Lateral Flow Urine Lipoarabinomannan Assay for Diagnosis of Active Tuberculosis in Adults With Human Immunodeficiency Virus Infection: A Prospective Cohort Study

Abstract

Background Detection of mycobacterial lipoarabinomannan antigen in urine has emerged as a potential point-of-care test for diagnosis of tuberculosis. This study aimed to evaluate the accuracy of the lateral flow urine lipoarabinomannan (LF-LAM) assay for diagnosis of active tuberculosis among Thai adults with advanced human immunodeficiency virus (HIV) infection. Methods HIV-infected adult patients with CD4 cell counts ≤200/μL and symptoms suggestive of active tuberculosis were prospectively recruited from both inpatient and outpatient settings at Siriraj Hospital and Chonburi Hospital in Thailand during the study period from December 2015 to March 2017. Freshly collected urine samples were applied to the Alere Determine TB LAM Ag test strip using a grade 1 cutoff, according to the manufacturer’s grading system. The diagnostic accuracy of the LF-LAM test was assessed against a microbiological reference standard (definite tuberculosis) or a composite reference standard (definite and probable tuberculosis). Results Of the 280 patients who were included, 72 (25.7%) had definite and 65 (23.2%) had probable tuberculosis. Among patients with definite tuberculosis, the LF-LAM test yielded a sensitivity of 75.0% and a specificity of 76.0%. It had the highest sensitivity (90.5%) in HIV-infected patients with CD4 cell counts <50/μL. It yielded a lower sensitivity (61.3%) but a higher specificity (86.0%) when compared with the composite reference standard. Among the 20 patients (14%) with false-positive results, strong band intensity was observed mostly in Mycobacterium avium complex infections. An incremental sensitivity of 11% was observed with use of acid-fast bacilli sputum smear or LF-LAM testing, compared with LF-LAM testing alone. Conclusions The LF-LAM test performed well in the diagnosis of active tuberculosis in selected patients with more advanced tuberculosis and coexisting HIV disease.

Lipoarabinomannan as a Point-of-Care Assay for Diagnosis of Tuberculosis: How Far Are We to Use It?

“…Worldwide, the use of a rapid test for TB diagnosis is not broadly accepted (Thit et al, 2017;Bjerrum et al, 2019;Songkhla et al, 2019). Studies show that a disadvantage of the tests based in LAM creates the high amount of positive/negativefalse results.…”

“…For instance, it is not recommended for LAM detection in patients with CD4 + T cell counts greater than 200 cells/mm 3 . AlereLAM has generated a large number of misinterpretations that depend on clinical characteristics such as CD4 + lymphocyte count, bacillary loads, or clinical symptoms that have been exposed in the WHO guidelines of 2019 (Bjerrum et al, 2019;Songkhla et al, 2019;World Health Organization, 2019). Unfortunately, AlereLAM has restricted use in clinical practice.…”

A systematic review of utility of urine lipoarabinomannan in detecting tuberculosis among HIV-positive tuberculosis suspects

“…Studies have considered OD at least 0.1 above the negative control as positive reading. Except for 4 studies,[ 19 38 50 51 ] 88% of the studies used 2+ as the cutoff in reading urine LAM test as positive. Besides urine LAM, other diagnostic tests included by these studies are SSM using ZN staining and auramine staining, culture of MTb using solid (LJ medium) culture and liquid (BACTEC MGIT) culture, Xpert MTB/Rif using sputum, chest X-Ray (CxR), tuberculin skin test (TST), and blood culture.…”

“…Of the Asian studies, the Indian research was published in 2009,[ 22 ] Myanmar study in 2017,[ 46 ] and the Thailand studies were published one each in 2017[ 44 ] and 2019. [ 50 ] This might be due to the high prevalence of HIV among African countries very much earlier than Asian countries and the interest of looking for alternate methods of rapid diagnosis of MTb increased only recently in Asian countries due to recent rise in HIV cases.…”

Performance of Lipoarabinomannan Assay using Cerebrospinal fluid for the diagnosis of Tuberculous meningitis among HIV patients

“…Assays based on the detection of mycobacterial lipoarabinomannan (TB-LAM) antigen in urine have emerged as potential point-of-care tests for extra-pulmonary TB 8 . There is evidence that urine TB-LAM may help to reduce mortality and predict poor outcomes 9, 10 .…”