Cryptococcus neoformans: Diagnostic Dilemmas, Electron Microscopy and Capsular Variants

Birkhead, Monica; Naicker, Serisha D.; Blasich, Nozuko P; Rukasha, Ivy; Thomas, Juno; Sriruttan, Charlotte; Abrahams, Shareef; Mavuso, Grisselda S.; Govender, Nelesh P.

doi:10.3390/tropicalmed4010001

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…An accompanying serum CrAg test was ordered in only 67.6% of the 34 patients in our study. Furthermore, reports of infection due to strains producing reduced levels of cryptococcal antigen where both CSF and serum CrAg tests are negative have also been described [19]. The diagnosis of CM is therefore multilayered and requires a multidiagnosticbased approach.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Biofire FilmArray meningitis/encephalitis assay for the detection of Cryptococcus neoformans/gattii

Van

Kim

Butler-Wu

2020

Clinical Microbiology and Infection

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Objectives: Cryptococcal meningitis (CM) remains an important cause of morbidity and mortality among immunocompromised patients. Laboratory diagnostics for CM includes antigen detection, staining and culture. Data on the performance of the Biofire® FilmArray® meningitis/encephalitis (ME) panel for detecting Cryptococcus neoformans/gattii is limited, with several reports describing false negativity for this target. Methods: A retrospective analysis of 1384 physician-ordered ME panel tests ordered between January 2017 to October 2018 was performed. ME panel results were compared to cerebrospinal fluid (CSF) cryptococcal antigen (CrAg) and CSF culture testing and clinical significance of cryptococcal detection was determined.Results: There were 34 patients positive for cryptococcal detection by either ME panel, CSF CrAg or CSF culture in 2.7% of CSF specimens tested (38/1384). Of the 34 patients positive for cryptococcal detection, 85.3% were human immunodeficiency virus positive (29/34). The ME panel detected 32/38 (84.2%) cryptococcal-positive specimens, culture detected 28/38 (73.7%) and CSF CrAg was positive in 37/38 specimens (97.4%). The ME panel had a sensitivity and specificity of 96.4% (95% CI 81.7e99.9%) and 99.6% (95% CI 99.2e99.9%) compared with culture, and 83.8% (95% CI 68.0e93.8%) and 99.9% (95% CI 99.6 e100.0%) compared to CSF CrAg testing, respectively. CrAg titres were lower among ME panel-negative, culture-negative specimens compared with ME panel-positive, culture-negative specimens (reciprocal median end-point titres of 128 ± 60 vs. 1920 ± 1730, p 0.04). All five CrAg-positive, ME panel-and culture-negative specimens were obtained from previously treated CM patients. Discussion: The ME panel had high correlation with CSF culture and a somewhat lower correlation with CSF CrAg testing. The potential utility of using negative ME panel test results to predict culture sterility among patients undergoing treatment for CM warrants further study.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the Biofire FilmArray meningitis/encephalitis assay for the detection of Cryptococcus neoformans/gattii

Van

Kim

Butler-Wu

2020

Clinical Microbiology and Infection

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“…Visualization of encapsulated yeast forms with narrow budding in the sputum, bronchoalveolar lavage (BAL) or lung tissue biopsy specimens is suggestive of cryptococcal infection. The pellet from pleural fluid or BAL can be mixed with India Ink and observed under a microscope[ 45 ]. A lung biopsy from a nodule of uncertain aetiology requires a fungal culture to be done, in addition to a histopathology examination.…”

Section: Diagnosis Of Cryptococcal Infectionmentioning

confidence: 99%

Cryptococcosis in kidney transplant recipients: Current understanding and practices

Meena,

Bhargava,

Singh

et al. 2023

World J Nephrol

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Cryptococcosis is the third most commonly occurring invasive fungal disease in solid organ transplant recipients (SOT). It is caused by encapsulated yeast, Cryptococcus species, predominantly Cryptococcus neoformans and Cryptococcus gattii. Though kidney transplant recipients are at the lowest risk of cryptococcosis when compared to other solid organ transplant recipients such as lung, liver or heart, still this opportunistic infection causes significant morbidity and mortality in this subset of patients. Mortality rates with cryptococcosis range from 10%-25%, while it can be as high as 50% in SOT recipients with central nervous system involvement. The main aim of diagnosis is to find out if there is any involvement of the central nervous system in disseminated disease or whether there is only localized pulmonary involvement as it has implications for both prognostication and treatment. Detection of cryptococcal antigen (CrAg) in cerebrospinal fluid or plasma is a highly recommended test as it is more sensitive and specific than India ink and fungal cultures. The CrAg lateral flow assay is the single point of care test that can rapidly detect cryptococcal polysaccharide capsule. Treatment of cryptococcosis is challenging in kidney transplant recipients. Apart from the reduction or optimization of immunosuppression, lipid formulations of amphotericin B are preferred as induction antifungal agents. Consolidation and maintenance are done with fluconazole; carefully monitoring its interactions with calcineurin inhibitors. This review further discusses in depth the evolving developments in the epidemiology, pathogenesis, diagnostic assays, and management approach of cryptococcosis in kidney transplant recipients.

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Capsule-Deficient Cryptococcal Meningitis

Singh

Shende

Xess

et al. 2022

Journal of Global Infectious Diseases

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Cryptococcosis is a serious systemic mycosis. Its incidence has escalated in the past four decades. Cryptococcus neoformans causes localized or disseminated infection in immunocompromised and immunocompetent patients. The capsulated form is commonly encountered which can be diagnosed on an India ink preparation or antigen detection. However, the noncapsulated forms are very rare and require a high index of suspicion for correct diagnosis. Herein, we present a case of cryptococcal meningitis due to a noncapsulated strain in an apparently immunocompetent patient with no proven immunodeficiencies along with review of world literature. Such cases are a diagnostic challenge for the clinician as well as microbiologist.

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Cryptococcus neoformans: Diagnostic Dilemmas, Electron Microscopy and Capsular Variants

Cited by 3 publications

References 23 publications

Evaluation of the Biofire FilmArray meningitis/encephalitis assay for the detection of Cryptococcus neoformans/gattii

Evaluation of the Biofire FilmArray meningitis/encephalitis assay for the detection of Cryptococcus neoformans/gattii

Cryptococcosis in kidney transplant recipients: Current understanding and practices

Capsule-Deficient Cryptococcal Meningitis

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