The Epidemiology of Herpes Zoster after Varicella Immunization under Different Biological Hypotheses: Perspectives from Mathematical Modeling

The impact of varicella vaccination on the epidemiology of herpes zoster (HZ) critically depends on the mechanism of immunological boosting, through which reexposures to varicella-zoster virus are thought to reduce the individual risk of HZ development. However, the qualitative and quantitative dynamics of this process are largely unknown. Consequently, mathematical models evaluating immunization strategies need to rely on theoretical assumptions. Available varicella-zoster virus models can be classified in 3 main families according to the postulated effect of exogenous boosting: 1) progressive accumulation of immunity following repeated reexposures; 2) partial protection that wanes over time; or 3) full but temporary immunity against HZ. In this work, we review and compare quantitative predictions from the 3 modeling approaches regarding the effect of varicella immunization on HZ. All models predict a qualitatively similar, but quantitatively heterogeneous, transient increase of HZ incidence. In particular, novel estimates from the progressive immunity model predict the largest increase in natural HZ and the largest incidence of HZ cases from reactivation of the vaccine strain, which in the long term will likely outnumber prevaccination numbers. Our results reinforce the idea that a better understanding of HZ pathogenesis is required before further mass varicella immunization programs are set out.