PubMed was searched for English-language literature using the following terms: “Aspergillus”, “aspergillosis”, “diagnosis”, “fungus”, “fungal”, “culture”, “histology”, “galactomannan”, “glucan”, “serology”, “antibody”, “PCR”, “molecular”, “metabolite”, “mannitol”, and “gliotoxin”. Further relevant references, not identified by this strategy, were retrieved from the primary publications.
ReviewLaboratory diagnosis of invasive aspergillosis
Introduction
Aspergillus spp are ubiquitous opportunistic moulds that cause both allergic and invasive syndromes. The genus comprises approximately 180 species, of which 33 have been associated with human disease. Most infections are caused by Aspergillus fumigatus, Aspergillus flavus, Aspergillus terreus, and Aspergillus niger;1 less commonly, Aspergillus nidulans can be implicated as the causative pathogen, especially in the setting of chronic granulomatous disease.2
An accurate diagnosis of invasive aspergillosis is important for clinical reasons; an earlier diagnosis is associated with improved patient survival3 and tests with a high negative predictive value may allow expensive and potentially toxic antifungal drugs to be withheld. New drugs—eg, voriconazole—exhibit differential mould activity; the ability to specifically exploit their anti-aspergillus properties requires a rapid and accurate laboratory diagnosis. The epidemiology of invasive aspergillosis is changing; invasive disease is increasingly observed in the non-neutropenic phase of haematopoietic stem cell transplantation4, 5, 6 and in non-classic settings such as critically ill patients in intensive care units.7 Aspergillus spp other than A fumigatus—some of which demonstrate inherent resistance to antifungal drugs—are increasingly recognised.8, 9, 10 An international collaborative effort recently produced standardised definitions for invasive fungal infections.11 Thus, a review of the diagnostic modalities and their use in establishing a diagnosis of invasive aspergillosis is timely.
Section snippets
Direct techniques
The advantages of direct techniques over culture include superior sensitivity and a relatively rapid turn around time. The principal disadvantage is the inability to definitively distinguish other filamentous fungi (eg, Penicillium spp and Scedosporium spp) or implicate Aspergillus spp as the causative pathogen in circumstances in which there are atypical or non-specific morphological features. This disadvantage may compromise diagnostic accuracy and hence estimates of therapeutic efficacy if
Laboratory isolates
Given the distinct differences in disease manifestations, prognosis, and antifungal susceptibility between different fungal genera and species, a rapid diagnosis will assume increasing importance. The inherent problems with identification using culture methods have been outlined. An increasing number of studies have examined the use of PCR to enable the accurate and rapid detection of laboratory isolates (table 3). The rapid identification of laboratory isolates using microarray technology with
Future challenges
Invasive aspergillosis continues to pose many challenges. From a diagnostic point of view, improving the test accuracy remains a priority for patient care, therapeutic research, and future diagnostic research. The question, of course, is the manner in which these improvements can be achieved. The progressive refinement of existing techniques and development of new diagnostic technologies is clearly a priority. Substantial work remains in areas related to cost-effectiveness and whether patients
Search strategy and selection criteria
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