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

John T. Connelly, Alfred Andama, Benjamin D. Grant, Alexey Ball, Sandra Mwebe, Lucy Asege, Martha Nakaye, Brianda Barrios Lopez, Helen V. Hsieh, David Katumba, Job Mukwatamundu, Mayimuna Nalubega, Victoria M. Hunt, Stephen Burkot, Harisha Ramachandraiah, Alok Choudhary, Lech Ignatowicz, Bernhard H. Weigl, Christine Bachman, Jerry MulondoFred Semitala, William Worodria, Abraham Pinter, Beston Hamasur, David Bell, Adithya Cattamanchi, Akos Somoskovi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbere0254156
JournalPloS one
Volume16
Issue number7 July
DOIs
StatePublished - Jul 2021

All Science Journal Classification (ASJC) codes

  • General

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