Diagnostic accuracy of a urine lipoarabinomannan strip-test for TB detection in HIV-infected hospitalised patients

Abstract

Lack of point-of-care tests for tuberculosis (TB) result in diagnostic delay, and increased mortality and healthcare-related costs. The urine Determine™ TB-LAM point-of-care strip-test was evaluated in 335 prospectively-recruited hospitalised patients with suspected TB-HIV co-infection (group 1) and from 88 HIV-infected hospitalised patients with non-TB diagnoses (group 2). Cut-off point-specific analyses were performed using: 1) a microbiological reference standard (culture positive versus.negative); and 2) a composite reference standard (exclusion of patients with clinical-TB from the culture-negative group). Using the microbiological reference and the manufacturer-recommended grade-1 cut-off point, LAM sensitivity and specificity was 66% (95% CI 57–74%). By contrast, using the composite reference sensitivity was 60% (95% CI 53–67%) and specificity improved to 96% (95% CI 89–100%) (p=0.001). The same pattern was seen when the grade-2 cut-off point was used (specificity 75% versus 96%; p=0.01). In group two patients specificity was poor using the grade-1 cut-off point, but improved significantly when the grade-2 cut-off point was used (90% versus 99%; p=0.009). The grade-2 cut-off point also offered superior inter-reader reliability (p=0.002). Sensitivity was highest in those with a CD4 <200 cells per mL. LAM combined with smear-microscopy was able to rule-in TB in 71% of Mycobacterium tuberculosis culture-positive patients. This preliminary study indicates that the LAM strip-test may be a potentially useful rapid rule-in test for TB in hospitalised patients with advanced immunosuppression. The grade 2, but not the manufacturer-recommended grade 1 cut-off point, offered superior rule-in utility and inter-reader reliability. Larger studies to evaluate cut-off points and diagnostic accuracy are urgently required.

Prevention of Early Mortality by Presumptive Tuberculosis Therapy Study: An Open Label, Randomized Controlled Trial

“…Second, WHO prequalification and endorsement of Xpert MTB/RIF during the study further increased the rate of detection of sputum smear-negative patients at the time of ART initiation. 32,33 New diagnostics such as urinary lipoarabinomannan (LAM) [34][35][36] and Xpert MTB/RIF or Ultra 37 may obviate the need for empiric treatment among hospitalized patients particularly if higher sensitivity can be achieved with a combination of LAM point-of-care (POC) and Xpert rapid diagnostics. A pragmatic four-country randomized controlled trial in 2,659 hospitalized adults suspected to have TB-HIV coinfection (48% on ART with a mean CD4 of 84 (IQR: 26-208) cells/μL showed a statistically significant effect of LAM testing on the proportion of patients starting anti-TB treatment, 52% versus 47% (P =0.024) participants, and on 8 week mortality (adjusted HR: 0.81, CI: 0.69-0.95, P = 0.009).…”

Diagnostic accuracy of nucleic acid amplification tests in urine for pulmonary tuberculosis: A meta-analysis

“…Our finding of higher urine TB PCR test sensitivity in HIV-positive than in HIV-negative individuals is consistent with results from urine lipoarabinomannan (LAM) studies for PTB. [22][23][24][25] The overall diagnostic accuracy of urine TB PCR in general, and in HIV sub-groups, was greater than was observed in diagnostic accuracy studies on urine LAM (sensitivity 28-66% and specificity 66-98%), [23][24][25] suggesting that mycobacterial PCR in urine may be a better diagnostic test for active PTB than urine LAM. Resistance testing would be an added advantage of urine TB PCR over urine LAM, despite the quadrupled cost, if leveraged on the existing Xpert platform.…”

Global evidence directing regional preventive strategies in Southeast Asia for fighting TB/HIV

“…A newer invention, the LAM strip test offers an easy-to-perform bedside TB diagnosis for PLWH with a very low CD4 count (< 200 cells/m 3 ) and most at risk of mortality [28]. Active TB cases were diagnosed at bedside within 25 minutes and at a cost of 3.5 US$ per test.…”