Effect of BCG revaccination on incidence of tuberculosis in school-aged children in Brazil: the BCG-REVAC cluster-randomised trial

Abstract

Many countries offer a second BCG vaccination to prevent tuberculosis, although there is little evidence of whether this confers additional protection. BCG vaccination is routine in Brazil but BCG revaccination procedures vary by state. We studied revaccination efficacy in two Brazilian cities with tuberculosis prevalence representative of Brazil. We did a cluster-randomised trial of the protection against tuberculosis from BCG revaccination in school-aged children who had had one BCG vaccination as infants. 767 schools in the cities of Salvador and Manaus, Brazil, participated; schools were the unit of randomisation. The study was open label with no placebo. Cases of tuberculosis were identified through record linkage to the Tuberculosis Control Programme. Revaccination status was masked during linkage and validation of cases. The incidence of tuberculosis was the primary outcome. Analysis was by intention to treat. 386 schools (176,846 children) were assigned BCG revaccination and 365 (171,293 children) no revaccination. 42,053 children in the vaccine group and 47,006 in the control group were absent from school on the day of the visit and were excluded. 31,163 and 27,146, respectively were also excluded because they had no BCG scar, two or more scars, or a doubtful scar on assessment. The crude incidence of tuberculosis in the intervention group was 29.3 per 100,000 person years and in the control group 30.2 per 100,000 person-years (crude-rate ratio 0.97; 95% CI 0.76-1.28). The efficacy of BCG revaccination was 9% (-16 to 29%). Revaccination given to children aged 7-14 years in this setting does not provide substantial additional protection and should not be recommended. Follow-up is ongoing and needed to assess the effect of other factors on revaccination efficacy: time since vaccination, age at vaccination, and high or low prevalence of environmental mycobacteria.