Prospective multicentre accuracy evaluation of the FUJIFILM SILVAMP TB LAM test for the diagnosis of tuberculosis in people living with HIV demonstrates lot-to-lot variability

Prospective multicentre accuracy evaluation of the FUJIFILM SILVAMP TB LAM test for the diagnosis of tuberculosis in people living with HIV demonstrates lot-to-lot variability. Székely, R., Sossen, B., Mukoka, M., Muyoyeta, M., Nakabugo, E., Hella, J., Nguyen, H. V., Ubolyam, S., Chikamatsu, K., Macé, A., Vermeulen, M., Centner, C. M, Nyangu, S., Sanjase, N., Sasamalo, M., Dinh, H. T., Ngo, T. A., Manosuthi, W., Jirajariyavej, S., Mitarai, S., Nguyen, N. V., Avihingsanon, A., Reither, K., Nakiyingi, L., Kerkhoff, A. D., MacPherson, P., Meintjes, G. A, Denkinger, C. M, Ruhwald, M., & FujiLAM Study Consortium PLOS ONE, 19(5):e0303846, Public Library of Science, may, 2024.

Paper doi abstract bibtex

There is an urgent need for rapid, non-sputum point-of-care diagnostics to detect tuberculosis. This prospective trial in seven high tuberculosis burden countries evaluated the diagnostic accuracy of the point-of-care urine-based lipoarabinomannan assay FUJIFILM SILVAMP TB LAM (FujiLAM) among inpatients and outpatients living with HIV. Diagnostic performance of FujiLAM was assessed against a mycobacterial reference standard (sputum culture, blood culture, and Xpert Ultra from urine and sputum at enrollment, and additional sputum culture ≤7 days from enrollment), an extended mycobacterial reference standard (eMRS), and a composite reference standard including clinical evaluation. Of 1637 participants considered for the analysis, 296 (18%) were tuberculosis positive by eMRS. Median age was 40 years, median CD4 cell count was 369 cells/ul, and 52% were female. Overall FujiLAM sensitivity was 54˙4% (95% CI: 48˙7–60˙0), overall specificity was 85˙2% (83˙2–87˙0) against eMRS. Sensitivity and specificity estimates varied between sites, ranging from 26˙5% (95% CI: 17˙4%–38˙0%) to 73˙2% (60˙4%–83˙0%), and 75˙0 (65˙0%–82˙9%) to 96˙5 (92˙1%–98˙5%), respectively. Post-hoc exploratory analysis identified significant variability in the performance of the six FujiLAM lots used in this study. Lot variability limited interpretation of FujiLAM test performance. Although results with the current version of FujiLAM are too variable for clinical decision-making, the lipoarabinomannan biomarker still holds promise for tuberculosis diagnostics. The trial is registered at clinicaltrials.gov (NCT04089423).

@article{Szekely2024,
abstract = {There is an urgent need for rapid, non-sputum point-of-care diagnostics to detect tuberculosis. This prospective trial in seven high tuberculosis burden countries evaluated the diagnostic accuracy of the point-of-care urine-based lipoarabinomannan assay FUJIFILM SILVAMP TB LAM (FujiLAM) among inpatients and outpatients living with HIV. Diagnostic performance of FujiLAM was assessed against a mycobacterial reference standard (sputum culture, blood culture, and Xpert Ultra from urine and sputum at enrollment, and additional sputum culture ≤7 days from enrollment), an extended mycobacterial reference standard (eMRS), and a composite reference standard including clinical evaluation. Of 1637 participants considered for the analysis, 296 (18{\%}) were tuberculosis positive by eMRS. Median age was 40 years, median CD4 cell count was 369 cells/ul, and 52{\%} were female. Overall FujiLAM sensitivity was 54{\textperiodcentered}4{\%} (95{\%} CI: 48{\textperiodcentered}7–60{\textperiodcentered}0), overall specificity was 85{\textperiodcentered}2{\%} (83{\textperiodcentered}2–87{\textperiodcentered}0) against eMRS. Sensitivity and specificity estimates varied between sites, ranging from 26{\textperiodcentered}5{\%} (95{\%} CI: 17{\textperiodcentered}4{\%}–38{\textperiodcentered}0{\%}) to 73{\textperiodcentered}2{\%} (60{\textperiodcentered}4{\%}–83{\textperiodcentered}0{\%}), and 75{\textperiodcentered}0 (65{\textperiodcentered}0{\%}–82{\textperiodcentered}9{\%}) to 96{\textperiodcentered}5 (92{\textperiodcentered}1{\%}–98{\textperiodcentered}5{\%}), respectively. Post-hoc exploratory analysis identified significant variability in the performance of the six FujiLAM lots used in this study. Lot variability limited interpretation of FujiLAM test performance. Although results with the current version of FujiLAM are too variable for clinical decision-making, the lipoarabinomannan biomarker still holds promise for tuberculosis diagnostics. The trial is registered at clinicaltrials.gov (NCT04089423).},
author = {Sz{\'{e}}kely, Rita and Sossen, Bianca and Mukoka, Madalo and Muyoyeta, Monde and Nakabugo, Elizabeth and Hella, Jerry and Nguyen, Hung Van and Ubolyam, Sasiwimol and Chikamatsu, Kinuyo and Mac{\'{e}}, Aur{\'{e}}lien and Vermeulen, Marcia and Centner, Chad M and Nyangu, Sarah and Sanjase, Nsala and Sasamalo, Mohamed and Dinh, Huong Thi and Ngo, The Anh and Manosuthi, Weerawat and Jirajariyavej, Supunnee and Mitarai, Satoshi and Nguyen, Nhung Viet and Avihingsanon, Anchalee and Reither, Klaus and Nakiyingi, Lydia and Kerkhoff, Andrew D. and MacPherson, Peter and Meintjes, Graeme A and Denkinger, Claudia M and Ruhwald, Morten and {FujiLAM Study Consortium}},
doi = {10.1371/JOURNAL.PONE.0303846},
editor = {Pham, Minh Duc},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Sz{\'{e}}kely et al. - 2024 - Prospective multicentre accuracy evaluation of the FUJIFILM SILVAMP TB LAM test for the diagnosis of tuberculosi.pdf:pdf},
isbn = {1111111111},
issn = {1932-6203},
journal = {PLOS ONE},
keywords = {HIV diagnosis and management,Mycobacterium tuberculosis,Nontuberculous mycobacteria,OA,OA{\_}PMC,Sputum,Tuberculosis,Tuberculosis diagnosis and management,Urine,Virus testing,fund{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,original},
month = {may},
number = {5},
pages = {e0303846},
pmid = {38820372},
publisher = {Public Library of Science},
title = {{Prospective multicentre accuracy evaluation of the FUJIFILM SILVAMP TB LAM test for the diagnosis of tuberculosis in people living with HIV demonstrates lot-to-lot variability}},
url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0303846},
volume = {19},
year = {2024}
}

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Sensitivity and specificity estimates varied between sites, ranging from 26˙5% (95% CI: 17˙4%–38˙0%) to 73˙2% (60˙4%–83˙0%), and 75˙0 (65˙0%–82˙9%) to 96˙5 (92˙1%–98˙5%), respectively. Post-hoc exploratory analysis identified significant variability in the performance of the six FujiLAM lots used in this study. Lot variability limited interpretation of FujiLAM test performance. Although results with the current version of FujiLAM are too variable for clinical decision-making, the lipoarabinomannan biomarker still holds promise for tuberculosis diagnostics. 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