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"False negative" CSF cryptococcal antigen with clinical meningitis: Case reports and review of literature
Morris K Rutakingirwa1, Tadeo K Kiiza1, Joshua Rhein1,2
1Infectious Diseases Institute, Makerere University, P.O. Box 22418, Kampala, Uganda.
Abstract:
There is an increasing recognition of patients presenting with cryptococcal meningitis despite having a negative CSF cryptococcal antigen (CrAg). In this report, we describe three cases of patients with advanced immunosuppression who presented to hospital with "false negative" CSF cryptococcal antigen, two of whom had a positive fungal culture. We describe the challenge of CSF-CrAg negative cryptococcal meningitis and explore ways to overcome this challenge using newer diagnostic techniques.
Insights
Cryptococcal meningitis can occur even with negative cerebrospinal fluid (CSF) cryptococcal antigen (CrAg) tests. This report highlights "false negative" CSF-CrAg results in advanced immunosuppression, emphasizing the need for advanced diagnostic methods.
Area of Science:
- Infectious Diseases
- Clinical Microbiology
- Neuroscience
Background:
- Cryptococcal meningitis is a serious opportunistic infection.
- Diagnosis can be challenging, especially with negative cerebrospinal fluid (CSF) cryptococcal antigen (CrAg) tests.
- Patients with advanced immunosuppression are at higher risk.
Purpose of the Study:
- To describe cases of cryptococcal meningitis with false negative CSF-CrAg results.
- To highlight diagnostic challenges in immunocompromised patients.
- To explore newer diagnostic techniques for improved detection.
Main Methods:
- Case report of three patients with advanced immunosuppression.
- Analysis of clinical presentation and diagnostic workup.
- Review of CSF cryptococcal antigen (CrAg) testing and fungal cultures.
- Exploration of alternative diagnostic strategies.
Main Results:
- Three cases of cryptococcal meningitis with false negative CSF-CrAg are presented.
- Two of the three cases had positive fungal cultures despite negative CSF-CrAg.
- This highlights a significant diagnostic pitfall in immunocompromised individuals.
Conclusions:
- False negative CSF-CrAg results can occur in cryptococcal meningitis, particularly in advanced immunosuppression.
- Fungal culture may remain positive when CSF-CrAg is negative.
- Utilizing advanced diagnostic techniques is crucial for accurate and timely diagnosis.

