BCG Revaccination Does Not Protect Against Leprosy in the Brazilian Amazon: A Cluster Randomised Trial

Background: Although BCG has been found to impart protection against leprosy in many populations, the utility of repeat or booster BCG vaccinations is still unclear. When a policy of giving a second BCG dose to school children in Brazil was introduced, a trial was conducted to assess its impact against tuberculosis, and a leprosy component was then undertaken in parallel. Objective: to estimate the protection against leprosy imparted by a second dose of BCG given to schoolchildren. Methods and Findings: This is a cluster randomised community trial, with 6 years and 8 months of follow-up. Study site: City of Manaus, Amazon region, a leprosy-endemic area in Brazil. Participants: 99,770 school children with neonatal BCG (aged 7-14 years at baseline), of whom 42,662 were in the intervention arm (revaccination). Intervention: BCG given by intradermal injection. Main outcome: Leprosy (all clinical forms). Results: The incidence rate ratio of leprosy in the intervention over the control arm within the follow-up, in schoolchildren with neonatal BCG, controlled for potential confounders and adjusted for clustering, was 0.99 (95% confidence interval: 0.68 to 1.45). Conclusions/Significance: There was no evidence of protection conferred by the second dose of BCG vaccination in school children against leprosy during the trial follow-up. These results point to a need to consider the effectiveness of the current policy of BCG vaccination of contacts of leprosy cases in Brazilian Amazon region.