Clinical Profile, Epidemiology, and Outcomes of Granulomatous Amebic Encephalitis: A Systematic Review

Abstract Background Granulomatous amebic encephalitis (GAE) is a rare but frequently fatal infection of the central nervous system, with poorly defined epidemiology, clinicoradiological features, and prognostic factors. Methods We conducted a PRISMA-compliant systematic review of confirmed GAE cases registered with PROSPERO (CRD420251120627). MEDLINE, Embase, and Web of Science were searched from inception to September 2025. Two reviewers independently screened studies, extracted data, and assessed quality using the Joanna Briggs Institute checklist. Comparative analyses were performed between Acanthamoeba and Balamuthia infections and between survivors and nonsurvivors. Results A total of 142 studies comprising 201 confirmed GAE cases were included. Cases were reported worldwide, predominantly from North America and Asia. Immunosuppression was documented in 58/196 (29.6%) cases. Headache, altered mental status, fever, and seizures were the most common presenting features. Neuroimaging most frequently demonstrated space-occupying lesions (148/190, 77.9%). Balamuthia mandrillaris accounted for 126/201 (62.7%) infections and Acanthamoeba for 67/201 (33.3%). Compared with Balamuthia infection, Acanthamoeba GAE was more often associated with immunocompromising conditions and meningeal involvement. Overall mortality was 146/191 (76.4%). Deaths were significantly more frequent in Balamuthia infection, and hypoglycorrhachia (50/101, 49.5%) emerged as a strong correlate of nonsurvival. Several antimicrobial agents were used more frequently among survivors, likely reflecting treatment intensity and survivor bias rather than definitive therapeutic efficacy. Conclusions Granulomatous amebic encephalitis remains a devastating infection with persistently high mortality. Distinct organism-specific phenotypes and markers of disease severity may aid early diagnosis and prognostication.

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