Cerebrospinal T-Cell Responses Aid in the Diagnosis of Tuberculous Meningitis in a Human Immunodeficiency Virus– and Tuberculosis-Endemic Population
- 15 August 2010
- journal article
- research article
- Published by American Thoracic Society in American Journal of Respiratory and Critical Care Medicine
- Vol. 182 (4), 569-577
- https://doi.org/10.1164/rccm.200912-1931oc
Abstract
Rationale: Current tools for the rapid diagnosis of tuberculous meningitis (TBM) are suboptimal. We evaluated the clinical utility of a quantitative RD-1 IFN-γ T-cell enzyme-linked immunospot (ELISPOT) assay (T-SPOT.TB), using cerebrospinal fluid cells for the rapid immunodiagnosis of TBM. Objectives: To evaluate the diagnostic utility of the RD1 antigen- specific ELISPOT assay for the diagnosis of tuberculous meningitis. Methods: The ELISPOT assay was evaluated in 150 patients with suspected TBM who were categorized as definite-TBM, probable-TBM, and non-TBM. Culture or polymerase chain reaction positivity for Mycobacerium tuberculosis served as the reference standard. To determine the diagnostic value of the ELISPOT assay, a clinical prediction rule was derived from baseline clinical and laboratory parameters using a multivariable regression model. Measurements and Main Results: A total of 140 patients (81% HIV-infected; median CD4 count, 160 cells/mm3) were included in the final analysis. When comparing the definite-TBM (n = 38) and non-TBM groups (n = 48), the ELISPOT assay (cut point of ≥228 spot-forming cells per 1 million mononuclear cells) was a useful rule-in test: sensitivity 58% (95% confidence interval [CI], 41–74); specificity 94% (95% CI, 83–99). However, ELISPOT outcomes improved when other rapid tests were concurrently used to exclude bacterial (Gram stain) and cryptococcal meningitis (latex-agglutination test) within the non-TBM group. Using this approach, the ELISPOT assay (cut point of ≥46 spot-forming cells) was an excellent rule-in test: sensitivity 82% (95% CI, 66–92); specificity 100% (95% CI, 78–100); positive predictive value, 100% (95% CI, 89–100); negative predictive value, 68% (95% CI, 45–86); area under the curve, 0.90. The ELISPOT assay had incremental diagnostic value compared with the clinical prediction rule. Conclusions: The RD-1 ELISPOT assay, using cerebrospinal fluid mononuclear cells and in conjunction with other rapid confirmatory tests (Gram stain and cryptococcal latex-agglutination test), is an accurate rapid rule-in test for TBM in a TB and HIV endemic setting.Keywords
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