Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in people living with HIV

Abstract

Background The lateral flow urine lipoarabinomannan (LF-LAM) assay Alere Determine™ TB LAM Ag is recommended by the World Health Organization (WHO) to help detect active tuberculosis in HIV-positive people with severe HIV disease. This review update asks the question, "does new evidence justify the use of LF-LAM in a broader group of people?", and is part of the WHO process for updating guidance on the use of LF-LAM. Objectives To assess the accuracy of LF-LAM for the diagnosis of active tuberculosis among HIV-positive adults with signs and symptoms of tuberculosis (symptomatic participants) and among HIV-positive adults irrespective of signs and symptoms of tuberculosis (unselected participants not assessed for tuberculosis signs and symptoms). The proposed role for LF-LAM is as an add on to clinical judgement and with other tests to assist in diagnosing tuberculosis.

Point-Of-Care Urine LAM Tests for Tuberculosis Diagnosis: A Status Update

“…Among symptomatic participants with CD4 counts >200 cells/µL, pooled sensitivity and specificity were 16% (95% CI: 8-31%) and 94% (95% CI: 81-97%) [21]. Among symptomatic participants with CD4 counts ≤200 cells/µL, pooled sensitivity and specificity were 45% (95% CI: 31-61%) and 89% (95% CI: 77-94%) [21]. Among children, data were limited, but five prospective pediatric cohort studies found a pooled sensitivity of 47% (95% CI: 27-69%) and specificity of 82% (95% CI: 71-89%) [24].…”

“…The AlereLAM test meets the operational characteristics of the WHO TPP for a biomarker-based, non-sputum TB test, but falls short on test accuracy (Table 1). In 2019, a meta-analysis by Bjerrum et al [21] compared pooled sensitivity and specificity against a microbiological reference standard (MRS), defined as a positive TB culture or TB nucleic acid amplification test (NAAT). When compared against an MRS, pooled sensitivity and specificity in HIV-positive adults were 42% (95% CI: 31-55%) and 91% (95% CI: 85-95%), respectively [21].…”

“…In 2019, a meta-analysis by Bjerrum et al [21] compared pooled sensitivity and specificity against a microbiological reference standard (MRS), defined as a positive TB culture or TB nucleic acid amplification test (NAAT). When compared against an MRS, pooled sensitivity and specificity in HIV-positive adults were 42% (95% CI: 31-55%) and 91% (95% CI: 85-95%), respectively [21]. It is likely that the MRS from Bjerrum and colleagues' meta-analysis underestimates AlereLAM specificity; an earlier meta-analysis reported 96-98% specificity against a composite reference standard (CRS) [26].…”

“…A possible reason for the lower specificity in children could be cross-reactivity of AlereLAM with bacteria from perineal skin or stool that contaminate the urine sample during collection, as urine bags may remain on the skin for several hours until the child produces urine [41], or limitations of the reference standard. Based on these meta-analysis results [21], the WHO announced updated guidelines for use of AlereLAM in 2019, which are summarized in Table 2 [42]. Table 2.…”

A multi-parameter diagnostic clinical decision tree for the rapid diagnosis of tuberculosis in HIV-positive patients presenting to an emergency centre

“…The use of urinary LF-LAM was the predictor with the best ability of creating pure groups (either with or without tuberculosis); classifying almost 25% of the study sample (75% of which were true positives) regardless of their CD4 cell count. The false positive rate of 25% is less than a recent Cochrane review, in which 33% of participants with tuberculosis symptoms had a false positive urinary LF-LAM result for microbiologically confirmed tuberculosis 32 . However, inappropriate exclusions (e.g.…”