunity includes either: 1) varicella vaccination; 2) a physician’s diagnosis of varicella; 3) a "reliable history of the disease" or 4) serologic evidence of immunity. The ACIP also suggests that "states should also consider implementing a policy that requires evidence of vaccination or other evidence of immunity for children entering middle school (or junior high school)."

Postexposure Vaccination. There are data from the United States and Japan following varicella exposure in household, hospital, and community settings that varicella vaccine is effective in preventing illness or modifying varicella severity if given within three days, and possibly up to five days, of exposure.3-5 The ACIP now recommends that varicella vaccine be given to susceptible persons following exposure to varicella. If exposure does not result in disease, then vaccination will provide protection for subsequent exposure. There is no evidence that vaccination during the presymptomatic or prodromal stage of varicella increases the risk for complications or vaccine-associated adverse events, or that administration of live virus vaccines to persons with pre-existing immunity is associated with any adverse effects. The need for postexposure prophylaxis of healthcare workers should be minimal because all healthcare workers should be immune to varicella (as well as to measles and rubella).6

Vaccination of Persons Younger than 13 Years of Age. Varicella vaccine has been recommended since 1996 for susceptible persons younger than 13 years of age at high risk for exposure or transmission; the updated recommendations now include susceptible adolescents and adults living in households with children as a new high-risk group. The recommendations for varicella vaccination of susceptible persons younger than 13 years of age now includes: 1) persons who live or work in environments where transmission of VZV is likely, such as teachers of young children, child daycare employees, and residents and staff members in institutional settings; 2) persons who live and work in environments where transmission can occur, such as college students, inmates and staff members of correctional institutions, and military personnel; 3) nonpregnant women of childbearing age; 4) adolescents and adults living in households with children; and 5) international travelers.

Persons with Altered Immunity The previous ACIP recommendations stated that varicella vaccine not be administered to any person with primary or acquired immune deficiency. The ACIP maintains the recommendation against varicella immunization of persons with cellular immunodeficiencies, but now recommends that persons with impaired humoral immunity may be vaccinated. In addition, some HIV-infected children, who are at greater risk for complications of varicella and zoster compared to healthy children, may now be considered for varicella vaccination. Unpublished data from the Pediatric AIDS Clinical Trial Group indicate that two doses of varicella vaccine administered to HIV-infected children with asymptomatic or mildly asymptomatic disease are immunogenic and effective. HIV-infected children who are CDC class N1 ("no signs or symptoms") or A1 ("mild signs or symptoms") and have age-specific CD4+ T lymphocyte percentages ³25% are eligible, and "varicella vaccine should be considered." The vaccination regimen for these children is two doses of varicella vaccine three months apart.

The vaccine has not been licensed for persons with blood dyscrasias, leukemia, lymphoma of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems. Varicella vaccine is available from the manufacturer (Merck) through a compassionate use protocol for children with acute lymphocytic leukemia (ALL) who are in remission, provided local approval by the appropriate institutional review board and informed consent have been obtained.

Update of Adverse Events Since Licensure

From March 1995 to July 1998, a total of 9.7 million doses of varicella vaccine were distributed in the United States. The Vaccine Adverse Event Reporting System (VAERS) has received 6850 reports of adverse events, approximately two-thirds of which are in children younger than 4 years of age. The most frequently reported adverse event is rash, which occurs at a rate of 37 per 100,000 vaccine doses. However, PCR analysis showed that most postvaccination rash illnesses occurring within two weeks of vaccination were caused by wild-type varicella-zoster virus. For other serious adverse events that have been reported, the rates following vaccination are lower than the expected levels after natural varicella infection or than the background rates of disease in the community. This finding confirms that vaccination is safer than natural infection, even though chickenpox in children is thought of as a benign disease.

Development of Zoster. The VAERS rate of zoster after varicella vaccination was 2.6 per 100,000 vaccine doses, less than the overall rate of zoster of 215 per 100,000 person years, or the rate among healthy children after natural varicella infection of 68 per 100,000 person years. Cases of postvaccination herpes zoster have been confirmed by PCR to be due to both vaccine virus and wild-type virus, suggesting that some cases of zoster in vaccinees actually result from antecedent natural varicella infection.

Transmission of Vaccine Virus. Transmission of vaccine virus is rare, and has only been documented on three occasions. All three cases resulted in mild disease without complications. In one case, a 12-month-old child transmitted the virus to his pregnant mother, who elected to terminate pregnancy. No vaccine virus was found in fetal tissue by PCR analysis. The other cases involved two 1-year-old children who transmitted vaccine virus to a healthy sibling and to a healthy father. Secondary transmission has not been documented in the absence of a postvaccination vesicular rash.

Conclusions

The varicella vaccine has been used extensively with good efficacy and safety. The updated recommendations reflect the experience and results of ongoing investigations of postexposure prophylaxis and use in HIV-infected children. Immunization for varicella is an important component of the recommended childhood vaccine regimen and should be provided to all children beginning at 12 months of age, to susceptible older children to the 13th birthday, and to susceptible family members of households with children. In addition, varicella vaccine should be used for postexposure prophylaxis of susceptible persons.

It is important to ensure that all children for whom vaccination is recommended receive the vaccine. Increased varicella vaccination levels in the community will mean less circulating wild-type virus and less exposure during childhood, with a greater likelihood of disease during adulthood and the associated higher risk of serious complications, including death.

References

1. Centers for Disease Control and Prevention. Prevention of varicella. Update recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 1999;48(RR-6):1-5.

2. Centers for Disease Control and Prevention: Prevention of varicella. Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rept 1996;45(RR-11):1-36.

3. Asano Y, et al. Protection against varicella in family contacts by immediate inoculation with varicella vaccine. Pediatrics 1977;59:3-7.

4. Arbeter AM, et al. Varicella vaccine studies in healthy children and adults. Pediatrics 1986;78 (Suppl): 748-756.

5. Salzman MB, Garcia C. Postexposure varicella vaccination in siblings of children with active varicella. Pediatr Infect Dis J 1998;17:256-257.

6. Centers for Disease Control and Prevention: Immunization of health-care workers. Recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Hospital Infection Control Practices Advisory Committee (HICPAC). MMWR Morb Mortal Wkly Rept 1997;46(RR-18):1-42.

True statements from the latest ACIP recommendations for varicella immunization include all of the following except:

a. All susceptible children entering daycare or elementary school should be immunized.

b. Evidence for lack of susceptibility includes a reliable history or diagnosis of varicella, a previous immunization, or a positive serologic test.

c. All susceptible children with HIV infections should be immunized.

d. Immunization has a higher rate of complications than natural infection.