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Scientifica  2013 

Laboratory Diagnosis of Invasive Aspergillosis: From Diagnosis to Prediction of Outcome

DOI: 10.1155/2013/459405

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Abstract:

Invasive aspergillosis (IA), an infection caused by fungi in the genus Aspergillus, is seen in patients with immunological deficits, particularly acute leukaemia and stem cell transplantation, and has been associated with high rates of mortality in previous years. Diagnosing IA has long been problematic owing to the inability to culture the main causal agent A. fumigatus from blood. Microscopic examination and culture of respiratory tract specimens have lacked sensitivity, and biopsy tissue for histopathological examination is rarely obtainable. Thus, for many years there has been a great interest in nonculture-based techniques such as the detection of galactomannan, β-D-glucan, and DNA by PCR-based methods. Recent meta-analyses suggest that these approaches have broadly similar performance parameters in terms of sensitivity and specificity to diagnose IA. Improvements have been made in our understanding of the limitations of antigen assays and the standardisation of PCR-based DNA detection. Thus, in more recent years, the debate has focussed on how these assays can be incorporated into diagnostic strategies to maximise improvements in outcome whilst limiting unnecessary use of antifungal therapy. Furthermore, there is a current interest in applying these tests to monitor the effectiveness of therapy after diagnosis and predict clinical outcomes. The search for improved markers for the early and sensitive diagnosis of IA continues to be a challenge. 1. Introduction Aspergillosis, which can be defined as an infection or disease caused by fungi in the genus Aspergillus constitutes a wide range of disease entities that form a continuum from allergic reactions to disseminated invasive disease in immunocompromised patients [1]. The specific term invasive aspergillosis (IA), often defined in relation to the primary affected organ as invasive pulmonary aspergillosis (IPA) is commonly considered to be defined by invasion of the pulmonary parenchyma by the growing hyphae of Aspergillus [2] and this is further refined being angioinvasive IPA if there is evidence of vascular invasion by the hyphae [2]. The most common aetiological agent of IA, Aspergillus fumigatus, is a ubiquitous fungus (Figure 1), with airborne conidia leading to almost universal and constant exposure in almost all humans. The corollary of this is that as the risk of IA is mainly a function of deficits in host defences, IA is seen primarily in patients with haematological malignancy and in solid organ and stem cell transplant recipients [3]. Diagnosis of IA is complicated by the fact that

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