Insights on the Impact of External and Internal Boosting on Varicella-Zoster Virus Reactivation Based on Evidence From the First Decade of the United States Universal Varicella Vaccination Program

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.

Examples of Outcome Reporting Bias in Vaccine Studies: Illustrating How Perpetuating Medical Consensus Can Impede Progress in Public Health

“…[ 16 ] Multiple studies support that exposure to children shedding wild-type varicella-zoster virus (VZV) boosts immunity in adults to suppress the reactivation of VZV as HZ. Thus, a decline in exogenous exposures through universal varicella vaccination might have an effect on increasing HZ incidence among adults [ 17 ].…”

“… Black lines: trend reported by Goldman [ 17 ] (excluding HZ incidence rate among varicella-vaccinated children). …”

“…Also, it is unusual that the HZ incidence rate corresponding to the last 2007 data point is lower than the 1997 HZ incidence rate ten years earlier. These last four data points are confounded as the result of the influence of a relatively low HZ incidence rate among the increasing numbers of varicella-vaccinated children that have been averaged with the increasing HZ incidence rate among adults [ 17 ]. Thus, Figure 3 demonstrates two distinct piecewise linear trends with a breakpoint in 1995 (the year of varicella vaccine licensure): an HZ incidence rate that changes from 2.8 cases/100,000 person-years (p-y) annually for the period of 1945 to 1995, to 17 cases/100,000 p-y annually for the period of 1995-2002 (and thereafter, when the lower HZ incidence rate among varicella-vaccinated children is excluded).…”

Herpes Zoster in Children; Should the Varicella Vaccine be Administered as a Single Dose or a Double Dose?

“…Since the VZV vaccine is a live attenuated vaccine, there is a risk of HZ in vaccinated children, which may be one of the reasons for the increase in the number of cases (4). However, there is controversy over whether vaccination results in an increased incidence of HZ (5). Because the risk in children with a history of varicella is much higher than in vaccinated children (6).…”

“…However, vaccination may reduce the opportunities for VZV immunity due to intermittent native varicella exposure, resulting in an increased incidence of HZ in older adults. Because intermittent exposure to wild-type virus is assumed to provide adequate support to the immune system to keep VZV-specific cellular immunity above a critical threshold and to prevent VZV reactivation (5,8). In addition, it should be kept in mind that the causative agent may not always be a vaccine type virus in HZ that develops after vaccination.…”