Diagnostic Accuracy of Lateral Flow Urine LAM Assay for TB Screening of Adults with Advanced Immunosuppression Attending Routine HIV Care in South Africa.

Yasmeen Hanifa,Lungiswa Adonis,Violet N Chihota,Kerrigan Mccarthy,Salome Charalambous,Gavin J Churchyard,Alison D Grant,Mark P Nicol,Faieza Sahid,Katherine L Fielding,Nontobeko T Ndlovu,Alan Karstaedt,Petros Isaakidis

doi:10.1371/journal.pone.0156866

Abstract

BackgroundWe assessed the diagnostic accuracy of Determine TB-LAM (LF-LAM) to screen for tuberculosis among ambulatory adults established in HIV care in South Africa.MethodsA systematic sample of adults attending for HIV care, regardless of symptomatology, were enrolled in the XPHACTOR study, which tested a novel algorithm for prioritising investigation with Xpert MTB/RIF. In this substudy, restricted to participants with enrolment CD4<200x106/l, urine was stored at enrolment for later testing with LF-LAM. Sputum was sent for immediate Xpert MTB/RIF if any of: current cough, fever ≥3 weeks, body mass index (BMI)<18.5kg/m2, CD4<100x106/l (or <200x106/l if pre-ART), weight loss ≥10% or strong clinical suspicion were present; otherwise, sputum was stored for Xpert testing at study completion. Participants were reviewed monthly, with reinvestigation if indicated, to 3 months, when sputum and blood were taken for mycobacterial culture. We defined tuberculosis as “confirmed” if Xpert, line probe assay or culture for M. tuberculosis within six months of enrolment were positive, and “clinical” if tuberculosis treatment started without microbiological confirmation.ResultsAmongst 424 participants, 61% were female and 57% were taking ART (median duration 22 months); median age, CD4 and BMI were 39 years, 111x106/l, and 23 kg/m2. 56/424 (13%) participants had tuberculosis (40 confirmed, 16 clinical). 24/424 (5.7%) vs. 8/424 (1.9%) were LAM-positive using grade 1 vs. grade 2 cut-off. Using grade 1 cut-off, sensitivity for confirmed TB (all clinical TB excluded) was 12.5% (95% CI 4.2%, 26.8%) and in CD4<100x106/l vs. CD4 ≥100x106/l was 16.7% (95% CI 4.7%, 37.4%) vs. 6.3% (95% CI 0.2%, 30.2%). Specificity was >95% irrespective of diagnostic reference standard, CD4 stratum, or whether grade 1 or grade 2 cut-off was used.ConclusionSensitivity of LF-LAM is too low to recommend as part of intensified case finding in ambulatory patients established in HIV care.

Highlights

The global HIV-associated tuberculosis (TB) epidemic remains a huge public health challenge, with sub-Saharan Africa accounting for the vast majority of HIV-positive individuals diagnosed with and dying from TB. [1] Diagnosis of TB in people living with HIV (PLHIV) is complicated by limitations of available diagnostics and the effect of immunosuppression on clinical presentation of TB, e.g. reliance on sputum samples, the high proportion with smear-negative or extrapulmonary disease, [2] and slow turnaround time for mycobacterial culture
Sensitivity of lateral-flow LAM assay (LF-LAM) is too low to recommend as part of intensified case finding in ambulatory patients established in HIV care
Evaluations of LF-LAM as a screening tool for TB have been undertaken in ambulatory patients in Ethiopia and South Africa either prior to antiretroviral therapy (ART) initiation, [4, 5] or on receiving a positive HIV diagnosis at HIV counselling and testing services (HCT). [6, 7] In these groups LF-LAM sensitivity, compared to bacteriologically-confirmed TB, was inadequate as a standalone test, though improved at lower CD4 cell counts

Summary

Introduction

The global HIV-associated tuberculosis (TB) epidemic remains a huge public health challenge, with sub-Saharan Africa accounting for the vast majority of HIV-positive individuals diagnosed with and dying from TB. [1] Diagnosis of TB in people living with HIV (PLHIV) is complicated by limitations of available diagnostics and the effect of immunosuppression on clinical presentation of TB, e.g. reliance on sputum samples, the high proportion with smear-negative or extrapulmonary disease, [2] and slow turnaround time for mycobacterial culture. Evaluations of LF-LAM as a screening tool for TB have been undertaken in ambulatory patients in Ethiopia and South Africa either prior to antiretroviral therapy (ART) initiation, [4, 5] or on receiving a positive HIV diagnosis at HIV counselling and testing services (HCT). There are no published studies, to our knowledge, evaluating LF-LAM as a screening tool for TB as part of intensified case finding for ambulatory patients established in HIV care (rather than at their initial assessment). The aim of our study was to evaluate the diagnostic accuracy of LF-LAM among adults with advanced immunosuppression (CD4

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Conclusion