Cryptococcus neoformans and Cryptococcus gattii species complexes cause meningoencephalitis with high fatality rates and considerable morbidity, particularly in persons with deficient T cell-mediated immunity, most commonly affecting people living with HIV. Whereas the global incidence of HIV-associated cryptococcal meningitis (HIV-CM) has decreased over the past decade, cryptococcosis still accounts for one in five AIDS-related deaths globally due to the persistent burden of advanced HIV disease. Moreover, mortality remains high (~50%) in low-resource settings. The armamentarium to decrease cryptococcosis-associated mortality is expanding: cryptococcal antigen screening in the serum and pre-emptive azole therapy for cryptococcal antigenaemia are well established, whereas enhanced pre-emptive combination treatment regimens to improve survival of persons with cryptococcal antigenaemia are in clinical trials. Short courses (≤7 days) of amphotericin-based therapy combined with flucytosine are currently the preferred options for induction therapy of cryptococcal meningitis. Whether short-course induction regimens improve long-term morbidity such as depression, reduced neurocognitive performance and physical disability among survivors is the subject of further study. Here, we discuss underlying immunology, changing epidemiology, and updates on the management of cryptococcal meningitis with emphasis on HIV-associated disease.
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