Field evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on HIV-positive and HIV-negative patients.

Detection of tuberculosis at the point-of-care (POC) is limited by the low sensitivity of current commercially available tests. We describe a diagnostic accuracy field evaluation of a prototype urine Tuberculosis Lipoarabinomannan Lateral Flow Assay (TB-LAM LFA) in both HIV-positive and HIV-negative patients using fresh samples with sensitivity and specificity as the measures of accuracy. This prototype combines a proprietary concentration system with a sensitive LFA. In a prospective study of 292 patients with suspected pulmonary tuberculosis in Uganda, the clinical sensitivity and specificity was compared against a microbiological reference standard including sputum Xpert MTB/RIF Ultra and solid and liquid culture. TB-LAM LFA had an overall sensitivity of 60% (95%CI 51-69%) and specificity of 80% (95%CI 73-85%). When comparing HIV-positive (N = 86) and HIV-negative (N = 206) patients, there was no significant difference in sensitivity (sensitivity difference 8%, 95%CI -11% to +24%, p = 0.4351) or specificity (specificity difference -9%, 95%CI -24% to +4%, p = 0.2051). Compared to the commercially available Alere Determine TB-LAM Ag test, the TB-LAM LFA prototype had improved sensitivity in both HIV-negative (difference 49%, 95%CI 37% to 59%, p<0.0001) and HIV-positive patients with CD4+ T-cell counts >200cells/μL (difference 59%, 95%CI 32% to 75%, p = 0.0009). This report is the first to show improved performance of a urine TB LAM test for HIV-negative patients in a high TB burden setting. We also offer potential assay refinement solutions that may further improve sensitivity and specificity.

Déclaration de conflit d'intérêts

I have read the journal’s policy and the authors of this manuscript have the following competing interests: HR, LI, and BH are employees of Biopromic AB. Biopromic AB is developing a point-of-care TB LAM test similar to the one presented. JTC, BDG, AB, BBL, HVH, VMH, SB, BHW, CB, DB, and AS were employees of Global Good Fund, Intellectual Ventures. BH is also an author on patents in the field of TB immunoassays, “Monoclonal antibody, method, kit and use” (WO2016012449) and “Method for removing inhibitory components” (US20190302115). JTC, BDG, and BHW are authors on a patent in the field of analyte concentration devices, “Device for rapid detection of tuberculosis-lipoarabinomannan (TB-LAM) with enhanced sensitivity” (US10830760). AP is an author on patents in the field of mycobacteria detection, “Novel anti-lam and anti-pim6/lam monoclonal antibodies for diagnosis and treatment of mycobacterium tuberculosis infections” (US20190038747) and “Methods for dual detection and differentiation of infection by mycobactierum tuberculosis complex and nontuberculous mycobacteria” (WO2020018806). None of the disclosed competing interest alter our adherence to PLOS ONE policies on sharing data and materials.