Estimation of age-specific rates of reactivation and immune boosting of the varicella zoster virus

Abstract

Studies into the impact of vaccination against the varicella zoster virus (VZV) have increasingly focused on herpes zoster (HZ), which is believed to be increasing in vaccinated populations with decreasing infection pressure. This idea can be traced back to Hope-Simpson's hypothesis, in which a person's immune status determines the likelihood that he/she will develop HZ. Immunity decreases over time, and can be boosted by contact with a person experiencing varicella (exogenous boosting) or by a reactivation attempt of the virus (endogenous boosting). Here we use transmission models to estimate age-specific rates of reactivation and immune boosting, exogenous as well as endogenous, using zoster incidence data from the Netherlands (2002-2011, n=7026). The boosting and reactivation rates are estimated with splines, enabling these quantities to be optimally informed by the data. The analyses show that models with high levels of exogenous boosting and estimated or zero endogenous boosting, constant rate of loss of immunity, and reactivation rate increasing with age (to more than 5% per year in the elderly) give the best fit to the data. Estimates of the rates of immune boosting and reactivation are strongly correlated. This has important implications as these parameters determine the fraction of the population with waned immunity. We conclude that independent evidence on rates of immune boosting and reactivation in persons with waned immunity are needed to robustly predict the impact of varicella vaccination on the incidence of HZ.

Trends in varicella and herpes zoster epidemiology before and after the implementation of universal one-dose varicella vaccination over one decade in South Korea, 2003–2015

“…However, VZV becomes latent in dorsal root ganglia, and its reactivation causes HZ later in life. 1 The reactivation of VZV is believed to be associated with waning cell-mediated immunity, 2 which is postulated to be boosted exogenously via re-exposure to VZV, through contact with varicellainfected individuals. 3 Varicella vaccination has proven effective in reducing the disease burden and severity of varicella.…”

Evaluation of impact of one dose varicella vaccine on the incidence of chickenpox in Argentina

“…A two-dose program might guarantee a high effectivity at the population level; however, comparative models of 1 dose versus 2 doses evidence that this depends on the efficiency of the first dose, and on the impact that it might have on zoster (37). Likewise, the impact on incidence decrease might affect specific cohorts, through the accumulation of the sensitive individuals among the non-vaccinated population, who might get the disease later in their life, as well as the behavior of the herpes zoster (HS) (38) (39). In that sense, one of the possible impacts of mass varicella vaccination is that an increase in herpes-zoster could be expected during the first 30 to 50 years (40).…”

The impact of childhood varicella vaccination on the incidence of herpes zoster in the general population: modelling the effect of exogenous and endogenous varicella-zoster virus immunity boosting

“…Using varicella and HZ data from the Netherlands, Marinelli et al [48], compared the performance of fitting various sets of model parameters based on statistical criteria: Akaike information criterion (AIC) and Bayesian information criterion (BIC). Both criteria modulate the quality of the fit obtained by introducing a penalty on the number of parameters used to fit the data, the penalty being more important for BIC.…”