Alternative sputum collection methods for diagnosis of childhood intrathoracic tuberculosis: a systematic literature review.

BACKGROUND: Diagnosis of intrathoracic tuberculosis (ITB) is limited in children partly by their difficulty to produce sputum specimen. OBJECTIVE: To systematically review the detection yields of mycobacterial culture and Xpert MTB/RIF from induced sputum (IS), nasopharyngeal aspirate (NPA) and gastric aspirate (GA) in children with presumptive ITB. DESIGN: Pubmed, Embase and Biosis databases and grey literature were searched. Randomised controlled trials, cohort, cross-sectional or case control studies using IS, GA and NPA for diagnosis of ITB published between January 1990 and January 2018 were included. Data were extracted on study design, case definition of presumptive ITB, sample collection methods, outcome measures and results. RESULTS: 30 studies were selected, including 11 554 children. Detection yields for culture ranged between 1% and 30% for IS, 1% and 45% for GA and 4% and 24% for NPA. For Xpert MTB/RIF, it was between 2% and 17% for IS, 5% and 51% for GA and 3% and 8% for NPA. There was a tendency of better yields with IS when the pretest probability of ITB was low to moderate and with GA when it was high. Sampling a second specimen contributed for 6%-33% of the cumulative yield and combination of different methods significantly increase the detection yields. CONCLUSIONS: Despite the important study heterogeneity, any of the specimen collection methods offers good potential to confirm childhood ITB. However, their operational challenges were poorly evaluated. In the absence of a sensitive non-sputum based test, only a minority of children with ITB can be confirmed.