Advances in the serological diagnosis of invasive Aspergillus infections in patients with haematological disorders Johan Maertens 1 , Koen Theunissen 1 , Tom Lodewyck 1 , Katrien Lagrou 2 and Johan Van Eldere 2 1 Department of Haematology, Universitaire Ziekenhuizen Leuven, Catholic University, Leuven, Belgium and 2 Department of Medical Diagnostic Sciences, Universitaire Ziekenhuizen Leuven, Catholic University, Leuven, Belgium Summary A reliable diagnosis of invasive aspergillosis in patients with haematological malignancies is seldom achieved antemortem. Conventional laboratory diagnostic methods are insensitive and time-consuming, resulting in late diagnosis and treatment and contributing to unacceptably high mortality. As a result, routine antifungal prophylaxis and early empirical treatment have been recommended. However, overtreatment associated with these strategies results in increased toxicity and cost. The use of sensitive and rapid non-culture-based diagnostic assays, such as detection of Aspergillus antigens (galactomannan, b-D-glucan) or detection of genomic DNA sequences may allow a shift in emphasis from empirical to pre-emptive therapy, especially when substantiated by suggestive radiological findings. These new tools may be used to confirm a presumed diagnosis of invasive aspergillosis, or, when used to screen high-risk patients, may identify an infection at the early stage of disease. The excellent negative predictive value of these assays should convince clinicians to withhold antifungal therapy in persistently febrile neutropenic patients with no other signs of fungal infection. On the other hand, consecutive positive results in a high-risk population should at least trigger a complete diagnostic work-up. This review will focus on the diagnostic utility as well as on the pitfalls of serial screening for the presence of circulating fungal antigens in haematology patients. Key words: Galactomannan, b-D-glucan, aspergillosis, neutropenia, diagnosis, pre-emptive. Introduction The incidence of deep fungal infections has increased over the last two decades, with the majority of these infections occurring in patients with haematological malignancies. To date, invasive fungal infection is a major direct or contributory cause of death in patients with acute leukaemia/myelodysplastic syndrome who undergo intensive chemotherapeutic treatment. 1 Inva- sive fungal infections are also the major cause of infectious mortality in haematopoietic stem cell trans- plant recipients, not only during the early neutropenic phase, but also later when graft-vs.-host disease (GvHD) develops. 2 In addition, recent treatment strategies that result in prolonged impairment of B and T cell-mediated immunity (e.g. monoclonal antibodies such as rituxim- ab or alemtuzumab; purine analogues) have created new populations at risk, including patients with low- grade haematological malignancies. 3 Species of the Aspergillus family account for a substantial number of these infections, and in particular pulmonary infection with Aspergillus fumigatus has emerged notably in the developed world. A recent Italian cohort study found that Aspergillus accounted for 90% of all mould infections in patients with haemato- logical malignancies. 4 Recent work from the Seattle group confirmed the 10–20% incidence of invasive aspergillosis in allogeneic stem cell transplant recipi- ents. 5 The spectrum of disease manifestations is heteroge- nous and determined by the inoculating dosage, the Correspondence: Johan Maertens MD, Department of Haematology, Acute Leukaemia and Stem Cell Transplantation Unit, University Hospital Gasth- uisberg, Herestraat 49, B-3000 Leuven, Belgium. Tel.: +32 16 34 68 80. Fax: + 32 16 34 68 81. E-mail: johan.maertens@uz.kuleuven.ac.be Accepted for publication 18 December 2006 Original article 2 Ó 2007 Blackwell Publishing Ltd • Mycoses, 50, (Suppl. 1) 2–17