Real-world diagnostic accuracy of lipoarabinomannan in three non-sputum biospecimens for pulmonary tuberculosis disease.

Diagnostic accuracy Electrochemiluminescence immunoassay HIV Lipoarabinomannan Non-sputum Tuberculosis

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
26 Sep 2024
Historique:
received: 29 03 2024
revised: 14 08 2024
accepted: 05 09 2024
medline: 28 9 2024
pubmed: 28 9 2024
entrez: 27 9 2024
Statut: aheadofprint

Résumé

Development of a non-sputum test using readily-obtainable biospecimens remains a global priority for tuberculosis (TB) control. We quantified lipoarabinomannan (LAM) concentrations, a pathogen biomarker for Mycobacterium tuberculosis, in urine, plasma and serum for real-world diagnostic accuracy of pulmonary TB among people living with and without HIV. We conducted a prospective diagnostic study among adults with TB symptoms in South Africa. We measured LAM concentrations in time-matched urine, plasma and serum with an electrochemiluminescence immunoassay using two capture antibodies (FIND 28 and S4-20). From the completed cohort, we randomly selected 210 participants (2 cases: 1 control) based on sensitivity estimates, and we compared diagnostic accuracy of LAM measurements against the microbiological reference standard. Urine and blood specimens from 210 of 684 adults enrolled were tested for LAM. Among 138 TB-positive adults (41% female), median urine LAM was 137 pg/mL and 52 pg/mL by FIND 28 and S4-20, respectively. Average LAM concentrations were highest in HIV-positive participants with CD4+ T cells <200 cells/mm Detection of LAM was achievable in non-sputum specimens for pulmonary TB, but additional analyte concentration or signal amplification may be required to achieve diagnostic accuracy targets. Bill and Melinda Gates Foundation.

Sections du résumé

BACKGROUND BACKGROUND
Development of a non-sputum test using readily-obtainable biospecimens remains a global priority for tuberculosis (TB) control. We quantified lipoarabinomannan (LAM) concentrations, a pathogen biomarker for Mycobacterium tuberculosis, in urine, plasma and serum for real-world diagnostic accuracy of pulmonary TB among people living with and without HIV.
METHODS METHODS
We conducted a prospective diagnostic study among adults with TB symptoms in South Africa. We measured LAM concentrations in time-matched urine, plasma and serum with an electrochemiluminescence immunoassay using two capture antibodies (FIND 28 and S4-20). From the completed cohort, we randomly selected 210 participants (2 cases: 1 control) based on sensitivity estimates, and we compared diagnostic accuracy of LAM measurements against the microbiological reference standard.
FINDINGS RESULTS
Urine and blood specimens from 210 of 684 adults enrolled were tested for LAM. Among 138 TB-positive adults (41% female), median urine LAM was 137 pg/mL and 52 pg/mL by FIND 28 and S4-20, respectively. Average LAM concentrations were highest in HIV-positive participants with CD4+ T cells <200 cells/mm
INTERPRETATION CONCLUSIONS
Detection of LAM was achievable in non-sputum specimens for pulmonary TB, but additional analyte concentration or signal amplification may be required to achieve diagnostic accuracy targets.
FUNDING BACKGROUND
Bill and Melinda Gates Foundation.

Identifiants

DOI: 10.1016/j.ebiom.2024.105353 PMID: 39332390
pubmed: 39332390
pii: S2352-3964(24)00389-X
doi: 10.1016/j.ebiom.2024.105353
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

105353

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests PKD and DW declare receiving grant funding, paid to the institution, from the Bill and Melinda Gates Foundation. PKD reports receiving consulting fees from ThermoFischer, InBios Internation, and Abbott Diagnostics, and advisory board fees from Abbvie and Cepheid. Rutgers University (AP) has a patent on the use of the A194-01 antibody for diagnosis of TB infections.

Auteurs

Paul K Drain (PK)

Department of Global Health, University of Washington, Seattle, WA, USA; Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA. Electronic address: pkdrain@uw.edu.

Xin Niu (X)

Department of Epidemiology, University of Washington, Seattle, WA, USA.

Adrienne E Shapiro (AE)

Department of Global Health, University of Washington, Seattle, WA, USA; Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.

Zanele P Magcaba (ZP)

Umkhuseli Research and Innovation Management, Pietermaritzburg, South Africa.

Zinhle Ngcobo (Z)

Umkhuseli Research and Innovation Management, Pietermaritzburg, South Africa.

M William Ngwane (MW)

Umkhuseli Research and Innovation Management, Pietermaritzburg, South Africa.

Katherine K Thomas (KK)

Department of Global Health, University of Washington, Seattle, WA, USA.

Ronit R Dalmat (RR)

Department of Global Health, University of Washington, Seattle, WA, USA.

Jennifer F Morton (JF)

Department of Global Health, University of Washington, Seattle, WA, USA.

Elvira Budiawan (E)

Department of Global Health, University of Washington, Seattle, WA, USA.

Abraham Pinter (A)

New Jersey Medical School, Rutgers University, Newark, NJ, USA.

Jason Cantera (J)

Global Health Labs, Bellevue, WA, USA.

Caitlin Anderson (C)

Global Health Labs, Bellevue, WA, USA.

Rose Buchmann (R)

Global Health Labs, Bellevue, WA, USA.

Doug Wilson (D)

Umkhuseli Research and Innovation Management, Pietermaritzburg, South Africa; University of KwaZulu-Natal, Pietermaritzburg, South Africa.

Ben Grant (B)

Global Health Labs, Bellevue, WA, USA.

Classifications MeSH