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<p>Microbiological tests for tuberculosis (TB) disease in children have suboptimal accuracy and respiratory samples are often challenging to obtain. Using liquid chromatography/mass spectrometry, we performed plasma high-resolution metabolomics (HRM) to identify blood-based biomarkers associated with TB disease in children. We analyzed plasma samples from 438 children 0–14&#xa0;years being evaluated for TB disease in India, Peru, Uganda, The Gambia, and South Africa. All children underwent a standard clinical evaluation and were followed up after 3&#xa0;months. Children were classified as Confirmed (n = 104), Unconfirmed (n = 108), or Unlikely TB (n = 226) as per NIH consensus definitions. Controlling for age and study site, we found creatine, alanine, retinol, citrulline, fumarate, and tryptophan to be significantly decreased in children with Confirmed TB disease versus those with Unlikely TB, while cortisol, nicotinamide, and butyrylcarnitine were increased (FDR-corrected p-value &lt; 0.2). Using logistic regression, we found this nine-metabolite signature had an area under the receiver operator characteristic curve (AUC) of 0.72 (95% CI (0.67 − 0.82) in the test set of participants with Confirmed and Unlikely TB and an AUC of 0.49 (95% CI 0.42 − 0.55) in the Unconfirmed TB group. These results show a nine-metabolite plasma signature has moderate accuracy for identification of Confirmed TB disease in children.</p>

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Multicohort assessment of plasma metabolic signatures of tuberculosis disease in children: a retrospective cross-sectional study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月23日

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  • Mary M. Nellis,
  • Juaneta Luiz,
  • Devan Jaganath,
  • Zaynab Mousavian,
  • Esin Nkereuwem,
  • Peter Wambi,
  • Roger Calderon,
  • Mandar Paradkar,
  • Robert Castro,
  • Rutuja Nerurkar,
  • Molly F. Franke,
  • Aarti Kinikar,
  • Eric Wobudeya,
  • Heather J. Zar,
  • Dean P. Jones,
  • Mark Segal,
  • George Sigal,
  • Danielle L. Swaney,
  • Adithya Cattamanchi,
  • Joel D. Ernst,
  • Thomas R. Ziegler,
  • Beate Kampmann,
  • Jeffrey M. Collins,
  • Cynthia Baard,
  • Yekiwe Hlombe,
  • Lesley Workman,
  • Margaretha Prins,
  • Abdoulie Tunkara,
  • Binta Saidy,
  • Francis S. Mendy,
  • Madikoi Danso,
  • Marie P. Gomez,
  • Martina Boakarie,
  • Sarjo Koita,
  • Sheriff Kandeh,
  • Jascent Nakafero,
  • Gertrude Nanyonga,
  • Juliet Namboowa,
  • Winnie Nabakka,
  • Nsereko Moses,
  • Ainebyona Aggrey,
  • Alfred Andama,
  • Moorine Sekadde,
  • Mary Mudiope,
  • Ezekiel Mupere,
  • Hellen Aanyu Tukamuhebwa,
  • Amita Gupta,
  • Vidya Mave

摘要

Microbiological tests for tuberculosis (TB) disease in children have suboptimal accuracy and respiratory samples are often challenging to obtain. Using liquid chromatography/mass spectrometry, we performed plasma high-resolution metabolomics (HRM) to identify blood-based biomarkers associated with TB disease in children. We analyzed plasma samples from 438 children 0–14 years being evaluated for TB disease in India, Peru, Uganda, The Gambia, and South Africa. All children underwent a standard clinical evaluation and were followed up after 3 months. Children were classified as Confirmed (n = 104), Unconfirmed (n = 108), or Unlikely TB (n = 226) as per NIH consensus definitions. Controlling for age and study site, we found creatine, alanine, retinol, citrulline, fumarate, and tryptophan to be significantly decreased in children with Confirmed TB disease versus those with Unlikely TB, while cortisol, nicotinamide, and butyrylcarnitine were increased (FDR-corrected p-value < 0.2). Using logistic regression, we found this nine-metabolite signature had an area under the receiver operator characteristic curve (AUC) of 0.72 (95% CI (0.67 − 0.82) in the test set of participants with Confirmed and Unlikely TB and an AUC of 0.49 (95% CI 0.42 − 0.55) in the Unconfirmed TB group. These results show a nine-metabolite plasma signature has moderate accuracy for identification of Confirmed TB disease in children.