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Comparative Study
. 2024 Dec 11;62(12):e0095024.
doi: 10.1128/jcm.00950-24. Epub 2024 Nov 4.

Serum antigen tests for the diagnosis of invasive aspergillosis: a retrospective comparison of five Aspergillus antigen assays and one beta-D-glucan assay

Thilo Schub #  1 , Isabel Klugherz #  1   2 , Johannes Wagener  3   4 , Juergen Prattes  5 , Martin Hoenigl  5   6 , Sebastian Suerbaum  1 , Jürgen Held  7 , Karl Dichtl  1   2
Affiliations
Comparative Study

Serum antigen tests for the diagnosis of invasive aspergillosis: a retrospective comparison of five Aspergillus antigen assays and one beta-D-glucan assay

Thilo Schub et al. J Clin Microbiol. .

Abstract

Invasive aspergillosis (IA) is a life-threatening infection. Early and specific diagnosis is pivotal to ensure adequate therapy. Antigen testing from blood is a widespread and convenient diagnostic approach. Various tests for the detection of Aspergillus antigen as well as for the panfungal antigen β-1,3-D-glucan (BDG) are available, for which comprehensive comparisons are still lacking. Blood samples of 82 proven/probable (11/71) IA patients and 52 controls were tested using two enzyme-linked immunosorbent assays (ELISAs) (Bio-Rad and Euroimmun), one chemiluminescent immunoassay (CLIA) (Vircell), one BDG assay (Fujifilm Wako), and two point of care (PoC) assays (Immy sōna and OLM). PoC assays were evaluated visually and used automated read out systems. Of the 82 IA patients, 37 had received solid organ transplantation (SOT) and 25 hematopoietic stem cell transplant (HSCT). Sensitivities and specificities for the eight test systems ranged from 27% to 71% and from 64% to 100%. Estimating a 10% prevalence of IA, test performance would have resulted in positive and negative predictive values of 14%-100% and 91%-95%. Areas under the curve (AUCs) for all tests except GM were below 0.7. When the cut-off values for quantitative tests were normalized to a specificity close to 95%, sensitivities ranged from 14% to 40%. The use of automated read out systems for the PoC assays had a significant impact. Combining different tests did not result in better test strategies. Sensitivity of Aspergillus antigen testing from single serum samples is low. Due to specificity issues, the majority of tests is not suited for screening purposes. The different assays can meet different needs in different diagnostic settings.

Keywords: 3-D-glucan; Aspergillus; antigen; beta-1; galactomannan; glucan; invasive aspergillosis; serum.

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Conflict of interest statement

J.W. received financial support (research grant) from Pfizer outside of this study, technical and financial support by Fujifilm Wako Chemicals Europe and Euroimmun Medizinische Labordiagnostika for past projects outside this study, and speaker fees from Pfizer, Wako, und Gilead. J.P. serves as President of the Austrian Society of Medical Mycology, received speaker fees from Gilead, Pfizer, Swedish Orphan BioVitrum, and Associates of Cape Cod, and holds stock in AbbVie Inc. and Novo Nordisk, all unrelated to the submitted work. M.H. received research funding from Gilead, Astellas, MSD, IMMY, Mundipharma, Scynexis, F2G, and Pfizer, all outside of the submitted work. J.H. received speaker fees from Pfizer, Gilead, Associates of Cape Cod, BD, and Biomerieux, research funding from Pfizer and Gilead, and technical support for projects outside this study from Associates of Cape Cod, Vircell, Virion\Serion, IMMY, and OLM. K.D. received technical and financial support by Fujifilm Wako Chemicals Europe and by Euroimmun Medizinische Labordiagnostika for past projects outside this study and technical support by Vircell, OLM, and IMMY for past projects outside this study. T.S., I.K., and S.S. have no conflicts of interest.

Figures

Fig 1
Fig 1
ROC curve analysis. ROC (receiver operator characteristic) curves and AUCs (areas under the curve) with 95% confidence interval for all quantitative assays. For GM testing, two different case cohorts were considered: GM (all cases) consists of all cases of IA included in this study, while GM (GM independent) only considers those cases, which were categorized as IA independently of serum antigen.
Fig 2
Fig 2
Logarithmic scatter plots of GM compared with all other quantitative tests. Cut-off values are depicted as dotted lines. Green full circles and red empty circles represent results of controls and cases, respectively.
See this image and copyright information in PMC

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