Evidence of an effect of BCG revaccination on incidence of tuberculosis in school-aged children in Brazil: Second report of the BCG-REVAC cluster-randomised trial

Abstract

BCG revaccination is still used in some tuberculosis endemic countries. Until now, the little evidence available suggested that BCG revaccination confers very limited additional protection, although there was no information on whether protection depends on the setting and age of revaccination, or if protection increases with time since vaccination. Here we report on an extended follow up of the BCG-REVAC trial, a cluster randomised trial conducted in the Brazilian cities Salvador and Manaus including over 200,000 children aged 7-14 years aimed to evaluate the efficacy of BCG revaccination in children who had received neonatal BCG vaccination. With the extended follow-up (9 years) and the additional cases accrued we now have enough power to report vaccine efficacy separately for the two cities (with different distances from Equator and presumably different prevalence of non-tuberculosis mycobacteria), and by age at vaccination and clinical form. The overall vaccine efficacy was 12% (-2 to 24%) as compared to 9% (-16 to 29%) for the 5-year follow up. Vaccine efficacy was higher in Salvador (19%, 3 to 33%) than in Manaus (1%, -27 to 27%) with the highest vaccine efficacy in children from Salvador aged <11 years at revaccination (33%, 3 to 54%). The findings are in line with the hypothesis that BCG vaccination offers higher efficacy in low NTMb prevalence, and show that revaccination with BCG can offer weak protection in selected subgroups.

Buruli ulcer

“…However, a protein vaccine is much less efficient BCG-REVAC cluster-randomized trial in Brazil has confirmed that revaccination with BCG does not increase its protective efficacy against TB, particularly not in regions with high incidence of nontuberculous mycobacteria. 46 In experimental animal models, decreased survival of guinea pigs infected with Mycobacterium tuberculosis was reported after multiple BCG vaccinations. 47 Finally, in an experimental mouse model, a booster vaccination with BCG did not improve the protective efficacy against BU.…”

Current status of new tuberculosis vaccine in children

“…With the extended 4 y of follow-up and the additional cases accrued, the previous study in Brazil revealed that the overall vaccine efficacy was 12% as compared with9% for the 5-year follow up, 97 indicating that the revaccination with BCG provided the additional protective efficacy against TB, and this efficacy varied with distance from equator, ranging from 1% of Manaus (with short distance from equator) to 19% of Salvador (with long distance from equator). 97 This difference further strengthened the earlier hypothesis that BCG vaccination offers higher efficacy in low NTM prevalence. Taken together, revaccination with BCG may have some available protective effectiveness in some certain settings.…”

Recommendations for pediatric tuberculosis vaccination in Italy

“…19 Barreto et al reported a duration of protection of 15-20 y in subjects vaccinated at birth (efficacy after 15-20 y 39%, 95% CI 9-58%), 25 and Weir et al a duration of immunological memory of at least 14 y in subjects vaccinated at birth or during adolescence. 31 The five BCG revaccination studies identified were 3 randomized clinical trials, [32][33][34] one cohort study, 35 and one casecontrol study, 36 none of which was carried out in Europe or North America. All of them showed that a second vaccination at the age of 19 months or during school age had no additional effect in comparison with a single administration, 32,33,35,36 although a follow-up study carried out 9 y after a clinical trial in Brazil has recently documented that, at higher latitudes, there may be some advantage in revaccinating children aged <11 y.…”

“…All of them showed that a second vaccination at the age of 19 months or during school age had no additional effect in comparison with a single administration, 32,33,35,36 although a follow-up study carried out 9 y after a clinical trial in Brazil has recently documented that, at higher latitudes, there may be some advantage in revaccinating children aged <11 y. 34 …”