Rapid diagnosis of tuberculous meningitis by T cell-based assays on peripheral blood and cerebrospinal fluid mononuclear cells.
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.
Kim
Sung-Han
SH
Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Cho
Oh-Hyun
OH
Park
Su-Jin
SJ
Lee
Eun Mi
EM
Kim
Mi-Na
MN
Lee
Sang-Oh
SO
Choi
Sang-Ho
SH
Kim
Yang Soo
YS
Woo
Jun Hee
JH
Lee
Sang-Ahm
SA
Kang
Joong Koo
JK
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*
D000243:Adenosine Deaminase