Urine lipoarabinomannan levels recorded among HIV-negative adults with pulmonary or extrapulmonary tuberculosis disease in Vietnam

Diagnostic tests using non-sputum specimens for tuberculosis (TB) disease are needed. Lipoarabinomannan (LAM) is a Mycobacterial cell wall glycolipid excreted in urine, and has been a target of rapid diagnostic tests (RDTs) for TB disease. While urine LAM (uLAM) testing by RDT has been approved for people living with HIV (PLWH), there have been limited data for uLAM concentrations in HIV-negative adults with TB disease. We conducted a longitudinal cohort study of adults >=18 years old who presented with TB-related symptoms at the National Lung Hospital in Hanoi, Vietnam. Urine specimens were obtained to measure uLAM concentration using two different capture antibodies (S4-20 and FIND28) and the same detector antibody (A194-01) on an electrochemiluminescent immunoassay. Sputum specimens were obtained for testing by GeneXpert Ultra and TB culture, which were combined to determine the microbiological reference standard (MRS). Additional microbiological testing was conducted for possible extrapulmonary TB, when clinically indicated. Among 745 participants enrolled, 335 (44.9 %) had pulmonary TB and 53 (7.1%) had extrapulmonary TB. [may add a line on the estimated mean concentration of uLAM by both antibody pairs]. From this study, the overall and TB-positive cohort measured mean uLAM concentration for S4-20/A194-01 (S/A) were 109 pg/mL and 553 pg/mL, respectively. The FIND28/A194-01 (F/A) antibody pair overall and TB-positive cohort measured mean uLAM was 1389 pg/mL and 4570 pg/mL, respectively. Overall, theS4-20/A194-01 (S/A) antibody pair had a sensitivity and specificity of 38% (95% Confidence Interval [CI] 0.33, 0.44) and 98% (95% CI 0.96, 0.99), respectively against the MRS. The FIND28/A194-01 (F/A) antibody pair had a sensitivity and specificity of 41% (95% CI 0.35, 0.47) and 80% (95% CI 0.75, 0.84) respectively. The pooled mean uLAM concentration using S/A was 51.0 pg/mL while F/A was 78.0 pg/mL. Receiver operating characteristic analysis using the samples screened by both pairs against the MRS data gave areas under the curve of 0.748 and 0.629 for S/A and F/A-01 respectively. Among HIV-negative adults, concentrations of uLAM remain relatively low for people with TB disease, which may present challenges for developing a rapid uLAM test suitable for widespread use.