Comparative performance evaluation of Wako β-glucan test and Fungitell assay for the diagnosis of invasive fungal diseases.

Elena De Carolis,Rita Murri,Brunella Posteraro,Giulia De Angelis,Federica Marchionni,Riccardo Torelli,Maurizio Sanguinetti,Gennaro De Pascale,Livio Pagano,Morandotti Grazia Angela,Jeffrey Chalmers

doi:10.1371/journal.pone.0236095

Elena De Carolis, Rita Murri + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0236095

Copy DOI

Journal: PloS one	Publication Date: Jul 29, 2020
Citations: 21	License type: CC BY 4.0

Affiliation: Università Cattolica del Sacro Cuore

Abstract

The Fungitell assay (FA) and the Wako β-glucan test (GT) are employed to measure the serum/plasma 1,3-β-D-glucan (BDG), a well-known invasive fungal disease biomarker. Data to convincingly and/or sufficiently support the GT as a valuable alternative to the FA are yet limited. In this study, we evaluated the FA and the GT to diagnose invasive aspergillosis (IA), invasive candidiasis (IC), and Pneumocystis jirovecii pneumonia (PJP). The FA and GT performances were compared in sera of patients with IA (n = 40), IC (n = 78), and PJP (n = 17) with respect to sera of control patients (n = 187). Using the manufacturer's cutoff values of 80 pg/mL and 11 pg/mL, the sensitivity and specificity for IA diagnosis were 92.5% and 99.5% for the FA and 60.0% and 99.5% for the GT, respectively; for IC diagnosis were 100.0% and 97.3% for the FA and 91.0% and 99.5% for the GT, respectively; for PJP diagnosis were 100.0% and 97.3% for the FA and 88.2% and 99.5% for the GT, respectively. When an optimized cutoff value of 7.0 pg/mL for the GT was used, the sensitivity and specificity were 80.0% and 97.3% for IA diagnosis, 98.7% and 97.3% for IC diagnosis, and 94.1% and 97.3% for PJP diagnosis, respectively. At the 7.0-pg/mL GT cutoff, the agreement between the assays remained and/or became excellent for IA (95.1%), IC (97.3%), and PJP (96.5%), respectively. In conclusion, we show that the GT performed as well as the FA only with a lowered cutoff value for positivity. Further studies are expected to establish the equivalence of the two BDG assays.

Highlights

One was the Fungitell assay (FA; Associates of Cape Cod, East Falmouth, MA), FDA cleared and Conformite Europeenne (CE) marked, which has been most used in the Western Hemisphere (Europe and United States), and another was the Wako β-glucan test (GT; FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan), CE marked, which has recently been introduced in Europe
We included 187 samples from 187 patients, for whom clinical, radiographic, and microbiological findings indicated no evidence of invasive fungal diseases (IFDs)
Using a similar study design, we compared the GT with the FA to diagnose IFD in 322 patients categorized into invasive candidiasis (IC) (n = 78), Invasive aspergillosis (IA) (n = 40), Pneumocystis jirovecii pneumonia (PJP) (n = 17), and non-IFD (n = 187) groups

Summary

Introduction

Invasive aspergillosis (IA), invasive candidiasis (IC), and Pneumocystis pneumonia (PJP, previously known as PCP) represent the most prevalent invasive fungal diseases (IFDs) worldwide. One was the Fungitell assay (FA; Associates of Cape Cod, East Falmouth, MA), FDA cleared and Conformite Europeenne (CE) marked, which has been most used in the Western Hemisphere (Europe and United States), and another was the Wako β-glucan test (GT; FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan), CE marked, which has recently been introduced in Europe. Both assays rely on the BDG ability to activate factor G, a serine protease zymogen, in the Limulus (horseshoe crab) coagulation cascade. Similar to previous studies [17, 18], we tried to define the optimal GT cutoff values which could allow to reliably exclude IFD (mainly due to Aspergillus, Candida, or P. jirovecii)

Ethics statement

Study design

Results

Discussion