Cryptococcal meningitis

• Published in: Nature reviews. Disease primers Vol. 9; no. 1; p. 62
• Main Authors: Tugume, Lillian, Ssebambulidde, Kenneth, Kasibante, John, Ellis, Jayne, Wake, Rachel M., Gakuru, Jane, Lawrence, David S., Abassi, Mahsa, Rajasingham, Radha, Meya, David B., Boulware, David R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.11.2023; Nature Publishing Group
• Subjects: 631/250/255/1672; 692/420/254; 692/699/255/1638; 692/699/255/1672; Acquired immune deficiency syndrome; AIDS; Amphotericin B - therapeutic use; Antifungal agents; Antifungal Agents - therapeutic use; Cancer Research; Cryptococcosis - complications; Cryptococcosis - drug therapy; Epidemiology; Fatalities; HIV; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - epidemiology; Human immunodeficiency virus; Humans; Internal Medicine; Medical Microbiology; Medicine; Medicine & Public Health; Meningitis; Meningitis, Cryptococcal - complications; Meningitis, Cryptococcal - drug therapy; Meningitis, Cryptococcal - epidemiology; Primer; Quality of Life Research
• ISSN: 2056-676X; 2056-676X
• DOI: 10.1038/s41572-023-00472-z

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. Cryptococcal meningitis affects people living with HIV and individuals who are immunosuppressed. HIV-associated disease underlies 20% of AIDS-related deaths, whereas the incidence of non-HIV cryptococcal meningitis is increasing. This Primer highlights efforts to better understand disease epidemiology and pathophysiology, and to further improve management.