Estimating Age-Specific Immunity and Force of Infection of Varicella Zoster Virus in Norway Using Mixture Models

Abstract

This study applies mixture modelling to examine age-specific immunity to varicella zoster virus (VZV) infection in Norway based on the first large-scale serological study in the general population. We estimated the seropositive proportions at different ages and calculated the underlying force of infection by using a sample of 2103 residual sera obtained from patients seeking primary and hospital care. A rapid increase in the VZV-associated immunity is observed in the first years of life with 63% of children being immune by age 5. The increase in the immunity levels slows down thereafter, with a large proportion of adults still susceptible by age 20 (around 14.5%), thus at risk of serious sequelae of varicella infection. The corresponding force of infection peaks during the preschool period, subsequently declines to a minimum between ages 10 and 20 years, and afterwards moderately increases to reach a plateau lasting throughout the childbearing period. In comparison with the traditional cut-off approach, mixture modelling used the whole data without producing any inconclusive cases, led to an unbiased classification of individuals between susceptible and immune, and provided a smoother immune profile by age. These findings represent an important step towards any decision about the introduction of varicella vaccination in Norway, as they are a primary input for mathematical transmission models aimed at evaluating potential vaccination scenarios.

Fig 1. Distribution of antibodies to VZV by age in Norway.

Histogram of the log-transformed antibody optical densities (log₁₀(OD+1)) against VZV by broad age group (preschool: 1–5 years; school: 6–18 years; adults: 19 years and more), with over imposed the corresponding density function estimated by the mixture model, for each component (dotted line), and for all the data (solid line). The vertical dashed lines represent the manufacturer’s fixed cut-offs and the data included between the two lines are usually classified as inconclusive under the conventional cut-off approach.

Fig 2. Proportions VZV-positive individuals in Norway.

Age-specific proportions seropositive determined using the fixed cut-off (grey bars) and the mixture model (black dots). For the latter ones, we also reported the 95% pointwise credible intervals (grey area).

Fig 3. Seroprevalence of VZV in Norway.

Posterior mean of the age-specific VZV seroprevalence in Norway (with 95% CI), determined using the mixture model.

Fig 4. FOI of VZV in Norway.

Posterior mean of the age-specific VZV FOI in Norway (with 95% CI), determined using the mixture model.