CROSS-REACTIVITY OF FUSARIUM SPP IN THE ASPERGILLUS GALACTOMANNAN ENZYME LINKED IMMUNOSORBENT ASSAY

Aspergillus galactomannan antigen assay (GM) using a sandwich enzyme linked immunosorbent assay (ELISA) has been a major advance for the diagnosis of invasive aspergillosis, especially in patients with haematological malignancy. The GM assay was recently included by the EORTC/MSG as a mycological criterion to define invasive aspergillosis. Cross-reaction with a large number of fungi, including yeasts, dimorphic fungi and some moulds, have been reported. Cross-reactivity of Fusarium spp in the GM assay is controversial.The aim of the present study was to check GM results in patients with disseminated fusariosis and to test the cross-reactivity of different Fusarium spp in the GM ELISA.A total of 12 Fusarium isolates - 2 F. oxysporum, 3 F. proliferatum, 4 F. solani species complex (FSSC) and 3 F. verticillioides - were grown in Sabouraud broth for 72 h at room temperature on a rotary shaker and the centrifuged supernatants were tested by ELISA (cutoff 0.5). Six out of eight leukaemia patients with disseminated Fusarium infection tested at least twice for GM had repeated positive GM ranging from 0.69 up to 4.16 in absence of isolation of Aspergillus spp.All the Fusarium isolates produced positive reactions when tested with ELISA undiluted showing index values ranging from 1.49 (F. proliferatum) up to 4.14 (FSSC). Only three isolates (one F. verticillioides and two FSSC) tested positive (0.55-2.56) at the 1:100 dilution.These results showed a cross-reactivity of Fusarium spp with Aspergillus GM that may constitute a drawback for the specificity of the ELISA test. Therefore a positive GM, like the presence of septate acute-angle branching hyphae in tissue and positive -D-glucan test, cannot help to reach a specific diagnosis. This may represent a crucial point for the choice of antifungal therapy and for the evaluation of treatment outcome of antifungals, such as echinocandins that were shown to be inactive in vitro against all Fusarium spp.