Project Details

Stool MTB polymerase chain reaction to improve pediatric TB diagnosis

Alexander Kay, MD

Summary

BACKGROUND: 1) Only 10-20% of children with TB are microbiologically confirmed due to poor performance of existing tests. 2) Pediatric diagnostic specimens, obtained through gastric aspirate, sputum induction or nasopharyngeal aspirate, are often not collected because they are invasive, require additional equipment and perform poorly. GAP: There is a research and data gap on child TB diagnostics using non-respiratory samples, such as stool, to increase test uptake while also maintaining and building on the performance characteristics of traditional samples. HYPOTHESIS: Hypothesis 1: Compared to the reference standard of culture, stool qPCR will have non-inferior sensitivity and specificity vs. Xpert (comparator test) completed on respiratory specimens. Hypothesis 2: Stool Xpert performance will be enhanced by stool homogenization and centrifugation, and the MTBDRplus will identify Mtb and molecular drug resistance in DNA isolated via MPFast soil DNA kits. METHODS: This will be a prospective, cross-sectional, case control study, stool diagnostics will be assessed compared to the traditional diagnostic pathway. Children (age 6 months- 18 years) who are being evaluated for TB will have stool collected in addition to standard diagnostic tests. RESULTS: Stool processing methods did not significantly impact the performance of stool Xpert Ultra in a direct laboratory comparison. Systematic review evidence from multiple studies indicates that Xpert Ultra testing on stool has a high degree of diagnostic accuracy and stool is now recommended by the World Health Organization as an acceptable diagnostic specimen for TB. Drug susceptibility testing from TB detected in stool has previously been limited; however, TB DNA isolation techniques optimized for stool in this study can support comprehensive drug resistance detection using targeted next generation sequencing. IMPACT: A test that performs similarly to current diagnostics but is used more frequently because it is non-invasive and requires no training for sample collection could increase the microbiologic diagnosis of pediatric

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