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New Insights Into Cryptococcus Spp. Biology and Cryptococcal Meningitis
Elvis Temfack1, Timothée Boyer-Chammard2,3, David Lawrence4,5
1Internal Medicine unit, Douala General Hospital, Douala, Cameroon.
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.
Insights
Cryptococcal meningitis (CM) is a fatal infection. Recent advances simplify diagnosis and recommend 7-day combination antifungal therapy, followed by high-dose fluconazole, alongside managing intracranial pressure and delayed antiretroviral therapy initiation.
Area of Science:
- Infectious Diseases
- Immunology
- Neurology
Background:
- Defective cell-mediated immunity significantly increases cryptococcosis risk.
- Cryptococcal meningitis (CM) arises from pulmonary Cryptococcus spread to the brain.
- Understanding yeast virulence factors is crucial for CM pathogenesis.
Purpose of the Study:
- To review recent advancements in the prevention of CM.
- To highlight new diagnostic strategies for CM.
- To discuss updated management protocols for CM.
Main Methods:
- Detection of Cryptococcal antigen (CrAg) using point-of-care lateral flow assays in blood and cerebrospinal fluid.
- Implementation of World Health Organization-recommended 7-day induction therapy with amphotericin B and flucytosine.
- Management of raised intracranial pressure through daily therapeutic lumbar punctures.
Main Results:
- Simplified diagnosis of CM is now possible.
- Recommended induction treatment involves 7-day amphotericin B plus flucytosine, followed by high-dose fluconazole.
- Delayed antiretroviral therapy initiation (4-6 weeks) is advised for HIV-associated CM to prevent immune reconstitution inflammatory syndrome.
Conclusions:
- CM remains a life-threatening condition requiring prompt diagnosis and treatment.
- Effective CM management necessitates antifungal combination therapy and intracranial pressure control.
- Mandatory screening for immune deficiency in all cryptococcosis patients is recommended.
