Pediatric Tuberculosis: Unraveling Immunity, Clinical Complexities, and Resource-Driven Disparities in the Pursuit of Prevention

Pediatric tuberculosis (TB) remains a critically underrecognized contributor to global childhood morbidity and mortality, with the highest burden concentrated in low-resource settings. Although children comprise a minority of overall TB cases, mortality is disproportionately high, particularly among those under five years of age, driven largely by delayed diagnosis, inadequate linkage to care, and limited access to effective treatment. The continued rise of pediatric multidrug-resistant TB (MDR-TB), especially in regions with low sociodemographic development, further highlights persistent gaps in current control strategies. This review synthesizes key aspects of pediatric TB pathogenesis and host immune responses that predispose young children to rapid disease progression and severe outcomes, including immune immaturity and paucibacillary infection. We summarize pulmonary and extrapulmonary disease manifestations and identify populations at heightened risk, including children with HIV, malnutrition, type 1 diabetes mellitus, and congenital or treatment-related immunosuppression. Ongoing challenges in diagnosis and treatment are discussed, including limitations of existing microbiologic and immunologic tests, specimen collection constraints, regimen toxicity, and barriers to adherence. Prevention remains central to reducing pediatric TB mortality. We highlight the sustained importance of bacille Calmette-Guérin (BCG) vaccination in preventing severe disease and death, the context-dependent variability in vaccine effectiveness, and the structural and socioeconomic determinants of vaccine coverage. We conclude that integrating equitable vaccine delivery, scalable preventive therapy, and child-adapted diagnostic strategies is essential to meaningfully reduce the global pediatric TB burden.