背景:2016年,世界卫生组织建议在2岁或2岁以上的人群中使用部分剂量的黄热病(YF)疫苗,以应对导致全球可用YF疫苗短缺的紧急情况。然而,这项建议没有扩展到获得YF疫苗许可的最年轻年龄组,因为没有关于9~23个月儿童的部分剂量YF疫苗接种的使用或安全性的公开数据.我们进行了一项单盲随机对照试验,在乌干达9-23个月大的儿童中,比较了五分之一和一半剂量的Bio-Manuinhos17DDYF疫苗与全剂量的免疫原性和安全性。在本文中,我们提出了安全性的中期分析。
方法:在三个研究中心之一招募了接受常规儿童服务的9-23个月儿童。我们在2019年3月26日至2020年8月31日期间收集了疫苗接种后28天积极监测期间免疫接种(AEFI)后所有不良事件的数据,使用多种收集工具,包括客观测量发热的日记卡。乌干达国家AEFI委员会的一个独立小组根据布莱顿合作标准对严重的AEFI(SAE)进行了调查和分类。
结果:在1053名注册儿童中,672(64%)被报告患有非严重的AEFI(NSAE),17(2%)被报告患有SAE。最常见的AEFI是腹泻,发烧,和皮疹,分别由355人(34%)报告,338(33%),188名(18%)参与者,分别。在17名SAE参与者中,据报告有8人癫痫发作,有5人因癫痫发作或其他原因住院(呼吸道症状,胃肠道疾病,疟疾)。接种疫苗后>28天发生4例SAE(死亡)。没有报告的预先指定或疫苗相关的SAE病例。我们观察到研究组之间不良事件的频率或严重程度没有显着差异。
结论:使用全面的主动监测监测,在接受YF疫苗接种的2岁以下儿童中,我们没有发现任何意外的安全问题,包括分数剂量。尽管我们发现了大量严重和非严重的AEFI,没有确定与YF疫苗接种有因果关系.这些结果为9-23个月儿童中部分剂量YF疫苗接种的安全性提供了证据。
BACKGROUND: In 2016, the World Health Organization recommended that a fractional dose of yellow fever (YF) vaccine could be used in persons 2 years of age or older in response to an emergency that resulted in a global shortage of available YF vaccine. However, this recommendation did not extend to the youngest age group licensed for YF vaccine because there were no published data on the use or safety of fractional dose YF vaccination in children aged 9-23 months. We conducted a single-blind randomized controlled trial, comparing the immunogenicity and safety of fractional one-fifth and one-half doses of Bio-Manguinhos 17DD YF vaccine with full dose in children aged 9-23 months old in Uganda. In this paper, we present the interim analysis on safety.
METHODS: Children aged 9-23 months presenting for routine well-child services were recruited for inclusion at one of three study sites. We collected data during March 26, 2019-August 31, 2020, on all adverse events following immunization (AEFI) during active surveillance for 28 days post-vaccination using multiple collection tools including a diary card with an objective measurement of fever. An independent team from the Uganda national AEFI Committee investigated and classified serious AEFI (SAE) according to Brighton Collaboration Criteria.
RESULTS: Among 1053 enrolled children, 672 (64%) were reported to have a non-serious AEFI (NSAE) and 17 (2%) were reported to have a SAE. The most common AEFI were diarrhoea, fever, and rash, each reported by 355 (34%), 338 (33%), and 188 (18%) participants, respectively. Among 17 participants with SAE, eight were reported to have had seizures and five were hospitalised for seizures or other causes (respiratory symptoms, gastrointestinal illness, malaria). Four SAEs (deaths) occurred >28 days after vaccination. There were no reported cases of pre-specified or vaccine-related SAEs. We observed no significant difference in frequency or severity of adverse events among the study groups.
CONCLUSIONS: Using comprehensive active surveillance monitoring, we did not identify any unexpected safety concerns among children aged <2 years receiving YF vaccination, including with the fractional doses. Although we identified a high number of both serious and non-serious AEFI, none were determined to be causally related to YF vaccination. These results provide evidence for the safety of fractional dose YF vaccination among children aged 9-23 months.