Factors associated with relapse are difficult to distinguish from those associated with poor survival. In general, the prognosis for both in cryptococcal meningitis appears to be variable. Survival has been reported in the range of days to more than 20 years in untreated cases. Among the factors that have been associated with relapse of cryptococcal meningitis following treatment are immunosuppression, neurologic manifestations at presentation, CSF leukocyte counts less than 20 cells/cu mm, CSF antigen titers greater than 1:32, positive CSF India ink studies following 4 weeks of treatment, and CSF antigen titers that exceed 1:8 after 4 weeks of treatment (Tantisiriwat and Powderly 2001). These factors should be considered general rules as considerable disparity exists between the studies exploring prognosis in cryptococcal meningitis. Often confounding factors were not addressed. In 1 study in which potential confounds were examined, only the initial level of consciousness and CSF antigen titer were strongly associated with therapeutic failure (Lu et al 1999).
An overall poor prognosis in cryptococcal meningitis has been associated with the following factors: young age (Cheng 1992), abrupt onset (Cheng 1992), seizures (Yu et al 1988), coma (Yu et al 1988; Kalra et al 1999), prolonged course over 6 weeks (Cheng 1992), extracerebral cryptococcosis (Cheng 1992), cryptococcemia (Aquinas et al 1996; Seaton et al 1996; Kalra et al 1999), underlying illnesses (Cheng 1992), corticosteroid administration (Cheng 1992), Cushing syndrome (Delgrange and Donckier 2000; Kuruvilla 2000), long-term antibiotics (Cheng 1992), high CSF pressure (Cheng 1992), and low CSF cells count (often neutrophilic leukocytes) (Cheng 1992). A study of mortality in cryptococcal meningitis unassociated with AIDS found lymphoma, semicoma, leukocytosis, and initial high titers of cryptococcal antigen in cerebral spinal fluid (especially greater than or equal to 1:512) to be the best correlates and, on multivariate analysis, determined that lymphoma and initial high cryptococcal antigen titers were independent predictors of mortality (Shih et al 2000). In HIV infection, significant prognostic factors include low CSF glucose; CSF with less than 20 cells/cu mm (Saag et al 1992); high CSF lactate; high CSF cryptococcal antigen titer (greater than or equal to 1:1024) (Zuger et al 1986; Saag et al 1992); positive cultures of extrameningeal specimens (Chuck and Sande 1989); initial level of consciousness; the presence of seizure, hydrocephalus, and central nervous system vasculitis (Lu et al 1999); neurologic impairment on initiation of therapy (Clark et al 1990; Saag et al 1992); abnormal CT scan (Clark et al 1990); and hyponatremia. A study of 501 HIV-infected patients with cryptococcal meningitis from 4 resource-poor countries demonstrated that CSF fungal burden, altered mental status, and rate of clearing of the infection were good predictors of acute mortality (Jarvis et al 2014).