Diagnostic accuracy of molecular detection of Mycobacterium tuberculosis in pediatric stool samples: A systematic review and meta-analysis

Abstract Background Stool is a promising specimen option to diagnose pediatric tuberculosis (TB), but studies have reported a wide range of test sensitivities. We conducted a meta-analysis to assess the accuracy of Xpert MTB/RIF or ‘in-house’ molecular tests on stool samples against culture or Xpert MTB/RIF on respiratory samples or clinically-diagnosed unconfirmed TB and aimed to identify factors that contribute to the heterogeneity of reported sensitivity. Methods We searched EMBASE and Pubmed databases and conference abstract books for studies reporting molecular stool testing against a clinical or microbiological reference standard among children. Results We identified 16 studies that included 2,481 children in stool test analyses. Pooled specificity was 98% [95%CI: 96–99], pooled sensitivity was 57% [95%CI: 40–72] against culture and 3% [95%CI: 2–6] among children with clinically-diagnosed, unconfirmed TB. There was much heterogeneity. Sensitivity was higher among children with a smear-positive sputum test. Rifampin resistance in stool was reported in two studies and detected in 5/14 children (36%). Conclusion Our results suggest molecular stool tests have potential as diagnostic rule-in tests, but it is challenging to optimize sensitivity due to between-study variation in methodology and test procedures. Therefore, we recommend future research with rigorous study design and standardized results reporting.