Background <p>Bacillus Calmette-Guérin (BCG) vaccination is well established for preventing severe tuberculosis (TB) in children; however, its effectiveness in reducing the progression of latent TB infection (LTBI) to active disease remains uncertain, particularly in real-world contact settings.</p> Methods <p>We conducted a systematic review and meta-analysis by searching EMBASE, PubMed, Web of Science, and the Cochrane Library, with data collection completed on December 21, 2024. Eligible studies included individuals with confirmed TB exposure and a positive interferon-gamma release assay (IGRA) result. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method under a random-effects model, with between-study variance estimated using restricted maximum likelihood (REML) and Wald-type confidence intervals applied for uncertainty estimation. Heterogeneity was quantified using the <i>I</i><sup><i>2</i></sup>and τ<sup>2</sup> statistics.</p> Results <p>Twenty studies comprising 3,056 participants were included. Using a random-effects model, prior administration of the Bacillus Calmette‑Guérin (BCG) vaccine was associated with a lower risk of LTBI progressing to active TB (RR = 0.57, 95% CI: 0.40–0.82; <i>I</i><sup><i>2</i></sup> = 38%). This association was stronger in low-incidence settings (RR = 0.48, 95% CI: 0.31–0.74; <i>I</i><sup><i>2</i></sup> = 30%) and among children under 15 years (RR = 0.44, 95% CI: 0.33–0.58; <i>I</i><sup><i>2</i></sup> = 10%). No significant association was observed in high-incidence settings (RR = 0.71, 95% CI: 0.27–1.83; <i>I</i><sup><i>2</i></sup> = 87%) or among individuals over 15 years (RR = 0.90, 95% CI: 0.31–2.64; <i>I</i><sup><i>2</i></sup> = 0%).</p> Conclusions <p>BCG vaccination was associated with a significantly lower risk of LTBI progression to active TB, with the strength of this association varying by geographic region and age. These findings highlight the need to consider regional TB burden and age-specific factors when formulating vaccination policies.</p>

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Effect of BCG vaccination on the progression of latent tuberculosis infection to active disease in contacts: a systematic review and meta-analysis

  • Shunli Cai,
  • Tianwei Yan,
  • Yutian Yang,
  • Xin Guo,
  • Xiang Li,
  • Hongbo Chen,
  • Jian He,
  • Yuan Xia,
  • Yingchen Zhou,
  • Qingtao Tan,
  • Xinhua Cun,
  • Guozhong Zhou

摘要

Background

Bacillus Calmette-Guérin (BCG) vaccination is well established for preventing severe tuberculosis (TB) in children; however, its effectiveness in reducing the progression of latent TB infection (LTBI) to active disease remains uncertain, particularly in real-world contact settings.

Methods

We conducted a systematic review and meta-analysis by searching EMBASE, PubMed, Web of Science, and the Cochrane Library, with data collection completed on December 21, 2024. Eligible studies included individuals with confirmed TB exposure and a positive interferon-gamma release assay (IGRA) result. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method under a random-effects model, with between-study variance estimated using restricted maximum likelihood (REML) and Wald-type confidence intervals applied for uncertainty estimation. Heterogeneity was quantified using the I2and τ2 statistics.

Results

Twenty studies comprising 3,056 participants were included. Using a random-effects model, prior administration of the Bacillus Calmette‑Guérin (BCG) vaccine was associated with a lower risk of LTBI progressing to active TB (RR = 0.57, 95% CI: 0.40–0.82; I2 = 38%). This association was stronger in low-incidence settings (RR = 0.48, 95% CI: 0.31–0.74; I2 = 30%) and among children under 15 years (RR = 0.44, 95% CI: 0.33–0.58; I2 = 10%). No significant association was observed in high-incidence settings (RR = 0.71, 95% CI: 0.27–1.83; I2 = 87%) or among individuals over 15 years (RR = 0.90, 95% CI: 0.31–2.64; I2 = 0%).

Conclusions

BCG vaccination was associated with a significantly lower risk of LTBI progression to active TB, with the strength of this association varying by geographic region and age. These findings highlight the need to consider regional TB burden and age-specific factors when formulating vaccination policies.