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Cryptococcal meningitis

Nature Reviews Disease Primers volume 9, Article number: 62 (2023) Cite this article

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Abstract

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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Fig. 1: Global map of estimated incidence of HIV-associated cryptococcal meningitis in 2020.
Fig. 2: Host response to Cryptococcus neoformans infection.
Fig. 3: Cryptococcal antigen screening in HIV–CM.

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Acknowledgements

L.T. was supported by the Fogarty International Center of the National Institutes of Health under grant D43TW009345 awarded to the Northern Pacific Global Health Fellows Program. J.K. and J.G. are supported by the Fogarty International Center and National Institute of Neurologic Disorders and Stroke (R01NS086312).

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Author notes

  1. These authors contributed equally: David B. Meya, David R. Boulware.

Authors and Affiliations

  1. Infectious Diseases Institute, Makerere University, Kampala, Uganda

    Lillian Tugume, Kenneth Ssebambulidde, John Kasibante, Jayne Ellis, Jane Gakuru & David B. Meya

  2. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Kenneth Ssebambulidde

  3. Clinical Research Department, Faculty of Infectious and Tropical Diseases London School of Hygiene and Tropical Medicine, London, UK

    Jayne Ellis & David S. Lawrence

  4. Institute for Infection and Immunity, St George’s University of London, London, UK

    Rachel M. Wake

  5. Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana

    David S. Lawrence

  6. Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    Mahsa Abassi, Radha Rajasingham, David B. Meya & David R. Boulware

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Contributions

Introduction (L.T.); Epidemiology (L.T. and R.R.); Mechanisms/pathophysiology (L.T., J.K., K.S. and D.B.M.); Diagnosis, screening and prevention (L.T., R.R. and R.M.W.); Management (L.T., D.S.L., J.E., D.B.M., J.G. and M.A.); Quality of life (L.T. and M.A.); Outlook (L.T., D.R.B. and D.B.M.); all authors researched data for this article, discussed content and made revisions.

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Correspondence to Lillian Tugume.

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Nature Reviews Disease Primers thanks Nelesh Govender; William G. Powderly, who co-reviewed with Adriana Rauseo Acevedo; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Tugume, L., Ssebambulidde, K., Kasibante, J. et al. Cryptococcal meningitis. Nat Rev Dis Primers 9, 62 (2023). https://doi.org/10.1038/s41572-023-00472-z

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