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

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.

本研究基于挪威首次针对普通人群的大规模血清学研究，采用混合模型（mixture modelling）分析挪威人群针对水痘带状疱疹病毒（varicella zoster virus, VZV）感染的年龄特异性免疫水平。研究团队利用2103份取自基层医疗及住院诊疗患者的剩余血清样本，估算了不同年龄段的血清阳性率，并计算了潜在感染力。研究观察到，生命早期与VZV相关的免疫水平快速上升，至5岁时已有63%的儿童获得免疫。此后免疫水平的上升速度放缓，至20岁时仍有近14.5%的成年人易感水痘，因此存在发生水痘感染严重后遗症的风险。对应的感染力在学龄前达到峰值，随后在10至20岁间降至最低，之后缓慢上升并进入持续至整个育龄期的平台期。相较于传统截断法，混合模型可利用全部数据且不会产生任何无法判定的样本，实现了易感与免疫个体的无偏分类，并得到了更为平滑的年龄相关免疫谱。本研究结果可为挪威引入水痘疫苗接种的相关决策提供重要支撑，因为它们可作为旨在评估潜在疫苗接种方案的数学传播模型的核心输入参数。