Tuberculosis Skin Test for the Diagnosis of Pediatric Tuberculosis: Comparison with Tuberculin Skin Test and Interferon-Gamma Release Assays

Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide, with children representing a particularly vulnerable population in whom diagnosis is often challenging. Pediatric TB is typically paucibacillary and presents with non-specific clinical manifestations, limiting the sensitivity of microbiological confirmation and increasing reliance on immunological tests. The Tuberculin Skin Test (TST) and Interferon-Gamma Release Assays (IGRAs) are the most widely used tools for detecting Mycobacterium tuberculosis infection, yet both have important limitations, especially in young children and in Bacillus Calmette–Guérin (BCG)-vaccinated populations. TST lacks specificity due to cross-reactivity with BCG and environmental mycobacteria, while IGRAs, although more specific, require laboratory infrastructure and may have reduced sensitivity in early childhood. The Tuberculosis Skin Test (TBST), based on M. tuberculosis-specific antigens such as ESAT-6 and CFP-10, has emerged as a promising alternative that combines the operational simplicity of TST with the antigenic specificity of IGRA. This paper reviews the immunological principles, diagnostic performance, and practical considerations of TBST in pediatric populations, with direct comparison to TST and IGRA. Evidence from recent studies suggests that TBST may offer improved specificity over TST, with broadly comparable diagnostic accuracy to IGRA in some settings, although findings are not fully consistent across studies. Particular attention is given to its performance in BCG-vaccinated children and, based on emerging evidence, in those under five years of age. The potential role of TBST in clinical algorithms and public health strategies is discussed, along with current evidence gaps and future research priorities.