肠道病毒A71型灭活疫苗(Vero细胞)上市后多中心安全性研究

Post-marketing multi-center safety surveillance of inactivated enterovirus A71 vaccine (Vero cell)

目的评价肠道病毒A71型(EV-A71)灭活疫苗(Vero细胞)(EV-A71疫苗)上市后常规接种的安全性。方法选取浙江全省11个地市,北京丰台区,广西壮族自治区平乐县、钦南区、平果县,江苏东台市作为研究现场,以2016年7月至2018年6月期间自愿自费接种EV-A71疫苗的儿童作为研究对象,其中,北京丰台区和江苏东台市以全部接种者作为观察对象;其余地区均采用系统抽样的方式。共45239名。在接种每剂EV-A71疫苗后30min、30min至3d和4~30d,通过现场观察、电话和面访的方式主动监测并收集儿童的不良反应发生情况,描述不同种类、症状和级别的不良反应发生率。结果45239名儿童共接种EV-A71疫苗71243剂次,总不良反应发生率为1.079%(769剂次);不同年龄组间,5~11月龄组不良反应发生率最高,为1.182%(177/14973),≥36月龄组最低,为0.849%(18/2119);征集性不良反应发生率较高,为1.047%(746剂次);1和2级不良反应发生率较高,分别为0.404%(288剂次)和0.554%(395剂次),未见4级不良反应发生。第1和2剂分别接种40736和30507剂次,不良反应发生率分别为1.281%(522剂次)和0.810%(247剂次);局部不良反应发生率分别为0.091%(37剂次)和0.043%(13剂次),全身不良反应发生率分别为1.168%(476剂次)和0.760%(232剂次);不良反应症状基本相同,局部反应均主要表现为注射部位发红,分别发生24和11剂次,全身反应均主要表现为发热,分别发生362和190剂次;不良反应均主要发生在接种后30min至3d内,发生率分别为1.016%(414剂次)和0.698%(213剂次)。结论儿童接种疫苗后不良反应发生率较低且多为轻中度,EV-A71疫苗安全性良好。

Objective To evaluate the post-marketing safety profiles of the inactivated enterovirus type 71 (EV-A71) vaccine (Vero cell) after routine inoculation.Methods Eleven cities of Zhejiang Province, Fengtai district of Beijing, Qinnan district, two counties as Pingle and Pingguo of Guangxi Zhuang Autonomous Region, and Dongtai city of Jiangsu Province were selected as the field sites. A total of 45 239 subjects were enrolled in this study from children who seeked the vaccination of EV-A71 vaccine during the period from July, 2016 to June, 2018. Different sampling method were adopted in different sites. All vaccinated children were invited to participate in the study in Fengtai and Dongtai, however, systematic sampling method were adopted in other sites. Active surveillance was conducted and information about adverse reactions (ARs) occurred in 30 min, 3 d and 30 d following each dose of EV-A71 immunization was collected by field observation, phone-call or face-to-face interview. The incidence of ARs in different types, symptoms and grades were described.Results In total, there were 45 239 children who received 71 243 doses EV-A71 vaccine. The overall incidence of ARs was 1.079%(769 doses), with the highest incidence of 1.182%(177/14 973) in 5-11 month group and the lowest incidence of 0.849%(18/2 119) in ≥ 36 month group among different age groups. There was a higher incidence in solicited ARs, which was 1.047%(746 doses). The incidences of grade 1 and grade 2 ARs were also higher, which were 0.404%(288 doses) and 0.554%(395 doses), respectively. No grade 4 ARs occurred. The doses of the first and the second vaccination was 40 736 and 30 507, respectively, and the incidences of ARs were 1.281%(522 doses) and 0.810%(247 doses). Also, the incidences of ARs were 0.091%(37 doses) and 0.043%(13 doses) in local, and 1.168%(476 doses) and 0.760%(232 doses) in system. The symptoms of ARs after the two doses of vaccination were basically the same. Redness at the injection site was the most common local ARs after each dose vaccination, with doses of 24 and 11, while fever was the most common systemic ARs, with doses of 362 and 190. Moreover, ARs mainly occurred in 30 min to 3 d after each dose vaccination, with incidence of 1.016%(414 doses) and 0.698%(213 doses) in the first and second dose, respectively.Conclusion The ARs had a low incidence after vaccination in children and most were mild or moderate. EV-A71 vaccine with good safety is suitable for inoculation in a large scale.