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Clin. Vaccine Immunol. doi:10.1128/CVI.00040-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Diagnosis of Central Nervous System Tuberculosis by T-cell-based Assays on Peripheral Blood and Cerebrospinal Fluid Mononuclear cells

Departments of Internal Medicine, and Neurology, Seoul National University College of Medicine, and Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea

^* To whom correspondence should be addressed. Email: mdohmd{at}snu.ac.kr.

	Abstract

M. tuberculosis-specific T-cells are more compartmentalized to the site of infection in active tuberculosis (TB) than to the circulating blood. Therefore, an M. tuberculosis-specific ELISPOT assay using samples taken from the site of infection may permit a more sensitive or specific diagnosis of active central nervous system tuberculosis (CNS-TB) than that the assay in blood alone. Therefore, we prospectively evaluated the usefulness of circulating and compartmentalized mononuclear cell (i.e. peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid mononuclear cells (CSF-MC))-based ELISPOT assays (i.e. T-SPOT.TB test) for diagnosing active TB in patients with suspected CNS-TB. The clinical category of CNS-TB was classified as described in the previous work (Thwaites, et al. 2002). Thirty-seven patients with suspected CNS-TB were enrolled over a 12-month period. Of these, 31 (84%) showed clinical manifestations of suspected TB meningitis and six (16%) gave indications of intracranial tuberculoma with disseminated TB. The final clinical categories of the 37 patients with suspected CNS-TB were as follows; 12 (32%) were classified as CNS-TB (7 confirmed TB, 3 probable TB, and 2 possible TB), and 25 (68%) as not active TB. The sensitivity and specificity of the PBMC ELISPOT were 91% (95% CI 59%-100%) and 63% (95% CI 41%-81%), respectively. By comparison, the sensitivity and specificity of the CSF-MC ELISPOT assay were 75% (95% CI 19%-99%) and 75% (95% CI 43%-95%), respectively. When the ratio of CSF-MC ELISPOT results to PBMC ELISPOT results was two or more, the sensitivity and specificity were 50% (95% CI 7%-93%) and 100% (95% CI 74%-100%), respectively. The ELISPOT assay using PBMC and CSF-MC is a useful adjunct to the current tests for diagnosing CNS-TB.