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Published on: February 27, 2018
Antigen Titers in Cryptococcal Meningitis: What Determines How Fast They Fall?
John E Bennett1, Peter R Williamson1
1Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
Abstract:
Follow-up of previously healthy patients surviving cryptococcal meningitis found that cryptococcal antigen could be detected for >1 year in serum from 38 of 44 (86%) patients and in cerebrospinal fluid (CSF) from 20 of 31 patients (67%), far beyond the time of culture conversion. The speed of titer decline, measured as the number of days for a 2-fold drop in titer to occur, was slower in serum than in CSF. The speed of decline of antigen titers was much slower in serum and CSF for patients infected with Cryptococcus gattii than Cryptococcus neoformans. The speed of decline in CSF and serum titers was also much slower in patients who had received a ventriculoperitoneal shunt for increased intracranial pressure. The variable and extraordinarily slow rate of clearance in our patients did not appear to reflect differences in disease control but rather differences in species and shunting for increased intracranial pressure.
Insights
Cryptococcal antigen persists for over a year in serum and cerebrospinal fluid (CSF) after meningitis. Factors like Cryptococcus species and shunting significantly slow antigen clearance in survivors.
Area of Science:
- Infectious Diseases
- Clinical Microbiology
- Neurology
Background:
- Cryptococcal meningitis is a serious infection, particularly in immunocompromised individuals.
- Long-term follow-up of survivors is crucial to understand disease persistence and potential complications.
- Detection of cryptococcal antigen beyond clinical resolution is not well-characterized.
Purpose of the Study:
- To investigate the duration and kinetics of cryptococcal antigen detection in serum and cerebrospinal fluid (CSF) in patients who survived cryptococcal meningitis.
- To identify factors influencing the rate of antigen titer decline.
Main Methods:
- Prospective follow-up study of patients recovering from cryptococcal meningitis.
- Serial measurement of cryptococcal antigen titers in serum and CSF.
- Analysis of antigen titer decline rates and correlation with species and treatment interventions.
Main Results:
- Cryptococcal antigen was detectable for over a year in 86% of serum samples and 67% of CSF samples, long after culture conversion.
- Antigen titer decline was slower in serum than in CSF.
- Clearance was significantly slower in patients infected with Cryptococcus gattii compared to Cryptococcus neoformans.
- Patients with ventriculoperitoneal shunts exhibited slower antigen titer decline in both serum and CSF.
Conclusions:
- Cryptococcal antigen can remain detectable for extended periods post-treatment, irrespective of clinical recovery.
- The rate of antigen clearance is influenced by the infecting Cryptococcus species and the presence of a ventriculoperitoneal shunt.
- These findings highlight the complex dynamics of cryptococcal antigen persistence and underscore the need for further research into their clinical significance.
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