■卡介苗(BCG)疫苗接种具有脱靶(非特异性)效应,与预防无关感染有关,并降低了婴儿的全因死亡率。我们旨在确定BCG疫苗接种是否可以预防成人的发热和呼吸道感染。
■这项随机对照3期试验在澳大利亚36个医疗中心进行,巴西,荷兰,西班牙,和英国。使用基于网络的程序,医护人员随机接受BCG-丹麦(单次0.1ml皮内注射)或不接受BCG,比例为1:1。按阶段分层,site,年龄,和合并症的存在。使用意向治疗(ITT)人群在12个月内(预设的次要结果)测量了发热或呼吸系统疾病发生率的差异。该试验已在ClinicalTrials.gov注册,NCT04327206。
■在2020年3月30日至2021年4月1日之间,6828名医护人员被随机分为BCG-丹麦(n=3417)或对照组(n=3411;无干预或安慰剂)。卡介苗组12个月校正后的≥1次发热或呼吸系统疾病发作的估计风险为66.8%(95%CI65.3%-68.2%),与对照组的63.4%(95%CI61.8%-65.0%)相比,差异为+3.4个百分点(95%CI+1.3%至+5.5%;p=0.002)。卡介苗组严重发作(定义为连续3天丧失工作能力或住院)的校正估计风险为19.4%(95%CI18.0%-20.7%),与对照组的18.8%(95%CI17.4%-20.2%)相比,差异为+0.6个百分点(95%CI-1.3%至+2.5%;p0.6).两组的疾病发作次数相似,肺炎,和住院。有3人死亡,都在对照组。BCG疫苗接种后没有安全性问题。
■与新生儿卡介苗在婴儿中报告的有益脱靶效应相反,在成人接种卡介苗后的12个月内,观察到症状性发热或呼吸系统疾病的风险略有增加.没有证据表明严重疾病的风险存在差异。
■比尔和梅琳达·盖茨基金会,Minderoo基金会,莎拉和拉克兰·默多克,皇家儿童医院基金会,新南威尔士州卫生服务联盟,PeterSowerby基金会,SA健康,保险顾问网基金会,NAB基金会,Calvert-Jones基金会,ModaraPines慈善基金会,UHG基金会私人有限公司,EpworthHealthcare,国家卫生和医学研究委员会,瑞士国家科学基金会和个人捐助者。
UNASSIGNED: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults.
UNASSIGNED: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206.
UNASSIGNED: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%-68.2%), compared with 63.4% in the control group (95% CI 61.8%-65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%-20.7%), compared with 18.8% in the control group (95% CI 17.4%-20.2%) a difference of +0.6 percentage points (95% CI -1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination.
UNASSIGNED: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease.
UNASSIGNED: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children\'s Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.