Clinical value of follow-up antigen titers in cryptococcal meningitis among immunocompetent survivors

Reviewed by Jose Lucar, MD, The George Washington University

In a cohort of previously healthy cryptococcal meningitis survivors, persistently positive follow up antigen titers were not associated with culture-proven relapses, and the rate of decline was associated with C. gattii infection and recipients of ventriculoperitoneal shunt for increased intracranial pressure.

Although there are no data supporting monitoring cryptococcal antigen (CrAg) testing after diagnosis of cryptococcal meningitis, uncertainty remains among clinicians on the clinical value and factors associated with the decline of CrAg titers among survivors. To address these questions, researchers at the NIH Clinical Center conducted a retrospective analysis of 46 patients who were previously healthy (HIV negative, no known immunocompromising condition) and were admitted with cryptococcal meningitis between 2006 and 2021. All patients had at least three positive samples of serum or CSF CrAg tested over a minimum of 90 days; both serum and CSF samples were available on 29/46, only serum on 15/46 and only CSF on 2/46. They found that although CrAg could be detected for more than 1 year in serum from 38/44 (86%) patients and in CSF from 20/31 patients (67%), all 46 patients had a negative CSF culture prior to discharge and there were no culture-proven relapses during follow up, which has implications for diagnostic and antifungal stewardship. Authors also noted that the rate of CrAg titer decline (number of days needed for a 2-fold drop in titer) was slower in serum than in CSF, for patients with Cryptococcus gattii infection, and for individuals who required a ventriculoperitoneal shunt for management of increased intracranial pressure.

Reference: Bennett JE, Williamson PR. Antigen titers in cryptococcal meningitis: what determines how fast they fall?. J Infect Dis. Published online July 11, 2024. doi:10.1093/infdis/jiae354

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