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Clin Infect Dis. 2019 Apr 24. pii: ciz305. doi: 10.1093/cid/ciz305. [Epub ahead of print]

The Impact of Varicella Vaccination on the Incidence of Varicella and Herpes Zoster in the United States: Updated Evidence From Observational Databases, 1991-2016.

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Merck & Co., Inc. Center for Observational and Real-World Evidence, Kenilworth, New Jersey.
Merck Sharp & Dohme Corp., Singapore.



Universal childhood vaccination against varicella began in the United States as a 1-dose schedule in 1996, changing to a 2-dose schedule in 2006. The exogenous boosting hypothesis, which postulates that reexposure to circulating wild-type varicella delays the onset of herpes zoster, predicts a transient increase in the incidence of herpes zoster, peaking in adults 15-35 years after the start of varicella vaccination.


This was a retrospective study of administrative claims data from the MarketScan Commercial and Medicare databases between 1991-2016. Outcome measures were the incidences of herpes zoster per 100 000 person-years, by calendar year and age category, and the annual rates of change in herpes zoster by age category, in an interrupted time series regression analysis, for the periods of 1991-1995 (prevaccine), 1996-2006 (1-dose vaccination period), and 2007-2016 (2-dose vaccination period).


The annual incidences of herpes zoster increased throughout the period of 1991-2012 in all adult age categories, with a plateau in 2013-2016 that was most evident in the ≥65 age group. In 1991-1995, the herpes zoster incidences increased at annual rates of 4-6% in age categories 18-34, 35-44, 45-54, and 55-64 years. In the same age categories during 1996-2006 and 2007-2016, the herpes zoster incidences increased at annual rates of 1-5%.


Although the annual incidence of herpes zoster in adults has continued to increase, the rates of change decreased during both the 1- and 2-dose vaccination periods. The hypothesized increase in herpes zoster predicted from modelling of the exogenous boosting hypothesis was not observed.


chicken pox vaccine; exogenous boosting; herpes zoster; varicella immunization; varicella-zoster virus


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