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Visualizing Non-lytic Exocytosis of Cryptococcus neoformans from Macrophages Using Digital Light Microscopy
Published on: October 21, 2014
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Cryptococcus neoformans: Diagnostic Dilemmas, Electron Microscopy and Capsular Variants.
Monica Birkhead1, Serisha D Naicker2,3, Nozuko P Blasich4
1National Institute for Communicable Diseases-a Division of the National Health Laboratory Service, 1 Modderfontein Road, Sandringham 2192, South Africa. monicab@nicd.ac.za.
Tropical Medicine and Infectious Disease
|December 23, 2018
Summary
Two cases of cryptococcal meningitis were missed by blood CrAg tests in South Africa. Reduced capsular material in the fungus likely caused these false negatives, highlighting the need for multidisciplinary diagnostic review.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Diagnostic Microbiology
Background:
- Cryptococcal meningitis is a major cause of mortality in immunocompromised individuals.
- Rapid diagnostics, such as cryptococcal antigen (CrAg) lateral flow assays, are crucial for early detection and treatment.
- Screen-and-treat programs aim to improve outcomes by proactively identifying and managing cryptococcal infections.
Observation:
- Two cases of cryptococcal meningitis were initially missed by a blood CrAg lateral flow assay in a South African screen-and-treat program.
- Cerebrospinal fluid cultures confirmed *Cryptococcus neoformans* in both patients, indicating discordant diagnostic results.
- No mutations in the CAP59 gene were found via multilocus sequence typing.
Findings:
- Transmission electron microscopy revealed a significant reduction (>50%) in capsular material in the *Cryptococcus neoformans* isolates from the discordant cases compared to controls.
- This reduction in capsular polysaccharide is a potential mechanism for the failure of the CrAg lateral flow assay.
Implications:
- The findings suggest that variations in fungal capsule expression can lead to false-negative results with CrAg lateral flow assays, potentially impacting patient management.
- A multidisciplinary approach is recommended for resolving complex or discordant diagnostic test results in infectious diseases.
- Further research into the factors affecting CrAg detection and the development of more robust diagnostic methods is warranted.
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