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The diagnostic potential of urine in paediatric patients undergoing initial treatment for tuberculous meningitis

Simon Isaiah1, Johan A Westerhuis2, Du Toit Loots1

  • 1Human Metabolomics, Faculty of Natural and Agricultural Sciences, North‒West University, Potchefstroom, South Africa.

Scientific Reports
|August 22, 2024
PubMed

Insights

Urine metabolite analysis shows potential for diagnosing severe tuberculous meningitis (TBM) in children. This non-invasive approach identified biomarkers that could aid in TBM diagnosis, particularly for advanced stages.

Area of Science:

  • * Neuroinfectious diseases
  • * Metabolomics
  • * Pediatric infectious diseases

Background:

  • * Tuberculous meningitis (TBM) is a severe complication of tuberculosis, especially in children.
  • * Current diagnostic methods for TBM, relying on cerebrospinal fluid (CSF), are invasive and often insufficient.
  • * Urine's metabolic profile remains largely unexplored for diagnosing neuroinfectious diseases.

Purpose of the Study:

  • * To investigate the diagnostic potential of urinary metabolites for TBM in a pediatric cohort.
  • * To compare metabolite profiles between TBM patients and healthy controls.
  • * To differentiate between mild and severe TBM stages using urine metabolomics.

Main Methods:

  • * Untargeted proton magnetic resonance (¹H-NMR) metabolomics was employed.
  • * Urine samples from 32 pediatric TBM patients (stages 1-3) and 39 controls were analyzed.
  • * Strict statistical criteria were applied to identify significant metabolites; ROC analysis was used for diagnostic potential assessment.

Main Results:

  • * Five significant urinary metabolites (1-methylnicotinamide, 3-hydroxyisovaleric acid, 5-aminolevulinic acid, N-acetylglutamine, methanol) were identified, independent of medication.
  • * Methanol showed low diagnostic sensitivity, while the other four metabolites demonstrated good diagnostic potential.
  • * A multivariate metabolic model successfully classified severe TBM (stages 2-3) but not mild TBM (stage 1).

Conclusions:

  • * Urine metabolomics offers a promising, non-invasive avenue for TBM diagnosis in children.
  • * Specific urinary metabolites show potential as biomarkers for identifying severe TBM.
  • * Further research could refine urine-based diagnostic strategies for TBM.

Keywords:
DiagnosticMetabolomicsPediatricProton magnetic resonance (1H-NMR)Tuberculous meningitis (TBM)Urine

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