Utility of Urinary Lipoarabinomannan (LAM) assays to monitor treatment outcomes in Tuberculosis patients co-infected with Human-Immunodeficiency-Virus (HIV)

Abstract

Tuberculosis (TB), which is caused by the bacterium Mycobacterium tuberculosis (M.tuberculosis), continues to be the biggest global public health concern, despite advances in treatment regimens and diagnostic tools. Existing diagnostic methods, which involve bacterial culture and nucleic acid amplification tests (NAATs), are limited, particularly for assessing treatment responses. Prolonged time-to diagnosis of TB facilitates the continued dissemination of the disease, increased mortality, and higher health care costs. Consequently, there is a demand for rapid cost-effective diagnostic methods that utilize non-sputum samples. A lipopolysaccharide, lipoarabinomannan (LAM), found in the cell wall structure of Mycobacterium tuberculosis, holds potential as a biomarker for monitoring tuberculosis treatment. Urine-based antigen tests, such as rapid strip tests and ELISA, are appealing due to their ease of use, non-invasive nature, and absence of aerosol risks. This study explores potential of LAM detection in plasma and urine samples as a potential indicator for monitoring TB therapeutic response. The goal was to develop a sandwich ELISA for LAM detection, but an indirect ELISA failed to optimize binding, preventing the sandwich ELISA’s development. However, a dot-blot assay successfully confirmed LAM-antibody binding. In the second part of the study, LAM concentrations were measured using the Determine LAM Ag rapid strip test at various time points. At baseline, 72.97% of participants tested positive for urine LAM, with a decline over time: 58.14% at month 1, 51.92% at month 2, and 13.04% at month 6 The average urine LAM grade, which represents the intensity of the test line, was measured on a scale from negative (0) to 4+. Positive samples demonstrated a reduction in the average LAM grade, from 1.4 at baseline to 1.2 at month 6. Among 140 participants, 70% were living with HIV, and this cohort exhibited a significant reduction in LAM grading. Also in this group, participants with CD4 counts ranging from 7 cells/mm³ to 514 cells/mm³, had the highest LAM grading at baseline (mean LAM grade 3.67). Considering these findings, it was conclude that urinary LAM seems to be a useful indictor for monitoring TB treatment especially amongst HIV positive individuals.