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

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.