The chickenpox vaccination may not have a substantial population-level effect on herpes zoster in nonvaccinated age groups, according to a study published in Clinical Infectious Diseases.

The reactivation of varicella zoster virus (VZV) that persists in neural ganglia causes herpes zoster. This reactivation often occurs years after the primary infection and is triggered by a decrease in cellular immunity as a result of immunodeficiency or senescence. It is unclear why the latency period between primary infection (during chickenpox) and herpes zoster is so long, but in 1965, a theory called the exogenous boosting hypothesis proposed that repeated re-exposure to circulating VZV over the life span (exogenous boosting) inhibits reactivation of VZV. So, if circulation of VZV is suppressed in a given population, the chance of re-exposure decreases and may lead to a rise in herpes zoster incidence. 

Further, it has been suggested that introduction of the chickenpox vaccine will reduce the possibility of exogenous boosting, leading to rising incidences of herpes zoster. However, previous case-controlled studies researching this effect have had mixed results. Because many national immunization programs have implemented universal childhood vaccination against chickenpox, the abovementioned effects of the exogenous boosting hypothesis should be apparent at the population level. Therefore, this systematic review and meta-analysis aimed to investigate quantitative effects of chickenpox vaccination on herpes zoster incidence at the population level.

Medline and Embase were systematically searched for interrupted time series reporting incidences of chickenpox and herpes zoster before and after implementation of chickenpox vaccination. From eligible studies (n=12), study location, data sources, age groups vaccination against chickenpox, age groups for which chickenpox and zoster were reported, pre-implementation period of chickenpox vaccination, implementation point of chickenpox vaccination, and postimplementation period of chicken vaccination data were extracted. Change in trend and incidence from the studies were pooled.

Researchers conducted a quantitative summarization of available studies, but were unable to confirm negative population-level effects of chickenpox vaccination on herpes zoster incidence. Six studies were eligible for meta-analysis; particularly in children aged 1 to 4 years, the meta-analysis showed a significant increase in chickenpox cases before implementation of chickenpox vaccination, and a reversed trend thereafter. There was a significant increase in age-adjusted herpes zoster incidence before implementation of the chickenpox vaccination, but this increase did not change after. Although this small effect did not occur in other age groups, a separate analysis of age groups revealed a net increase of hospitalized herpes zoster cases in people aged 10 to 49 years after implementation of the chickenpox vaccination.

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Overall, the study authors concluded that, “Taken together, this systematic review shows that, based on published [interrupted time series] studies, no conclusive evidence exists that vaccination against chickenpox has a population-level impact on the incidence of herpes zoster in non-vaccinated age groups.”


Harder T, Siedler A. Systematic review and meta-analysis of chickenpox vaccination and risk of herpes zoster: a quantitative view on the “exogenous boosting hypothesis” [published online December 24, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy1099/5258112