Evaluation of the effect of chickenpox vaccination on shingles epidemiology using agent-based modeling

BACKGROUND: Biological interactions between varicella (chickenpox) and herpes zoster (shingles), two diseases caused by the varicella zoster virus (VZV), continue to be debated including the potential effect on shingles cases following the introduction of universal childhood chickenpox vaccination programs. We investigated how chickenpox vaccination in Alberta impacts the incidence and age-distribution of shingles over 75 years post-vaccination, taking into consideration a variety of plausible theories of waning and boosting of immunity. METHODS: We developed an agent-based model representing VZV disease, transmission, vaccination states and coverage, waning and boosting of immunity in a stylized geographic area, utilizing a distance-based network. We derived parameters from literature, including modeling, epidemiological, and immunology studies. We calibrated our model to the age-specific incidence of shingles and chickenpox prior to vaccination to derive optimal combinations of duration of boosting (DoB) and waning of immunity. We conducted paired simulations with and without implementing chickenpox vaccination. We computed the count and cumulative incidence rate of shingles cases at 10, 25, 50, and 75 years intervals, following introduction of vaccination, and compared the difference between runs with vaccination and without vaccination using the Mann–Whitney U-test to determine statistical significance. We carried out sensitivity analyses by increasing and lowering vaccination coverage and removing biological effect of boosting. RESULTS: Chickenpox vaccination led to a decrease in chickenpox cases. The cumulative incidence of chickenpox had dropped from 1,254 cases per 100,000 person-years pre chickenpox vaccination to 193 cases per 100,000 person-years 10 years after the vaccine implementation. We observed an increase in the all-ages shingles cumulative incidence at 10 and 25 years post chickenpox vaccination and mixed cumulative incidence change at 50 and 75 years post-vaccination. The magnitude of change was sensitive to DoB and ranged from an increase of 22–100 per 100,000 person-years at 10 years post-vaccination for two and seven years of boosting respectively (p < 0.001). At 75 years post-vaccination, cumulative incidence ranged from a decline of 70 to an increase of 71 per 100,000 person-years for two and seven years of boosting respectively (p < 0.001). Sensitivity analyses had a minimal impact on our inferences except for removing the effect of boosting. DISCUSSION: Our model demonstrates that over the longer time period, there will be a reduction in shingles incidence driven by the depletion of the source of shingles reactivation; however in the short to medium term some age cohorts may experience an increase in shingles incidence. Our model offers a platform to further explore the relationship between chickenpox and shingles, including analyzing the impact of different chickenpox vaccination schedules and cost-effectiveness studies.