Information was identified by searches in Medline, references of relevant articles, and of the extensive files of the authors. Views and concepts evolved from discussions with colleagues who are specialists in mycology. Search terms were “invasive aspergillosis”, “Aspergillus”, “fungal”, “diagnosis”, “management”, “antigen”, “antigenaemia”, “galactomannan”, “galactofur*”, “glycoprotein”, “carbohydrate”, “polysaccharide”, “oligosaccharide”, “(lipo)glycan”, “amphiphile”, and “(lipo)teichoic
ReviewDetection of circulating galactomannan for the diagnosis and management of invasive aspergillosis
Section snippets
Causes of variability
There are several reasons that might explain the reported differences in performance, relating to (i) the fungus (strain, growth, release of antigen), (ii) the host (underlying condition, location and extent of fungal disease, antifungal treatment, age), and (iii) definition and method (ELISA, sampling and storage, definition of case, definition of results; table 1). At present the kinetics of galactomannan (release at the site of infection, leakage to the circulation, characteristics of
The galf-antigen
In-vivo studies to identify the molecules secreted by the fungus during invasive growth in host tissues have been confounded by the small amount of antigens present. Only one study deals with antigens secreted in vivo during infection of mouse kidney.18 This and earlier studies suggested that circulating Aspergillus sp antigens in patients with invasive aspergillosis varied in size from 35 to greater than 100 kDa, although the nature of the antigens was not characterised.19 The presence of
Exposure to antifungal agents
An important factor that affects the release of galf-antigens is antifungal drug therapy. Amphotericin B is known to suppress the expression of galactomannan antigenaemia in neutropenic rabbits with primary pulmonary aspergillosis.44 Rohrlich et al8 reported that in vitro this negative effect is caused by a reduction in mycelial growth and not by a direct effect of amphotericin B on the secretion of galactomannan, although the method used was not described. Exposure to amphotericin B resulted
Cut-off value
Other factors that have been under debate are the cut-off value of a positive result. When the ELISA kit was launched in Europe a decade ago, a cut-off serum ratio of 1·5 was recommended in the manufacturers manual. Although the course of the antigen titre is considered more important than the actual cut-off, several studies indicated that 1·5 was too high. Over the past years many investigators have used 1·0 as cut-off and a receiver operating characteristic analysis indicated that a cut-off
Conclusions
The sandwich ELISA allows detection of circulating galf-antigens (galactomannan) in the blood of patients with invasive aspergillosis with high sensitivity and specificity. There is, however, considerable variation in performance. This variability is multifactorial and is far from being understood. Some of the factors that might affect the release of the Aspergillus antigen bearing the epitope that reacts with the monoclonal antibody EB-A2 used in the ELISA include those relating to fungal
Recommendations for use of antigen detection in clinical practice
Despite many uncertainties with respect to the release and detection of galactomannan and the variable performance in clinical practice, the commercial ELISA test Platelia Aspergillus is routinely used worldwide in the management of patients at high risk of invasive aspergillosis. The fact that circulating antigen can be detected at an early stage of infection makes prospective monitoring of serum or plasma feasible. Patients that are at high risk include those with acute myeloid leukaemia,
Search strategy and selection criteria
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