Multidimensional determinants of BCG-induced false-positivity in tuberculin skin testing: a global meta-analysis of 242 studies
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Background The tuberculin skin test (TST), widely used for latent tuberculosis infection (LTBI) screening, shows reduced specificity in Bacillus Calmette–Guérin (BCG)-vaccinated individuals due to antigenic cross-reactivity. We aimed to quantify the impact of BCG vaccination on false-positive TST results and to identify key modifying factors. Methods We systematically searched Embase, PubMed, Web of Science and the Cochrane Library up to 24 February 2025. A dual-comparison design was applied: head-to-head comparisons of interferon-γ release assay (IGRA)TST in BCG-vaccinated populations and between-group comparisons of TST positivity in vaccinatedunvaccinated groups. Random-effects models were used to calculate risk differences (RDs) for false-positive results. Results A total of 242 studies were included, with 166 head-to-head (50 341 participants) and 176 between-group comparisons (456 429 participants). Both approaches yielded consistent estimates, including a head-to-head RD of 13% (95% CI 9–16%) and a between-group RD of 12% (95% CI 9–14%). False positivity decreased with increasing tuberculosis incidence and latitude. Immunosuppressed individuals showed lower RDs than general populations. BCG strain, age at vaccination and number of doses significantly influenced false positivity. Conclusions We identified key modifiers of BCG-related TST false positivity. TST remains appropriate in high-incidence settings and for BCG specific strains, whereas IGRA may be preferred in lo
Abstract
Background The tuberculin skin test (TST), widely used for latent tuberculosis infection (LTBI) screening, shows reduced specificity in Bacillus Calmette–Guérin (BCG)-vaccinated individuals due to antigenic cross-reactivity. We aimed to quantify the impact of BCG vaccination on false-positive TST results and to identify key modifying factors. Methods We systematically searched Embase, PubMed, Web of Science and the Cochrane Library up to 24 February 2025. A dual-comparison design was applied: head-to-head comparisons of interferon-γ release assay (IGRA)TST in BCG-vaccinated populations and between-group comparisons of TST positivity in vaccinatedunvaccinated groups. Random-effects models were used to calculate risk differences (RDs) for false-positive results. Results A total of 242 studies were included, with 166 head-to-head (50 341 participants) and 176 between-group comparisons (456 429 participants). Both approaches yielded consistent estimates, including a head-to-head RD of 13% (95% CI 9–16%) and a between-group RD of 12% (95% CI 9–14%). False positivity decreased with increasing tuberculosis incidence and latitude. Immunosuppressed individuals showed lower RDs than general populations. BCG strain, age at vaccination and number of doses significantly influenced false positivity. Conclusions We identified key modifiers of BCG-related TST false positivity. TST remains appropriate in high-incidence settings and for BCG specific strains, whereas IGRA may be preferred in low-incidence areas, in individuals vaccinated multiple times or in immunosuppressed individuals. Shareable abstract BCG vaccination can cause false-positive TST results, but the effect is not uniform. This global analysis shows that TST is less affected in high TB incidence settings, while false positivity is more pronounced in low-incidence settings. https://bit.ly/4aCB9g5 short abstract-1