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What Is It if It’s not Pulmonary Tuberculosis in Children? A Systematic Review and Narrative Synthesis
20 Pages Posted: 26 Dec 2025
More...Abstract
Background: Diagnosing pulmonary tuberculosis (PTB) in children is often challenging due to non-specific clinical presentation, which frequently overlap with other respiratory illnesses in childhood. Although the World Health Organization (WHO) in the 2022 operational handbook recommends considering and treat alternative diagnoses in children presenting with presumptive PTB, there is limited evidence describing the range, frequency and clinical characteristics of these alternative conditions. This study synthesizes existing evidence on alternative diagnoses among children and adolescents evaluated for presumptive PTB, to inform future diagnostic approaches.
Methods: We conducted a systematic review of original research studies published between January 1, 2000, and March 10, 2025, using MEDLINE Complete, CINAHL Complete, Global Health, Scopus, and PubMed databases. Eligible studies were those conducted in low- and middle-income countries (LMICs) that included children (0–9 years) and adolescents (10–19 years) with presumptive PTB, and that reported alternative diagnoses. Data were analysed descriptively and categorized into three age groups < 5 years, 5- 10 years, and >10 years. The review was prospectively registered (PROSPERO CRD42024601334).
Findings: This systematic review included 11 studies comprising 5,493 children and adolescents with presumptive PTB. A wide spectrum of alternative diagnoses was identified, with notable age-related variation. Among children under five years, nontuberculous mycobacteria (NTM) was the most prevalent diagnosis (33.1%), followed by malignancy (2.6%), viral pneumonia (1.0%), lymphoid interstitial pneumonia (0.4%), and bacterial pneumonia (0.3%). In those aged 5–10 years, bacterial pneumonia predominated (61.8%), followed by fungal pneumonia (9.4%), empyema or abscess (7.7%), bronchiectasis (3.6%), structural anomalies, immunodeficiency (0.8% each), and malignancy (0.4%). Among children over ten years, NTM (4.5%) and paragonimiasis (1.0%) were the only alternative diagnoses described. In studies reporting unclassified 0–19-year groups, the most frequent diagnoses were NTM (4.4%), bacterial pneumonia (3.6%), empyema or abscess (1.0%), structural anomalies (0.7%), valvular heart disease (0.5%), bronchiectasis (0.2%), lymphoid interstitial pneumonia (LIP 0.2%), and malignancy (0.2%).
Interpretation: Children and adolescents evaluated for presumptive PTB were diagnosed with a diverse range of alternative conditions, varying by age groups. These findings underscore the importance of comprehensive diagnostic evaluation to minimize unnecessary TB treatment, reduce health, psychosocial, and economic burdens, and ensure timely identification and management of alternative conditions. Improving access to microbiological and imaging diagnostics and integrating differential diagnosis into clinical algorithms are vital to reduce misdiagnosis and ensure timely, appropriate care for children in high TB-burden settings.
Keywords: tuberculosis, paediatrics, diagnosis, respiratory infections, global health
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