Urine lipoarabinomannan concentrations among HIV-uninfected adults with pulmonary or extrapulmonary tuberculosis disease in Vietnam

Lipoarabinomannan (LAM) is a Mycobacterial cell wall glycolipid excreted in urine, and a target biomarker of rapid diagnostic tests (RDTs) for tuberculosis (TB) disease. Urine LAM (uLAM) testing by RDT has been approved for people living with HIV, but there is limited data regarding uLAM levels in HIV-negative adults with TB disease. We conducted a clinical study of adults presenting with TB-related symptoms at the National Lung Hospital in Hanoi, Vietnam. The uLAM concentrations were measured using electrochemiluminescent immunoassays and compared to a microbiological reference standard (MRS) of sputum, GeneXpert Ultra and TB culture. Additional microbiological testing was conducted for possible extrapulmonary TB, when clinically indicated. Among 745 participants enrolled, 335 (44.9 %) participants recruited from the pulmonary TB wards (PR-PTBW) and 6 (11.3%) participants recruited from the EPTB wards (PR-EPTBW) had confirmed TB disease. The MRS positive cohort measured median uLAM concentration for S4-20/A194-01 (S/A) were 14.5 pg/mL and 51.5 pg/mL, respectively. The FIND28/A194-01 (F/A) antibody pair overall and TB-positive cohort measured mean uLAM was 44.4 pg/mL and 78.1 pg/mL, respectively. Overall, the S/A antibody pair had a sensitivity of 39% (95% Confidence Interval [CI] 0.33, 0.44) and specificity of 97% (95% CI 0.96, 0.99) against the MRS. The F/A antibody pair had a sensitivity of 41% (95% CI 0.35, 0.47) and specificity of 79% (95% CI 0.75, 0.84). The areas under the receiver operating curves were 0.748 for S/A and 0.629 for F/A. There was little difference between the S/A median uLAM concentration with pulmonary (55 pg/mL) and extrapulmonary (36 pg/mL) TB disease. With F/A the medians for pulmonary and extrapulmonary TB disease were 79% and 76.5% respectively. Among HIV-negative adults in Vietnam, concentrations of uLAM remained relatively low for people with TB disease, which may present challenges for developing a more sensitive rapid uLAM test. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement DSB was the sole recipient of the award to perform this study. The study was funded by the Bill & Melinda Gates Foundation (https://www.gatesfoundation.org/). The donor had no role role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The institutional review boards (IRBs) at the National Lung Hospital (NLH, Hanoi, Vietnam reference No: 26/21/CN-HDDD) and the Vietnam Ministry of Health (Hanoi, Vietnam reference No: 95/CN-HDDD) approved the study and the PATH Office of Research Affairs (ORA) gave approval contingent on the NLH IRB decision. Written informed consent was obtained from each eligible participant prior to enrollment. The immunoassay testing at the PATH laboratory was determined as non-human subjects research by the PATH ORA before any analysis was performed on the samples. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All of the data generated in this study can be publicly accessed at Dataverse (https://doi.org/10.7910/DVN/AOL0LP). This includes all of the relevant clinical and statistical data and also the data from the laboratory testing.