title: Diagnostic usefulness of T-cell based assays for tuberculous meningitis in HIV-uninfected patients.
abstract: OBJECTIVE
  Early diagnosis and treatment of tuberculous meningitis (TBM) is essential for a positive outcome, but sensitive, specific, and rapid diagnostic tests for TBM are lacking. We evaluated the diagnostic utility of enzyme-linked immunosorbent spot (ELISPOT) assays in HIV-uninfected patients with suspected TBM.
  
  
  METHODS
  All HIV-uninfected patients with suspected TBM were prospectively enrolled at a tertiary care hospital in an intermediate TB-burden country, during a 6-year period. ELISPOT assays were performed on peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid-mononuclear cells (CSF-MC).
  
  
  RESULTS
  Of the 276 evaluable patients, 90 (33%) were classified as having TBM (30 definite cases, 19 probable, and 41 possible), and 186 (67%) as having non-TBM. When comparing definite TBM versus non-TBM, the sensitivity and specificity of the PBMC ELISPOT assay (≥6 spots; manufacturer's recommended cut-off) for diagnosing TBM were 96% (95% CI, 82-100) and 58% (95% CI, 50-66), respectively. The CSF-MC ELISPOT assay (≥38 spots; receiver operating characteristic [ROC]-derived cut-off) was a useful rule-in test with specificity of 95% (96% CI, 90-98). Its sensitivity was 68% (95% CI, 45-86), which was superior those of AFB smear microscopy (14%; P < 0.001) and CSF Mycobacterium tuberculosis PCR (41%; P = 0.07). Combining this assay with M. tuberculosis PCR, clinical score, and both together increased sensitivity to 86%, 91%, and 95%, respectively, while retaining about 95% specificity.
  
  
  CONCLUSIONS
  The CSF-MC ELISPOT assay appears to be a rapid and accurate rule-in test for the diagnosis of TBM and a useful adjunct for diagnosing TBM in HIV-uninfected patients.
authors: Division of Infectious Diseases, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
authors: Ki-Ho
authors: KH
authors: Park
authors: Division of Infectious Diseases, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
authors: Mi Suk
authors: MS
authors: Lee
authors: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Sun-Mi
authors: SM
authors: Kim
authors: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Su-Jin
authors: SJ
authors: Park
authors: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Yong Pil
authors: YP
authors: Chong
authors: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Sang-Oh
authors: SO
authors: Lee
authors: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Sang-Ho
authors: SH
authors: Choi
authors: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Yang Soo
authors: YS
authors: Kim
authors: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Jun Hee
authors: JH
authors: Woo
authors: Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Joong Koo
authors: JK
authors: Kang
authors: Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Sang-Ahm
authors: SA
authors: Lee
authors: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: kimsunghanmd@hotmail.com.
authors: Sung-Han
authors: SH
authors: Kim
mesh_terms: D000328:Adult; D000465:Algorithms; D002555:Cerebrospinal Fluid / Q000166:cytology; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D056910:Republic of Korea; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014390:Tuberculosis, Meningeal / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000276:immunology*
keywords: Cerebrospinal fluid; Diagnosis; Meningitis; Tuberculosis