Evaluation of the Performance of the IMMY sona Aspergillus Galactomannan Lateral Flow Assay When Testing Serum To Aid in Diagnosis of Invasive Aspergillosis

Abstract

Management of invasive aspergillosis has been improved by biomarker assays, but limited accessibility and batch testing limit the impact. Lateral flow assays (LFA) are a simple method for use outside specialist centers, provided performance is acceptable. The objective of this study was to determine the performance of the recently released IMMY sona Aspergillus LFA when testing serum samples. The study took the form of a retrospective, anonymous case/control study comprising 179 serum samples from 136 patients with invasive fungal disease, previously documented using recently revised internationally accepted definitions. The LFA was performed following the manufacturer’s instructions using a cube reader to generate a galactomannan index (GMI). Performance parameters were determined, and receiver operator characteristic (ROC) analysis was used to identify an optimal threshold. Concordance with the Bio-Rad Aspergillus Ag assay (GM-EIA) was performed. At the recommended positivity threshold (GMI ≥ 0.5), LFA sensitivity and specificity were 96.9% (31/32) and 98% (98/100), respectively. ROC analysis confirmed the optimal threshold and generated an area under the curve of 0.9919. Qualitative agreement between LFA and GM-EIA was 89.0%, generating a Kappa statistic of 0.698, representing good agreement, with most discordance arising due to false-negative GM-EIA samples that were positive by LFA. The median GMI generated by the LFA was significantly greater than that generated by the GM-EIA. The IMMY sona Aspergillus LFA, when used with a cube reader, provides a rapid alternative to the well-established GM-EIA, potentially detecting more GM epitopes and enhancing sensitivity.

COVID-19 Associated Invasive Pulmonary Aspergillosis: Diagnostic and Therapeutic Challenges

“…The BALF/ETA GM indices were ≥1 in 16 of 23 patients, and the serum GM ODI was ≥0.5 in only 9 of 33 cases. New point-of-care tests for the detection of the Aspergillus -specific antigen or for GM from serum or BALF may also be useful as early evidence of CAPA in critically ill COVID-19 patients [ 43 , 44 , 45 , 46 , 47 ]. One patient with CAPA was reported to have the Aspergillus specific antigen detected from an ETA utilizing a lateral flow device [ 20 ].…”

The Aspergillus Lateral Flow Assay for the Diagnosis of Invasive Aspergillosis: an Update

“…In a recent single-center retrospective case control study of 179 serum samples from 136 patients with invasive fungal disease, the GM-LFA with digital reader had a sensitivity of 96.9% (31/32) and a specificity of 98% (98/100) at a positive GM threshold of > 0.5. Furthermore, the agreement between the LFA and ELISA GM test was 89%, with the most common discordance due to false negative ELISA GM values that were positive with GM-LFA [42]. Finally, a recent multicenter study that included BALF samples from 63 patients with hematological malignancies, including 35 with probable or proven IPA, found a AUC of 0.917 (95% CI 0.847-0.988) for differentiating probable/proven versus no IPA, and a sensitivity of 80% and specificity of 89% when using a LFA cutoff of 1.0 ODI, while specificity increased to 96% (sensitivity 71%) when increasing the cutoff to 2.0 ODI [43••].…”

The Evolving Landscape of Fungal Diagnostics, Current and Emerging Microbiological Approaches

“…Like the GM-EIA, the LFA assay targets galactomannan but uses two mABs which may provide greater sensitivity [ 104 ]. It has demonstrated good qualitative agreement with GM-EIA [ 105 ]. Both assays show better performance in BAL fluid than serum, and among hematology patients as compared to other patient subgroups [ 104 ].…”