Objective. —To quantify the efficacy of BCG vaccine against tuberculosis (TB). Data Sources. —MEDLINE with index termsBCG vaccine, tuberculosis, andhuman. Experts from the Centers for Disease Control and Prevention and the World Health Organization, among others, provided lists of all known studies. Study Selection. —A total of 1264 articles or abstracts were reviewed for details on BCG vaccination, concurrent vaccinated and unvaccinated groups, and TB outcome; 70 articles were reviewed in depth for method of vaccine allocation used to create comparable groups, equal surveillance and follow-up for recipient and concurrent control groups, and outcome measures of TB cases and/or deaths. Fourteen prospective trials and 12 case-control studies were included in the analysis. Data Extraction. —We recorded study design, age range of study population, number of patients enrolled, efficacy of vaccine, and items to assess the potential for bias in study design and diagnosis. At least two readers independently extracted data and evaluated validity. Data Synthesis. —The relative risk (RR) or odds ratio (OR) of TB provided the measure of vaccine efficacy that we analyzed. The protective effect was then computed by 1 —RR or 1 —OR. A random-effects model estimated a weighted average RR or OR from those provided by the trials or case-control studies. In the trials, the RR of TB was 0.49 (95% confidence interval [Cl], 0.34 to 0.70) for vaccine recipients compared with nonrecipients (protective effect of 51%). In the case-control studies, the OR for TB was 0.50 (95% CI, 0.39 to 0.64), or a 50% protective effect. Seven trials reporting tuberculous deaths showed a protective effect from BCG vaccine of 71% (RR, 0.29; 95% Cl, 0.16 to 0.53), and five studies reporting on meningitis showed a protective effect from BCG vaccine of 64% (OR, 0.36; 95% Cl, 0.18 to 0.70). Geographic latitude of the study site and study validity score explained 66% of the heterogeneity among trials in a random-effects regression model. Conclusion. —On average, BCG vaccine significantly reduces the risk of TB by 50%. Protection is observed across many populations, study designs, and forms of TB. Age at vaccination did not enhance predictiveness of BCG efficacy. Protection against tuberculous death, meningitis, and disseminated disease is higher than for total TB cases, although this result may reflect reduced error in disease classification rather than greater BCG efficacy. (JAMA. 1994;271:698-702)

https://jamanetwork.com/journals/jama/articlepdf/366365/jama_271_9_038.pdf

Efficacy of BCG Vaccine in the Prevention of Tuberculosis: Meta-analysis of the Published Literature

Variation in protection by BCG: implications of and for heterologous immunity

OBJECTIVE\nTo quantify the efficacy of BCG vaccine against tuberculosis (TB).\n\n\nDATA SOURCES\nMEDLINE with index terms BCG vaccine, tuberculosis, and human. Experts from the Centers for Disease Control and Prevention and the World Health Organization, among others, provided lists of all known studies.\n\n\nSTUDY SELECTION\nA total of 1264 articles or abstracts were reviewed for details on BCG vaccination, concurrent vaccinated and unvaccinated groups, and TB outcome; 70 articles were reviewed in depth for method of vaccine allocation used to create comparable groups, equal surveillance and follow-up for recipient and concurrent control groups, and outcome measures of TB cases and/or deaths. Fourteen prospective trials and 12 case-control studies were included in the analysis.\n\n\nDATA EXTRACTION\nWe recorded study design, age range of study population, number of patients enrolled, efficacy of vaccine, and items to assess the potential for bias in study design and diagnosis. At least two readers independently extracted data and evaluated validity.\n\n\nDATA SYNTHESIS\nThe relative risk (RR) or odds ratio (OR) of TB provided the measure of vaccine efficacy that we analyzed. The protective effect was then computed by 1-RR or 1-OR. A random-effects model estimated a weighted average RR or OR from those provided by the trials or case-control studies. In the trials, the RR of TB was 0.49 (95% confidence interval [CI], 0.34 to 0.70) for vaccine recipients compared with nonrecipients (protective effect of 51%). In the case-control studies, the OR for TB was 0.50 (95% CI, 0.39 to 0.64), or a 50% protective effect. Seven trials reporting tuberculous deaths showed a protective effect from BCG vaccine of 71% (RR, 0.29; 95% CI, 0.16 to 0.53), and five studies reporting on meningitis showed a protective effect from BCG vaccine of 64% (OR, 0.36; 95% CI, 0.18 to 0.70). Geographic latitude of the study site and study validity score explained 66% of the heterogeneity among trials in a random-effects regression model.\n\n\nCONCLUSION\nOn average, BCG vaccine significantly reduces the risk of TB by 50%. Protection is observed across many populations, study designs, and forms of TB. Age at vaccination did not enhance predictiveness of BCG efficacy. Protection against tuberculous death, meningitis, and disseminated disease is higher than for total TB cases, although this result may reflect reduced error in disease classification rather than greater BCG efficacy.

The efficacy of bcg vaccine in the prevention of tuberculosis: meta-analysis of the published literature

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(06)68507-3.pdf

Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness

Over the past 50 years, the Mycobacterium bovis bacille Calmette-Guerin (BCG) vaccine against tuberculosis (TB) has maintained its position as the world's most widely used vaccine, despite showing highly variable efficacy (0-80%) in different trials. The efficacy of BCG in adults is particularly poor in tropical and subtropical regions. Studies in animal models of TB, supported by data from clinical BCG trials in humans, indicate that this failure is related to pre-existing immune responses to antigens that are common to environmental mycobacteria and Mycobacterium tuberculosis. Here, we discuss the potential mechanisms behind the variation of BCG efficacy and their implications for an improved TB vaccination strategy.

The success and failure of BCG - implications for a novel tuberculosis vaccine.

A retrospective case-control study was conducted in Argentina to determine the protection conferred by BCG vaccination against tuberculosis in children under six years of age, in an area where coverage is about 55%. A total of 175 tuberculosis patients were included. Five controls selected from patients treated at the same hospital as those under study for reasons other than tuberculosis were matched to each case on the basis of age, socioeconomic origin, nutritional status and place of residence. Information on BCG vaccination status was collected by an independent examiner. Tuberculosis localizations were as follows: 152 pulmonary, pleural and/or miliary; 18 meningitis; 2 lymphadenitis; 2 osteoarticular; and 1 otic. The diagnosis was based on bacteriological and histopathological tests, computerized tomography, radiology, clinical examination, endoscopy, and proved source of infection. The protective effect of BCG among those who were vaccinated was 73.0% with 95% confidence limits of 82% and 62%. According to these results BCG vaccination given early in life is very effective in preventing tuberculosis.

Irene Cutillo

Papers

Evaluation of the effectiveness of BCG vaccination using the case-control method in Buenos Aires, Argentina.