Pitfalls in Serological Diagnosis of Cryptococcus gattii Infections

Kathrin Tintelnot1, Ferry Hagen2, Chang Ok Han3

  • 1Division of Mycology, Robert Koch Institute, Berlin, Germany tintelnotk@rki.de.

Medical Mycology
|September 5, 2015
PubMed

Insights

Certain latex agglutination tests (LATs) show insufficient sensitivity for detecting Cryptococcus gattii infections. Broader specificity assays are recommended for accurate cryptococcal antigen screening to prevent delayed diagnosis.

Area of Science:

  • Medical Mycology
  • Infectious Diseases
  • Diagnostic Immunology

Background:

  • Cryptococcal antigen detection is crucial for diagnosing Cryptococcus infections.
  • Cryptococcus gattii is expanding geographically, posing new diagnostic challenges.
  • Existing latex agglutination tests (LATs) may lack sensitivity for certain Cryptococcus species.

Purpose of the Study:

  • To evaluate the sensitivity of commercially available latex agglutination tests (LATs) and a lateral flow assay (LFA) for detecting Cryptococcus gattii antigen.
  • To assess the diagnostic performance of these assays in patients with C. gattii or hybrid Cryptococcus infections.
  • To highlight the implications of assay sensitivity on the diagnosis of cryptococcosis.

Main Methods:

  • Cerebrospinal fluid and/or serum samples from 10 patients with C. gattii or hybrid Cryptococcus infections were tested.
  • Three LATs (IMMY Latex-Crypto, Pastorex Crypto Plus, Remel Cryptococcus Antigen Test Kit) and one LFA (Immuno-Mycologics) were utilized.
  • Assay performance was evaluated based on antigen detection sensitivity.

Main Results:

  • Monoclonal antibody-based LATs demonstrated insufficient sensitivity, failing to detect four out of 10 C. gattii infections.
  • One hybrid C. gattii and C. neoformans infection was also missed by these sensitive LATs.
  • This highlights a significant risk of delayed diagnosis due to inadequate assay sensitivity.

Conclusions:

  • Current LATs, particularly those using monoclonal antibodies, exhibit limited sensitivity for C. gattii and its hybrids.
  • The geographical spread of C. gattii necessitates the use of diagnostic assays with broad specificity and sensitivity.
  • Preliminary screening for cryptococcal antigen should employ methods capable of detecting both C. neoformans and C. gattii, including hybrids, to ensure timely and accurate diagnosis.

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