Mayo Clinic Infectious Diseases
Mayo Clinic Infectious Diseases

@MayoClinicINFD

6 Tweets 1 reads Apr 22, 2023
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5 months after liver transplant, a man had recurrent fever. Blood culture: Cryptococcus neoformans. Serum cryptococcal antigen negative. What are the potential reasons for CrAg-negative culture-positive cryptococcal infection?
2/
CrAg LFA (IMMY Diagnostics) was persistently negative despite serial dilutions.
Blood cultures on 3 consecutive days positive for C neoformans.
India ink shown (photo).
What is the most likely reason for negative CrAg?
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One possible answer for negative CrAg is infection with a strain of Cryptococcus neoformans that is not captured by some CrAg assays.
The assay used in this case should detect the majority, as suggested in this study.
doi.org
4/
CrAg may be negative if there is low antigen titer / below the limit of assay sensitivity.
In this ICH case, blood culture for 3 days are positive, suggesting a high fungal burden.
Could this CrAg (-) test be postzone effect of antigen excess ?
5/
Excess antibody (prozone) or antigen (postzone) —> false-negative CrAg.
Serial dilution of sample is suggested to resolve this issue.
In this case, serial dilution resulted in persistently negative CrAg, suggesting there is likely another reason.
6/
MCQ Answer: Capsule-deficient Cryptococcus neoformans (see photo)
CrAg detects antigen in the fungal capsule, hence, deficient capsule may lead to false-negative CrAg.
You can read this case here: @ZYetmar @PascalisID @ETheelPhD @JClinMicro
doi.org

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