With this success, however, came a new challenge, as breakthrough varicella disease received increasing attention from both public health officials and the general population. Prelicensure efficacy trials of a single dose of the vaccine had documented virtually 100% effectiveness in preventing moderate to severe varicella disease, and 80%–85% efficacy in the prevention of any varicella disease. As severe varicella disease became increasingly rare because of the overwhelming success of the 1-dose schedule, and as mild disease decreased as well, those outbreaks of mild breakthrough cases that did occur received increased visibility. In the late 1990s and early 2000s, hundreds of such outbreaks occurred annually. Although this number of outbreaks unquestionably represented a significant improvement over the prevaccine era, the outbreaks still were costly to public health systems and created some confusion among parents who mistakenly thought that 1 dose of the vaccine was supposed to eliminate all risk of varicella disease.
It was against this backdrop that the CDC ACIP and AAP COID recommended in 2006 the incorporation of a second dose of varicella vaccine at 4–6 years of age in the US vaccination schedule. Data were limited at the time of the recommendation but suggested that 2 doses of varicella vaccine generate higher antibody titers and greater protection against breakthrough disease. The study by Shapiro et al is the first to evaluate the effectiveness of 2 doses of varicella vaccine in a “real-world” setting following the AAP and CDC recommendations, and the high effectiveness of 98.3% found in this investigation supports the programmatic change instituted 4 years ago.
One issue that is left unresolved is whether the second dose of varicella vaccine is overcoming a primary vaccine failure in which a proportion of vaccine recipients fail to generate adequate protection after only 1 dose, or whether the second dose diminishes secondary vaccine failures by boosting varicella immunity that has waned since the first dose was given. Given the high effectiveness demonstrated in this trial, however, this distinction is more of an academic exercise than a clinical conundrum. What matters is that 2 doses work. A child receiving the recommended 2 doses of the vaccine is 95% less likely to develop breakthrough chickenpox than a child receiving only 1 vaccine dose. We are now in the second period of varicella control, and version 2.0 looks promising indeed.