Abstract
Since the licensure of the varicella vaccine in the United States in 1995 and the implementation of the universal varicella vaccination program, varicella infection rates, and associated morbidity and mortality rates have decreased. However, controversy exists over whether universal vaccination has resulted in an increased incidence of herpes zoster (HZ). In 1965, Dr. Hope-Simpson hypothesized that exogenous exposures to the wild-type varicella-zoster virus (wt-VZV) provide immune boosts that inhibit HZ; therefore, reducing the amount of circulating wt-VZV may have the negative effect of increasing the incidence of HZ. A historical review of data from the Centers for Disease Control and Prevention-sponsored Antelope Valley Varicella Active Surveillance Project, along with other studies, is provided to investigate the exogenous boosting hypothesis in the first decade post-vaccine licensure. These data indicated that adoption of universal varicella vaccination led to (1) significant HZ incidence rate increases among children, adolescents, and adults with a history of wild-type varicella and (2) decline in varicella vaccine efficacy after the initial post-licensure period. These effects were likely due to reduced exogenous exposures from children shedding wt-VZV. Appropriate methodologies for ongoing research are also discussed, both in studies during the first decade post-licensure and more recent work.
Highlights
BackgroundVaricella-zoster virus and initiation of the universal vaccination programThe varicella-zoster virus (VZV) is responsible for both varicella and herpes zoster (HZ)
In a study published in JAMA, Centers for Disease Control and Prevention (CDC)/Varicella Active Surveillance Project (VASP) used capture-recapture analysis as evidence that reporting completeness had increased over the study period and, decreases in varicella incidence were not the result of decreases in the level of reporting [30]
National Health and Information Survey (NHIS) age-specific varicella incidence rates compared favorably with those ascertainment-corrected rates reported by VASP and under-reporting of varicella cases among individuals aged 1-19 years was 50% based on the capture-recapture analysis [23]
Summary
The varicella-zoster virus (VZV) is responsible for both varicella (chickenpox) and herpes zoster (HZ) (shingles). This early and large increase, occurring first among children, was anticipated by various models that predicted that the impact of varicella vaccination on HZ incidence would be greatest among cohorts that previously received the most exogenous boosts This post-licensure figure among children with a history of natural (i.e., wild-type) varicella in a study community in which exogenous boosts were rare and asymptomatic endogenous reactions served as the primary boosting mechanism was remarkably similar to the pre-licensure HZ incidence among adults aged 50-59 who demonstrated similar HZ incidence rates in the range of 500 to 550 cases/100,000 p-y. With vaccine efficacy declining annually and resultant waning of specific anti-VZV immunity, there will continue to be a segment of the population susceptible to breakthrough varicella, who may experience varicella at older ages, when illness is more severe, and who may experience the higher rates of reactivation of wt-VZV as HZ
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