Prospective Evaluation of the Turbidimetric β-D-Glucan Assay and 2 Lateral Flow Assays on Serum in Invasive Aspergillosis

Background. Invasive aspergillosis (IA) remains a potentially lethal disease and requires timely diagnosis and initiation of antifungal therapy. Recently, the IMMY lateral flow assay (LFA), the OLM Diagnostics lateral flow device (LFD), and the Wako turbidimetric beta-d-glucan assay have been approved for use as a diagnostic aid. However, their performance in diagnosing IA on serum samples from at-risk patients and the added value to the existing detection of serum galactomannan remain to be investigated. Methods. We prospectively collected serum samples from 239 hematology patients and evaluated the diagnostic performance of these 3 assays while using the 2019 EORTC/MSG definitions (study number S59863/S61797, NCT03004092). Results. We identified 5 cases of proven IA, 36 cases of probable IA, and 188 controls. The LFA had the highest negative predictive value (NPV) and sensitivity (0.90 and 0.49, respectively) while galactomannan detection had the highest positive predictive value and specificity (0.93 and 0.99, respectively). Sensitivity was not significantly different between both tests. When used in combination, the highest NPV was seen in patients with a negative LFA and a negative beta-d-glucan test. The sensitivity of the LFD was significantly lower than the LFA. After omitting serum galactomannan from the definitions to control for incorporation bias, the sensitivity of the LFA outperformed galactomannan detection (0.41 vs 0.31, P = .046). Conclusions. The LFA is a fast and effective alternative to serum galactomannan detection for the diagnosis of IA and is especially useful for centers with low sample throughputs. The addition of the Wako beta-D-glucan assay further improves the diagnostic performance.

Automated summary

The study evaluated the diagnostic performance of three assays for diagnosing invasive aspergillosis in serum samples, finding that the LFA had the highest negative predictive value and sensitivity, while galactomannan detection had the highest positive predictive value and specificity. Combining LFA with beta-D-glucan test improved the negative predictive value. The LFD showed lower sensitivity compared to LFA and omitting galactomannan improved the sensitivity of LFA for diagnosing IA.