School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
Thorax. 2021 Nov;76(11):1131-1141. doi: 10.1136/thoraxjnl-2020-216794. Epub 2021 Apr 23.
The heterogeneity in efficacy observed in studies of BCG vaccination is not fully explained by currently accepted hypotheses, such as latitudinal gradient in non-tuberculous mycobacteria exposure.
We updated previous systematic reviews of the effectiveness of BCG vaccination to 31 December 2020. We employed an identical search strategy and inclusion/exclusion criteria to these earlier reviews, but reclassified several studies, developed an alternative classification system and considered study demography, diagnostic approach and tuberculosis (TB)-related epidemiological context.
Of 21 included trials, those recruiting neonates and children aged under 5 were consistent in demonstrating considerable protection against TB for several years. Trials in high-burden settings with shorter follow-up also showed considerable protection, as did most trials in settings of declining burden with longer follow-up. However, the few trials performed in high-burden settings with longer follow-up showed no protection, sometimes with higher case rates in the vaccinated than the controls in the later follow-up period.
The most plausible explanatory hypothesis for these results is that BCG protects against TB that results from exposure shortly after vaccination. However, we found no evidence of protection when exposure occurs later from vaccination, which would be of greater importance in trials in high-burden settings with longer follow-up. In settings of declining burden, most exposure occurs shortly following vaccination and the sustained protection observed for many years thereafter represents continued protection against this early exposure. By contrast, in settings of continued intense transmission, initial protection subsequently declines with repeated exposure to or other pathogens.
卡介苗接种研究中观察到的疗效异质性不能用目前公认的假设（如非结核分枝杆菌暴露的纬度梯度）完全解释。
我们更新了之前对卡介苗接种效果的系统评价，更新至 2020 年 12 月 31 日。我们采用了与之前的综述相同的搜索策略和纳入/排除标准，但对几项研究进行了重新分类，制定了替代分类系统，并考虑了研究人群、诊断方法和与结核病（TB）相关的流行病学背景。
在 21 项纳入的试验中，招募新生儿和 5 岁以下儿童的试验一致表明，在几年内对结核病有相当大的保护作用。在高负担环境中进行的随访时间较短的试验也显示出相当大的保护作用，在负担下降的环境中进行的大多数试验也是如此，随访时间较长。然而，在高负担环境中进行的随访时间较长的少数试验没有显示出保护作用，有时在后期随访中，接种组的病例数高于对照组。
这些结果最合理的解释性假设是卡介苗可以预防接种后不久发生的结核病。然而，我们没有发现当暴露发生在接种后时卡介苗具有保护作用的证据，这在高负担环境中进行的随访时间较长的试验中更为重要。在负担下降的环境中，大多数暴露发生在接种后不久，此后多年观察到的持续保护代表了对这种早期暴露的持续保护。相比之下，在持续高强度传播的环境中，最初的保护随后会随着重复接触 或其他病原体而下降。
