BCG Revaccination for the Prevention of Mycobacterium tuberculosis Infection

This double-blind, phase 2b, randomized, placebo-controlled trial evaluated the efficacy of BCG revaccination in 1836 HIV-negative adolescents (10–18 years old) in South Africa who initially tested negative for Mycobacterium tuberculosis using the QuantiFERON-TB (QFT) test. The primary endpoint was prevention of sustained QFT conversion (defined as three consecutive positive tests over six months). Over a median 30-month follow-up, sustained QFT conversion occurred in 7.1% of BCG recipients and 7.0% of placebo recipients (hazard ratio 1.04; 95% CI, 0.73–1.48; vaccine efficacy −3.8%). Despite an increase in cytokine-positive CD4 T-cell responses, no protective efficacy was demonstrated. Adverse events primarily local injection-site reactions were more frequent in the BCG group, but most were mild or moderate. The findings suggest BCG revaccination did not prevent sustained M. tuberculosis infection and is unlikely to support disease prevention policy in this population. 

This double-blind, phase 2b, randomized, placebo-controlled trial evaluated the efficacy of BCG revaccination in 1836 HIV-negative adolescents (10–18 years old) in South Africa who initially tested negative for Mycobacterium tuberculosis using the QuantiFERON-TB (QFT) test. The primary endpoint was prevention of sustained QFT conversion (defined as three consecutive positive tests over six months). Over a median 30-month follow-up, sustained QFT conversion occurred in 7.1% of BCG recipients and 7.0% of placebo recipients (hazard ratio 1.04; 95% CI, 0.73–1.48; vaccine efficacy −3.8%). Despite an increase in cytokine-positive CD4 T-cell responses, no protective efficacy was demonstrated. Adverse events primarily local injection-site reactions were more frequent in the BCG group, but most were mild or moderate. The findings suggest BCG revaccination did not prevent sustained M. tuberculosis infection and is unlikely to support disease prevention policy in this population.