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. 2013 Apr 17;8(4):e60732.
doi: 10.1371/journal.pone.0060732. Print 2013.

Perspectives on the impact of varicella immunization on herpes zoster. A model-based evaluation from three European countries

Piero Poletti  1 , Alessia Melegaro, Marco Ajelli, Emanuele Del Fava, Giorgio Guzzetta, Luca Faustini, Giampaolo Scalia Tomba, Pierluigi Lopalco, Caterina Rizzo, Stefano Merler, Piero Manfredi
Affiliations

Perspectives on the impact of varicella immunization on herpes zoster. A model-based evaluation from three European countries

Piero Poletti et al. PLoS One. .

Abstract

The introduction of mass vaccination against Varicella-Zoster-Virus (VZV) is being delayed in many European countries because of, among other factors, the possibility of a large increase in Herpes Zoster (HZ) incidence in the first decades after the initiation of vaccination, due to the expected decline of the boosting of Cell Mediated Immunity caused by the reduced varicella circulation. A multi-country model of VZV transmission and reactivation, is used to evaluate the possible impact of varicella vaccination on HZ epidemiology in Italy, Finland and the UK. Despite the large uncertainty surrounding HZ and vaccine-related parameters, surprisingly robust medium-term predictions are provided, indicating that an increase in HZ incidence is likely to occur in countries where the incidence rate is lower in absence of immunization, possibly due to a higher force of boosting (e.g. Finland), whereas increases in HZ incidence might be minor where the force of boosting is milder (e.g. the UK). Moreover, a convergence of HZ post vaccination incidence levels in the examined countries is predicted despite different initial degrees of success of immunization policies. Unlike previous model-based evaluations, our investigation shows that after varicella immunization an increase of HZ incidence is not a certain fact, rather depends on the presence or absence of factors promoting a strong boosting intensity and which might or not be heavily affected by changes in varicella circulation due to mass immunization. These findings might explain the opposed empirical evidences observed about the increases of HZ in sites where mass varicella vaccination is ongoing.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Schematic representation of the model. Natural varicella and HZ.
M represents individuals protected by maternal antibodies; VS, VE, VI represent varicella susceptible, latent and infective; VR represents individuals recovered from varicella and temporally protected by CMI against HZ; ZS, ZI, ZR represent individuals susceptible, infected and permanently immune to HZ. Vaccine protection, varicella and HZ among vaccines. VP represents vaccine protected individuals. VBS, VBE and VBI represent vaccinated individuals susceptible, latent and infective for breakthrough varicella; VBR represents individuals recovered from breakthrough varicella and temporally protected by CMI against (breakthrough) HZ. ZBS, ZBI, ZBR represent individuals susceptible, infected and permanently immune to HZ that experienced varicella breakthrough after vaccination. ZVS, ZVI, ZVR represent individuals susceptible, infected and permanently immune to HZ for the vaccine strain. Details in Text S1.
Figure 2
Figure 2. VZV seroprevalence, HZ incidence and boosting incidence in Finland, Italy and the UK.
Top Row. VZV seroprevalence by age as observed in (in green) and as predicted by the model (average in blue, 95% CI in cyan) for Finland (a), Italy (b), UK (c). Mid Row. Yearly HZ incidence by age(cases per 1,000 individuals) as observed in , , (in green) and as predicted by the model (average in blue, 95% CI in cyan) for Finland (d), Italy (e), UK (f); Bottom row. Predicted HZ susceptibility age profile for Finland (g), Italy (h), UK (i). Results are based on 1,000 model realizations.
Figure 3
Figure 3. The impact of VZV vaccination on varicella incidence.
Top row. Yearly incidence of varicella (average in dark green, 95% CI in light green) and of natural varicella (average in red, 95% CI in orange) per 1,000 individuals as predicted by simulating a single vaccine dose administered to 1 year-old infants with 100% coverage in Finland (a) in Italy (b) and in the UK (c). Mid row. As the top row but obtained by considering 70% coverage in Finland (d) in Italy (e) and in the UK (f). Bottom row. As the top row but for the two-dose scenario, which assumes the administration of a first dose to 1 year-old individuals (90% coverage) and a second dose to 5 years-old individuals (80% coverage) in Finland (g) in Italy (h) and in the UK (i). Results are based on 1,000 model realizations.
Figure 4
Figure 4. The impact of VZV vaccination on the age distribution of varicella cases.
Average yearly distribution of varicella cases among individuals aged 0–20 (red), 21–40 (blue), 41–60 (orange) and 61+ (green) as predicted by simulating a single vaccine dose administered to 1 year-old infants with 100% coverage in Finland (a) Italy (b) and the UK (c). Results are based on 1,000 model realizations.
Figure 5
Figure 5. The impact of different vaccination schedules and coverages on HZ incidence.
Top row. Yearly incidence of HZ (average in dark green, 95% CI in light green), of natural HZ (i.e., HZ cases occurring among unvaccinated individuals that have experienced natural varicella (average in red, 95% CI in orange) and of HZ caused by the vaccine strain (average in blue, 95% CI in light blue) per 1,000 individuals as predicted by simulating a single vaccine dose administered to 1 year-old infants with 100% coverage in Finland (a) in Italy (b) and in the UK (c). Mid row. As the top row but obtained by considering 70% coverage in Finland (d) in Italy (e) and in the UK (f). Bottom row. As the top row but for the two-dose scenario, which assumes the administration of a first dose to 1 year-old individuals (90% coverage) and a second dose to 5 years-old individuals (80% coverage) in Finland (g) in Italy (h) and in the UK (i). Results are based on 1,000 model realizations.
Figure 6
Figure 6. HZ post-vaccination dynamics obtained by adopting the parallel fit approach.
Top row. Yearly incidence of HZ (average in dark green, 95% CI in light green),of natural HZ – i.e., by HZ cases occurring among unvaccinated individuals that have experienced natural varicella – (average in red,95% CI in orange) and of HZ caused by the vaccine strain (average in blue, 95% CI in light blue) per 1,000 individuals as obtained by adopting the parallel fit approach and by simulating the two-dose scenario, which assumes the administration of a first dose to 1 year-old individuals (90% coverage) and a second dose to 5 years-old individuals (80% coverage), in Finland (a) in Italy (b) and in the UK (c). Results are based on 1,000 model realizations.
Figure 7
Figure 7. The impact of VZV vaccination on the age distribution of HZ cases.
Top row. Average yearly distribution of HZ cases among individuals aged 0–20 (red), 21–40 (blue), 41–60 (orange) and 61+ (green) as predicted by simulating a single vaccine dose administered to 1 year-old infants with 100% coverage in Finland (a) Italy (b) and the UK (c). Results are based on 1,000 model realizations. Bottom row. The absolute HZ incidence by age at various time points following the introduction of the vaccine for Finland (d) Italy (e) and the UK (f).
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Grants and funding

PP, GG, PM, AM would like to thank the ECDC GRANT/2009/002 project for research funding. MA and SM would like to thank the EU FP7 EPIWORK project (contract no. 231807) for research funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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