Clinical Utility of Molecular Diagnostics for Invasive Fungal Diseases

Various mycological tests, including culture and biomarker assays, are used for diagnosing invasive fungal diseases (IFDs) or deep-seated mycosis. However, these conventional diagnostics often have limitations in sensitivity and specificity. Accurate identification of the causative fungus is essential for appropriate treatment, yet this often requires invasive sampling procedures. Recently, molecular diagnostics with greater accuracy than conventional methods have been increasingly used for diagnosis of IFDs. Multiplex polymerase chain reaction (PCR) assays covered by health insurance, such as the FilmArray Blood Culture Panel and Meningitis/Encephalitis Panel, include select fungal pathogens and are used in specific diagnostic contexts. Additionally, several fungal PCR tests are available in Japan but not yet covered by health insurance system. Species-specific PCR assays, such as real-time PCR for Pneumocystis jirovecii and Aspergillus spp., have been incorporated into the revised consensus definition for IFDs published by the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium in 2020, although standardization across laboratories remains a challenge. Panfungal PCR assays, which detect and identify fungi from clinical specimens (e.g., blood, body fluids, biopsy samples, formalin-fixed paraffin-embedded tissues), are also in use. Furthermore, next-generation sequencing-based fungal diagnostics targeting microbial cell-free DNA in blood, also referred to as liquid biopsy, are already commercially available in the United States. This review provides an overview of the clinical utility of molecular diagnostics for IFDs.