Ultra-sensitive urinary lipoarabinomannan (LAM) immunoassay for tuberculosis detection: a performance evaluation

作者：Qisheng Jiang, Carolyn Duncan, Harisha Ramachandraiah, Ige George, Sumanth Gandra, Marcos Perez, Lorraine Lillis, David S. Boyle, Scott L. Crick, Morten Rühwald, Srikanth Singamaneni · 发表于：EBioMedicine · 年份：2025 · DOI：10.1016/j.ebiom.2025.105885 · 被引用次数：4 · 研究领域：Tuberculosis Research and Epidemiology、Biosensors and Analytical Detection、Diagnosis and treatment of tuberculosis

BACKGROUND: The development of rapid non-sputum tests remains a global priority to accelerate Tuberculosis (TB) diagnosis and treatment initiation. The only WHO-recommended rapid diagnostic test (RDT), the Alere Determine TB Lipoarabinomannan Ag (AlereLAM) has suboptimal sensitivity. A laboratory-based electrochemiluminescence LAM assay (EclLAM) is the current sensitivity benchmark for RDT development and the gold standard for urinary LAM detection. We assessed the diagnostic accuracy of an ultra-sensitive, Plasmonic Fluor-linked Immunosorbent LAM assay (PFLISA-LAM) compared to Sputum Xpert MTB/RIF, sputum culture and urine EclLAM. METHODS: We developed and evaluated the assay performance of PFLISA-LAM. Two sub-studies were conducted using banked urine samples: 1. Preclinical study using 337 well-characterised urine samples for cutoff determination and initial evaluation of the performance of PFLISA-LAM compared to sputum Xpert MTB/RIF and culture. 2. A Diagnostic accuracy assessment study using 77 blinded samples to evaluate the performance of PFLISA-LAM compared to EclLAM versus microbiological reference standard (MRS, Xpert positive and/or culture positive). FINDINGS: PFLISA-LAM has a limit of detection (LOD) of 0.84 ± 0.9 pg/mL when detecting purified LAM spiked in urine. In the preclinical study, the optimal assay cutoff was determined to be 1.7 pg/mL. The sensitivities of PFLISA-LAM and sputum Xpert MTB/RIF compared to culture were 51% (95% confidence interval [CI]: 43%...