title: 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.
authors.affiliation: Dipartimento di Matematica, Università di Trento, Trento, Italy; Basque Center for Applied Mathematics, Bilbao, Spain.
authors.forename: Isabella
authors.initials: I
authors.lastname: Marinelli
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Alies
authors.initials: A
authors.lastname: van Lier
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Hester
authors.initials: H
authors.lastname: de Melker
authors.affiliation: Dipartimento di Matematica, Università di Trento, Trento, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pugliese
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands. Electronic address: michiel.van.boven@rivm.nl.
authors.forename: Michiel
authors.initials: M
authors.lastname: van Boven
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D015995:Prevalence; D014611:Vaccination / Q000706:statistics & numerical data*; D000073618:Varicella Zoster Virus Infection / Q000453:epidemiology* / Q000276:immunology* / Q000517:prevention & control; D055815:Young Adult
keywords: Statistical inference; Transmission model; Vaccination; Varicella; Zoster