Urine lipoarabinomannan concentrations among HIV-negative adults with pulmonary or extrapulmonary tuberculosis disease in Vietnam.

Lipoarabinomannan (LAM) is a promising target biomarker for diagnosing subclinical and clinical tuberculosis (TB). Urine LAM (uLAM) testing using rapid diagnostic tests (RDTs) has been approved for people living with HIV (PLWH), however there is limited data regarding uLAM levels in HIV-negative (HI...

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Main Authors: Nguyen B Hoa, Mark Fajans, Hung Nguyen Van, Bao Vu Ngoc, Nhung Nguyen Viet, Hoa Nguyen Thi, Lien Tran Thi Huong, Dung Tran Minh, Cuong Nguyen Kim, Trinh Ha Thi Tuyet, Tri Nguyen Huu, Diep Bui Ngoc, Hai Nguyen Viet, An Tran Khanh, Lorraine Lillis, Marcos Perez, Katherine K Thomas, Roger B Peck, Jason L Cantera, Eileen Murphy, Olivia R Halas, Helen L Storey, Abraham Pinter, Morten Ruhwald, Paul K Drain, David S Boyle
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-01-01
Series:PLOS Global Public Health
Online Access:https://doi.org/10.1371/journal.pgph.0003891
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author Nguyen B Hoa
Mark Fajans
Hung Nguyen Van
Bao Vu Ngoc
Nhung Nguyen Viet
Hoa Nguyen Thi
Lien Tran Thi Huong
Dung Tran Minh
Cuong Nguyen Kim
Trinh Ha Thi Tuyet
Tri Nguyen Huu
Diep Bui Ngoc
Hai Nguyen Viet
An Tran Khanh
Lorraine Lillis
Marcos Perez
Katherine K Thomas
Roger B Peck
Jason L Cantera
Eileen Murphy
Olivia R Halas
Helen L Storey
Abraham Pinter
Morten Ruhwald
Paul K Drain
David S Boyle
author_facet Nguyen B Hoa
Mark Fajans
Hung Nguyen Van
Bao Vu Ngoc
Nhung Nguyen Viet
Hoa Nguyen Thi
Lien Tran Thi Huong
Dung Tran Minh
Cuong Nguyen Kim
Trinh Ha Thi Tuyet
Tri Nguyen Huu
Diep Bui Ngoc
Hai Nguyen Viet
An Tran Khanh
Lorraine Lillis
Marcos Perez
Katherine K Thomas
Roger B Peck
Jason L Cantera
Eileen Murphy
Olivia R Halas
Helen L Storey
Abraham Pinter
Morten Ruhwald
Paul K Drain
David S Boyle
author_sort Nguyen B Hoa
collection DOAJ
description Lipoarabinomannan (LAM) is a promising target biomarker for diagnosing subclinical and clinical tuberculosis (TB). Urine LAM (uLAM) testing using rapid diagnostic tests (RDTs) has been approved for people living with HIV (PLWH), however there is limited data regarding uLAM levels in HIV-negative (HIV-ve) adults with clinical TB. We conducted a clinical study of adults presenting with clinical TB-related symptoms at the National Lung Hospital in Hanoi, Vietnam. The uLAM concentrations were measured using electrochemiluminescent (ECL) immunoassays and compared to a microbiological reference standard (MRS) using GeneXpert Ultra and TB culture testing. Estimated uLAM concentrations above plate specific calculated limit of detection (LOD) were considered uLAM positive. Additional microbiological testing was conducted for possible extrapulmonary TB (EPTB). Among 745 participants enrolled, 335 (44.9%) participants with presumptive pulmonary TB (PTB) and 6 (11.3%) participants with presumptive EPTB had confirmed TB disease. Overall, the S/A antibody pair had a sensitivity of 39% (95% Confidence Interval [CI] 0.33, 0.44) and a specificity of 97% (95% CI 0.96, 0.99) compared to the MRS. The F/A antibody pair had a sensitivity of 41% (95% CI 0.35, 0.47) and a specificity of 79% (95% CI 0.75, 0.84). S/A provided greater discriminatory ability compared to F/A for both individuals with presumptive PTB (AUROC: 0.74 vs 0.63, p<0.0001) and presumptive EPTB (0.76 vs 0.54, p = 0.045) when using the MRS. Among HIV-ve participants in an adult cohort in Vietnam, the concentrations of uLAM remained relatively low for people with clinical TB, which may present challenges for improving RDT sensitivity.
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spelling doaj-art-166403e595db4f38a8a7f2969d664e6c2025-08-20T03:05:55ZengPublic Library of Science (PLoS)PLOS Global Public Health2767-33752024-01-01411e000389110.1371/journal.pgph.0003891Urine lipoarabinomannan concentrations among HIV-negative adults with pulmonary or extrapulmonary tuberculosis disease in Vietnam.Nguyen B HoaMark FajansHung Nguyen VanBao Vu NgocNhung Nguyen VietHoa Nguyen ThiLien Tran Thi HuongDung Tran MinhCuong Nguyen KimTrinh Ha Thi TuyetTri Nguyen HuuDiep Bui NgocHai Nguyen VietAn Tran KhanhLorraine LillisMarcos PerezKatherine K ThomasRoger B PeckJason L CanteraEileen MurphyOlivia R HalasHelen L StoreyAbraham PinterMorten RuhwaldPaul K DrainDavid S BoyleLipoarabinomannan (LAM) is a promising target biomarker for diagnosing subclinical and clinical tuberculosis (TB). Urine LAM (uLAM) testing using rapid diagnostic tests (RDTs) has been approved for people living with HIV (PLWH), however there is limited data regarding uLAM levels in HIV-negative (HIV-ve) adults with clinical TB. We conducted a clinical study of adults presenting with clinical TB-related symptoms at the National Lung Hospital in Hanoi, Vietnam. The uLAM concentrations were measured using electrochemiluminescent (ECL) immunoassays and compared to a microbiological reference standard (MRS) using GeneXpert Ultra and TB culture testing. Estimated uLAM concentrations above plate specific calculated limit of detection (LOD) were considered uLAM positive. Additional microbiological testing was conducted for possible extrapulmonary TB (EPTB). Among 745 participants enrolled, 335 (44.9%) participants with presumptive pulmonary TB (PTB) and 6 (11.3%) participants with presumptive EPTB had confirmed TB disease. Overall, the S/A antibody pair had a sensitivity of 39% (95% Confidence Interval [CI] 0.33, 0.44) and a specificity of 97% (95% CI 0.96, 0.99) compared to the MRS. The F/A antibody pair had a sensitivity of 41% (95% CI 0.35, 0.47) and a specificity of 79% (95% CI 0.75, 0.84). S/A provided greater discriminatory ability compared to F/A for both individuals with presumptive PTB (AUROC: 0.74 vs 0.63, p<0.0001) and presumptive EPTB (0.76 vs 0.54, p = 0.045) when using the MRS. Among HIV-ve participants in an adult cohort in Vietnam, the concentrations of uLAM remained relatively low for people with clinical TB, which may present challenges for improving RDT sensitivity.https://doi.org/10.1371/journal.pgph.0003891
spellingShingle Nguyen B Hoa
Mark Fajans
Hung Nguyen Van
Bao Vu Ngoc
Nhung Nguyen Viet
Hoa Nguyen Thi
Lien Tran Thi Huong
Dung Tran Minh
Cuong Nguyen Kim
Trinh Ha Thi Tuyet
Tri Nguyen Huu
Diep Bui Ngoc
Hai Nguyen Viet
An Tran Khanh
Lorraine Lillis
Marcos Perez
Katherine K Thomas
Roger B Peck
Jason L Cantera
Eileen Murphy
Olivia R Halas
Helen L Storey
Abraham Pinter
Morten Ruhwald
Paul K Drain
David S Boyle
Urine lipoarabinomannan concentrations among HIV-negative adults with pulmonary or extrapulmonary tuberculosis disease in Vietnam.
PLOS Global Public Health
title Urine lipoarabinomannan concentrations among HIV-negative adults with pulmonary or extrapulmonary tuberculosis disease in Vietnam.
title_full Urine lipoarabinomannan concentrations among HIV-negative adults with pulmonary or extrapulmonary tuberculosis disease in Vietnam.
title_fullStr Urine lipoarabinomannan concentrations among HIV-negative adults with pulmonary or extrapulmonary tuberculosis disease in Vietnam.
title_full_unstemmed Urine lipoarabinomannan concentrations among HIV-negative adults with pulmonary or extrapulmonary tuberculosis disease in Vietnam.
title_short Urine lipoarabinomannan concentrations among HIV-negative adults with pulmonary or extrapulmonary tuberculosis disease in Vietnam.
title_sort urine lipoarabinomannan concentrations among hiv negative adults with pulmonary or extrapulmonary tuberculosis disease in vietnam
url https://doi.org/10.1371/journal.pgph.0003891
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