Multiple serum antigenic assays for diagnosis of invasive fungal infections in non-neutropenic adult patients

Abstract

To evaluate the value of plasma 1, 3-β-D-glucan (G), serum mannan, galactomannan (GM) and cryptococcus capsular antigen assays for diagnosis of invasive fungal infections (IFI) in non-neutropenic adult patients. This was a prospective case control study. Plasma and serum samples from 25 patients with IFI (candidiasis, aspergillosis, cryptococcosis, zygomycosis, pneumocystis carinii pneumonia), 27 patients with bacterial infections, and 25 healthy adults were collected from February 2007 to February 2009 in Beijing Hospital. The serum antigenic assays were performed and their sensitivity and specificity were analyzed. Optimal cut-off level of G test and mannan was established with receiver operating characteristic curve (ROC). The concentration of G test in plasma of patients with IFI [89.4 (25.8, 336.9) ng/L] was significantly higher than that of patients with bacterial infection [8.1 (5.0, 34.9) ng/L, U = 120.5, P < 0.001] and healthy adults [3.8 (3.8, 26.0) ng/L, U = 76.5, P < 0.001]. The area under curve (AUC) was 0.858, and the optimal cut-off value was 71.7 ng/L. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 65.0% (13/20), 92.3% (48/52), 76.5% (13/17) and 87.2% (48/55) respectively. The concentration of mannan in serum from patients with candidiasis [1.13 (0.44, 1.22) µg/L] was significantly higher than that from patients with non-candidiasis IFI [0.21 (0.14, 0.27) µg/L, U = 19, P < 0.05], bacterial infection [0.26 (0.22, 0.32) µg/L, U = 36.5, P < 0.001] and healthy adults [0.25 (0.22, 0.30) µg/L, U = 29.5, P < 0.001]. The AUC was 0.894, and the optimal cut-off value was 0.41 µg/L. The sensitivity, specificity, PPV and NPV were 83.3% (10/12), 90.4% (47/52), 66.7% (10/15) and 96.0% (47/49) respectively. The sensitivity, specificity, PPV and NPV of GM antigen to diagnose aspergillosis were 25.0% (1/4), 96.1% (50/52), 33.3% (1/3) and 92.6% (50/54) respectively. The sensitivity, specificity, PPV and NPV of cryptococcus capsular antigen to diagnose cryptococcosis were all 100%. 1,3-β-D-glucan, mannan and cryptococcus capsular antigen were useful for diagnosis of IFI in non-neutropenic adult patients. GM antigen did not show a good sensitivity for diagnosis of aspergillosis in non-neutropenic adult patients.