Stowe Julia, Andrews Nick, Ladhani Shamez, Miller Elizabeth
Immunisation and Blood safety Department, Public Health England, 61 Colindale Avenue, London NW9 5EQ, United Kingdom.
Statistics and Modelling Economics Unit, Public Health England, London NW9 5EQ, United Kingdom.
Vaccine. 2016 Jul 12;34(32):3684-9. doi: 10.1016/j.vaccine.2016.04.050. Epub 2016 Jun 7.
To investigate the risk of intussusception after monovalent rotavirus vaccine (RV1) given to infants aged 2 and 3 months in England.
Hospital Episode Statistics (HES) were used to identify infants aged 48-183 days admitted between 11/03/2013 and 31/10/2014 with intussusception. Diagnosis was confirmed from medical records and HES procedure codes. Vaccination status was obtained from general practitioners. The risk of admission within 1-7 and 8-21 days of vaccination was analysed using the self-controlled case-series (SCCS) method with age effect adjustment by including historical data before RVI introduction in July 2013.
A total of 119 cases were identified during the study period and intussusception confirmed in 95 of whom 39 were vaccinated 1-21 days before onset. An increased relative incidence (RI) in this period was found, 4.53 (95% confidence interval 2.34-8.58) and 2.60 (1.43-4.81) respectively after the 1st and 2nd doses with an attributable risk of 1.91 and 1.49 per 100,000 doses respectively. The peak risk was 1-7 days after the first dose, RI 13.81 (6.44-28.32), with an estimated 93% of the 15 cases being vaccine-attributable. Mean interval between onset and admission, and clinical features were similar between vaccine-associated and background cases. Despite intussusception being a contraindication to rotavirus vaccination, 10 infants received a further dose; none had a recurrence. The RIs in a meta-analysis combing our results with Australia, Mexico, Brazil and Singapore using RV1, a 2, 4 month schedule and SCCS gave pooled RI estimates of 2.35 (1.45-3.8) and 1.77 (1.29-2.43) in the 21 day period after the 1st and 2nd doses, respectively. The earlier age at the 2nd dose in England did not affect the risk.
We estimate that the RVI programme causes around 21 intussusception admissions annually in England but, since it prevents around 25,000 gastro-intestinal infection admissions, its benefit/risk profile remains strongly positive.
调查在英格兰给2至3个月大婴儿接种单价轮状病毒疫苗（RV1）后发生肠套叠的风险。
利用医院事件统计数据（HES）来确定在2013年3月11日至2014年10月31日期间入院的48 - 183天大且患有肠套叠的婴儿。通过病历和HES程序代码确诊诊断。疫苗接种状况从全科医生处获取。采用自控病例系列（SCCS）方法分析接种疫苗后1 - 7天和8 - 21天内入院的风险，并通过纳入2013年7月引入RV1之前的历史数据进行年龄效应调整。
在研究期间共确定了119例病例，其中95例确诊为肠套叠，39例在发病前1 - 21天接种了疫苗。在此期间发现相对发病率（RI）有所增加，第一剂和第二剂后分别为4.53（95%置信区间2.34 - 8.58）和2.60（1.43 - 4.81），每100,000剂的归因风险分别为1.91和1.49。风险高峰出现在第一剂后的1 - 7天，RI为13.81（6.44 - 28.32），估计15例病例中有93%可归因于疫苗。疫苗相关病例和背景病例在发病至入院的平均间隔以及临床特征方面相似。尽管肠套叠是轮状病毒疫苗接种的禁忌证，但仍有10名婴儿接种了后续剂量；均未复发。在将我们的结果与澳大利亚、墨西哥、巴西和新加坡使用RV1、2、4月龄接种程序及SCCS方法进行的荟萃分析中，第一剂和第二剂后21天期间的合并RI估计值分别为2.35（1.45 - 3.8）和1.77（1.29 - 2.43）。英格兰第二剂接种年龄较早并未影响风险。
我们估计在英格兰RV1接种计划每年导致约21例肠套叠入院，但由于它可预防约25,000例胃肠道感染入院，其效益/风险状况仍然非常积极。
