A systematic review 4 included 18 randomized controlled trials reporting pulmonary tuberculosis and 6 reporting miliary or meningeal tuberculosis. Protection against pulmonary tuberculosis appeared greatest in children stringently tuberculin tested, to try to exclude prior infection with Mycobacterium tuberculosis or sensitization to environmental mycobacteria (RR 0.26, 95% CI 0.18 to 0.37; 4 trials), or infants (RR 0.41, 95% CI 0.29 to 0.58; 5 trials). Protection was weaker in children not stringently tested (RR 0.59, 95% CI 0.35 to 1.01; 2 trials) and older individuals. Protection was higher in trials further from the equator where environmental mycobacteria are less and with lower risk of diagnostic detection bias. 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 0.01 to 0.77; 2 trials) and children stringently tuberculin tested (RR 0.08, 95% CI 0.03 to 0.25; 2 trials).
Another systematic review and meta-analysis 3 included 132 studies. Protection against pulmonary tuberculosis in adults was variable, ranging from substantial protection in the UK MRC trial (RR 0.22, 95% CI 0.16 to 0.31) to absence of clinically important benefit, and greater in latitudes further away from the equator. BCG vaccination efficacy was usually high, and varied little by form of disease (with higher protection against meningeal and miliary tuberculosis) or study design when BCG vaccination was given only to infants or to children after strict screening for tuberculin sensitivity. High levels of protection against death were observed from both trials and observational studies. Vaccination protects against pulmonary and extrapulmonary tuberculosis for up to 10 years. Most studies either did not follow up participants for long enough or had very few cases after 15 years. Five studies (one trial and 4 observational studies) provided evidence of measurable protection at least 15 years after vaccination. Efficacy declined with time.
A systematic review 1 including 26 studies with a total of subjects was abstracted in DARE. There were 14 prospective trials (n=360,000), 2 trials with alternative allocation, 4 trials with systematic allocation, and 12 case-control studies.
In the 13 prospective trials, the RR of tuberculosis was 0.49 (95% CI 0.34 to 0.70)(protective effect of 51%). In the 10 case-control studies, the OR for tuberculosis was 0.50 (95% CI 0.39 to 0.64), or a 50% protective effect. Seven trials reporting tuberculous death showed a protective effect of 71% (RR 0.29, 95% CI 0.16 to 0.53), and five studies on meningitis showed a protective effect of 64% (OR 0.36, 95% CI 0.18 to 0.70).
Another systematic review 2 including 5 RCTs and 11 case-control studies was abstracted in DARE. According to 4 RCTs, the relative risk for tuberculosis was 0.258 (95% CI 0.174 to 0.384). According to case-control studies the OR was 0.476. The OR for laboratory confirmed cases was 0.174 (95% CI 0.072 to 0.418) according to case-control studies. The relative risk of tuberculosis death was 0.352 (95% CI 0.140 to 0.882) according to 5 RCTs. The OR for tuberculous meningitis was 0.356 according to case-control studies. Most of the duration-specific evidence suggests that BCG efficacy may persist through 10 years after infant vaccination.
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