Enhanced diagnosis accuracy of tuberculous meningitis using mycolic and tuberculostearic acid via advanced mass spectrometry.

BACKGROUND: Tuberculous meningitis (TBM) remains challenging to diagnoses, especially in resource-limited settings. This study assessed the diagnostic utility of cerebrospinal fluid (CSF) biomarkers, mycolic acid (MA) and tuberculostearic acid (TBSA) in diagnosing TBM, comparing their performance against microbiological confirmation and Marais scoring system.

METHODS: This was a tertiary hospital-based prospective study conducted on (n = 172) meningitis who were classified into the definite TBM, probable TBM, possible TBM, and non TBM groups, based on microbiological gold standards and the Marais scoring system. CSF parameters, including glucose, protein, white blood cell (WBC) count, and adenosine deaminase (ADA) levels, were measured. MA and TBSA biomarker levels were quantified by tandem mass spectrometry. Diagnostic performance was evaluated based on sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the receiver operating characteristic curve (AUC) by comparing between definite TBM and non TBM categories.

RESULTS: Definite TBM exhibited the lowest CSF glucose and highest WBC and ADA levels. Protein content was also the highest among the probable and definite categories. MA demonstrated excellent diagnostic performance with a sensitivity of 93.1 %, specificity of 100 %, PPV of 100 %, and NPV of 94.7 % (AUC = 0.96). TBSA showed slightly lower sensitivity (82.8 %), but high specificity (94.4 %), with a PPV of 92.3 % and NPV of 87.2 % (AUC = 0.97). Among the indeterminate cases, both MA and TBSA showed higher positivity in the probable TBM group and minimal positivity in the non TBM group, highlighting their high specificity.

CONCLUSION: MA and TBSA are highly sensitive and specific biomarkers for the diagnosis of TBM. These biomarkers, in conjunction with clinical parameters, may offer significant diagnostic value for enhancing TBM diagnosis as depicted in our results on comparison between definite and non-TBM.