Diagnostic Accuracy of a Novel and Rapid Lipoarabinomannan Test for Diagnosing Tuberculosis Among People With Human Immunodeficiency Virus

Abstract

Background The novel Fujifilm SILVAMP TB-LAM (FujiLAM) assay detects mycobacterial lipoarabinomannan in urine and has demonstrated superior sensitivity to the Alere Determine TB-LAM Ag (AlereLAM) assay for detection of tuberculosis among hospitalized people with human immunodeficiency virus (PWH). This is the first study to evaluate the assay among a broad population referred for antiretroviral therapy including both outpatients (mainly) and inpatients. Methods We assessed diagnostic accuracy of FujiLAM and AlereLAM assays in biobanked urine samples from a cohort of adults referred for antiretroviral therapy in Ghana against a microbiological and a composite (including clinical judgement) reference standard, and we assessed the association of FujiLAM test positivity with mortality. Results We evaluated urine samples from 532 PWH (462 outpatients, 70 inpatients). Against a microbiological reference standard, the sensitivity of FujiLAM was 74.2% (95% confidence interval [CI], 62.0–84.2) compared to 53.0% (95% CI, 40.3–65.4) for AlereLAM, a difference of 21.2% (CI, 13.1–32.5). Specificity was 89.3% (95% CI, 85.8–92.2) versus 95.6% (95% CI, 93.0–97.4) for FujiLAM and AlereLAM, a difference of −6.3% (95% CI −9.6 to −3.3). Specificity estimates for FujiLAM increased markedly to 98.8% (95% CI, 96.6–99.8) in patients with CD4 >100 cells/µL and when using a composite reference standard. FujiLAM test positivity was associated with increased cumulative risk of mortality at 6 months (hazard ratio, 4.80; 95% CI, 3.01–7.64). Conclusions FujiLAM offers significantly increased diagnostic sensitivity in comparison to AlereLAM. Specificity estimates for FujiLAM were lower than for AlereLAM but were affected by the limited ability of the reference standard to correctly diagnose tuberculosis in individuals with low CD4 counts.

Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients

“…Specificity of FujiLAM in this study with HIV-negative patients was 98.9%, higher than AlereLAM’s specificity at 92.3% ( Figure 2 ). Earlier studies reported a lower specificity for FujiLAM ( 16 , 19 , 26 ) and the result from this study underlines the importance of a very comprehensive reference standard for a proper specificity assessment of urine biomarker tests ( 27 ).…”

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

“…FujiLAM showed approximately 30% improved diagnostic sensitivity in HIV-positive inpatients compared to AlereLAM at 95.7% specificity [27]. Additional studies in HIV-infected outpatients [31] and a recent meta-analysis of 1595 HIV-positive inpatients and outpatients [22] have confirmed FujiLAM's superiority over AlereLAM. The meta-analysis reported 70.7% (95% CI: 59.0-80.8%) sensitivity for FujiLAM, a sensitivity increase of 35.8% compared to AlereLAM [22].…”

“…FujiLAM also showed high performance for the detection of EPTB in HIV-infected patients [56]. Two recent studies [31,32] showed that FujiLAM could have rapidly diagnosed TB in up to 90% of HIV-positive patients that died within 3 to 6 months, whereas the probability of survival in the case of a FujiLAM-negative result was 86-97%. A limitation of published FujiLAM studies is their use of biobanked samples and, accordingly, testing in a laboratory setting.…”

Diagnostic accuracy of a novel tuberculosis point-of-care urine lipoarabinomannan assay for people living with HIV: A meta-analysis of individual in- and outpatient data

“…Study protocols and statistical analysis plans for the different studies are available upon request. A study that combines inpatient cohorts from South Africa (cohorts 1A, 2, and 3) [11] and the study from Ghana (cohort 5) [12] have been published.…”

“…Here, we present all available individual patient data (IPD), both published [11,12] and unpublished, from SILVAMP-LAM testing ("intervention" per PRISMA guidelines [13]) in adult inpatients and outpatients with HIV ("patients") in comparison to LF-LAM ("comparator") across 5 prospective cohorts ("studies") and analyze its diagnostic accuracy ("outcome"). These data contributed to a guidance development group consultation of the World Health Organization in May 2019.…”