Cryptococcus detection technologies: An overview of conventional, immunological, and molecular methods, and future development directions.

Cryptococcus, notably Cryptococcus neoformans and Cryptococcus gattii, is a pathogenic fungus that poses a significant threat to global health. Early and rapid detection is pivotal for reducing mortality, yet conventional diagnostic techniques suffer from inherent limitations-including slow turnaround times, low sensitivity in early infection, and heavy reliance on specialized expertise-that delay clinical intervention. Advancements in detection technology have established immunological and molecular methods as essential tools for identifying Cryptococcus. This review moves beyond descriptive summary to provide a critical analytical evaluation of conventional (microscopy, histopathology, fungal culture), immunological (ELISA, LAT, LFA), and molecular (PCR variants, isothermal amplification, NGS) detection technologies, with a focus on dissecting the mechanistic drivers of performance variability, technical bottlenecks, and practical limitations across clinical scenarios. Among them, the lateral flow assay and isothermal amplification are particularly notable for their simplicity, speed, efficiency, and low cost. These integrated systems have the potential to overcome the limitations of single-method approaches, enabling simultaneous antigen screening, species identification, and fungal load quantification to support precise, timely antifungal therapy in both resource-rich and resource-limited settings.