Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine.
Clin Infect Dis. 2014 Feb;58(4):470-80. doi: 10.1093/cid/cit790. Epub 2013 Dec 13.
Randomized trials assessing BCG vaccine protection against tuberculosis have widely varying results, for reasons that are not well understood.
We examined associations of trial setting and design with BCG efficacy against pulmonary and miliary or meningeal tuberculosis by conducting a systematic review, meta-analyses, and meta-regression.
We identified 18 trials reporting pulmonary tuberculosis and 6 reporting miliary or meningeal tuberculosis. Univariable meta-regression indicated efficacy against pulmonary tuberculosis varied according to 3 characteristics. Protection appeared greatest in children stringently tuberculin tested, to try to exclude prior infection with Mycobacterium tuberculosis or sensitization to environmental mycobacteria (rate ratio [RR], 0.26; 95% confidence interval [CI], .18-.37), or infants (RR, 0.41; 95% CI, .29-.58). Protection was weaker in children not stringently tested (RR, 0.59; 95% CI, .35-1.01) and older individuals stringently or not stringently tested (RR, 0.88; 95% CI, .59-1.31 and RR, 0.81; 95% CI, .55-1.22, respectively). Protection was higher in trials further from the equator where environmental mycobacteria are less and with lower risk of diagnostic detection bias. These associations were attenuated in a multivariable model, but each had an independent effect. There was no evidence that efficacy was associated with BCG strain. Protection against meningeal and miliary tuberculosis was also high in infants (RR, 0.1; 95% CI, .01-.77) and children stringently tuberculin tested (RR, 0.08; 95% CI, .03-.25).
Absence of prior M. tuberculosis infection or sensitization with environmental mycobacteria is associated with higher efficacy of BCG against pulmonary tuberculosis and possibly against miliary and meningeal tuberculosis. Evaluations of new tuberculosis vaccines should account for the possibility that prior infection may mask or block their effects.
评估卡介苗（BCG）疫苗预防结核病的随机试验结果差异很大，原因尚不清楚。
我们通过系统评价、荟萃分析和荟萃回归，研究了试验设置和设计与卡介苗预防肺型和粟粒型或脑膜型结核的疗效之间的关系。
我们确定了 18 项报告肺型结核的试验和 6 项报告粟粒型或脑膜型结核的试验。单变量荟萃回归表明，肺型结核的疗效因 3 个特征而异。在严格进行结核菌素检测以试图排除先前感染结核分枝杆菌或对环境分枝杆菌致敏的儿童（率比[RR]，0.26；95%置信区间[CI]，0.18-0.37）或婴儿（RR，0.41；95%CI，0.29-0.58）中，保护作用最大。在未严格检测的儿童（RR，0.59；95%CI，0.35-1.01）和严格或不严格检测的年龄较大的个体（RR，0.88；95%CI，0.59-1.31 和 RR，0.81；95%CI，0.55-1.22）中，保护作用较弱。在离赤道更远的地方，环境分枝杆菌较少，诊断检测偏倚的风险较低的试验中，保护作用更高。这些关联在多变量模型中减弱，但每个关联都有独立的影响。没有证据表明疗效与卡介苗菌株有关。婴儿（RR，0.1；95%CI，0.01-0.77）和严格进行结核菌素检测的儿童（RR，0.08；95%CI，0.03-0.25）中，脑膜和粟粒型结核的保护作用也很高。
无先前结核分枝杆菌感染或对环境分枝杆菌致敏与卡介苗预防肺型结核以及可能预防粟粒型和脑膜型结核的更高疗效相关。新结核病疫苗的评估应考虑到先前的感染可能会掩盖或阻断其效果的可能性。
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