Novel lipoarabinomannan point-of-care tuberculosis test for people with HIV: a diagnostic accuracy study

Abstract

Summary Background Most tuberculosis-related deaths in people with HIV could be prevented with earlier diagnosis and treatment. The only commercially available tuberculosis point-of-care test (Alere Determine TB LAM Ag [AlereLAM]) has suboptimal sensitivity, which restricts its use in clinical practice. The novel Fujifilm SILVAMP TB LAM (FujiLAM) assay has been developed to improve the sensitivity of AlereLAM. We assessed the diagnostic accuracy of the FujiLAM assay for the detection of tuberculosis in hospital inpatients with HIV compared with the AlereLAM assay. Methods For this diagnostic accuracy study, we assessed biobanked urine samples obtained from the FIND Specimen Bank and the University of Cape Town Biobank, which had been collected from hospital inpatients (aged ≥18 years) with HIV during three independent prospective cohort studies done at two South African hospitals. Urine samples were tested using FujiLAM and AlereLAM assays. The conduct and reporting of each test was done blind to other test results. The primary objective was to assess the diagnostic accuracy of FujiLAM compared with AlereLAM, against microbiological and composite reference standards (including clinical diagnoses). Findings Between April 18, 2018, and May 3, 2018, urine samples from 968 hospital inpatients with HIV were evaluated. The prevalence of microbiologically-confirmed tuberculosis was 62% and the median CD4 count was 86 cells per μL. Using the microbiological reference standard, the estimated sensitivity of FujiLAM was 70·4% (95% CI 53·0 to 83·1) compared with 42·3% (31·7 to 51·8) for AlereLAM (difference 28·1%) and the estimated specificity of FujiLAM was 90·8% (86·0 to 94·4) and 95·0% (87·7–98·8) for AlereLAM (difference −4·2%). Against the composite reference standard, the specificity of both assays was higher (95·7% [92·0 to 98·0] for FujiLAM vs 98·2% [95·7 to 99·6] for AlereLAM; difference −2·5%), but the sensitivity of both assays was lower (64·9% [50·1 to 76·7] for FujiLAM vs 38·2% [28·1 to 47·3] for AlereLAM; difference 26·7%). Interpretation In comparison to AlereLAM, FujiLAM offers superior diagnostic sensitivity, while maintaining specificity, and could transform rapid point-of-care tuberculosis diagnosis for hospital inpatients with HIV. The applicability of FujiLAM for settings of intended use requires prospective assessment. Funding Global Health Innovative Technology Fund, UK Department for International Development, Dutch Ministry of Foreign Affairs, Bill & Melinda Gates Foundation, German Federal Ministry of Education and Research, Australian Department of Foreign Affairs and Trade, Wellcome Trust, Department of Science and Technology and National Research Foundation of South Africa, and South African Medical Research Council.

Adoption and uptake of the lateral flow urine LAM test in countries with high tuberculosis and HIV/AIDS burden: current landscape and barriers

“…The barriers identified in our questionnaire, along with advocacy reports by groups such as TAG and MSF, can help policy makers, country governments, and donors build better strategies for Alere-LAM implementation and scale-up. These questionnaire results should help guide efforts to develop higher-sensitivity urine LAM tests [33][34][35] and rapidly roll them out, as country adoption of improved products must anticipate challenges from the field.…”

T Cell Responses to Mycobacterial Glycolipids: On the Spectrum of “Innateness”

“…Notably, diagnostics targeting cell surface mycolipids are already being used for both TB and leprosy. High-affinity IgG antibodies targeting LAM have been incorporated into a urinebased assay for TB and have shown clinical utility in the setting of HIV co-infection (94). IgM antibodies targeting phenolic glycolipids (PGLs) are being used for the diagnosis of leprosy (95).…”

Point-Of-Care Urine LAM Tests for Tuberculosis Diagnosis: A Status Update

“…This work by Sigal et al informed the development of the Fujifilm SILVAMP TB LAM test ("FujiLAM"; Fujifilm, Tokyo, Japan, Figure 1), which is a well-advanced next-generation LAM test (CE-marked) [20,27,55] (Table 1). The assay combines a pair of high-affinity monoclonal antibodies directed towards the largely Mtb-specific MTX-LAM epitopes and a silver-based amplification step that increases the visibility of test and control lines of a lateral-flow assay to reach a cut-off around 30 pg/mL [27]. This enables the detection of approximately 30-fold lower concentrations of LAM in urine compared to the AlereLAM test.…”