Prospective Comparison of the Diagnostic Potential of Real-Time PCR, Double-Sandwich Enzyme-Linked Immunosorbent Assay for Galactomannan, and a (1→3)-β- d -Glucan Test in Weekly Screening for Invasive Aspergillosis in Patients with Hematological Disorders

Abstract

The establishment of an optimal noninvasive method for diagnosing invasive aspergillosis (IA) is needed to improve the management of this life-threatening infection in patients with hematological disorders, and a number of noninvasive tests for IA that target different fungal components, including galactomannan, (133)-␤-D-glucan (BDG), and Aspergillus DNA, have been developed. In this study, we prospectively evaluated the diagnostic potential of three noninvasive tests for IA that were used in a weekly screening strategy: the double-sandwich enzyme-linked immunosorbent assay (ELISA) for galactomannan (Platelia Aspergillus), a real-time PCR assay for Aspergillus DNA (GeniQ-Asper), and an assay for BDG (␤-glucan Wako). We analyzed 149 consecutive treatment episodes in 96 patients with hematological disorders who were at high risk for IA and diagnosed 9 proven IA cases, 2 probable IA cases, and 13 possible invasive fugal infections. In a receiver-operating characteristic (ROC) analysis, the area under the ROC curve was greatest for ELISA, using

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“…Similar results have been found by Maertens et al, Kawazu et al and Lai et al [14,15,16]. Cut off values have also been reviewed by Mycoses study group.…”

“…Next best cut off in our study was found to be ≥ 1.0 (Table 3). False positive cases were also low at cut off of 1.5 (12%).Similar results have been found by Maertens et al, Kawazu et al and Lai et al [14,15,16]. Cut off values have also been reviewed by Mycoses study group.…”

ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients

“…21 The prerequisite of two consecutive positive tests for IFD diagnosis was investigated in four studies and resulted in a specificity approaching 100% and a lower sensitivity ranging between 45 and 65%. 17,19,23,26 The diagnostic performance of BG was similar in IC and IA, while utility in other less common IFD could not be assessed because of lacking data. Few data on the timing of BG positivity compared with conventional diagnostic tools are available: one study suggested that BG detection might precede IFD diagnosis according to the EORTC/MSG criteria.…”

“…Overall, the results of cohort studies tend to exhibit a larger variability of test performance when compared with case-control studies. Different cutoffs for positivity have been investigated in seven studies, 17,[19][20][21][22]24,26 suggesting that the optimal cutoff if compared with the recommended value may be lower for the Wako and Maruha assays 19,26 and higher for the Fungitec-G assay. 21 The prerequisite of two consecutive positive tests for IFD diagnosis was investigated in four studies and resulted in a specificity approaching 100% and a lower sensitivity ranging between 45 and 65%.…”

“…As the design of these studies was very variable, only 10 (4 case-control and 6 cohort studies) [17][18][19][20][21][22][23][24][25][26] were considered appropriate for analysis on the basis of the following parameters: type of population (hematological patients), sample size (X20 IFD cases and X50 non-IFD controls) and reference standard of IFD (definition according to the EORTC/MSG criteria). 10 Whereas sensitivity, specificity, positive and negative predictive values derived from these analyses in hematological patients were variable (Table 3), no major differences were observed among the different assays.…”