AVALIAÇÃO DO EFEITO DA VACINAÇÃO COM BCG, NA PREVENÇÃO DA INFECÇÃO POR MYCOBACTERIUM TUBERCULOSIS, EM PROFISSIONAIS DE SAÚDE ADULTOS NO BRASIL

Abstract

The Bacillus Calmette-Guérin (BCG) vaccine is currently the only licensed vaccine for tuberculosis (TB), providing proven protection against severe forms of the disease in childhood. In addition, BCG is able to induce immunological memory in innate immunity, known as trained immunity, which may contribute not only to reducing the risk of illness from Mycobacterium tuberculosis but also to preventing infection itself. However, its effectiveness in adults remains uncertain and shows considerable variability among different populations. Healthcare workers are at higher risk of Mtb infection due to contact with patients, making them more exposed to the disease. Thus, the aim of this study was to evaluate the effectiveness of the protective response of BCG vaccination against Mycobacterium tuberculosis infection in adult healthcare workers in three Brazilian cities. This study is derived from a randomized controlled clinical trial, the BRACE study (NCT04327206). The study included healthcare professionals over 18 years of age from three locations in Brazil: Manaus/AM, Campo Grande/MS, and Rio de Janeiro/RJ, regardless of prior BCG vaccination. Eligible participants were randomized in a 1:1 ratio to receive the BCG vaccine or a placebo. The QuantiFERON-TB Gold Plus (QFT) test was used to assess TB infection before the intervention and at the 12th month post-vaccination. The primary outcome was QFT conversion (≥0.35 IU/mL) up to 12 months after BCG or placebo vaccination, among participants who were QFT negative at baseline. The secondary outcome was sustained conversion (two consecutive positive results), with a minimum interval of 6 months, among individuals with negative QFT at enrollment. Additional exploratory analyses included the use of alternative thresholds for QFT conversion (≥0.7; ≥2.0; and ≥4.0 IU/mL) and conversion up to 12 months in individuals with a baseline QFT value ≤0.2 IU/mL. Between October 2020 and April 2021, a total of 1,985 participants were enrolled in the study, 996 individuals (50.2%) in the BCG group and 989 (49.8%) in the placebo group. Of the participants, 1,475 (74.3%) were women, with a median age of 39 years (interquartile range: 32-47). During the first year, 34 (3.4%) of 996 participants in the BCG group had initial QFT conversion, compared to 32 (3.2%) of 989 in the placebo group (risk ratio [RR]: 1.09; p=0.791). Among those who converted QFT in the 12-month period, 49 underwent a subsequent test. In the BCG group, 15 (1.5%) showed sustained conversion, compared to 19 (1.9%) of the 989 in the placebo group (RR: 0.80; p=0.510). Using a threshold of 0.7 IU/mL or higher, conversions occurred in 15 (1.5%) BCG and 13 (1.3%) placebo participants (RR: 1.15; p=0.713). With a threshold of 2.0 IU/mL or higher, there were 6 (0.6%) BCG conversions and 5 (0.5%) placebo conversions (RR: 1.18; p=0.788). Among those with a baseline QFT of 0.2 IU/mL, conversion to 0.35 IU/mL occurred in 22 (2.3%) BCG group participants and 23 (2.4%) in the placebo group (RR: 0.96; p=0.903). BCG vaccination did not reduce the risk of initial and sustained QFT conversion among healthcare workers, even with the application of alternative thresholds, which showed no significant differences. These results reinforce the lack of evidence regarding the efficacy of BCG revaccination in adults for the prevention of TB, and therefore do not justify its use for this purpose.