Performance of Lipoarabinomannan Assay using Cerebrospinal fluid for the diagnosis of Tuberculous meningitis among HIV patients

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.

Diagnostic value of the cerebrospinal fluid lipoarabinomannan assay for tuberculous meningitis: a systematic review and meta-analysis

“…All studies (n = 6) were published after 2009 and conducted in African countries, including South Africa (n = 2) (14, 15), Uganda (n = 3) (16,17,19), and Zambia (n = 1) (18). Three (14,16,17) were designed retrospectively and others (n = 3) prospectively. Only one study had a study period of less than 1 year (16).…”

“…Only one study had a study period of less than 1 year (16). Definite TBM was defined in all six studies, and clinical diagnoses were defined in five studies (14)(15)(16)(17)19). In five studies, CSF samples were collected by lumbar puncture, and in the remaining study (n = 1) ( 16), they were collected from the fourth ventricle.…”

“…Unprepared CSF samples were evaluated in all six studies, and only one study evaluated the CSF supernatant (16). The ELISA method for LAM measurement was evaluated in three studies (14-16), and the lateral flow assay was evaluated in four studies (16)(17)(18)(19). The cutoff values of urinary LAM assays were assessed in all studies.…”

Improving Technology to Diagnose Tuberculous Meningitis: Are We There Yet?

“…In a prospective study of PLHIV in Uganda, CSF Alere TB-LAM had a sensitivity of 33% (95% CI : 9.9–65.1%) and a specificity of 96% (95% CI : 85.5–99.5%) vs. probable or definite TBM diagnosed by Xpert Ultra ( 31 ). In another cohort made up predominantly of PLHIV in Zambia, CSF Alere LAM had a sensitivity of 21.9% and a specificity of 94.2% compared with CSF culture ( 32 ).…”

Neurologic Complications of Tuberculosis

“…However, efforts to utilize this assay on CSF for tuberculous meningitis have been suboptimal with poor sensitivity, although a positive CSF lipoarabinomannan antigen in people with HIV and tuberculous meningitis was correlated with higher mortality compared with patients with negative CSF lipoarabinomannan antigen. 20,24 Interferon gamma release assays are blood tests for detecting levels of interferon gamma released by T cells when exposed to TB antigens and are widely used to diagnose systemic TB. These assays include QuantiFERON (Qiagen), TB Gold (Qiagen), and T-Spot.TB (Oxford Immunotec).…”