Low-complexity manual nucleic acid amplification tests for pulmonary tuberculosis in children

Area of Science:

• Pediatric infectious diseases
• Molecular diagnostics
• Tuberculosis research

Background:

• Diagnosing childhood tuberculosis is challenging due to non-specific symptoms and low bacterial loads.
• World Health Organization-recommended low-complexity manual nucleic acid amplification tests (LC-mNAATs), like TB-LAMP, offer rapid molecular diagnostics.
• These tests demonstrate good accuracy in adults, even in resource-limited settings.

Purpose of the Study:

• To determine the diagnostic accuracy of LC-mNAATs for pulmonary tuberculosis in children under 10 years.
• To compare LC-mNAATs against Xpert MTB/RIF Ultra and smear microscopy.
• To assess LC-mNAATs as an add-on test and investigate heterogeneity factors.

Main Methods:

• Systematic review and meta-analysis of cross-sectional and cohort studies.
• Inclusion of studies evaluating LC-mNAATs (TB-LAMP) in children (<10 years) against microbiological reference standards.
• Comparisons made with Xpert MTB/RIF Ultra and smear microscopy, with risk of bias assessment using QUADAS-2.

Main Results:

• Four studies (303 participants) were included, with limited data preventing meta-analysis.
• Diagnostic accuracy varied by specimen type: respiratory samples (60-100% sensitivity, 95-100% specificity), gastric aspirate (64% sensitivity), gastric lavage (100% sensitivity, 96% specificity), nasopharyngeal aspirate (58% sensitivity, 94% specificity), and stool (100% sensitivity, 92% specificity).
• Evidence certainty was low to very low for sensitivity and specificity.

Conclusions:

• Evidence on LC-mNAAT diagnostic accuracy in children is limited due to few, small studies.
• The utility of LC-mNAATs like TB-LAMP in pediatric tuberculosis diagnosis requires further investigation.
• Larger, adequately powered studies are essential to confirm diagnostic performance in diverse pediatric populations.