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New Insights Into Cryptococcus Spp. Biology and Cryptococcal Meningitis

  • Infection (John Halperin, Section Editor)
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Abstract

Purpose of Review

Defective cell–mediated immunity is a major risk factor for cryptococcosis, a fatal disease if untreated. Cryptococcal meningitis (CM), the main presentation of disseminated disease, occurs through hematogenous spread to the brain from primary pulmonary foci, facilitated by yeast virulence factors. We revisit remarkable recent improvements in the prevention, diagnosis and management of CM.

Recent Findings

Cryptococcal antigen (CrAg), main capsular polysaccharide of Cryptococcus spp. is detectable in blood and cerebrospinal fluid of infected patients with point of care lateral flow assays. Recent World Health Organization guidelines recommend 7-day amphotericin B plus flucytosine, then 7-day high dose (1200 mg/day) fluconazole for induction treatment of HIV-associated CM. Management of raised intracranial pressure, a consequence of CM, should rely mainly on daily therapeutic lumbar punctures until normalisation. In HIV-associated CM, following introduction of antifungal therapy, (re)initiation of antiretroviral therapy should be delayed by 4–6 weeks to prevent immune reconstitution inflammatory syndrome, common in CM.

Summary

CM is a fatal disease whose diagnosis has recently been simplified. Treatment should always include antifungal combination therapy and management of raised intracranial pressure. Screening for immune deficiency should be mandatory in all patients with cryptococcosis.

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Acknowledgements

The authors wish to thank Dr. John C.M. Brust for providing the full review of this article.

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  1. Elvis Temfack and Timothée Boyer-Chammard contributed equally to this work.

Authors and Affiliations

  1. Internal Medicine unit, Douala General Hospital, Douala, Cameroon

    Elvis Temfack

  2. Molecular Mycology Unit, UMR2000, CNRS, Institut Pasteur, 25 – 28 Rue du Dr Roux, 75015, Paris, France

    Timothée Boyer-Chammard, Angela Loyse, Fanny Lanternier, Alexandre Alanio & Olivier Lortholary

  3. Necker Pasteur Center for Infectious Diseases and Tropical Medicine, Hôpital Necker Enfants malades, AP-HP, IHU Imagine, Paris Descartes University, Université de Paris, Paris, France

    Timothée Boyer-Chammard, Sarah Delliere, Fanny Lanternier & Olivier Lortholary

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

    David Lawrence

  5. Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana

    David Lawrence

  6. Centre for Global Health, Institute for Infection and Immunity, St Georges University of London, London, UK

    Angela Loyse

  7. Laboratory of Parasitology-Mycology, Saint-Louis Hospital, University Paris Diderot, Sorbonne Paris Cité, Université de Paris, Paris, France

    Alexandre Alanio

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Correspondence to Olivier Lortholary.

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Conflict of Interest

Elvis Temfack, David Lawrence, Sarah Delliere, Angela Loyse each declare no potential conflicts of interest. Alexandre Alanio reports personal fees (Educational symposium) from Gilead sciences, outside the submitted work. Fanny Lanternier reports personal fees from Gilead, and from Basilea, outside the submitted work. Olivier Lortholary reports personal fees (Speaker during congresses) from Gilead, Merck, Pfizer, Astellas, outside the submitted work. Timothée Boyer-Chammard reports personal fees (Educational symposium) from Gilead Science, outside the submitted work.

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Temfack, E., Boyer-Chammard, T., Lawrence, D. et al. New Insights Into Cryptococcus Spp. Biology and Cryptococcal Meningitis. Curr Neurol Neurosci Rep 19, 81 (2019). https://doi.org/10.1007/s11910-019-0993-0

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