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Characterization of CSF tryptophan metabolites in South African children with tuberculous meningitis

Ontefetse Neo Plaatjie1, A Marceline Tutu van Furth2, Regan Solomons3

  • 1Department of Biochemistry, Biomedical and Molecular Metabolism (BioMMet), Faculty of Natural and Agricultural Sciences, North-West University, Potchefstroom, South Africa.

International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases
|November 19, 2025
PubMed

Insights

Cerebrospinal fluid (CSF) tryptophan depletion is common in childhood meningitis, but elevated kynurenine metabolites, particularly quinolinic acid, may help diagnose tuberculous meningitis (TBM). Quinolinic acid shows potential as a specific biomarker for TBM in children.

Area of Science:

  • Neuroscience
  • Infectious Diseases
  • Biochemistry

Background:

  • Tuberculous meningitis (TBM) is a severe form of tuberculosis, particularly dangerous in children due to immature immune systems.
  • Diagnosis of TBM is challenging due to nonspecific symptoms, often leading to advanced disease at presentation.
  • Tryptophan metabolism's role in pediatric TBM is understudied, despite its link to disease severity in adults.

Purpose of the Study:

  • To investigate cerebrospinal fluid (CSF) tryptophan metabolism in pediatric TBM.
  • To analyze both the serotonin and kynurenine pathways of tryptophan metabolism.
  • To identify potential biomarkers for TBM in children.

Main Methods:

  • Liquid chromatography-tandem mass spectrometry was used to measure tryptophan and its metabolites in CSF.
  • 130 CSF samples were analyzed: 51 TBM, 49 non-meningitis controls (NMC), and 30 viral meningitis (VM) cases.
  • Metabolite levels were correlated with CSF parameters and magnetic resonance imaging (MRI) findings.

Main Results:

  • CSF tryptophan levels were significantly reduced in both TBM and VM compared to NMC, indicating a common immune response.
  • Quinolinic acid was significantly elevated in TBM compared to both VM and NMC, showing potential diagnostic utility (AUCs 0.736-0.804).
  • Quinolinic acid levels positively correlated with basal enhancement and hydrocephalus, key MRI features of TBM.

Conclusions:

  • CSF tryptophan depletion is not specific to TBM, reflecting general immune activation.
  • Elevated kynurenine pathway metabolites, especially quinolinic acid, suggest greater pathway activation in TBM.
  • Quinolinic acid shows promise as a specific biomarker for pediatric TBM, correlating with disease-specific imaging findings.
Abstract

Keywords:
Cerebrospinal fluid (CSF)Liquid chromatrography-mass spectrometry (LC-MS)MetabolomicsPediatricsQuinolinic acidTryptophanTuberculous meningitis (TBM)

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