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

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. 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. 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