Cerebrospinal T-cell responses aid in the diagnosis of tuberculous meningitis in a human immunodeficiency virus- and tuberculosis-endemic population.
BACKGROUND
Current tools for the rapid diagnosis of tuberculous meningitis (TBM) are suboptimal. We evaluated the clinical utility of a quantitative RD-1 IFN-gamma T-cell enzyme-linked immunospot (ELISPOT) assay (T-SPOT.TB), using cerebrospinal fluid cells for the rapid immunodiagnosis of TBM.


OBJECTIVE
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.


RESULTS
A total of 140 patients (81% HIV-infected; median CD4 count, 160 cells/mm(3)) 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 > or =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 > or =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.
Patel
Vinod B
VB
Department of Neurology, University of KwaZulu-Natal, South Africa.
Singh
Ravesh
R
Connolly
Cathy
C
Coovadia
Yacoob
Y
Peer
Abdool K C
AK
Parag
Priyashini
P
Kasprowicz
Victoria
V
Zumla
Alimuddin
A
Ndung'u
Thumbi
T
Dheda
Keertan
K
D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology* / Q000276:immunology; D019540:Area Under Curve; D002555:Cerebrospinal Fluid / Q000276:immunology*; D015897:Comorbidity; D019353:Endemic Diseases; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013019:South Africa; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000453:epidemiology / Q000276:immunology; D014390:Tuberculosis, Meningeal / Q000175:diagnosis* / Q000453:epidemiology* / Q000276:immunology
D007371:Interferon-gamma