PLoS ONE (Jan 2021)

Field evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on HIV-positive 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 Mulondo,
  • Fred Semitala,
  • William Worodria,
  • Abraham Pinter,
  • Beston Hamasur,
  • David Bell,
  • Adithya Cattamanchi,
  • Akos Somoskovi

DOI
https://doi.org/10.1371/journal.pone.0254156
Journal volume & issue
Vol. 16, no. 7
p. e0254156

Abstract

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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%, p200cells/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.