Real-world diagnostic accuracy of lipoarabinomannan in three non-sputum biospecimens for pulmonary tuberculosis diseaseResearch in context
Paul K. Drain,
Xin Niu,
Adrienne E. Shapiro,
Zanele P. Magcaba,
Zinhle Ngcobo,
M William Ngwane,
Katherine K. Thomas,
Ronit R. Dalmat,
Jennifer F. Morton,
Elvira Budiawan,
Abraham Pinter,
Jason Cantera,
Caitlin Anderson,
Rose Buchmann,
Doug Wilson,
Ben Grant
Affiliations
Paul K. Drain
Department of Global Health, University of Washington, Seattle, WA, USA; Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Corresponding author. 325 Ninth Ave, UW Box 359927, Seattle, WA, 98104-2420.
Xin Niu
Department of Epidemiology, University of Washington, Seattle, WA, USA
Adrienne E. Shapiro
Department of Global Health, University of Washington, Seattle, WA, USA; Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
Zanele P. Magcaba
Umkhuseli Research and Innovation Management, Pietermaritzburg, South Africa
Zinhle Ngcobo
Umkhuseli Research and Innovation Management, Pietermaritzburg, South Africa
M William Ngwane
Umkhuseli Research and Innovation Management, Pietermaritzburg, South Africa
Katherine K. Thomas
Department of Global Health, University of Washington, Seattle, WA, USA
Ronit R. Dalmat
Department of Global Health, University of Washington, Seattle, WA, USA
Jennifer F. Morton
Department of Global Health, University of Washington, Seattle, WA, USA
Elvira Budiawan
Department of Global Health, University of Washington, Seattle, WA, USA
Abraham Pinter
New Jersey Medical School, Rutgers University, Newark, NJ, USA
Jason Cantera
Global Health Labs, Bellevue, WA, USA
Caitlin Anderson
Global Health Labs, Bellevue, WA, USA
Rose Buchmann
Global Health Labs, Bellevue, WA, USA
Doug Wilson
Umkhuseli Research and Innovation Management, Pietermaritzburg, South Africa; University of KwaZulu-Natal, Pietermaritzburg, South Africa
Summary: Background: Development of a non-sputum test using readily-obtainable biospecimens remains a global priority for tuberculosis (TB) control. We quantified lipoarabinomannan (LAM) concentrations, a pathogen biomarker for Mycobacterium tuberculosis, in urine, plasma and serum for real-world diagnostic accuracy of pulmonary TB among people living with and without HIV. Methods: We conducted a prospective diagnostic study among adults with TB symptoms in South Africa. We measured LAM concentrations in time-matched urine, plasma and serum with an electrochemiluminescence immunoassay using two capture antibodies (FIND 28 and S4–20). From the completed cohort, we randomly selected 210 participants (2 cases: 1 control) based on sensitivity estimates, and we compared diagnostic accuracy of LAM measurements against the microbiological reference standard. Findings: Urine and blood specimens from 210 of 684 adults enrolled were tested for LAM. Among 138 TB-positive adults (41% female), median urine LAM was 137 pg/mL and 52 pg/mL by FIND 28 and S4–20, respectively. Average LAM concentrations were highest in HIV-positive participants with CD4+ T cells <200 cells/mm3. Urine LAM by S4–20 achieved diagnostic sensitivity of 62% (95% CI: 53%–70%) and specificity of 99% (95% CI: 96%–100%). Plasma and serum LAM by FIND 28 showed similar sensitivity (70%, 95% CI: 62%–78%) and comparable specificities (90%, 95% CI: 82%–97%; 94%, 95% CI: 88%–99%). Diagnostic sensitivity of urine LAM by S4–20 was higher among participants without HIV (41%, 95% CI: 24%–61%) compared to HIV-positive participants with CD4 ≥200 cells/mm3 (20%, 95% CI: 8%–39%). Interpretation: Detection of LAM was achievable in non-sputum specimens for pulmonary TB, but additional analyte concentration or signal amplification may be required to achieve diagnostic accuracy targets. Funding: Bill and Melinda Gates Foundation.
