GSK, Siena, Italy.
GSK, Amsterdam, The Netherlands.
BMC Infect Dis. 2021 Dec 11;21(1):1244. doi: 10.1186/s12879-021-06906-x.
The four-component serogroup B meningococcal 4CMenB vaccine (Bexsero, GSK) has been routinely given to all infants in the United Kingdom at 2, 4 and 12 months of age since September 2015. After 3 years, Public Health England (PHE) reported a 75% [95% confidence interval 64%; 81%] reduction in the incidence of serogroup B invasive meningococcal disease (IMD) in age groups eligible to be fully vaccinated. In contrast, vaccine effectiveness (VE) evaluated in the same immunization program applying the screening method was not statistically significant. We re-analyzed the data using an incidence model.
Aggregate data-stratified by age, year and doses received-were provided by PHE: serogroup B IMD case counts for the entire population of England (years 2011-2018) and 4CMenB vaccine uptake in infants. We combined uptake with national population estimates to obtain counts of vaccinated and unvaccinated person-time by age and time. We re-estimated VE comparing incidence rates in vaccinated and non-vaccinated subjects using a Bayesian Poisson model for case counts with person-time data as an offset. The model was adjusted for age, time and number of doses received.
The incidence model showed that cases decreased until 2013-2014, followed by an increasing trend that continued in the non-vaccinated population during the immunization program. VE in fully vaccinated subjects (three doses) was 80.1% [95% Bayesian credible interval (BCI): 70.3%; 86.7%]. After a single dose, VE was 33.5% [12.4%; 49.7%] and after two doses, 78.7% [71.5%; 84.5%]. We estimated that vaccination averted 312 cases [252; 368] between 2015 and 2018. VE was in line with the previously reported incidence reduction.
Our estimates of VE had higher precision than previous estimates based on the screening method, which were statistically not significant, and in line with the 75% incidence reduction previously reported by PHE. When disease incidence is low and vaccine uptake is high, the screening method applied to cases exclusively from the population eligible for vaccination may not be precise enough and may produce misleading point-estimates. Precise and accurate VE estimates are fundamental to inform public health decision making. VE assessment can be enhanced using models that leverage data on subjects not eligible for vaccination.
自 2015 年 9 月以来，英国已将四组份 B 群脑膜炎奈瑟球菌 4CMenB 疫苗（Bexsero，GSK）常规接种给所有 2、4 和 12 个月龄的婴儿。3 年后，英国公共卫生署（PHE）报告称，在有资格完全接种疫苗的年龄组中，B 群侵袭性脑膜炎奈瑟球菌病（IMD）的发病率降低了 75%[95%置信区间 64%；81%]。相比之下，在同一免疫计划中应用筛查方法评估的疫苗有效性（VE）并不具有统计学意义。我们使用发病率模型重新分析了数据。
PHE 提供了按年龄、年份和接种剂量分层的汇总数据：英格兰全人群 B 群 IMD 病例数（2011-2018 年）和婴儿中 4CMenB 疫苗接种率。我们将接种率与全国人口估计数相结合，按年龄和时间计算接种和未接种的人数。我们使用病例计数的贝叶斯泊松模型和作为偏移量的人数数据重新估计 VE，比较接种和未接种人群的发病率。该模型根据年龄、时间和接种剂量进行了调整。
发病率模型显示，病例数量在 2013-2014 年下降，随后在免疫计划期间，未接种人群的病例数量呈上升趋势。完全接种（三剂）的 VE 为 80.1%[95%贝叶斯可信区间（BCI）：70.3%；86.7%]。接种一剂后的 VE 为 33.5%[12.4%；49.7%]，接种两剂后的 VE 为 78.7%[71.5%；84.5%]。我们估计 2015 年至 2018 年间疫苗接种预防了 312 例病例[252 例；368 例]。VE 与 PHE 先前报告的发病率降低情况一致。
我们的 VE 估计值比之前基于筛查方法的估计值更精确，而之前的估计值没有统计学意义，与 PHE 之前报告的 75%发病率降低情况一致。当疾病发病率较低且疫苗接种率较高时，仅从有资格接种疫苗的人群中筛选病例应用的筛查方法可能不够精确，并且可能产生误导性的点估计。准确和精确的 VE 估计值是为公共卫生决策提供信息的基础。可以使用针对不符合接种条件的人群的病例数据的模型来增强 VE 评估。
