Aspergillus Galactomannan Enzyme-Linked Immunosorbent Assay Cross-Reactivity Caused by Invasive Geotrichum capitatum

Abstract

We report three cases of invasive Geotrichum capitatum infection in patients with acute leukemia for which an enzyme-linked immunosorbent assay (ELISA) for Aspergillus galactomannan was positive, with no evidence of aspergillosis. Supernatants obtained from suspensions of 17 G. capitatum strains gave positive reactions with the Aspergillus galactomannan ELISA. These clinical and laboratory data seem to suggest that G. capitatum produces a soluble antigen that is cross-reactive with Aspergillus galactomannan.Aspergillus galactomannan detection by a sandwich enzymelinked immunosorbent assay (ELISA) is widely used throughout the world in diagnosing invasive aspergillosis, and it has been introduced among the international microbiological criteria for the diagnosis of this fungal infection in immunocompromised hosts (2, 11). A major problem with the detection of circulating galactomannan is the occurrence of false-positive results, which, in some cases, have been shown to be related to cross-reactivity with other opportunistic fungi (11). We report cases of three acute-leukemia patients who developed disseminated infection by Geotrichum capitatum for which ELISA for Aspergillus galactomannan was positive, with no evidence of aspergillosis.Patient 1 was a 7-year-old child with acute lymphoblastic leukemia in second relapse who underwent salvage chemotherapy in February 2004. Ten days after this treatment, the patient developed fever and periorbital edema; broad-spectrum antibiotics and liposomal amphotericin B were administered. A week later, several serum samples were positive for galactomannan antigen and caspofungin was added. A computedtomography scan showed an abscess of the cerebral base starting from the ethmoidal plan and involving the hypophyseal region. Therefore, a surgical debridement was performed; G. capitatum was isolated from samples of pus, liquor, and bone (identification was performed with the VITEK system [bioMerieux Italia, Rome, Italy]). Galactomannan antigen was detected in the pus. Histology of a bone fragment disclosed necrotic tissue in which mycotic invasion was evident. On periodic acid-Schiff-and Grocott-stained sections, the fungi consisted of septate hyphae, slightly bent with parallel disposition and only occasional branching at a wide acute angle or budding at a right angle. A few spores and fragmentation of the mycelium in arthroconidia were also observed. Caspofungin was replaced with voriconazole. Within a few days, the patient's clinical condition improved and galactomannan antigen, for which tests were previously constantly positive, disappeared from the blood. Two months after surgery, while under voriconazole treatment, the child underwent two consecutive aploidentical bone marrow transplants from his father and his mother, but after a few weeks, the child died from sepsis of an unknown origin. Serum galactomannan antigen was no longer detected.Patient 2 was a 9-year-old girl with a diagnosis of myelodysplasia secondary to acute lymphoblastic leukemia and who underwent an allog...

Breakthrough disseminated Saprochaete capitata infection in a child with acute myeloid leukaemia receiving caspofungin therapy

“…In fact, this is a case of breakthrough S. capitata infection, where the patient was treated empirically with caspofungin for more than 3 weeks. Consistent with our case, there are previous reports of breakthrough S. capitata infections in leukaemic patients on caspofungin/micafungin prophylaxis (Giacchino et al, 2006;Bonini et al, 2008;Chittick et al, 2009;Schuermans et al, 2011). All these cases succumbed to S. capitata infection (Schuermans et al, 2011).…”

Biomarkers for Invasive Aspergillosis: The Challenges Continue

“…fumigatus Aspergillus species [47]. Other studies challenge the specificity of the GM ELISA: it detects a soluble antigen produced during infection with Geotrichum capitatum, with no evidence of aspergillosis [48], crossreacts with other opportunistic fungi in some other fungal infections such as histoplasmosis [49] react with antigens from Cryptococcus neoformans in patients with cryptococcosis [50]. Early problems with false-positive results from patients receiving β-lactam antibiotics [51] may have been caused by the presence of cross-reacting antigens from Penicillium during manufacturing [52], and are largely resolved [53].…”

Galactomannan Enzymatic Immunoassay Cross-Reactivity Caused by Prototheca Species

“…Since its introduction, some false-positive results caused by cross-reactivity with other fungi and yeasts, such as Cryptococcus neoformans, Geotrichum capitatum, Penicillium spp., Alternaria spp., Histoplasma spp., and Paecilomyces spp., have been demonstrated (2,5,18,20,22). To the best of our knowledge, no data are available on the detection of galactomannan antigen in serum from patients with invasive protothecosis.…”