An estimated 25% of household tuberculosis case contacts in the Innate Factors and Early Clearance of Mycobacterium tuberculosis, or INFECT, study in Indonesia were considered early clearers, and researchers found that protection against M. tuberculosis was strongly associated with bacille Calmette-Guérin, or BCG, vaccination.
“The scientific community has focused on why only some infected individuals develop TB, rather than on why some people do not develop [M. tuberculosis (Mtb)] infection in the first place. An exposed but uninfected group is consistently observed in TB case contact studies and in TB outbreaks in closed environments,” Ayesha J. Verrall, MB ChB, MBHL, MSc, senior lecturer in the department of pathology and molecular medicine at the University of Otego in New Zealand, and colleagues wrote. “We term this group early clearers, to emphasize that these individuals likely eradicate Mtb infection before specific adaptive responses to Mtb develop.”
In the study, Indonesian household contact patients with smear-positive TB received an interferon-gamma release assay (IGRA) at baseline and 14 weeks later, Verrall and colleagues explained. According to the study, the researchers assessed contact characteristics, exposure and disease phenotype for association with a positive IGRA at each time point.
In total, 1,347 contacts of 462 TB cases were included, 57.9% of whom were IGRA-positive and 36.3% of whom were IGRA negative. According to the study, after 14 weeks, 26.1% of 445 initially negative contacts were IGRA converters and 71.2% remained persistently negative.
Verrall and colleagues found that BCG vaccination reduced the risk for a positive baseline IGRA (RR = 0.89; 95% CI, 0.83–0.97), and strongly reduced the risk of IGRA conversion (RR = 0.56; 95% CI, 0.40–0.77),
In summary, contacts who had received BCG vaccination were 45% less likely to experience IGRA conversion during the study, showing that the vaccine’s protection among people with known household TB exposure may be “stronger than previously thought,” Verrall and colleagues wrote. BCG protection decreased with increasing exposure and increasing age.
“To the best of our knowledge, INFECT is the first study designed specifically to explore early clearance of Mtb. A household contact study framework holds considerable promise as a study platform,” the authors concluded. “We have shown that BCG protection against development of Mtb infection from exposure to a known index case is substantial, whereas it decreases with increasing age and with increasing exposure. Further studies will hopefully provide insights for the development of new vaccines and other immune-based therapies that provide enhanced protection.” – by Caitlyn Stulpin
Disclosures: The authors report no relevant financial disclosures.