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Size Matters: Measurement of Capsule Diameter in Cryptococcus neoformans
Published on: February 27, 2018
Diagnostic Challenges of Cryptococcus neoformans in an Immunocompetent Individual Masquerading as Chronic
Kedar R Mahajan1, Amity L Roberts2, Mark T Curtis2
1Department of Neurology, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.
Abstract:
Cryptococcus neoformans can cause disseminated meningoencephalitis and evade immunosurveillance with expression of a major virulence factor, the polysaccharide capsule. Direct diagnostic assays often rely on the presence of the cryptococcal glucuronoxylomannan capsular antigen (CrAg) or visualization of the capsule. Strain specific phenotypic traits and environmental conditions influence differences in expression that can thereby compromise detection and timely diagnosis. Immunocompetent hosts may manifest clinical signs and symptoms indolently, often expanding the differential and delaying appropriate treatment and diagnosis. We describe a 63-year-old man who presented with a progressive four-year history of ambulatory dysfunction, headache, and communicating hydrocephalus. Serial lumbar punctures (LPs) revealed elevated protein (153-300 mg/dL), hypoglycorrhachia (19-47 mg/dL), lymphocytic pleocytosis (89-95% lymphocyte, WBC 67-303 mg/dL, and RBC 34-108 mg/dL), and normal opening pressure (13-16 cm H2O). Two different cerebrospinal fluid (CSF) CrAg assays were negative. A large volume CSF fungal culture grew unencapsulated C. neoformans. He was initiated on induction therapy with amphotericin B plus flucytosine and consolidation/maintenance therapy with flucytosine, but he died following discharge due to complications. Elevated levels of CSF Th1 cytokines and decreased IL6 may have affected the virulence and detection of the pathogen.
Insights
Diagnosis of cryptococcal meningoencephalitis can be challenging, especially with unencapsulated Cryptococcus neoformans strains. This case highlights difficulties in detection despite standard antigen tests, emphasizing the need for improved diagnostic approaches.
Area of Science:
- * Infectious Diseases
- * Neuroscience
- * Clinical Microbiology
Background:
- * Cryptococcus neoformans causes meningoencephalitis and evades immune surveillance via its polysaccharide capsule.
- * Standard diagnostic assays often detect the cryptococcal glucuronoxylomannan capsular antigen (CrAg).
- * Variations in capsule expression can hinder detection and diagnosis, particularly in immunocompetent hosts with indolent symptoms.
Purpose of the Study:
- * To report a case of cryptococcal meningoencephalitis caused by an unencapsulated C. neoformans strain.
- * To highlight diagnostic challenges associated with atypical presentations and negative antigen tests.
- * To explore potential roles of cytokine profiles in pathogen virulence and detection.
Main Methods:
- * Case report of a 63-year-old man with a four-year history of neurological symptoms.
- * Analysis of cerebrospinal fluid (CSF) parameters including protein, glucose, cell counts, and opening pressure.
- * Cerebrospinal fluid (CSF) cryptococcal antigen (CrAg) assays and fungal cultures were performed.
Main Results:
- * Cerebrospinal fluid (CSF) analysis revealed elevated protein, hypoglycorrhachia, and lymphocytic pleocytosis.
- * Two different CSF cryptococcal antigen (CrAg) assays were negative.
- * Fungal culture identified unencapsulated Cryptococcus neoformans.
Conclusions:
- * Unencapsulated C. neoformans can cause cryptococcal meningoencephalitis, posing diagnostic challenges.
- * Negative cryptococcal antigen (CrAg) results do not exclude infection, necessitating fungal culture.
- * Altered cytokine profiles (Th1, IL6) may influence virulence and diagnostic test performance.
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