Evaluation of the Dynamiker® Fungus (1-3)-β-D-Glucan Assay for the Diagnosis of Invasive Aspergillosis in High-Risk Patients with Hematologic Malignancies

Introduction: The Dynamiker (R) Fungus (1-3)-beta-D-glucan assay (DFA) allows the testing of samples in smaller batches compared to the well-established Fungitell (R) assay (FA) making the assay cost-effective in centers with small numbers of samples. Evaluations of its performance for the diagnosis of invasive aspergillosis (IA) are limited. Therefore, we compared the two assays and evaluated their clinical performance in diagnosing IA. Methods: A total of 60 adult hematology patients were screened for IA, 13 with probable IA, 19 with possible IA, and 28 with no IA. Serum specimens (n = 166) were collected twice-weekly and tested for (1-3)-beta-D-glucan (BDG) using FA and DFA which were compared quantitatively with Spearman rank correlation analysis and qualitatively with the Chi-square test. Agreement and error rates were determined using FA as the reference method. Sensitivity, specificity, and positive predictive and negative predictive values in diagnosing IA were calculated. Results: The performance of the DFA was highly consistent with that of the FA, both quantitatively (r(s) = 0.913) and qualitatively (kappa = 0.725). The agreement was 85% with 8% minor, no major, and 7% very major errors (FA+/DFA-). Using a cut-off value of 20 pg/mL for DFA, very major errors were reduced to 1%, although 5% major errors were detected. BDG levels were lower with DFA than FA (slope 0.653 +/- 0.031). Sensitivity, specificity, positive predictive value, and negative predictive value (NPV) was 67%, 53%, 44%, and 74% for FA, and 53%, 67%, 49%, and 71% for DFA, respectively. The optimal BDG positivity threshold calculated did not lead to significant test quality improvement for either assay. However, a higher % of patients with probable IA (62%) had >= 2 consecutive positive specimens compared to patients with no IA (FA-BDG 26%, p = 0.10, and DFA-BDG 10%, p = 0.01) leading to improved sensitivity and NPV (71% and 85% for DFA, and 95% and 96% for FA, respectively). Conclusion: DFA could be a valuable alternative to the FA, particularly in laboratories with small numbers of samples. The results of the BDG testing should be carefully interpreted in the high-risk setting of patients with hematologic malignancies. Higher NPV was found using as criterion >= 2 consecutive positive samples for diagnosing IA.

Automated summary

This study evaluated the performance of the Dynamiker (R) Fungus (1-3)-beta-D-glucan assay (DFA) for diagnosing invasive aspergillosis (IA) and found that it was highly consistent with the well-established Fungitell (R) assay (FA). The study also found that using consecutive positive samples as the criterion for diagnosing IA improved the negative predictive value in high-risk patients with hematologic malignancies.