Title
Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients
Date Issued
02 November 2020
Access level
open access
Resource Type
journal article
Author(s)
Broger T.
Nicol M.P.
Sigal G.B.
Zimmer A.J.
Surtie S.
Caceres-Nakiche T.
Mantsoki A.
Reipold E.I.
Székely R.
Tsionsky M.
van Heerden J.
Plisova T.
Chikamatsu K.
Lowary T.L.
Pinter A.
Mitarai S.
Moreau E.
Schumacher S.G.
Denkinger C.M.
Publisher(s)
American Society for Clinical Investigation
Abstract
BACKGROUND. Inadequate tuberculosis (TB) diagnostics are a major hurdle in the reduction of disease burden, and accurate point-of-care tests (POCTs) are urgently needed. We assessed the diagnostic accuracy of Fujifilm SILVAMP TB lipoarabinomannan (FujiLAM) POCT for TB diagnosis in HIV-negative outpatients and compared it with Alere Determine TB LAM Ag (AlereLAM) POCT and a laboratory-based ultrasensitive electrochemiluminescence LAM research assay (EclLAM). METHODS. In this multicenter diagnostic test accuracy study, we recruited HIV-negative adults with symptoms suggestive of pulmonary TB presenting to outpatient health care centers in Peru and South Africa. Urine samples were tested using FujiLAM, AlereLAM, and EclLAM, and the diagnostic accuracy was assessed against a microbiological reference standard (MRS) and a composite reference standard. RESULTS. Three hundred seventy-two HIV-negative participants were included and the prevalence of microbiologically confirmed TB was 30%. Compared with the MRS, the sensitivities of AlereLAM, FujiLAM, and EclLAM were 10.8% (95% confidence interval [CI] 6.3%–18.0%), 53.2% (95% CI 43.9%–62.1%), and 66.7% (95% CI 57.5%–74.7%), respectively. The specificities of AlereLAM, FujiLAM, and EclLAM were 92.3% (95% CI 88.5%–95.0%), 98.9% (95% CI 96.7%–99.6%), and 98.1% (95% CI 95.6%–99.2%), respectively. Positive likelihood ratios of AlereLAM, FujiLAM, and EclLAM were 1.4, 46.2, and 34.8, respectively, and positive predictive values were 37.5%, 95.2%, and 93.7%, respectively. CONCLUSION. Compared with AlereLAM, FujiLAM detected 5 times more patients with TB in HIV-negative participants, had a high positive predictive value, and has the potential to improve rapid diagnosis of TB at the point-of-care. EclLAM demonstrated that additional sensitivity gains are possible, which highlights LAM’s potential as a biomarker. Additional research is required to assess FujiLAM’s performance in prospective cohorts, its cost-effectiveness, and its impact in real-world clinical settings. FUNDING. Global Health Innovative Technology Fund, the UK Department for International Development, the Dutch Ministry of Foreign Affairs, the Bill and Melinda Gates Foundation, the Australian Department of Foreign Affairs and Trade, the German Federal Ministry of Education and Research through Kreditanstalt für Wiederaufbau, and the NIH and National Institute of Allergy and Infectious Diseases.
Start page
5756
End page
5764
Volume
130
Issue
11
Language
English
OCDE Knowledge area
Sistema respiratorio Inmunología
Scopus EID
2-s2.0-85094957362
PubMed ID
Source
Journal of Clinical Investigation
ISSN of the container
00219738
Sponsor(s)
Authorship note: TB and MPN contributed equally and are co–first authors. EM, SGS, and CMD contributed equally. Conflict of interest: TB, AM, EIP, RS, EM, SGS, and CMD were previously or are currently employed by FIND. GBS, MT, and TP are employed by Meso Scale Diagnostics LLC and received funding from FIND. AP is an author on patents in the field of lipoarabinomannan (LAM) detection, “Novel anti-lam and anti-pim6/lam monoclonal antibodies for diagnosis and treatment of mycobacterium tuberculosis infections” (US20190038747) and “Methods for dual detection and differentiation of infection by mycobactierum tuberculosis complex and nontuberculous mycobacteria” (WO2020018806). TB is an author on a patent in the field of LAM detection, “Antibody or antibody combination and method using same for detection of an antigen related to mycobacterium in a urine sample of a subject” (WO2019186486). Role of funding source: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2020, Broger et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License. Submitted: May 20, 2020; Accepted: July 16, 2020; Published: September 28, 2020. Reference information: J Clin Invest. 2020;130(11):5756–5764. https://doi.org/10.1172/JCI140461. FUNDING. Global Health Innovative Technology Fund, the UK Department for International Development, the Dutch Ministry of Foreign Affairs, the Bill and Melinda Gates Foundation, the Australian Department of Foreign Affairs and Trade, the German Federal Ministry of Education and Research through Kreditanstalt für Wiederaufbau, and the NIH and National Institute of Allergy and Infectious Diseases. The authors thank Mark D. Perkins and Ranald Sutherland for helping with the conceptualization of this work; Michelle A. Bulterys, Amanda Jackson, Celeste Worship, Meagan McMaster, Aur?lien Mac?, Stefano Ongarello, and Andr? Trollip for data management; and the clinical and laboratory teams, including Jimena Collantes, Cesar Ugarte, Nchimunya Hapeemla, and Widaad Zemanay, at the partner sites for their efforts in the implementation, conduct, and timely completion of the study. This work was funded by the Global Health Innovative Technology Fund (grant G2015-201), the UK Department for International Development (grant 300341-102), the Dutch Ministry of Foreign Affairs (grant PDP15CH14), the Bill and Melinda Gates Foundation (grant OPP1151258), the Australian Department of Foreign Affairs and Trade (grant 70957), the German Federal Ministry of Education and Research through Kreditanstalt f?r Wiederaufbau (grant 2020 60 457), and the National Institute of Allergy and Infectious Diseases, NIH (grant 1R01AI104589).
Sources of information: Directorio de Producción Científica Scopus