Granulomatous amoebic encephalitis: pathogenesis, diagnostic advances, therapeutic challenges, and emerging treatment strategies.

Granulomatous amoebic encephalitis (GAE) is a rare but highly fatal central nervous system infection caused primarily by Acanthamoeba spp. and Balamuthia mandrillaris. Delayed diagnosis and the absence of standardized treatment protocols contribute to mortality exceeding 90%. This review summarizes current knowledge regarding GAE pathogenesis, diagnosis, therapeutic challenges, and emerging treatment strategies. The pathogenesis involves amoebic adhesion, secretion of proteases and phospholipases, host inflammatory responses, and blood-brain barrier disruption. Recent advances in molecular diagnostics improve early pathogen detection, while drug repurposing, nanotechnology-based delivery systems, and cyst-targeted approaches represent promising therapeutic strategies. Nevertheless, treatment remains challenging because of poor blood-brain barrier penetration, cyst-associated resistance, and limited clinical evidence. Continued integration of molecular diagnostics, mechanistic studies, translational research, and multicentre clinical investigations is essential for improving outcomes in this devastating disease.