Update on the diagnosis, pathophysiology and treatment strategies in non-HIV-associated cryptococcal meningoencephalitis.

INTRODUCTION

Cryptococcal meningoencephalitis (CM) is the leading cause of non-viral meningitis in the United States, reflecting both the rise in immunocompromised populations and the prevention of bacterial meningitis through vaccination. Formerly linked primarily to HIV-associated immunodeficiency, effective antiretroviral therapy has reshaped CM epidemiology: solid-organ transplant recipients and apparently healthy individuals now constitute the main risk groups, with mortality remaining 30-40%.

AREAS COVERED: This review synthesizes emerging evidence on post-infectious inflammatory syndromes complicating CM, highlighting new insights into their pathogenesis, clinical recognition, and management. It also examines advances in rapid diagnostic approaches aimed at accelerating detection and guiding targeted therapy. Literature was identified through PubMed/MEDLINE and Embase searches, as detailed in the Introduction.

EXPERT OPINION: Persistently high CM mortality stems from delayed or missed diagnosis and under-recognized post-infectious inflammatory injury. Current antifungal regimens, although microbiologically effective, are limited by toxicity and poor tolerability. Improving outcomes will require the integration of rapid, sensitive diagnostic tools for both acute infection and inflammatory sequelae, alongside development of safer, orally bioavailable antifungal agents. These strategies offer the greatest potential to reduce mortality, preserve neurological function, and improve the long-term clinical course of this devastating disease.