Perspectives on optimal control of varicella and herpes zoster by mass routine varicella vaccination

Abstract

Herpes zoster arises from reactivation of the varicella-zoster virus (VZV), causing varicella in children. As reactivation occurs when cell-mediated immunity (CMI) declines, and there is evidence that re-exposure to VZV boosts CMI, mass varicella immunization might increase the zoster burden, at least for some decades. Fear of this natural zoster boom is the main reason for the paralysis of varicella immunization in Europe. We apply optimal control to a realistically parametrized age-structured model for VZV transmission and reactivation to investigate whether feasible varicella immunization paths that are optimal in controlling both varicella and zoster exist. We analyse the optimality system numerically focusing on the role of the cost functional, of the relative zoster-varicella cost and of the planning horizon length. We show that optimal programmes will mostly be unfeasible for public health owing to their complex temporal profiles. This complexity is the consequence of the intrinsically antagonistic nature of varicella immunization programmes when aiming to control both varicella and zoster. However, we show that gradually increasing-hence feasible-vaccination schedules can perform better than routine programmes with constant vaccine uptake. Finally, we show the optimal profiles of feasible programmes targeting mitigation of the post-immunization natural zoster boom with priority.

Peer Review #4 of "Evaluation of the effect of chickenpox vaccination on shingles epidemiology using agent-based modeling (v0.5)"

“…To date the majority of chickenpox and shingles models, including the only model representing a Canadian population 44 are aggregate compartmental models, which limit their flexibility and heterogeneity. 20,[45][46][47][48][49] To our knowledge, the only individual-based model was created by Ogunjimi et al 25 to combine within-and between host dynamics, and VZV immunological data Our model concurs with previous models and biological studies that suggest exogenous boosting of VZV immunity is a likely factor in the reactivation of VZV, as we were not able to recreate the empirical data observed in Alberta without incorporating some element of boosting. 6 Longitudinal immunological studies show individuals re-exposed to chickenpox, either on a onetime or continuous basis, have a corresponding increase in VZV-specific immunity.…”

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

“…Infectious disease models can provide valuable insight into the complex relationship between chickenpox and shingles, allowing epidemiologists and biologists to test theories, study the impact of different parameters, and judge the outcomes of various interventions. To date the majority of chickenpox and shingles models, including the only model representing a Canadian population ( Brisson et al, 2000 ) are aggregate compartmental models, which limit their flexibility and heterogeneity ( Ouwens et al, 2015 ; Riche et al, 2016 ; Betta et al, 2016 ; Marziano et al, 2015 ; Poletti et al, 2013 ; Gao et al, 2010 ). To our knowledge, the only individual-based model was created by Ogunjimi et al (2015) to combine within- and between-host dynamics, and VZV immunological data to estimate boosting characteristics.…”

Varicella vaccination - the global experience

“…If routine infant varicella vaccination causes an albeit small increase in the incidence of HZ, there is a potential ethical dilemma whereby varicella vaccination although protecting one population (children) might have a deleterious effect on older individuals [39]. Other workers have proposed a more pragmatic approach in which zoster vaccination is used to supplement the varicella program and prevent HZ in older adults [40,41]. Nevertheless, long-term data within general populations are needed to determine the potential direct impact of universal varicella vaccination on HZ incidence.…”