Evaluation of a novel aspergillus IgG lateral flow assay for the diagnosis of non-neutropenic patients with acute and subacute invasive aspergillosis

Abstract

Purpose: This study aimed to assess a novel lateral flow assay (LFA) for Aspergillus IgG detection in patients with non-neutropenic invasive aspergillosis (IA).

Methods: Aspergillus IgG LFA and enzyme-linked immunosorbent assay (ELISA) were performed in non-neutropenic IA patients and control group (proven community acquired pneumonia and healthy persons), respectively. The diagnostic performance of Aspergillus IgG LFA for IA was evaluated and compared with ELISA method.

Results: 33 cases of acute IA, 30 cases of subacute IA and 80 controls were enrolled in this study. The level of plasma Aspergillus IgG LFA in the IA group was significantly higher than that in the control group (190.5 AU/mL vs. 50.3 AU/mL, P < 0.001). In total, the sensitivity/specificity/PPV/NPV of Aspergillus IgG LFA was 65.1%/97.5%/95.4%/78.0%. The sensitivity and specificity of Aspergillus IgG LFA were equivalent to those of Aspergillus IgG ELISA with a 120 AU/mL cut-off, but exhibited significantly higher specificity (97.5% vs 87.5%, P = 0.021) compared to the ELISA with an 80 AU/mL cut-off. The consistency was strong among the two methods (P < 0.001, Kappa = 0.67/0.68). The sensitivities/specificities/PPVs/NPVs of Aspergillus IgG LFA were 57.6%/97.5%/90.5%/84.8% for patients with acute IA, and 73.3%/97.5%/91.7%/90.7% for patients with subacute IA, respectively. The "any-positive" strategy, which combined Aspergillus IgG LFA with sputum culture and serum galactomannan (GM), had a sensitivity/specificity/PPV/NPV of 81.1%/94.7%/95.6%/78.3%. The sensitivity/specificity/PPV/NPV of bronchoalveolar lavage fluid (BALF) GM was 65.0%/90.0%/92.9%/56.3%. When combined Aspergillus IgG LFA with BALF GM, the figures were 87.5%/85.0%/92.1%/77.3%.

Conclusions: Compared to the Aspergillus IgG ELISA, the Aspergillus IgG LFA exhibits comparable or superior diagnostic efficiency in IA patients, while offering a faster and more convenient option for clinical diagnosis. The "any-positive" strategy of combined diagnosis with Aspergillus IgG LFA serves as a valuable supplement to current diagnostic approaches, particularly benefiting patients who cannot tolerate invasive bronchoscopic procedures.

Keywords: acute invasive aspergillosis; aspergillus IgG lateral flow assay; diagnosis; non-neutropenic patients; subacute invasive aspergillosis.

Figure 1

The flow chart of the Aspergillus IgG assay via fluorescence lateral flow technique. Step 1: Blood samples were centrifuged, then the plasma was diluted 1:200. Step 2: 90–100 μL of the diluted sample was added to the sample well of the test card. Step 3: A 15–20 minute incubation period was allowed. Step 4: Detection was performed using an optical device.

Figure 2

(A, B) The levels of Aspergillus IgG LFA and Aspergillus IgG ELISA in overall IA and control groups; (C, D) The levels of Aspergillus IgG LFA and Aspergillus IgG ELISA in acute IA and subacute IA groups; (E, F) Scatter diagram of Aspergillus IgG LFA vs Aspergillus IgG ELISA in overall and IA patients. **** P < 0.001; ns, not significant (P > 0.05); the value of r represented correlation coefficient. LFA, lateral flow assay; IA, invasive aspergillosis; ELISA, enzyme-linked immunosorbent assay.

Figure 3

Receiver operating characteristic curves were used to evaluate the performance of Aspergillus IgG LFA and ELISA in diagnosing acute IA, subacute IA or overall IA group, compared to CAP group and healthy control. (A) LFA vs ELISA in overall IA; (B) LFA vs ELISA in acute IA; (C) LFA vs ELISA in subacute IA; (D) LFA in acute IA and subacute IA. IA, invasive aspergillosis; ELISA, enzyme-linked immunosorbent assay; LFA, lateral flow assay.