THE EFFICACY OF BACILLUS-CALMETTE-GUERIN VACCINATION OF NEWBORNS AND INFANTS IN THE PREVENTION OF TUBERCULOSIS - METAANALYSES OF THE PUBLISHED LITERATURE

Objective. To quantify the efficacy of vaccination of infants with bac illus Calmette-Guerin (BCG) against tuberculosis. Data sources. MEDLIN E with index terms BCG vaccine, tuberculosis, and human; lists of all known studies provided by experts at the Centers for Disease Control a nd Prevention, the World Health Organization, and other organizations. Study selection. A total of 1264 articles and abstracts were reviewed for details on BCG vaccination, the availability of concurrent vaccin ated and unvaccinated groups, and a tuberculosis outcome. Seventy arti cles were reviewed in depth for method of vaccine allocation used to c reate comparable groups, age at vaccination of study participants, com parability of surveillance and follow-up of recipient and concurrent c ontrol groups in trials, an appropriately defined control group in cas e-control studies, and outcome measures (tuberculosis cases and/or dea ths). Five prospective trials and eleven case-control studies of vacci nation during infancy were included in the present analyses. Data extr action. We recorded study design, age range of study population, numbe r of patients enrolled, efficacy of vaccine, location of the study, an d a series of items to assess the potential for bias in study design, follow-up, and diagnosis. We extracted or computed vaccine efficacy by years since vaccination wherever possible. At least two readers indep endently extracted data and evaluated data validity. Data synthesis. T he relative risk (RR) or odds ratio (OR) for tuberculosis in vaccinate d versus unvaccinated infants was the measure of vaccine efficacy anal yzed. A random-effects method estimated a weighted average RR or OR fr om data extracted from the trials and case-control studies. The protec tive effect was then computed by 1-RR or 1-OR, Overall, the protective effect of vaccination against cases of tuberculosis was 0.74 (95% con fidence interval [95% CI], 0.62 to 0.83) when estimated from four rand omized controlled trials, and 0.52 (95% CI, 0.38 to 0.64) when estimat ed from nine case-control studies. Five trials reporting deaths from t uberculosis showed a BCG protective effect of 0.65 (95% CI, 0.12 to 0. 86), five studies reporting on meningitis showed a protective effect o f 0.64 (95% CI, 0.30 to 0.82), and three studies of disseminated tuber culosis showed a protective effect of 0.78 (95% CI, 0.58 to 0.88). Thr ee case-control studies included separate results for laboratory-confi rmed cases of tuberculosis. These studies documented a protective effe ct of 0.83 (95% CI, 0.58 to 0.93). In a random-effects regression mode l of the nine case-control studies, study validity score explained 15% of the heterogeneity among study-estimated protective effects, sugges ting that better studies reported greater efficacy. Three trials and s ix case-control studies provided some age-specific information that al lowed us to examine the duration of BCG efficacy. Most of this evidenc e suggested that BCG efficacy may persist through 10 years after infan t vaccination. Conclusion. BCG vaccination of newborns and infants sig nificantly reduces the risk of tuberculosis-by over 50%, on average. P rotection has been observed across many populations, study designs, an d forms of tuberculosis. Rates of protection against cases that are co nfirmed by laboratory tests, reflecting reduced error in disease class ification and consequently more accurate estimates of BCG efficacy, ar e highest at 83%.