Diagnostic accuracy of three urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients

Tobias Broger; Mark Nicol; George Sigal; Eduardo Gotuzzo; Alexandra J Zimmer; Shireen Surtie; Tatiana Caceres-Nakiche; Anna Mantsoki; Elena Ivanova Reipold; Rita Székely; Michael Tsionsky; Judith van Heerden; Tatiana Plisova; Kinuyo Chikamatsu; Todd L Lowary; Abraham Pinter; Satoshi Mitarai; Emmanuel Moreau; Samuel G Schumacher; Claudia M Denkinger

doi:10.1172/JCI140461

Diagnostic accuracy of three urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients

Tobias Broger, Mark Nicol, George Sigal, Eduardo Gotuzzo, Alexandra J Zimmer, Shireen Surtie, Tatiana Caceres-Nakiche, Anna Mantsoki, Elena Ivanova Reipold, Rita Székely, Michael Tsionsky, Judith van Heerden, Tatiana Plisova, Kinuyo Chikamatsu, Todd L Lowary, Abraham Pinter, Satoshi Mitarai, Emmanuel Moreau, Samuel G Schumacher, Claudia M Denkinger

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Abstract

BACKGROUND: Inadequate tuberculosis (TB) diagnostics are a major hurdle in the reduction of disease burden and accurate point-of-care tests (POCT) are urgently needed. We assessed the diagnostic accuracy of Fujifilm SILVAMP TB LAM (FujiLAM) for TB diagnosis in HIV-negative outpatients compared to Alere Determine TB LAM Ag (AlereLAM) and a laboratory-based ultrasensitive electrochemiluminescence LAM research assay (EclLAM).

METHODS: In this multicentre diagnostic test accuracy study, we recruited HIV-negative adults with symptoms suggestive of pulmonary TB presenting to outpatient healthcare centres in Peru and South Africa. Urine samples were tested using FujiLAM, AlereLAM and EclLAM and the diagnostic accuracy was assessed against microbiological (MRS) and composite reference standards.

RESULTS: 372 HIV-negative participants were included and the prevalence of microbiologically confirmed TB was 30%. Compared to the MRS, the sensitivities of AlereLAM, FujiLAM and EclLAM were 10.8% (95% CI 6.3to18.0), 53.2% (43.9to62.1), and 66.7% (57.5to74.7) respectively. The specificities of AlereLAM, FujiLAM and EclLAM were 92.3% (88.5to95.0), 98.9% (96.7to99.6), and 98.1% (95.6to99.2) respectively. Positive Likelihood Ratio of AlereLAM, FujiLAM and EclLAM were 1.4, 46.2, and 34.8 and positive predictive values 37.5%, 95.2%, and 93.7% respectively.

CONCLUSION: Compared to AlereLAM, FujiLAM detected five times more TB patients in HIV-negative participants, has 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 LAMs potential as a biomarker. Additional research is required to assess FujiLAMs performance in prospective cohorts, its cost-effectiveness, and its impact in real-world clinical settings.

Original language	English
Pages (from-to)	5756-5764
Number of pages	9
Journal	The Journal of clinical investigation
Volume	130
Issue number	11
Early online date	21 Jul 2020
DOIs	https://doi.org/10.1172/JCI140461
Publication status	Published - 2 Nov 2020

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Broger, T., Nicol, M., Sigal, G., Gotuzzo, E., 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. (2020). Diagnostic accuracy of three urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients. The Journal of clinical investigation, 130(11), 5756-5764. https://doi.org/10.1172/JCI140461

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title = "Diagnostic accuracy of three urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients",

abstract = "BACKGROUND: Inadequate tuberculosis (TB) diagnostics are a major hurdle in the reduction of disease burden and accurate point-of-care tests (POCT) are urgently needed. We assessed the diagnostic accuracy of Fujifilm SILVAMP TB LAM (FujiLAM) for TB diagnosis in HIV-negative outpatients compared to Alere Determine TB LAM Ag (AlereLAM) and a laboratory-based ultrasensitive electrochemiluminescence LAM research assay (EclLAM).METHODS: In this multicentre diagnostic test accuracy study, we recruited HIV-negative adults with symptoms suggestive of pulmonary TB presenting to outpatient healthcare centres in Peru and South Africa. Urine samples were tested using FujiLAM, AlereLAM and EclLAM and the diagnostic accuracy was assessed against microbiological (MRS) and composite reference standards.RESULTS: 372 HIV-negative participants were included and the prevalence of microbiologically confirmed TB was 30%. Compared to the MRS, the sensitivities of AlereLAM, FujiLAM and EclLAM were 10.8% (95% CI 6.3to18.0), 53.2% (43.9to62.1), and 66.7% (57.5to74.7) respectively. The specificities of AlereLAM, FujiLAM and EclLAM were 92.3% (88.5to95.0), 98.9% (96.7to99.6), and 98.1% (95.6to99.2) respectively. Positive Likelihood Ratio of AlereLAM, FujiLAM and EclLAM were 1.4, 46.2, and 34.8 and positive predictive values 37.5%, 95.2%, and 93.7% respectively.CONCLUSION: Compared to AlereLAM, FujiLAM detected five times more TB patients in HIV-negative participants, has 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 LAMs potential as a biomarker. Additional research is required to assess FujiLAMs performance in prospective cohorts, its cost-effectiveness, and its impact in real-world clinical settings.",

author = "Tobias Broger and Mark Nicol and George Sigal and Eduardo Gotuzzo and Zimmer, {Alexandra J} and Shireen Surtie and Tatiana Caceres-Nakiche and Anna Mantsoki and Reipold, {Elena Ivanova} and Rita Sz{\'e}kely and Michael Tsionsky and {van Heerden}, Judith and Tatiana Plisova and Kinuyo Chikamatsu and Lowary, {Todd L} and Abraham Pinter and Satoshi Mitarai and Emmanuel Moreau and Schumacher, {Samuel G} and Denkinger, {Claudia M}",

year = "2020",

month = nov,

day = "2",

doi = "10.1172/JCI140461",

language = "English",

volume = "130",

pages = "5756--5764",

journal = "The Journal of clinical investigation",

issn = "0021-9738",

publisher = "The American Society for Clinical Investigation",

number = "11",

}

Broger, T, Nicol, M, Sigal, G, Gotuzzo, E, Zimmer, AJ, Surtie, S, Caceres-Nakiche, T, Mantsoki, A, Reipold, EI, Székely, R, Tsionsky, M, van Heerden, J, Plisova, T, Chikamatsu, K, Lowary, TL, Pinter, A, Mitarai, S, Moreau, E, Schumacher, SG & Denkinger, CM 2020, 'Diagnostic accuracy of three urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients', The Journal of clinical investigation, vol. 130, no. 11, pp. 5756-5764. https://doi.org/10.1172/JCI140461

TY - JOUR

T1 - Diagnostic accuracy of three urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients

AU - Broger, Tobias

AU - Nicol, Mark

AU - Sigal, George

AU - Gotuzzo, Eduardo

AU - Zimmer, Alexandra J

AU - Surtie, Shireen

AU - Caceres-Nakiche, Tatiana

AU - Mantsoki, Anna

AU - Reipold, Elena Ivanova

AU - Székely, Rita

AU - Tsionsky, Michael

AU - van Heerden, Judith

AU - Plisova, Tatiana

AU - Chikamatsu, Kinuyo

AU - Lowary, Todd L

AU - Pinter, Abraham

AU - Mitarai, Satoshi

AU - Moreau, Emmanuel

AU - Schumacher, Samuel G

AU - Denkinger, Claudia M

PY - 2020/11/2

Y1 - 2020/11/2

N2 - BACKGROUND: Inadequate tuberculosis (TB) diagnostics are a major hurdle in the reduction of disease burden and accurate point-of-care tests (POCT) are urgently needed. We assessed the diagnostic accuracy of Fujifilm SILVAMP TB LAM (FujiLAM) for TB diagnosis in HIV-negative outpatients compared to Alere Determine TB LAM Ag (AlereLAM) and a laboratory-based ultrasensitive electrochemiluminescence LAM research assay (EclLAM).METHODS: In this multicentre diagnostic test accuracy study, we recruited HIV-negative adults with symptoms suggestive of pulmonary TB presenting to outpatient healthcare centres in Peru and South Africa. Urine samples were tested using FujiLAM, AlereLAM and EclLAM and the diagnostic accuracy was assessed against microbiological (MRS) and composite reference standards.RESULTS: 372 HIV-negative participants were included and the prevalence of microbiologically confirmed TB was 30%. Compared to the MRS, the sensitivities of AlereLAM, FujiLAM and EclLAM were 10.8% (95% CI 6.3to18.0), 53.2% (43.9to62.1), and 66.7% (57.5to74.7) respectively. The specificities of AlereLAM, FujiLAM and EclLAM were 92.3% (88.5to95.0), 98.9% (96.7to99.6), and 98.1% (95.6to99.2) respectively. Positive Likelihood Ratio of AlereLAM, FujiLAM and EclLAM were 1.4, 46.2, and 34.8 and positive predictive values 37.5%, 95.2%, and 93.7% respectively.CONCLUSION: Compared to AlereLAM, FujiLAM detected five times more TB patients in HIV-negative participants, has 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 LAMs potential as a biomarker. Additional research is required to assess FujiLAMs performance in prospective cohorts, its cost-effectiveness, and its impact in real-world clinical settings.

AB - BACKGROUND: Inadequate tuberculosis (TB) diagnostics are a major hurdle in the reduction of disease burden and accurate point-of-care tests (POCT) are urgently needed. We assessed the diagnostic accuracy of Fujifilm SILVAMP TB LAM (FujiLAM) for TB diagnosis in HIV-negative outpatients compared to Alere Determine TB LAM Ag (AlereLAM) and a laboratory-based ultrasensitive electrochemiluminescence LAM research assay (EclLAM).METHODS: In this multicentre diagnostic test accuracy study, we recruited HIV-negative adults with symptoms suggestive of pulmonary TB presenting to outpatient healthcare centres in Peru and South Africa. Urine samples were tested using FujiLAM, AlereLAM and EclLAM and the diagnostic accuracy was assessed against microbiological (MRS) and composite reference standards.RESULTS: 372 HIV-negative participants were included and the prevalence of microbiologically confirmed TB was 30%. Compared to the MRS, the sensitivities of AlereLAM, FujiLAM and EclLAM were 10.8% (95% CI 6.3to18.0), 53.2% (43.9to62.1), and 66.7% (57.5to74.7) respectively. The specificities of AlereLAM, FujiLAM and EclLAM were 92.3% (88.5to95.0), 98.9% (96.7to99.6), and 98.1% (95.6to99.2) respectively. Positive Likelihood Ratio of AlereLAM, FujiLAM and EclLAM were 1.4, 46.2, and 34.8 and positive predictive values 37.5%, 95.2%, and 93.7% respectively.CONCLUSION: Compared to AlereLAM, FujiLAM detected five times more TB patients in HIV-negative participants, has 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 LAMs potential as a biomarker. Additional research is required to assess FujiLAMs performance in prospective cohorts, its cost-effectiveness, and its impact in real-world clinical settings.

U2 - 10.1172/JCI140461

DO - 10.1172/JCI140461

M3 - Article

C2 - 32692731

VL - 130

SP - 5756

EP - 5764

JO - The Journal of clinical investigation

JF - The Journal of clinical investigation

SN - 0021-9738

IS - 11

ER -

Diagnostic accuracy of three urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients

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