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.
Rita SzékelyBianca SossenMadalo MukokaMonde MuyoyetaElizabeth NakabugoJerry HellaHung Van NguyenSasiwimol UbolyamKinuyo ChikamatsuAurélien MacéMarcia VermeulenChad M CentnerSarah NyanguNsala SanjaseMohamed SasamaloHuong Thi DinhThe Anh NgoWeerawat ManosuthiSupunnee JirajariyavejSatoshi MitaraiNhung Viet NguyenAnchalee AvihingsanonKlaus ReitherLydia NakiyingiAndrew D KerkhoffPeter MacPhersonGraeme MeintjesClaudia M DenkingerMorten Ruhwaldnull nullPublished in: PloS one (2024)
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).
Keyphrases
- mycobacterium tuberculosis
- pulmonary tuberculosis
- study protocol
- clinical trial
- decision making
- cystic fibrosis
- health insurance
- induced apoptosis
- stem cells
- phase ii
- high throughput
- high resolution
- signaling pathway
- phase iii
- single cell
- emergency department
- hiv aids
- bone marrow
- big data
- artificial intelligence
- cell death
- open label
- mass spectrometry
- hepatitis c virus
- double blind
- deep learning
- nk cells