New Insights Into Cryptococcus Spp. Biology and Cryptococcal Meningitis

  • Elvis Temfack
  • Timothée Boyer-Chammard
  • David Lawrence
  • Sarah Delliere
  • Angela Loyse
  • Fanny Lanternier
  • Alexandre Alanio
  • Olivier LortholaryEmail author
Infection (John Halperin, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Infection


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.


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.


Cryptococcus Cryptococcal antigen Lateral flow assay Intracranial pressure Induction therapy 



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

Compliance with Ethical Standards

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.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: •   Of importance ••  Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Elvis Temfack
    • 1
  • Timothée Boyer-Chammard
    • 2
    • 3
  • David Lawrence
    • 4
    • 5
  • Sarah Delliere
    • 3
  • Angela Loyse
    • 2
    • 6
  • Fanny Lanternier
    • 2
    • 3
  • Alexandre Alanio
    • 2
    • 7
  • Olivier Lortholary
    • 2
    • 3
    Email author
  1. 1.Internal Medicine unitDouala General HospitalDoualaCameroon
  2. 2.Molecular Mycology Unit, UMR2000, CNRSInstitut PasteurParisFrance
  3. 3.Necker Pasteur Center for Infectious Diseases and Tropical Medicine, Hôpital Necker Enfants malades, AP-HP, IHU ImagineParis Descartes University, Université de ParisParisFrance
  4. 4.Department of Clinical Research, Faculty of Infectious and Tropical DiseasesLondon School of Hygiene and Tropical MedicineLondonUK
  5. 5.Botswana Harvard AIDS Institute PartnershipGaboroneBotswana
  6. 6.Centre for Global Health, Institute for Infection and ImmunitySt Georges University of LondonLondonUK
  7. 7.Laboratory of Parasitology-Mycology, Saint-Louis HospitalUniversity Paris Diderot, Sorbonne Paris Cité, Université de ParisParisFrance

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