Balamuthia mandrillaris is a free-living amoeba that causes granulomatous amoebic encephalitis, a rare but frequently fatal infection of the central nervous system. In contrast to primary amoebic meningoencephalitis caused by Naegleria fowleri, B. mandrillaris infection is typically subacute to chronic and is commonly associated with haematogenous dissemination from extra-cranial sites. Here, we present a comparative analysis of the neuropathology of B. mandrillaris infection in humans and animals, highlighting conserved features of angiocentric invasion, granulomatous inflammation, necrotizing vasculitis and multifocal parenchymal injury. Across species, both trophozoites and cysts are consistently identified within affected tissue, reflecting sustained tissue persistence rather than explosive proliferation. Despite differences in disease kinetics and host immunity, the pathological signature of Balamuthia encephalitis is remarkably conserved. These findings validate the use of animal models for mechanistic investigation and therapeutic development and clarify key biological processes underlying this devastating disease.
