Effect of BCG Vaccination on Tuberculosis and Its Severity in Children from a High-Burden Setting in Pakistan: A Hospital-Based Study

Abstract

Pakistan ranks among the countries with the highest tuberculosis (TB) burden globally. Although the Bacille Calmette-Guerin (BCG) vaccine is administered at birth, its real-world effectiveness against pulmonary TB and disease severity in older children in high-transmission settings remains uncertain. This study assessed the association of BCG vaccination with TB diagnosis, severity, site of disease, and microbiological confirmation among children evaluated for presumptive TB in Lahore, Pakistan.
Methods
We performed an analysis of routine hospital data from 550 children aged <15 years who presented with presumptive TB at Gulab Devi Teaching Hospital between December 2022 and March 2024. BCG vaccination status was determined by vaccination history and/or presence of a BCG scar. Children were classified as having TB (confirmed or unconfirmed) or no TB using a composite reference standard. Among TB cases, disease severity, site (pulmonary vs extrapulmonary), and microbiological confirmation were assessed. Crude and adjusted relative risks (aRR) with 95% confidence intervals (CI) were estimated using Poisson regression with robust variance estimation, adjusting a priori for age, sex, nutritional status, and history of TB contact.
Results
Overall, 297 (54%) children were BCG-vaccinated. TB was diagnosed in 322 (58.5%) children. BCG vaccination was not associated with TB diagnosis (aRR 0.89, 95% CI 0.77-1.02; p=0.10), severe TB (aRR 0.95, 95% CI 0.81-1.11; p=0.52), pulmonary versus extrapulmonary disease (aRR 0.78, 95% CI 0.48-1.26; p=0.31), or microbiological confirmation (aRR 0.94, 95% CI 0.79-1.15; p=0.62). Independent risk factors for TB diagnosis were age >=10 years (aRR 1.68, 95% CI 1.38-2.04; p<0.0001), female sex (aRR 1.25, 95% CI 1.07-1.47; p=0.005), and Severe Acute Malnutrition (SAM) (aRR 1.35, 95% CI 1.15-1.58; p<0.0001). SAM was most strongly associated with severe TB (aRR 2.28, 95% CI 1.82-2.85; p=0.001).
Conclusions
BCG vaccination showed no significant protective effect against TB occurrence, severity, or disease type in this high-burden cohort. Older age, female sex, and SAM emerged as key modifiable and non-modifiable risk factors. These findings underscore the urgent need for strengthened nutritional support, enhanced contact tracing, and next-generation vaccines to improve pediatric TB control in high-burden settings.