Current and future effects of varicella and herpes zoster vaccination in Germany - Insights from a mathematical model in a country with universal varicella vaccination

Abstract

Varicella zoster virus (VZV) is primarily known for causing varicella in childhood, but can reactivate again as herpes zoster (HZ) after a period of latency, mainly in persons older than 50 years. Universal varicella vaccination was introduced in Germany in 2004, while HZ vaccination has not been recommended yet. We aimed to quantify the potential long-term effects of universal childhood varicella vaccination and HZ vaccination of the elderly on varicella and HZ incidence in Germany over a time horizon of 100 years, using a transmission model calibrated to pre-vaccination data and validated against early post-vaccination data. Using current vaccination coverage rates of 87% (64%) with one (two) varicella vaccine dose(s), the model predicts a decrease in varicella cases by 89% for the year 2015. In the long run, the incidence reduction will stabilize at about 70%. Under the assumption of the boosting hypothesis of improved HZ protection caused by exposure to VZV, the model predicts a temporary increase in HZ incidence of up to 20% for around 50 years. HZ vaccination of the elderly with an assumed coverage of 20% has only limited effects in counteracting this temporary increase in HZ incidence. However, HZ incidence is shown to decrease in the long-term by 58% as vaccinated individuals get older and finally reach age-classes with originally high HZ incidence. Despite substantial uncertainties around several key variables, the model's results provide valuable insights that support decision-making regarding national VZV vaccination strategies.

Keywords: herpes zoster; transmission model; uncertainty; varicella; varicella vaccination; zoster vaccination.

Figure 1.

Varicella and herpes zoster cases over time in model population (see methods; no HZ vaccination).

Figure 2.

Hospitalizations and deaths associated with varicella zoster virus over time. + vaccine breakthrough = reactivation of vaccine virus after varicella vaccination. *breakthrough = reactivation of wild virus after varicella infection in vaccinated individuals.

Figure 3.

Age-specific varicella incidence for all varicella cases and for natural varicella only.

Figure 4.

Left panel: Age-dependent HZ incidence at different time points (without HZ vaccination, introduction of varicella vaccination in 2004); Right panel: Relative reduction of HZ incidence by age predicted for 2103 when comparing scenarios with and without HZ vaccination (introduction of HZ vaccination in 2015, coverage 20%).

Figure 5.

Effects of different varicella vaccination coverage rates over time (coverage for first/second dose) on varicella (left) and HZ (right) incidence.

Figure 6.

Effects of different boosting (left) and waning scenarios (right, duration in years) on varicella incidence.

Figure 7.

Effects of different boosting scenarios on HZ incidence: varying proportions of contacts boosting protection (left) and durations of protection against HZ in years (right).

Figure 8.

Effects of introducing HZ vaccination at different ages in 2015 for the whole population over time (left) and by age for the year 2030 (right), assuming coverage of 100% in both cases.

Figure 9.

Seroprevalence of varicella in Germany, by age. EIA: Enzyme immunoassay (Enzygnost Anti-VZV-IgG (DADE Behring); FAMA: Fluorescent antibody to membrane antigen assay (FAMA); KiGGS: Studie zur Gesundheit von Kindern und Jugendlichen in Deutschland.

Figure 10.

Incidence of herpes zoster in Germany, by sex and age (reported data and model predictions; SHI = statutory health insurance).

Figure 11.

Hospitalization probability and case fatality rate of varicella and herpes zoster.

Figure 12.

Varicella vaccination coverage (at the age of 24 months) as obtained from surveillance data for Germany (left) and vaccine uptake as used in the model (right).