EFFICACY OF BCG VACCINE IN THE PREVENTION OF TUBERCULOSIS - METAANALYSIS OF THE PUBLISHED LITERATURE

Objective.-To quantify the efficacy of BCG vaccine against tuberculosi s (TB). Data Sources.-MEDLINE with index terms BCG vaccine, tuberculos is, and human. Experts from the Centers for Disease Control and Preven tion and the World Health Organization, among others, provided lists o f all known studies. Study Selection.-A total of 1264 articles or abst racts were reviewed for details on BCG vaccination, concurrent vaccina ted and unvaccinated groups, and SB outcome; 70 articles were reviewed in depth for method of vaccine allocation used to create comparable g roups, equal surveillance and follow-up for recipient and concurrent c ontrol groups, and outcome measures of TB cases and/or deaths. Fourtee n prospective trials and 12 case-control studies were included in the analysis. Data Extraction.-We recorded study design, age range of stud y population, number of patients enrolled, efficacy of vaccine, and it ems 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 prov ided the measure of vaccine efficacy that we analyzed. The protective effect was then computed by 1-RR or 1-OR. A random-effects model estim ated 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% confid ence 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 e ffect. Seven trials reporting tuberculous deaths showed a protective e ffect from BCG vaccine of 71% (RR, 0.29; 95% CI, 0.16 to 0.53), and fi ve 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 hetero geneity 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 for ms of TB. Age at vaccination did not enhance predictiveness of BCG eff icacy. Protection against tuberculous death, meningitis, and dissemina ted disease is higher than for total TB cases, although this result ma y reflect reduced error in disease classification rather than greater BCG efficacy.