Does the efficacy of BCG decline with time since vaccination?

OBJECTIVE To investigate whether the protective efficacy of bacille Calmette-Guérin (BCG) against tuberculosis decreases with time since vaccination. DESIGN A quantitative review of all 10 randomized trials of BCG against tuberculosis in purified protein derivative (PPD)-negative individuals, that presented data for discrete periods. For each trial, we derived log rate ratios for the annual change in the efficacy of BCG. We also compared efficacy in the first two years, and the first 10 years, to that in the rest of the trial. RESULTS There was considerable heterogeneity between trials in the annual change in the efficacy of BCG. In seven efficacy decreased overtime, while in three it increased. Average annual change in efficacy was not related to overall efficacy. Efficacy also varied between trials in the first two years after vaccination, at more than two years after vaccination and in the first ten years after vaccination. However the variation in efficacy between trials more than 10 years after vaccination was not statistically significant (P = 0.26). We therefore calculated that the average efficacy more than 10 years after vaccination was 14% (95% confidence interval -9% to 32%). CONCLUSION BCG protection can wane with time since vaccination. There is no good evidence that BCG provides protection more than 10 years after vaccination.