Background
An urgent need exists for non-sputum based point-of-care diagnostics to detect tuberculosis (TB) among people with advanced HIV disease. The Fujifilm SILVAMP TB LAM (FujiLAM) is a novel point-of-care assay that detects mycobacterial lipoarabinomannan (LAM) antigen in urine to identify TB. We present a validation of the updated FujiLAM assay on prospectively collected urine samples from outpatient adults with advanced HIV disease in Uganda.
Methods
We performed a prospective diagnostic accuracy study of the FujiLAM TB assay among 617 outpatients with advanced HIV disease at 16 clinics in the Kampala and Wakiso districts of Uganda. We prospectively performed urine Alere LAM testing. Participants with symptoms of TB underwent additional testing including sputum Xpert MTB/Rif (Cepheid, Sunnyvale CA) and sputum culture as per the Ugandan Ministry of Health guidelines. FujiLAM was subsequently run on cryopreserved urine. We determined diagnostic performance for the FujiLAM test against the cases of confirmed TB (defined as Xpert or mycobacterial culture positive) versus negative controls. We additionally assessed the diagnostic performance of the FujiLAM assay for confirmed TB among pre-specified subgroups: people with CD4<100 cells/µL vs. CD4 100-200 cells/µL, antiretroviral therapy (ART) naive vs. ART experienced, and serum C-reactive protein (CRP) <5 mg/L vs. CRP ≥5 mg/L.
Results
Overall, we performed FujiLAM testing on 617 participants with Advanced HIV disease. The FujiLAM assay demonstrated 49% (27/55) sensitivity to identify confirmed TB and 97% (172/178) specificity to identify the absence of TB (Figure 1). The positive predictive value was 82%, and negative predictive value was 86%. Among those with CD4 cell counts <100 cells/µL, FujiLAM sensitivity was 61% and specificity was 95%. Among participants with serum CRP >5 mg/L, the FujiLAM assay exhibited a sensitivity of 58% and specificity of 96%.
Conclusions
In this diagnostic accuracy study performed on urine samples collected from ambulatory patients with advanced HIV disease in Uganda, the new iteration of the FujiLAM test exhibited moderate sensitivity at 49% and excellent specificity of 97% in identifying confirmed TB. Sensitivity to identify confirmed TB was maximal at 61% in the subgroup of participants with a CD4<100 cells/µL.
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