Diagnosis and Management of Tuberculosis Infection in Pediatric Populations

Childhood tuberculosis (TB) remains a global health priority, with one million new paediatric infections and hundreds of thousands of related deaths annually. Compared with adult disease, paediatric TB often presents with non-specific symptoms and radiographic findings, and young children progress more rapidly from infection to active disease. Early identification of latent tuberculosis infection (LTBI) is essential to interrupt transmission and to prevent severe outcomes such as miliary or meningeal TB. Diagnosis relies on immunological assays and clinical evaluation: the tuberculin skin test (TST) has long been used but may be confounded by BCG vaccination, while interferon-gamma release assays (IGRAs) offer improved specificity in BCG-vaccinated populations. Management of confirmed infection includes preventive therapy—typically with isoniazid alone or shorter rifapentine–isoniazid regimens—tailored to age, weight and regional drug-resistance patterns. Adherence support, monitoring for drug toxicity and integration into child health services are critical to ensure completion of preventive courses. Advances in biomarker discovery and age-calibrated diagnostic thresholds promise to refine risk stratification in children, aligning global TB control strategies with the unique immunological and developmental characteristics of paediatric populations.

Research from Nature Portfolio

Seminal work on age-related cytokine dynamics has demonstrated that baseline and antigen-stimulated levels of key mediators such as interferon-γ, tumour necrosis factor-α and interleukins vary markedly across childhood. This study quantified cytokine responses in healthy children and revealed that both unstimulated and mitogen-stimulated profiles shift with age, with younger children exhibiting lower interferon-γ release yet higher interleukin-1 receptor antagonist. These findings underscore the need for age-specific reference ranges in cytokine-based assays and suggest that future diagnostic platforms incorporate developmental norms to enhance accuracy in detecting tuberculosis infection in paediatric cohorts.

Diagnosis and Management of Tuberculosis Infection in Pediatric Populations publication trend

The graph below shows the total number of articles in diagnosis and management of tuberculosis infection in pediatric populations across all publications each year (not limited to Nature Index journals).

Technical terms

Latent tuberculosis infection (LTBI): A state in which Mycobacterium tuberculosis persists in the host without causing clinical disease, detectable only by immunological tests.

Tuberculin skin test (TST): An in vivo diagnostic assay involving intradermal injection of purified protein derivative to elicit a delayed-type hypersensitivity reaction.

Interferon-gamma release assay (IGRA): An ex vivo blood test measuring interferon-γ released by T cells in response to M. tuberculosis-specific antigens.

Cytokine: A small protein released by immune cells that mediates inflammation and cell signalling, crucial for host defence and diagnostic biomarker development.

Indeterminate result: An IGRA outcome in which neither the tuberculosis antigen nor the positive control elicits an adequate interferon-γ response, rendering the test inconclusive.

References

1. Tuberculosis in Infants and Children. Microbiology Spectrum (2017).
2. Cytokine profiling in healthy children shows association of age with cytokine concentrations. Scientific Reports (2017).
3. Risk Factors for Indeterminate Interferon-Gamma Release Assay for the Diagnosis of Tuberculosis in Children—A Systematic Review and Meta-Analysis. Frontiers in Pediatrics (2019).
4. The impact of BCG vaccination on tuberculin skin test responses in children is age dependent: evidence to be considered when screening children for tuberculosis infection. Thorax (2016).
5. A Three-Way Comparison of Tuberculin Skin Testing, QuantiFERON-TB Gold and T-SPOT.TB in Children. PLOS ONE (2008).