GSK Vaccines, Value Evidence, Wavre, Belgium.
Present address: Bayer AG, Epidemiology, Medical Affairs and Pharmacovigilance, Berlin, Germany.
BMC Infect Dis. 2019 Feb 6;19(1):126. doi: 10.1186/s12879-019-3759-z.
A controversy exists about the potential effect of childhood varicella vaccination on Herpes Zoster (HZ) incidence. Mathematical models projected temporary HZ incidence increase after vaccine introduction that was not confirmed by real-world evidence. These models assume that absence of contacts with infected children would prevent exogenous boosting of Varicella-Zoster-Virus (VZV) immunity and they do not include an endogenous VZV immunity-boosting mechanism following asymptomatic VZV reactivation. This study aims to explore the effect of various assumptions on exogenous and endogenous VZV immunity-boosting on HZ incidence in the general population after introduction of routine childhood varicella vaccination.
An age-structured dynamic transmission model was adapted and fitted to the seroprevalence of varicella in France in absence of vaccination using the empirical contact matrix. A two-dose childhood varicella vaccination schedule was introduced at 12 and 18 months. Vaccine efficacy was assumed at 65%/95% (dose 1/dose 2), and coverage at 90%/80% (dose 1/dose 2). Exogenous boosting intensity was based on assumptions regarding HZ-immunity duration, age-dependent boosting effect, and HZ reactivation rates fitted to observed HZ incidence. Endogenous boosting was the same as pre-vaccination exogenous boosting but constant over time, whilst exogenous boosting depended on the force of infection. Five scenarios were tested with different weightings of exogenous (Exo) - endogenous (Endo) boosting: 100%Exo-0%Endo, 75%Exo-25%Endo, 50%Exo-50%Endo, 25%Exo-75%Endo, 0%Exo-100%Endo.
HZ incidence before varicella vaccination, all ages combined, was estimated at 3.96 per 1000 person-years; it decreased by 64% by year 80 post vaccine introduction, for all boosting assumptions. The 100%Exo-0%Endo boosting scenario, predicted an increase in HZ incidence for the first 21 years post vaccine introduction with a maximum increase of 3.7% (4.1/1000) at year 9. However, with 0%Exo-100%Endo boosting scenario an immediate HZ decline was projected. The maximum HZ incidence increases at 10, 3, and 2 years post vaccination were 1.8% (75%Exo-25%Endo), 0.8% (50%Exo-50%Endo) and 0.2% (25%Exo-75%Endo), respectively.
Assuming modest levels of endogenous boosting, the increase in HZ incidence following childhood varicella vaccination was smaller and lasted for a shorter period compared with 100%Exo-0%Endo boosting assumption. Endogenous boosting mechanism could partly explain the divergence between previous HZ-incidence projections and real-world evidence.
关于儿童水痘疫苗接种对带状疱疹（HZ）发病率的潜在影响存在争议。数学模型预测疫苗接种后 HZ 发病率会暂时增加，但这一预测并未得到实际证据的证实。这些模型假设与感染儿童的接触缺失会阻止水痘-带状疱疹病毒（VZV）免疫力的外源性增强，并且它们不包括无症状 VZV 再激活后 VZV 免疫力的内源性增强机制。本研究旨在探讨在常规儿童水痘疫苗接种后，各种假设对内源性和外源性 VZV 免疫力增强对普通人群 HZ 发病率的影响。
本研究采用了一种年龄结构动态传播模型，并使用经验接触矩阵对法国在没有疫苗接种情况下的水痘血清阳性率进行了拟合。在 12 个月和 18 个月时，采用两剂儿童水痘疫苗接种方案。疫苗效力假设为 65%/95%（剂量 1/剂量 2），覆盖率假设为 90%/80%（剂量 1/剂量 2）。外源性增强强度基于 HZ 免疫持续时间、年龄相关增强效应和观察到的 HZ 发病率拟合的 HZ 再激活率的假设。内源性增强与疫苗接种前的外源性增强相同，但随时间恒定，而外源性增强取决于感染强度。研究共测试了五种不同外源性（Exo）-内源性（Endo）增强权重的方案：100%Exo-0%Endo、75%Exo-25%Endo、50%Exo-50%Endo、25%Exo-75%Endo、0%Exo-100%Endo。
水痘疫苗接种前，所有年龄组的 HZ 发病率估计为每 1000 人年 3.96 例；在疫苗接种后 80 年内，所有增强假设下 HZ 发病率下降了 64%。100%Exo-0%Endo 增强方案预测，疫苗接种后前 21 年内 HZ 发病率会增加，第 9 年时最大增幅为 3.7%（4.1/1000）。然而，0%Exo-100%Endo 增强方案预测 HZ 发病率会立即下降。接种疫苗后 10、3 和 2 年时 HZ 发病率最大增幅分别为 1.8%（75%Exo-25%Endo）、0.8%（50%Exo-50%Endo）和 0.2%（25%Exo-75%Endo）。
与 100%Exo-0%Endo 增强假设相比，假设内源性增强适度，儿童水痘疫苗接种后 HZ 发病率的增加较小，持续时间较短。内源性增强机制可以部分解释之前 HZ 发病率预测与实际证据之间的差异。
