Real-world diagnostic accuracy of lipoarabinomannan in three non-sputum biospecimens for pulmonary tuberculosis diseaseResearch in context

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