ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2025
The Three-Gene Xpert Host Response Signature for Pediatric Tuberculosis Screening: A Prospective Diagnostic Accuracy Study.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Diagnostic accuracy of GeneReady MTB assay on sputum for detecting pulmonary tuberculosis: a prospective multicenter study in China.Journal of clinical microbiology · 2026Article
- Exploring non-sputum biosignatures for tuberculosis triage and diagnosis in children living with HIV.Expert review of molecular diagnostics · 2025Review
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Authors and funding
14 authors.
Funding
Abstract
backgroundBlood-based gene signatures offer potential as a near point-of-care tuberculosis (TB) screening tool. We examined the accuracy of the GeneXpert MTB Host Response (Xpert-HR) cartridge to screen for TB in children.
methodsWe enrolled children under 15 years from The Gambia and Uganda being evaluated for pulmonary TB. Each child provided a blood sample for Xpert-HR and underwent standard TB assessments, including chest X-ray (CXR) and sputum Xpert Ultra testing, followed by National Institutes of Health (NIH) case classification of Confirmed, Unconfirmed, or Unlikely TB. We measured cycle threshold (Ct) values for GBP5, DUSP3, and TBP, calculated an HR TB score, and generated ROC curves. Specificity was assessed at 90% sensitivity according to strict (SRS, Confirmed vs Unlikely TB), microbiological (MRS, Confirmed TB vs Unlikely or Unconfirmed TB), and composite (CRS, Confirmed or Unconfirmed TB vs Unlikely TB) reference standards compared with other TB evaluations.
resultsAmong 181 children (median age 4 years; 53% female; 16% with HIV; 14.4% confirmed TB), the HR TB score cut-point of -0.65 showed 88.5% sensitivity with specificity at 33.3% (SRS) and 30.3% (MRS). Sensitivity was lower for the CRS at 75.7%, with similar specificity (33.3%). Sensitivity was higher in children aged 5-9 and 10-14 years compared with those under 5 years, but specificity remained low (22.7%-28.6%). Combining Xpert-HR with CXR, Xpert Ultra, or TB treatment decision algorithms did not significantly enhance accuracy.
conclusionsGeneXpert MTB Host Response showed high sensitivity for detecting confirmed TB but had low specificity, risking overdiagnosis. Improved pediatric-specific gene signatures are necessary for better accuracy in children.
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