Performance of lipoarabinomannan assay using cerebrospinal fluid for the diagnosis of tuberculous meningitis among HIV patients [version 1; peer review: 2 approved]

Richard Kwizera, Fiona V. Cresswell, Gerald Mugumya, Micheal Okirwoth, Enock Kagimu, Ananta S. Bangdiwala, Darlisha A. Williams, Joshua Rhein, David R. Boulware, David B. Meya

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3 Scopus citations

Abstract

Background: The diagnostic utility of the Mycobacteria tuberculosis lipoarabinomannan (TB-LAM) antigen lateral flow assay on cerebrospinal fluid (CSF) for the diagnosis of tuberculous meningitis (TBM) has not been extensively studied and the few published studies have conflicting results. Methods: Lumbar CSF from 59 HIV-positive patients with suspected TBM was tested with TB-LAM and Xpert MTB/Rif Ultra. The diagnostic performance of CSF TB-LAM was compared to positive CSF Xpert MTB/Rif Ultra (definite TBM) and a composite reference of probable or definite TBM according to the uniform case definition. Results: Of 59 subjects, 12 (20%) had definite TBM and five (9%) had probable TBM. With reference to definite TBM, CSF TB-LAM assay had a diagnostic sensitivity of 33% and specificity of 96%. When compared to a composite reference of definite or probable TBM, the sensitivity was 24% and specificity was 95%. There were two false positive tests with TB-LAM (3+ grade). In-hospital mortality in CSF TB-LAM positive patients was 17% compared to 0% in those with definite TBM by Xpert MTB/Rif Ultra but negative LAM. Conclusions: Lumbar CSF TB-LAM has a poor performance in diagnosing TBM. Both urine TB-LAM and Xpert Ultra should be further investigated in the diagnosis of TBM.

Original languageEnglish (US)
Article number123
JournalWellcome Open Research
Volume4
DOIs
StatePublished - 2019

Bibliographical note

Funding Information:
This work was supported by the Wellcome Trust [107742, 107743 and 210772]. This research was also supported in part by the National Institute of Neurologic Diseases and Stroke (NINDS) and Fogarty International Center [R01NS086312, K01TW010268]. DBM and RK are currently supported through the DELTAS Africa Initiative grant [DEL-15-011] to THRiVE-2, from Wellcome Trust grant [107742] and the UK government. FVC is supported through a Wellcome Clinical PhD Fellowship [210772]. FVC is an honorary fellow of the Makerere University ? UVRI Centre of Excellence for Infection and Immunity Research and Training (MUII-plus). MUII-plus is supported through the DELTAS Africa Initiative [107743]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD) with funding from the Wellcome Trust [107743] and the UK Government. The MRC/UVRI and LSHTM Uganda Research Unit is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 programme supported by the European Union. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript..

Publisher Copyright:
© 2019 Kwizera R et al.

Keywords

  • Cerebrospinal fluid
  • Diagnostics
  • Extra-pulmonary TB
  • HIV
  • Lipoarabinomannan
  • TB-LAM
  • Tuberculous meningitis
  • Xpert MTB/Rif Ultra

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