Elvis Temfack1, Timothée Boyer-Chammard2,3, David Lawrence4,5, Sarah Delliere3, Angela Loyse2,6, Fanny Lanternier2,3, Alexandre Alanio2,7, Olivier Lortholary8,9. 1. Internal Medicine unit, Douala General Hospital, Douala, Cameroon. 2. Molecular Mycology Unit, UMR2000, CNRS, Institut Pasteur, 25 - 28 Rue du Dr Roux, 75015, Paris, France. 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. 4. Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. 5. Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. 6. Centre for Global Health, Institute for Infection and Immunity, St Georges University of London, London, UK. 7. Laboratory of Parasitology-Mycology, Saint-Louis Hospital, University Paris Diderot, Sorbonne Paris Cité, Université de Paris, Paris, France. 8. Molecular Mycology Unit, UMR2000, CNRS, Institut Pasteur, 25 - 28 Rue du Dr Roux, 75015, Paris, France. olivier.lortholary@pasteur.fr. 9. 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. olivier.lortholary@pasteur.fr.
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. 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.
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 infectedpatients 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.
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