Diagnostic Algorithm for Invasive Fungal Infections

Abstract

Invasive fungal infections (IFI) pose diagnostic and therapeutic challenges due to nonspecific clinical presentations and imaging, particularly in immunocompromised patients. Rapid and accurate diagnosis is crucial for optimal management. Conventional diagnostic methods are considered as “gold standard”; however, they are based on culture, phenotypic identification, and antifungal susceptibility of the isolates, which lack sensitivity and are time-consuming, resulting in delayed diagnosis and therapy. To allow for fast detection and characterization of fungal pathogens, there are sustained efforts to switch to non-culture-based diagnostic methods to provide early and appropriate antifungal treatment. Although detection of biomarkers, such as 1, 3-β-d-glucan, (BDG), galactomannan (GM), Candida mannan (Mn), and Candida-anti-mannan antibodies (A-Mn) are useful for rapid diagnosis, there are still issues associated with sensitivities, specificities, and standardization in specific cohort of patients. Histopathological examination of tissue biopsy can provide rapid diagnosis; however, invasive specimens are often not readily available due to associated comorbidities. PCR-based assays, DNA sequencing, and other molecular methods have shown great promise to be used as primary diagnostic tools alone or to complement culture-based methods; however, these tests require standardization and are yet to be incorporated as a diagnostic criterion in routine clinical laboratory. In the absence of detection of BDG and GM biomarkers, DNA-based detection methods are essential for the diagnosis of mucormycosis. T2 magnetic resonance (T2MR), a nano-platform, approved by the US FDA is a timely and important advancement in the early diagnosis of candidemia. The test has a sensitivity of 89% in patients at the time of blood culture positivity. Likewise, proteomic approaches such as matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has also been applied directly to blood specimens to identify Candida species with reduced turnaround time. Two lateral flow assays for point-of-care diagnosis of cryptococcosis and aspergillosis have also been developed.