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AspergillusGalactomannan Detection in the Diagnosis of Invasive Aspergillosis in Cancer Patients

From the Département d’Hématologie et d’Oncologie and Département d’Onco-Hématologie Pédiatrique, Hôpitaux Universitaires de Strasbourg, and Institut de Parasitologie et de Pathologie Tropicale, Faculté de Médecine, Strasbourg, France.

Address reprint requests to Raoul Herbrecht, MD, Département d’Hématologie et d’Oncologie, Hôpital de Hautepierre, 67098 Strasbourg, France; email: raoul.herbrecht{at}chru-strasbourg.fr

PURPOSE: To assess the Aspergillus galactomannan enzyme-linked immunosorbent assay (ELISA) in the diagnosis of invasive aspergillosis (IA) in adult and pediatric oncohematologic patients.

PATIENTS AND METHODS: The study was conducted in four patient groups: those with fever of unknown origin (FUO) during neutropenia, suspected pulmonary infection (PI), or nonpulmonary aspergillosis (NPA) and those undergoing surveillance (S) after hematopoietic stem-cell transplantation (HSCT). IA was classified as definite, probable, or possible, according to European Organization for Research and Treatment of Cancer/Mycosis Study Group definitions.

RESULTS: A total of 3,294 serum samples were collected during 797 episodes (FUO, 261; PI, 297; NPA, 28; and surveillance, 211), and 153 episodes of IA were diagnosed (31 definite, 67 probable, and 55 possible). Three episodes were first suspected from galactomannan ELISA; the remaining 150 cases were diagnosed from clinical or radiologic evidence. Sensitivity of the ELISA was 64.5%, 16.4%, and 25.5% in definite, probable, and possible episodes of IA, respectively, and was lower in patients positive for anti-Aspergillus antibodies than in antibody-negative patients. Most false-positive results occurred in children and in allogeneic HSCT (allo-HSCT) patients. Overall specificity of the ELISA was 94.8%. It was lower in children compared with adults (P < .0001) and in allo-HSCT patients compared with non–allo-HSCT adults (P = .0002). Lowering the ELISA cutoff value from 1.500 to 0.700 seemed more relevant for non–allo-HSCT adults (sensitivity, 73.1%, 44.3%, and 44.7% in definite, probable, and possible IA, respectively; specificity, 94%).

CONCLUSION: Galactomannan ELISA seems less sensitive than previously described, and sensitivity can be further reduced by the presence of anti-Aspergillus antibodies. A new cutoff value for the ELISA of 0.700 is proposed for non–allo-HSCT adults.

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