Varicella vaccines: Time for a second dose

It's official: The American Academy of Pediatrics (AAP) is now recommending a second dose of varicella-containing vaccine for children 12 months through 12 years of age. The new recommendation appears in the July issue of the Academy's journal Pediatrics.

Until now, the AAP's Committee on Infectious Diseases has held off changing its initial recommendation-that children routinely receive one shot of a varicella vaccine at 12 to 18 months of age. The Advisory Committee on Immunization Practices (ACIP) issued a provisional recommendation for a second dose last year, and the two-dose recommendation was included in the Recommended Immunization Schedule for 2007.¹ The Recommended Schedule now calls for a first dose of a varicella-containing vaccine (Varivax or ProQuad, the measles-mumps-rubella-varicella combination vaccine) at 12 to 15 months of age, and a second dose at 4 to 6 years. While the 4- to 6-year visit is optimum, the second dose may be administered at any time, as long as at least 3 months has elapsed since the first dose. The 11- to 12-year visit is recommended as the opportunity for those who missed immunization in childhood to catch up. For persons 13 years of age or older without evidence of immunity (verified varicella infection or documented two doses of vaccine), the recommendation is for two doses, given at least 28 days apart. Now the AAP, too, has caught up.

What's behind the change?

But there have been caveats. Breakthrough disease in immunized children has occurred with some frequency, although it is generally much less severe than infection with the wild virus. But although these breakthrough cases are relatively mild, they are sufficiently infectious to set off outbreaks. Further, because a single dose of the vaccine is only 85% effective, some immunized children remained susceptible to infection with wild virus. Finally, evidence has accumulated that the immunity conferred by the first dose wanes over time, lasting only 5 years or so.³ To back up that observation, a shift in the peak age of incidence has occurred. In the pre-vaccine era, varicella incidence peaked at ages 3 to 6, but in the vaccine era, where most of that age group has been immunized, the peak has shifted to older children and now occurs at ages 9 to 11.

According to David Kimberlin, MD, of the AAP Committee on Infectious Disease, two doses of vaccine more closely approximates the natural immune response to the wild virus.⁴ More than 99% of children who get two doses achieve an antibody concentration of over 5 U/mL, and have a marked increase in geometric mean antibody titers after the second dose. The estimated vaccine efficacy of the two-dose regimen over a 10-year observation period is 98% (compared to 94% after 1 dose), and efficacy for preventing severe disease is 100%. Moreover, recipients of two doses are three times less likely than those who get only one dose to have breakthrough disease during the 10 years following immunization.

In general, the AAP recommends children receive combination vaccines like ProQuad wherever possible, to minimize the total number of shots. But for the time being, that alternative will not be available for varicella immunization. Manufacturing problems have caused Merck to temporarily suspend production of the bulk vaccine used to prepare Varivax, ProQuad, and Zostavax, the shingles vaccine. To conserve existing vaccine, production of Varivax has been prioritized over ProQuad because Varivax requires less of the vaccine strain. Fortunately, supplies of Varivax are expected to be sufficient for implementing the two-dose schedule.

For more information from the CDC's Vaccines and Immunizations Web site, visit http://www.cdc.gov/vaccines

References

1. CDC. Recommended Childhood and Adolescent Immunization Schedule-US. Morb Mortal Wkly Rpt 2006;545:Q1