Source: Baxter R, Ray P, Tran TN, et al. Long-term effectiveness of varicella vaccine: a 14-year, prospective cohort study. Pediatrics. 2013; 131(5): 1– 8; doi: 10.1542/peds.2012-3303Investigators from multiple institutions prospectively evaluated the effectiveness of varicella vaccine in a cohort of children in the Kaiser Permanente Northern California (KPNC) healthcare system. Parents or guardians of children who were 12 to 23 months old when they received their first varicella vaccine dose between June and November 1995 were approached to participate. Telephone interviews were conducted with participants every 6 months for 14 years to ask about the occurrence of varicella and herpes zoster (HZ) episodes. Varicella cases were based entirely on parental report; HZ cases required a diagnosis by a physician and were confirmed by chart review. For varicella episodes, parents were asked to estimate whether the number of lesions was ≤50 (mild), 51–300 (moderate), or >300 (severe). At each interview, parents were reminded of the clinical features of varicella and HZ and were instructed to call using a toll-free line if these occurred before the next scheduled telephone interview. A proportion of child participants received a second dose of varicella beginning in 2006. The primary outcomes of interest were incidence rates of a first episode of breakthrough varicella and HZ. Historical varicella and HZ incidence rates in unvaccinated children in the prevaccine era were used as a comparison.Of 9,316 parents approached in 1995, 7,585 (81%) participated. At the end of the 14-year follow-up in 2009, 7,386 (>97%) parents remained enrolled and 2,829 children had received a second varicella dose. A total of 103,098 person-years (PY) follow-up data were collected.There were 1,505 cases of breakthrough varicella reported, of which 74% were mild (or unknown number of lesions), 24% moderate, and 2% severe. There were 5.3% repeat episodes, none of which occurred after the second vaccine dose. The average incidence rate of a first episode of breakthrough varicella over the 14 years of follow-up was 15.9 per 1,000 PY (95% CI, 15.1–16.7). This observed rate was 9 to 10 times lower compared to historical rates for children aged 1 to 15 years prior to vaccine licensure.There were 113 HZ cases and, of these, 46 were confirmed by a physician. The incidence rate of HZ was 0.45 per 1,000 PY (95% CI, 0.33–0.60) compared to historical rates following naturally-acquired varicella of 0.73 per 1,000 PY. The average time from vaccination to HZ diagnosis was 8.4 years and no cases occurred after the second varicella dose of vaccine.The authors conclude that breakthrough varicella cases and HZ cases in this cohort were lower than corresponding historical rates in unvaccinated children. Varicella vaccine effectiveness did not wane during 14 years of follow-up.Dr Tolan has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.This study comprises the largest and longest follow-up study of varicella vaccine effectiveness reported to date. For the cohort retention (>97%) alone, it deserves attention and the authors’ praise. That is a remarkable achievement, rendering the results much less open to concern for bias.Some limitations are noteworthy, however. The study population may not be representative, and despite vigorous episode ascertainment (telephone calls to the entire cohort twice a year), it is likely that some recall bias affected parental reports regarding remote episodes (numbers of lesions would appear to have been most susceptible to this effect, particularly for cases in adolescents). Further, there is potential for misclassification given the reliance solely on parental report for cases of varicella. Also, since there was no unvaccinated cohort, historical controls were required. Historical rates were calculated from the best available studies (2 for breakthrough varicella1,2 and 1 for HZ2), but changes over time and lack of matching may influence comparisons between the individuals in this study and the historical controls. Lastly, it is important to note that the study was funded by Merck Sharp & Dohme Corporation, the manufacturers of Varivax.Nonetheless, this remarkable study suggests the overall varicella vaccine effectiveness is approximately 90%. The absence of any breakthrough episode of HZ after the second dose of vaccine is particularly reassuring, and validates the recommendation of the Advisory Committee on Immunization Practices from 20063 (see also AAP Grand Rounds, June 2011;25[6]:654).