Cerebrospinal T-cell responses aid in the diagnosis of tuberculous meningitis in a human immunodeficiency virus- and tuberculosis-endemic population.

Abstract

RATIONALE:

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.

OBJECTIVES:

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.

MEASUREMENTS AND MAIN 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.

• Authors: Vinod B Patel, Ravesh Singh, Cathy Connolly, Yacoob Coovadia, Abdool K C Peer, Priyashini Parag, Victoria Kasprowicz, Alimuddin Zumla, Thumbi Ndung'u, Keertan Dheda
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 182 Issue 4 Pg. 569-77 (Aug 15 2010) ISSN: 1535-4970 [Electronic] United States
• PMID: 20442433 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon-gamma

Topics

• AIDS-Related Opportunistic Infections (epidemiology, immunology)
• Area Under Curve
• Cerebrospinal Fluid (immunology)
• Comorbidity
• Endemic Diseases
• Enzyme-Linked Immunosorbent Assay (methods)
• HIV Infections (epidemiology, immunology)
• HIV-1 (immunology)
• Humans
• Interferon-gamma (immunology)
• Mycobacterium tuberculosis (immunology)
• Prospective Studies
• ROC Curve
• Sensitivity and Specificity
• South Africa
• T-Lymphocytes (immunology)
• Tuberculosis (epidemiology, immunology)
• Tuberculosis, Meningeal (diagnosis, epidemiology, immunology)