Pittet Laure F, Messina Nicole L, McDonald Ellie, Orsini Francesca, Barry Simone, Bonten Marc, Campbell John, Croda Julio, Croda Mariana G, Dalcolmo Margareth, Gardiner Kaya, Gwee Amanda, Jardim Bruno, Lacerda Marcus V G, Lucas Michaela, Lynn David J, Manning Laurens, Perrett Kirsten P, Post Jeffrey J, Prat-Aymerich Cristina, Richmond Peter C, Rocha Jorge L, Rodriguez-Baño Jesus, Warris Adilia, Wood Nicholas J, Davidson Andrew, Curtis Nigel
Infectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Department of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
EClinicalMedicine. 2024 May 13;72:102616. doi: 10.1016/j.eclinm.2024.102616. eCollection 2024 Jun.
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.
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.
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.
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.
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.
卡介苗（BCG）接种具有非靶向（非特异性）效应，与预防婴儿的无关感染及降低全因死亡率相关。我们旨在确定BCG接种能否预防成人的发热性和呼吸道感染。
这项随机对照3期试验在澳大利亚、巴西、荷兰、西班牙和英国的36个医疗中心进行。医护人员通过基于网络的程序按1:1比例随机接受丹麦卡介苗（单次0.1毫升皮内注射）或不接种卡介苗，并按阶段、地点、年龄和合并症情况进行分层。使用意向性分析（ITT）人群在12个月内测量发热或呼吸道疾病发生情况的差异（预设次要结局）。本试验已在ClinicalTrials.gov注册，注册号为NCT04327206。
在2020年3月30日至2021年4月1日期间，6828名医护人员被随机分为丹麦卡介苗组（n = 3417）或对照组（n = 3411；无干预或安慰剂）。卡介苗组12个月内≥1次发热或呼吸道疾病的调整后估计风险为66.8%（95%CI 65.3%-68.2%），而对照组为63.4%（95%CI 61.8%-65.0%），差异为+3.4个百分点（95%CI +1.3%至+5.5%；p = 0.002）。严重发作（定义为连续≥3天无行为能力或住院）的调整后估计风险在卡介苗组为19.4%（95%CI 18.0%-20.7%），对照组为18.8%（95%CI 17.4%-20.2%），差异为+0.6个百分点（95%CI -1.3%至+2.5%；p = 0.6）。两组的疾病发作、肺炎和住院次数相似。有3例死亡，均在对照组。接种卡介苗后无安全问题。
与婴儿期新生儿卡介苗接种后报告的有益非靶向效应相反，在成人接种卡介苗后的12个月内，观察到有症状的发热或呼吸道疾病风险略有增加。没有证据表明严重疾病风险存在差异。
比尔及梅琳达·盖茨基金会、明德罗基金会、莎拉和拉克伦·默多克、皇家儿童医院基金会、新南威尔士州卫生服务联盟、彼得·索尔比基金会、南澳大利亚州卫生部、保险顾问网基金会、国民银行基金会、卡尔弗特-琼斯基金会、莫达拉派恩斯慈善基金会、UHG基金会私人有限公司、伊普沃思医疗保健公司、澳大利亚国家卫生与医学研究委员会、瑞士国家科学基金会及个人捐赠者。
