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Comparison of a Clinical Prediction Rule and a LAM Antigen-Detection Assay for the Rapid Diagnosis of TBM in a High HIV Prevalence Setting

Patel, VB; Singh, R; Connolly, C; Kasprowicz, V; Zumla, A; Ndungu, T; Dheda, K; (2010) Comparison of a Clinical Prediction Rule and a LAM Antigen-Detection Assay for the Rapid Diagnosis of TBM in a High HIV Prevalence Setting. PLOS ONE , 5 (12) , Article e15664. 10.1371/journal.pone.0015664. Green open access

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Abstract

Background/Objective: The diagnosis of tuberculous meningitis (TBM) in resource poor TB endemic environments is challenging. The accuracy of current tools for the rapid diagnosis of TBM is suboptimal. We sought to develop a clinical-prediction rule for the diagnosis of TBM in a high HIV prevalence setting, and to compare performance outcomes to conventional diagnostic modalities and a novel lipoarabinomannan (LAM) antigen detection test (Clearview-TB (R)) using cerebrospinal fluid (CSF).Methods: Patients with suspected TBM were classified as definite-TBM(CSF culture or PCR positive), probable-TBM and non-TBM.Results: Of the 150 patients, 84% were HIV-infected (median [IQR] CD4 count = 132 [54; 241] cells/mu l). There were 39, 55 and 54 patients in the definite, probable and non-TBM groups, respectively. The LAM sensitivity and specificity (95% CI) was 31% (17; 48) and 94% (85; 99), respectively (cut-point >= 0.18). By contrast, smear-microscopy was 100% specific but detected none of the definite-TBM cases. LAM positivity was associated with HIV co-infection and low CD4 T cell count (CD4<200 vs.>200 cells/mu l; p = 0.03). The sensitivity and specificity in those with a CD4<100 cells/mu l was 50% (27; 73) and 95% (74; 99), respectively. A clinical-prediction rule >= 6 derived from multivariate analysis had a sensitivity and specificity (95% CI) of 47% (31; 64) and 98% (90; 100), respectively. When LAM was combined with the clinical-prediction-rule, the sensitivity increased significantly (p<0.001) to 63% (47; 68) and specificity remained high at 93% (82; 98).Conclusions: Despite its modest sensitivity the LAM ELISA is an accurate rapid rule-in test for TBM that has incremental value over smear-microscopy. The rule-in value of LAM can be further increased by combination with a clinical-prediction rule, thus enhancing the rapid diagnosis of TBM in HIV-infected persons with advanced immunosuppression.

Type: Article
Title: Comparison of a Clinical Prediction Rule and a LAM Antigen-Detection Assay for the Rapid Diagnosis of TBM in a High HIV Prevalence Setting
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0015664
Publisher version: http://dx.doi.org/10.1371/journal.pone.0015664
Language: English
Additional information: © 2010 Patel et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by the Columbia University-Southern African Fogarty AIDS International Training and Research Program funded by the Fogarty International Center, National Institutes of Health (grant # D43TW00231; VP), a South African Medical Research Council (SA MRC) grant (VP and KD), the European Union Seventh Framework Programme (TBsusgent; VP and KD), the South African National Research Foundation Research Chairs Initiative (SARChI; TN and KD), a SA MRC Career Development Award (KD), and the European and Developing Countries Clinical Trials Partnership (TESA and TB-NEAT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: HUMAN-IMMUNODEFICIENCY-VIRUS, CENTRAL-NERVOUS-SYSTEM, ACUTE BACTERIAL-MENINGITIS, TUBERCULOUS MENINGITIS, EXTRAPULMONARY TUBERCULOSIS, MYCOBACTERIUM-TUBERCULOSIS, URINARY LIPOARABINOMANNAN, MEDICAL-CENTER, ADULTS, INFECTION
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/706274
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