-D-Glucan as a Diagnostic Adjunct for Invasive Fungal Infections: Validation, Cutoff Development, and Performance in Patients with Acute Myelogenous Leukemia and Myelodysplastic Syndrome

Abstract

The Glucatell (1r3)-b-D-glucan (BG) detection assay (Associates of Cape Cod) was studied as a diagnostic adjunct for invasive fungal infections (IFIs). On the basis of findings from a preliminary study of 30 candidemic subjects and 30 healthy adults, a serum BG level of у60 pg/mL was chosen as the cutoff. Testing was performed with serial serum samples obtained from 283 subjects with acute myeloid leukemia or myelodysplastic syndrome who were receiving antifungal prophylaxis. At least 1 serum sample was positive for BG at a median of 10 days before the clinical diagnosis in 100% of subjects with a proven or probable IFI. IFIs included candidiasis, fusariosis, trichosporonosis, and aspergillosis. Absence of a positive BG finding had a 100% negative predictive value, and the specificity of the test was 90% for a single positive test result and у96% for у2 sequential positive results. The Glucatell serum BG detection assay is highly sensitive and specific as a diagnostic adjunct for IFI.The mortality rate for invasive fungal infections in neutropenic subjects is 50% for subjects with Candida infection [1,2] and may approach 100% for those with invasive aspergillosis [3,4], fusariosis [5], or trichosporonosis [6]. Early diagnosis of invasive fungal infection in neutropenic subjects has the potential to increase antifungal therapeutic response, but meaningful diagnostic tests have proven to be elusive. Histopathologic demonstration of organisms in tissue specimens or growth of fungal agents in culture media is still the

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

“…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.…”

“…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.…”

A prospective randomized controlled trial comparing PCR-based and empirical treatment with liposomal amphotericin B in patients after allo-SCT

“…5 With the exception of the Aspergillus-directed galactomannan enzyme immunoassay and 1,3-b-glucan detection assays, the serological kits available for the detection of fungal antigens have inconsistent sensitivity, specificity or both. [6][7][8][9][10][11] Thus, techniques with higher sensitivity and specificity for detection of fungal pathogens, such as fungus-specific DNA probes and the PCR assays, are urgently needed.…”

Detection of (1→3)-β- d -Glucan as an Adjunct to Diagnosis in a Mixed Population with Uncommon Proven Invasive Fungal Diseases or with an Unusual Clinical Presentation

“…Different studies have established its diagnostic value in invasive candidiasis and invasive aspergillosis (9,10). However, currently numerous non-Candida and non-Aspergillus fungi are important causes of IFD in the immunocompromised host, and in this setting, clinical and mycological experience with the use of BG as a tool for diagnosis is scarce (7)(8)(9)(10)(11). The aim of this report was to assess the usefulness of BG detection (Fungitell; Associates of Cape Cod, Falmouth, MA) as a diagnostic adjunct in proven IFD in a mixed population with uncommon fungal infections due to emerging dematiaceous and hyaline septate molds (14) or with an unusual clinical presentation.…”