Exposure to varicella boosts immunity to herpes-zoster: implications for mass vaccination against chickenpox
Introduction
Primary infection with varicella zoster virus (VZV) results in varicella (chickenpox) after which the virus becomes latent in dorsal root ganglia and may reactivate decades later, as a result of waning cell-mediated immunity, to cause herpes-zoster (shingles) [1]. Zoster is mostly suffered by the elderly and is the cause of significant morbidity [2]. Hope–Simpson first hypothesized that exposure to varicella reduces the risk of reactivation by boosting specific immunity to the virus (exogenous boosting) [1]. This hypothesis has yet to be supported by strong epidemiological evidence.
A live attenuated VZV (Oka) vaccine was developed by Takahashi et al. in the beginning of the 1970s [3], and was introduced into the routine infant immunization schedule of the US in 1995 [4]. On account of the strong evidence in favour of varicella vaccination [5], [6], [7], [8], [9], its introduction is imminent in many countries. However, one potential danger of varicella immunisation is often neglected. If exposure to VZV reduces the rate of reactivation, then reduction of varicella cases after mass vaccination could increase the incidence of zoster [10], [11], [12], [13], [14], leading to adverse public health consequences [12], [13], [15]. Here, we present convincing data in support of this hypothesis. We use these data to parameterise a mathematical model of VZV transmission which is used to estimate the impact of mass vaccination on the incidence of zoster.
Section snippets
Data
Data were taken from the fourth National Survey of Morbidity in General Practice (MSGP4), a survey of general practices covering a 1% sample (over 500,000 patients) of England and Wales during 1991/92 [16]. Details of all consultations were recorded during the study year, along with socio-economic information on the patients [16]. For children under 16 years, all first episodes of varicella and zoster were included in the analysis. For adults, first episodes of varicella and zoster were
Results
The overall age-specific incidence of zoster observed in the MSGP4 study was similar to other industrialised countries [17], [19]. Here, we present the age-specific annual incidence rate of zoster in England and Wales by household exposure to children (Fig. 2a). Living with children was found to be significantly protective against zoster (P<0.001) with an incidence ratio of 0.75 (95% CI, 0.63–0.89). There was no evidence of confounding by sex, ethnicity or socio-economic class (a range of
Discussion
We present strong epidemiological evidence supporting the hypothesis that exposure to varicella inhibits herpes-zoster. Primarily, our analysis shows that exposure to varicella is greater in adults living with children and that this exposure is highly protective against zoster. We further estimate that the average period of immunity conferred by exposure to varicella is 20 years. Previously, only indirect evidence has supported the hypothesis that re-exposure to VZV offers protection against
Acknowledgements
The United Kingdom Medical Research Council, Grant number G9818303, provided financial support. We thank Dr Elizabeth Miller for comments on the manuscript. The MSGP4 data are Crown Copyright and are reproduced with permission.
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