Molecular diagnosis of invasive aspergillosis in patients with hematologic malignancies – new answers to a diagnostic challenge?

Abstract

Within recent years, new molecular methods have been developed to improve the diagnosis of life-threatening invasive aspergillosis in patients at high risk, especially patients with malignant hematological diseases undergoing intensive chemotherapy. Both early diagnosis and treatment are crucial for adequate therapeutic management, which, however, often remains difficult and unclear, because most of the conventional diagnostic tools used clinically at present lack either specificity or acceptable sensitivity at the critical, early phase of the infection. To review the clinical value, advantages and problems and drawbacks of molecular approaches, especially polymerase chain reaction (PCR)-based assays, to detect genomic DNA of Aspergillus species, still the most emerging fungal pathogens, in blood, BAL and tissue samples. A review of the literature was carried out and expert opinions expressed. Summarizing the results of numerous attempts to diagnose invasive aspergillosis by PCR-based detection of fungal genome in clinical samples, at least four clinically well-evaluated assays highlight the potential of the PCR technique to improve early diagnosis of invasive aspergillosis in patients with hematological malignancies under intensive antineoplastic treatment, especially in combination with imaging surveillance and serologic diagnostic tools, other important parts of the diagnostic mosaic. Further clinical comparative validation of reliable assays in prospective multi-center studies is mandatory and needed urgently, leading finally to a standardization, so that one or more 'gold standard assays' may be incorporated into diagnostic and therapeutic algorithms, to improve the prognosis of patients with life-threatening infections caused by Aspergillus species.