Thøstesen Lisbeth Marianne, Nissen Thomas Nørrelykke, Kjærgaard Jesper, Pihl Gitte Thybo, Birk Nina Marie, Benn Christine Stabell, Greisen Gorm, Kofoed Poul-Erik, Pryds Ole, Ravn Henrik, Jeppesen Dorthe Lisbeth, Aaby Peter, Stensballe Lone Graff
Department of Paediatrics, Kolding Hospital, Skovvangen 2-8, DK-6000 Kolding, Denmark.
Department of Paediatrics 460, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark.
Contemp Clin Trials. 2015 May;42:213-8. doi: 10.1016/j.cct.2015.04.006. Epub 2015 Apr 18.
Studies from low-income countries report positive non-specific effects of early Bacillus Calmette-Guérin (BCG) immunisation on childhood health and survival. Neonatal immunisation with BCG may prime the immune system and offer partial protection against other infectious and possibly allergic diseases. The potential clinical value of these non-specific effects has not yet been examined in a large randomised trial in high-income countries.
The Danish Calmette Study is a multicentre randomised clinical trial conducted between October 2012 and November 2015. Within the first 7 days of life, infants were randomly assigned to intra-dermal vaccination with BCG or no intervention. At 3 and 13 months of age structured telephone interviews and clinical examinations of the children were conducted. In a subgroup of children blood samples were drawn and stool samples collected at age 4 days, 3 and 13 months. Thymus index was assessed by ultrasound in a subgroup at randomisation and at 3 months. The primary study outcome is hospitalisation within the first 15 months of life as assessed in Danish health registers. Secondary outcomes include infectious disease hospitalisations, wheezing, eczema, use of prescribed medication, growth, development, thymus index, T- and B-cell subpopulations assessed by flow cytometry, in vitro cytokine responses and specific antibody responses to other vaccines. Adverse reactions were registered.
With participation of 4184 families and more than 93% adherence to clinical follow-up at 3 and 13 months, this randomised clinical trial has the potential to create evidence regarding non-specific effects of BCG vaccination in a high-income setting.
来自低收入国家的研究报告称，早期卡介苗（BCG）免疫接种对儿童健康和生存具有积极的非特异性影响。新生儿接种卡介苗可能会启动免疫系统，并对其他传染病以及可能的过敏性疾病提供部分保护。这些非特异性影响的潜在临床价值尚未在高收入国家的大型随机试验中得到检验。
丹麦卡介苗研究是一项多中心随机临床试验，于2012年10月至2015年11月进行。在出生后的前7天内，婴儿被随机分配接受卡介苗皮内接种或不进行干预。在儿童3个月和13个月大时，进行了结构化电话访谈和临床检查。在一个儿童亚组中，于出生4天、3个月和13个月时采集了血样和粪便样本。在随机分组时和3个月时，通过超声对一个亚组的胸腺指数进行了评估。主要研究结局是根据丹麦健康登记册评估的出生后前15个月内的住院情况。次要结局包括传染病住院、喘息、湿疹、处方药使用、生长、发育、胸腺指数、通过流式细胞术评估的T细胞和B细胞亚群、体外细胞因子反应以及对其他疫苗的特异性抗体反应。记录了不良反应。
这项随机临床试验有4184个家庭参与，在3个月和13个月时临床随访的依从率超过93%，有可能为高收入环境下卡介苗接种的非特异性影响提供证据。
