Systematic Review and Meta-analysis of Chickenpox Vaccination and Risk of Herpes Zoster: A Quantitative View on the "Exogenous Boosting Hypothesis"

Background. The "exogenous boosting hypothesis" postulates that reexposure to circulating varicella zoster virus (VZV) over the life span inhibits reactivation of VZV. Consequently, if circulation of VZV is suppressed by introduction of chickenpox vaccination, incidences of herpes zoster may rise. Methods. We performed a systematic review and metaanalysis on impact of chickenpox vaccination on herpes zoster incidence and time trend, focusing on population-level effects by analyzing interrupted time-series (ITS) studies. We searched Medline and Embase for ITS reporting incidences of chickenpox and herpes zoster before and after implementation of chickenpox vaccination. Autoregressive integrated moving average models were calculated. Change in trend and incidence from studies were pooled. Results. Twelve studies were included, of which 6 were eligible for metaanalysis. Metaanalysis revealed a significant increase in chickenpox cases prior to implementation of chickenpox vaccination and a reversed trend thereafter, particularly in individuals aged 1-4 years. The increase in age-adjusted herpes zoster incidence before implementation of chickenpox vaccination did not change thereafter. However, separate analysis of age groups revealed a net increase of hospitalized herpes zoster cases in individuals aged 10-49 years after implementation of chickenpox vaccination. This very small effect (fewer than 2 additional cases per 100 000 persons) did not occur in other age groups. Conclusions. To date, no conclusive evidence exists that chickenpox vaccination has a substantial population-level impact on herpes zoster in nonvaccinated age groups. While exogenous boosting may exist, the effect size generated by chickenpox vaccination might be rather small on the population level.