Using the galactomannan assay in the diagnosis of invasive aspergillosis.

Aspergillus species are ubiquitous molds to which humans are commonly exposed. Of approximately 180 species, it is estimated that 34 are medically significant.1 Most persons who come in contact with the fungus remain asymptomatic. However, some experience mild morbidity demonstrated by recurrent sinusitis, asthma exacerbations, or allergic bronchopulmonary aspergillosis. Patients who are immunocompromised, however, are susceptible to more severe invasive disease, usually marked by an acute progressive infection, often resulting in death. A survey of 89 physicians whose experience with a combined 595 patients with proven or probable invasive aspergillosis (IA) showed that 32% of patients had undergone bone marrow transplantation, 29% had a hematological malignancy, 9% had undergone solid organ transplant or had another condition requiring immunosuppressive therapy, 9% had pulmonary disease, and 8% had AIDS.2 The prognosis of IA is grim, with a case mortality rate of 58%.3 Although newer, less toxic antifungal agents have been developed, successful management of IA is contingent on early detection, which, unfortunately, can be difficult. DIAGNOSIS OF IA IA is usually suspected when signs of infection refractory to broad-spectrum antibiotics develop in an immunocompromised patient. The gold standard for the diagnosis of IA is tissue biopsy demonstrating invasion on histopathological examination and identification of the organism in culture. The finding of acute-angle branching, septated, nonpigmented hyphae on histopathological examination is not specific for IA because other molds, including Fusarium, Paecilomyces, and Pseudallescheria boydii, can have a similar appearance. For unclear reasons, growth of Aspergillus in culture occurs in only 30% to 50% of histopathologically suggestive cases.4 Obtaining tissue specimens for the diagnosis of IA is often difficult, because patients in whom IA is suspected often have medical conditions, such as thrombocytopenia, that preclude biopsy. GALACTOMANNAN ANTIGEN TESTS A recent diagnostic modality for IA is the galactomannan (GM) assay. GM is a cell wall component of many fungi, including Aspergillus, Penicillium, Paecilomyces, and Geotrichum species. An enzyme-linked immunosorbent assay-based kit is commercially available as the Platelia Aspergillus EIA (Bio-Rad Laboratories, Redmond, Wash) and was cleared by the FDA for diagnostic use in May 2003. GM antigen positivity is among the microbiological criteria proposed by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group for the diagnosis of IA. The Platelia EIA is an immunoenzymatic sandwich microplate assay that uses monoclonal antibodies that bind to side-chain residues of the GM molecule.5 A sandwich enzyme immunoassay format is used for detection. The performance of the assay varies according to the threshold value used. When the Platelia EIA became available in Europe a decade ago, the manufacturer recommended an