Pathogen and host biomarkers to aid early diagnosis and prognosis of tuberculous meningitis.

BACKGROUND

Tuberculous meningitis (TBM) is the most sinister form of extrapulmonary tuberculosis (EPTB), associated with high mortality due to delayed diagnosis and limited sensitivity of conventional and molecular tests. Current study evaluated the diagnostic utility of Lipoarabinomannan antigen (LAM) detection in CSF and urine and explored host inflammatory biomarkers for diagnosis and prognosis of TBM.

METHODS

This prospective observational cohort study enrolled 80 HIV-negative adults with presumptive TBM at a tertiary care center. Patients were classified according to the uniform TBM case definition, based on clinical, CSF, radiological, and microbiological findings. CSF samples were subjected to AFB microscopy, liquid culture (MGIT-960), GeneXpert MTB/RIF (GX), and LAM lateral flow assay. Urine LAM was performed at baseline. Serum and CSF levels of IL-1β, IL-6, TNF-α, IFN-γ, IL-17 A, and IP-10 were measured at baseline and after 1 month of treatment.

RESULTS

Among 80 HIV-negative participants, 23 (28.7%) had definite TBM and 46 (57.5%) had probable TBM. CSF LAM sensitivity and specificity against microbiological reference standards were 43.5% and 80.7%, while urine LAM sensitivity (60.9%) and specificity 82.5% were higher. Against composite reference standards, both CSF and urine LAM showed reduced sensitivity but achieved 100% specificity. Serum IL-1β demonstrated the highest diagnostic performance for distinguishing TBM from non-TBM patients (AUC 0.943; sensitivity 88.9%, specificity 90.9%). Elevated serum and CSF IP-10 levels were associated with on-treatment mortality, whereas declining IL-6 and TNF-α levels correlated with treatment response.

CONCLUSION

LAM detection in CSF and urine may serve as a useful adjunct to existing diagnostic approaches for TBM when interpreted alongside clinical, radiological, and microbiological findings. Host inflammatory biomarkers, especially IL-1β and IP-10, show additional diagnostic and prognostic value. Combining LAM testing with cytokine biomarkers may improve early diagnosis and efficient clinical management of TBM. However, larger multicentre studies are required to validate these findings before routine clinical implementation.