Open AccessField evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on HIV-positive and HIV-negative patients
Author(s) -
John T. Connelly,
Alfred Andama,
Benjamin D. Grant,
Alexey Ball,
Sandra Mwebe,
Lucy Asege,
Martha Nakaye,
Betsy Jazmín Peralta López,
Helen Hsieh,
David Katumba,
Job Mukwatamundu,
Mayimulubega,
Victoria Hunt,
Stephen Burkot,
Harisha Ramachandraiah,
Alok Choudhary,
Lech Ignatowicz,
Bernhard H. Weigl,
Christine Bachman,
Jerry Mulondo,
Fred C. Semitala,
William Worodria,
Abraham Pinter,
Beston Hamasur,
David Bell,
Adithya Cattamanchi,
Ákos Somoskövi
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0254156
Subject(s) - lipoarabinomannan , medicine , tuberculosis , sputum , human immunodeficiency virus (hiv) , urine , gastroenterology , prospective cohort study , mycobacterium tuberculosis , immunology , pathology
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.