Pediatric pulmonary and extrapulmonary tuberculosis: immunological and diagnostic perspectives

Pediatric tuberculosis (TB) remains a significant global health issue due to its diagnostic complexity and paucibacillary nature. This study aimed to evaluate the clinical, diagnostic, and immunological characteristics of pulmonary TB (PTB) and extrapulmonary TB (EPTB) in children. A retrospective review was conducted on 88 pediatric TB cases (38 PTB, 50 EPTB) at a referral children’s hospital in Iran from 2020 to 2024. Diagnostic methods included nucleic acid amplification tests (NAATs), interferon-gamma release assay (IGRA), tuberculin skin test (TST), mycobacterial culture, and imaging studies such as chest X-ray (CXR) and computed tomography (CT). Flow cytometry was used to assess immune profiles. Among the 88 pediatric TB cases included in the study, 82 (93%) were caused by Mycobacterium tuberculosis (MTB), while 6 cases (7%) were attributed to nontuberculous mycobacteria (NTM). EPTB accounted for the majority of cases (57%). Drug susceptibility testing of MTB showed 87% sensitivity to all antibiotics; rifampicin and isoniazid resistance were found in 10% and 4%, respectively. Diagnostic test results for PTB and EPTB caused by MTB showed that NAATs had the highest positivity rates (100% for PTB and 96% for EPTB). IGRA was positive in 47% of PTB and 25% of EPTB cases. TST showed high positivity for both groups (80% PTB, 75% EPTB). Culture results were positive in 67% of PTB and 76% of EPTB cases. CXR was positive in 82% of PTB and 55% of EPTB cases, and CT scans showed 86% positivity for PTB and 58% for EPTB. A significant difference in immune profiles was observed between PTB and EPTB patients. The EPTB group exhibited notably reduced levels of CD3⁺ and CD8⁺ T cells, along with elevated CD19⁺, CD16⁺, and myeloperoxidase (MPO) levels. EPTB and PTB in children display distinct immunological patterns. PTB is characterized by a stronger T-cell response, whereas EPTB exhibits greater humoral immune activation and T-cell suppression. The distinct immunological profiles suggest that different immune pathways contribute to disease localization. Integrating molecular diagnostics and immune profiling can enhance early detection and guide better clinical management of childhood TB.