title: Rapid diagnosis of tuberculous meningitis by T cell-based assays on peripheral blood and cerebrospinal fluid mononuclear cells.
abstract: BACKGROUND
  The role of the new Myocbacterium tuberculosis-specific enzyme-linked immunosorbent spot (ELISPOT) assay for diagnosis of tuberculous meningitis (TBM) has not yet been fully assessed. Here, we conducted a prospective, blinded, observational study to evaluate the diagnostic accuracy of this assay, compared with the conventional tests, for diagnosing TBM.
  
  
  METHODS
  All adult patients with suspected TBM were enrolled at a tertiary care hospital (Seoul, South Korea) during a 12-month period. ELISPOT assays were performed on peripheral mononuclear cells and mononuclear cells from cerebrospinal fluid (CSF).
  
  
  RESULTS
  Eighty-nine patients with suspected TBM were enrolled. Of these, 31 (35%) were classified as having TBM (10 confirmed, 6 highly probable, and 15 probable cases), and 55 (62%) were classified as not having active tuberculosis. The remaining 3 (3%) with possible TBM were excluded from the final analysis. The sensitivities and specificities, respectively, of the tested methods for diagnosing TBM were as follows: CSF adenosine deaminase level >5.8 U/L, 89% (95% confidence interval [CI], 69%-98%) and 73% (95% CI, 58%-84%); peripheral mononuclear cells ELISPOT, 71% (95% CI, 51%-86%) and 57% (95% CI, 42%-70%); and CSF mononuclear cells ELISPOT assay, 59% (95% CI, 36%-79%) and 89% (95% CI, 72%-98%). The combined sensitivity of an adenosine deaminase level >5.8 U/L or a positive peripheral mononuclear cells ELISPOT assay result was 94% (95% CI, 79%-99%), conferring a negative likelihood ratio of 0.14 (95% CI, 0.03-0.55) when both test results were negative.
  
  
  CONCLUSIONS
  ELISPOT assays using peripheral mononuclear cells and CSF mononuclear cells are useful adjuncts to the current tests for diagnosing TBM, particularly when used in combination with the assessment of adenosine deaminase level in CSF.
authors.affiliation: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Sung-Han
authors.initials: SH
authors.lastname: Kim
authors.forename: Oh-Hyun
authors.initials: OH
authors.lastname: Cho
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Lee
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kim
authors.forename: Sang-Oh
authors.initials: SO
authors.lastname: Lee
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Choi
authors.forename: Yang Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Jun Hee
authors.initials: JH
authors.lastname: Woo
authors.forename: Sang-Ahm
authors.initials: SA
authors.lastname: Lee
authors.forename: Joong Koo
authors.initials: JK
authors.lastname: Kang
mesh_terms: D000243:Adenosine Deaminase / Q000134:cerebrospinal fluid; D000328:Adult; D000818:Animals; D001769:Blood / Q000276:immunology*; D002555:Cerebrospinal Fluid / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D056910:Republic of Korea; D012680:Sensitivity and Specificity; D014390:Tuberculosis, Meningeal / Q000175:diagnosis*
chemical_list: D000243:Adenosine Deaminase