Enhancing Molecular Approaches for Diagnosis of Fungal Infections

Sean X Zhang


Future Microbiol. 2013;8(12):1599-1611. 

In This Article

Abstract and Introduction


Molecular tests can improve the diagnosis of fungal infections. Despite the increasing application for fungal detection, molecular tests are still not accepted as a diagnostic criterion to define invasive fungal diseases. This limitation is largely due to a lack of a standardized method. Method standardization can be achieved by following a consensus protocol developed by a working group, by performing a molecular test in a centralized laboratory or by using a commercial assay that provides a standardized method and quality-controlled reagents. Forming a consortium or a working group consisting of large-scale diagnostic mycology laboratories can accelerate the process of validating and implementing a commercial molecular assay for clinical use through a joint effort between industry partners and clinicians. Development of molecular tests not only for the detection of fungi but also for the identification of antifungal drug resistance directly in blood, bronchoalveolar lavage fluid, cerebrospinal fluid, and formalin-fixed and paraffin-embedded tissues greatly enhances fungal diagnostic capacities. Advances of developing quantitative assays and RNA detection platforms may provide another avenue to further improve fungal diagnostics.


Fungi are eukaryotic organisms and are ubiquitous in our living environment. The incidence of human infections caused by fungi has increased dramatically over the past two to three decades, owing to an enlarging immunocompromised patient population.[1–5] Recent epidemiology data indicate that fungal infection has become one of the most common infection-associated mortalities in the USA.[6,7] The laboratory diagnosis of fungal infections is still largely dependent on microscopic and culture-based methods, and these methods do not always meet clinical needs owing to poor sensitivity and lengthy incubation time. Therefore, the area holding the most promise for fungal diagnostics is the development of nucleic acid amplification and detection platforms because they offer ultrasensitive and rapid detection of fungal pathogens directly in clinical samples.[8] These molecular assays are widely used by clinical laboratories to aid in diagnosis of viral and bacterial infections; however, their application for diagnosis of fungal disease in clinical settings is still limited. In fact, none of the molecular assays are even included in the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Disease Mycoses Study Group (EORTC/MSG)'s criteria to define invasive fungal disease.[9] In this article, the current status of applying molecular assays for diagnosis of fungal infections is reviewed and the future direction of enhancing molecular approaches for fungal diagnostics is elaborated.