Update on the contribution of galactomannan for the diagnosis of invasive aspergillosis

Abstract

The diagnosis of invasive fungal infections (IFI) remains a challenge, particularly for diseases caused by filamentous fungi such as Aspergillus species. Unfortunately, many patients affected by these conditions are not identified before autopsy. Therefore, there is a need for new diagnostic methods for IFI. Galactomannan is a soluble antigen released during hyphal growth in tissues. A commercially available sandwich ELISA assay that detects galactomannan has been used in Europe for many years and is now approved for use in the USA. The test has an excellent negative predictive value in the detection of invasive aspergillosis (IA) in high-risk patients. In addition, it is more sensitive than culture and allows IA to be diagnosed before clinical manifestations occur. However, false-negative and false-positive results in certain populations are the main limitations to its use. The purpose of this review is to summarize the current knowledge about galactomannan testing in patients at risk for IA.

Capítulo 1: diagnóstico laboratorial das micoses pulmonares

“…One of the tests recently approved by the Brazilian National Health Products Oversight Agency is the sandwich ELISA technique, developed to detect galactomannan, a hydrosoluble polysaccharide present in the cell wall of fungi of the genus Aspergillus that is released in the blood during hyphae growth in the host tissues ( Figure 4C). (37,38) This technique can detect low concentrations of galactomannan (0.5 ng/mL) in clinical samples and is commercially available (Platelia Aspergillus EIA; Bio-Rad, Hercules, CA, USA). Sandwich ELISA yields fast results (approximately 4 h); however, its use as a diagnostic tool is approved only for serum samples of neutropenic patients (hematologic patients or bone marrow transplant recipients).…”

“…The frequency of false-positive results usually ranges from 8% to 14% and is mainly caused by the use of cytotoxic chemotherapeutic agents (causing damage to the intestinal mucosa), host versus graft disease, autoreactive antibodies, infection caused by other fungi such as those of the genera Penicillium and Paecilomyces, transfusions, antibiotics of fungal origin (piperacillin-tazobactam, amoxicillin with clavulanic acid) and laboratory contamination. (37,39,(41)(42)(43)(44) Recently, cross-reaction with Histoplasma sp. has also been demonstrated, resulting in positive galactomannan results in patients with histoplasmosis.…”

Has Aspergillus PCR Come to the Age of Maturity?

“…Nowadays, most patients with IA enroll clinical trials or receive antifungal therapy based on GM testing. Nevertheless, there are a number of caveats that sometimes cloud the interpretation of GM results, including a high rate of false-positive results, cross-reaction with fungi other than the Aspergilli, and the reduced sensitivity of serum testing in nonneutropenic patients [2]. Therefore, the scientific community has been at a constant search for alternative non-culture-based and noninvasive diagnostic tests.…”

Cross-Reactivity of Paracoccidioides brasiliensis , Histoplasma capsulatum , and Cryptococcus Species in the Commercial Platelia Aspergillus Enzyme Immunoassay

“…The assay detects galactofuranose-containing side chains of galactomannan, an antigen released from Aspergillus hyphae during growth in the host (1). In addition to varied sensitivity, the test is limited by false-positive results, mostly due to the use of antibiotics.…”

“…Discordant results occurred for one individual with histoplasmosis and for another one with C. neoformans infection. In both cases, a positive sample was followed by a negative test after antifungal therapy was started, a very well-known phenomenon (1). Sera from seven patients with C. gattii infection were tested more than once.…”