Clinical Presentation
Varicella is generally a mild disease in children. It usually lasts 4-7 days and is characterized by a short (1- to 2-day) or absent prodromal period (low-grade fever, malaise) and by a pruritic rash consisting of crops of macules, papules, vesicles, and eventual crusting, which appear in three or more successive waves. Serious complications are the exception but can occur, mainly in infants, adolescents, adults, and immunocompromised persons. They include secondary bacterial infections of skin lesions, pneumonia, cerebellar ataxia, and encephalitis. Because the vaccine is 70%-90% effective, a modified varicella, known as breakthrough disease, can occur in some vaccinated persons. Breakthrough disease is most commonly (~ 70% - 80% of cases) mild, with fewer than 50 skin lesions, no fever and shorter duration of rash. The rash may be atypical in appearance with fewer vesicles and predominance of macular popular lesions. Nevertheless, breakthrough varicella is contagious and cases should be isolated for as long as lesions persist.
Prevention
Although vaccination against varicella is not a requirement for entry into any country (including the United States), persons traveling or living abroad should ensure that they are immune.
VACCINE
Varicella vaccine contains live, attenuated VZV. It is available as a monovalent formulation and in combination formulation, as measles-mumps-rubella-varicella (MMRV) vaccine, which is licensed in the U.S for children 1–12 years only. In June 2005 and June 2006, the Advisory Committee on Immunization Practices (ACIP) approved changes to the 1996 and 1999 recommendations for use of varicella-containing vaccines and approved new criteria for evidence of immunity to varicella (4-6). Two doses of varicella-containing vaccine are now recommended for routine immunization of all children younger than 13 years of age who are without contraindications. The first dose should be administered at 12 – 15 months of age and the second dose at 4 – 6 years of age. A second dose of catch-up varicella vaccination is recommended for children, adolescents, and adults who previously had received one dose. The ACIP now recommends that all others at least 13 years of age without evidence of immunity be vaccinated with two doses of varicella vaccine at an interval of 4-8 weeks. In case of uncertainty, prior varicella disease is not a contraindication to varicella vaccination.
After one dose of varicella vaccine, 85% to 90% of children achieve antibody levels that are an approximate correlate of immunity and after two doses, >99% of children achieve this antibody level. (7,8). Vaccine-induced immunity is believed to be long lasting but has not been assessed in the absence of external boosting to varicella zoster virus through exposures. Vaccine efficacy is estimated to be most commonly 80% to 85% (range 44% to 100%) against disease of any severity and 95% against severe disease (9).
Revised criteria for evidence of immunity to varicella include any of the following:
- Documentation of age-appropriate vaccination:
- a. Preschool-aged children at least 12 months of age: one dose
- b. School-aged children, adolescents, and adults: two doses
- Laboratory evidence of immunity or laboratory confirmation of disease
- Born in the United States before 1980
- A health-care provider’s diagnosis of varicella or a health-care provider’s verification of history of varicella disease
- History of herpes zoster based on health-care provider’s diagnosis
Another vaccine that contains live VZV has been recently licensed and recommended for use in the US. On October 2006, the ACIP recommended the use of a single dose of zoster vaccine for adults 60 years of age and older, whether or not they reported a prior episode of herpes zoster (10).
Adverse Reactions
The most common adverse reactions following varicella vaccine are injection site complaints (pain, soreness, redness, and swelling) that are self-limited. In uncontrolled trials, fever was reported in 15% of children and 10% of adolescents and adults. A macular or vaccine rash usually consisting of a few lesions at the injection site is reported in 3% of children and 1% of adolescents and adults after the second dose. A generalized rash with a small number of lesions may rarely occur, within 3 weeks of vaccination.
Varicella vaccine is a live-virus vaccine and results in a latent infection similar to that caused by wild VZV. Consequently, zoster caused by the vaccine virus has been reported. This appears to occur at a lower rate than following natural infection but longer term follow up is needed. Not all reported cases have been confirmed as having been caused by vaccine virus; some were caused by the wild virus.
Precautions and Contraindications
Allergy
Persons with severe allergy (hives, swelling of the mouth or throat, difficulty breathing, hypotension, and shock) to gelatin or neomycin or who have had a severe allergic reaction to a prior dose should not be vaccinated with varicella vaccine. Varicella vaccine does not contain egg protein or preservative.
Immunosuppression
Persons with immunosuppression of cellular immune function resulting from leukemia, lymphomas of any type, generalized malignancy, immunodeficiency disease, or immunosuppressive therapy should not be vaccinated. Treatment with low-dose prednisone (e.g., <2 mg/kg of body weight/day or <20 mg/day) or aerosolized steroid preparations is not a contraindication to varicella vaccination. Persons whose immunosuppressive therapy with steroids has been stopped for 1 month (3 months for chemotherapy) may be vaccinated. In addition, persons with impaired humoral immunity may now be vaccinated. Because children infected with HIV are at greater risk for morbidity from varicella and herpes zoster than are healthy children, the ACIP recommends that varicella vaccine should be considered for HIV-infected children at least 12 months of age in CDC clinical class N, A, or B with CD4 T-lymphocyte counts of at least 15% and without evidence of varicella immunity (4). Eligible children should receive two doses of single-antigen varicella vaccine, with a minimum 3-month interval between doses. The use of varicella vaccine in other HIV-infected children is being investigated.
No adverse events following varicella vaccination related to the use of salicylates (e.g., aspirin) have been reported to date. However, the manufacturer recommends that vaccine recipients avoid the use of salicylates for 6 weeks after receiving varicella vaccine because of the association between aspirin use and Reye syndrome following varicella.
Pregnancy
Women known to be pregnant or attempting to become pregnant should not receive varicella vaccine. Pregnancy should be avoided for 1 month following varicella vaccination. Breastfeeding is not a contraindication to the varicella vaccination.
POSTEXPOSURE PROPHYLAXIS
Use of Vaccine
Administration of varicella vaccine to susceptible healthy persons within 72 hours and possibly up to 120 hours after varicella exposure may prevent or significantly modify disease and should be considered in these circumstances. Physicians should advise parents and their children that the vaccine may not protect against disease in all cases. In several studies protective efficacy was 90% when children were vaccinated within 3 days of exposure (5).
Use of Varicella Zoster Immune Globulin (VZIG)
In certain circumstances, postexposure prophylaxis with VZIG is recommended. The decision to administer VZIG to a person exposed to varicella should be based on 1) whether the patient is susceptible, 2) whether the exposure is likely to result in infection, and 3) whether the patient is at greater risk for complications than the general population (immunocompromised persons, pregnant women, neonates whose mothers had signs and symptoms of varicella within 5 days before and 2 days after delivery, and premature neonates exposed postnatally). VZIG provides maximum benefit when it is administered as soon as possible after the presumed exposure, but it may be effective if administered as late as 96 hours after exposure. The product currently in use in the United States, VariZIGTM (Cangene Corporation, Winnipeg, Canada), is available under an Investigational New Drug protocol. VariZIG can be obtained from the US sole authorized distributor, FFF enterprises (Temecula, California) (24-hour telephone, 800-843-7477, http://www.fffenterprises.com) (11).
GENERAL VACCINE RECOMMENDATIONS, PEDIATRIC AND CATCH-UP SCHEDULES, AND RECOMMENDATIONS FOR SPECIAL POPULATIONS
Refer to Chapters 1, 8 and 9.