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The Three-Gene Xpert Host Response Signature for Pediatric Tuberculosis Screening: A Prospective Diagnostic Accuracy

Hayley Poore1,2, Peter Wambi3, Esin Nkereuwem4

  • 1Division of Pulmonary Diseases & Critical Care Medicine, University of California, Irvine, Orange, California, USA.

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
|August 20, 2025
PubMed

Insights

The GeneXpert MTB Host Response (Xpert-HR) blood test shows high sensitivity for detecting tuberculosis (TB) in children but low specificity, risking overdiagnosis. Further research is needed for accurate pediatric TB screening tools.

Area of Science:

  • Infectious Diseases
  • Molecular Diagnostics
  • Pediatric Medicine

Background:

  • Blood-based gene signatures are promising for near point-of-care tuberculosis (TB) screening.
  • The GeneXpert MTB Host Response (Xpert-HR) cartridge was evaluated as a TB screening tool for children.

Purpose of the Study:

  • To assess the accuracy of the Xpert-HR cartridge for screening pulmonary TB in pediatric populations.
  • To compare the performance of Xpert-HR against established TB diagnostic methods and case classifications.

Main Methods:

  • 181 children under 15 years from The Gambia and Uganda were enrolled.
  • Blood samples were analyzed using Xpert-HR, alongside chest X-ray (CXR) and sputum Xpert Ultra testing.
  • NIH case classification (Confirmed, Unconfirmed, Unlikely TB) and ROC curves were used to determine sensitivity and specificity.

Main Results:

  • The Xpert-HR score achieved 88.5% sensitivity but low specificity (30.3-33.3%) across different reference standards.
  • Sensitivity varied by age group, and specificity remained consistently low across all pediatric age strata.
  • Combining Xpert-HR with CXR, Xpert Ultra, or treatment algorithms did not significantly improve diagnostic accuracy.

Conclusions:

  • Xpert-HR demonstrates high sensitivity for confirmed TB in children but is limited by low specificity, potentially leading to overdiagnosis.
  • There is a need for improved, pediatric-specific gene signatures to enhance the accuracy of TB screening in children.
Abstract

Keywords:
biomarkerchilddiagnosticscreeningtuberculosis

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