Prognosis

Mortality and morbidity

Unrecognized and untreated cryptococcosis can be fatal, especially in immunocompromised patients, and untreated cryptococcal meningoencephalitis is uniformly fatal. The estimated 1-year mortality for people with HIV-associated cryptococcal meningitis is 70% in low-income countries and 20% to 30% in high-income countries.[10][23]​​ Outcomes in other immunosuppressed patients vary according to the underlying disease. Patients with idiopathic CD4 lymphopenia seem to have relatively favorable outcomes.[74] Early appropriate treatment reduces morbidity and prevents progression to potentially life-threatening central nervous system disease. The cryptococcal polysaccharide antigen (CrAg) status has been found to be an independent predictor of mortality in HIV-positive patients.[55] Toxic side effects from antifungal therapy are common, and up to 30% of patients with cryptococcal meningitis and HIV develop immune reconstitution inflammatory syndrome (IRIS) following initiation or reinitiation of antiretroviral treatment (ART).[20][55][58]

Treatment failure and relapse

Treatment failure is defined as the lack of clinical improvement after 2 weeks of therapy (including management of increased intracranial pressure [ICP] with continued positive cultures) or relapse after initial clinical response (i.e., recurrence of symptoms with a positive cerebrospinal fluid [CSF] culture after ≥4 weeks of treatment).[20] Patients requiring suppressive therapy for more than 1 to 2 years are also considered treatment failures.[58]

In the absence of maintenance therapy, there is a high risk of relapse among HIV-positive patients with cryptococcal meningitis who have been treated successfully. Positive CSF cultures after 2 weeks of therapy are predictive of future relapse and a less favorable clinical outcome.[1] Serum CrAg titers do not correlate with clinical improvement; however, pre-ART serum CrAg titers are predictive of future IRIS.[1][75][76] If new clinical symptoms arise, a careful lumbar puncture should be performed to rule out the possibility of increased ICP or IRIS. The risk of recurrence seems to be low in HIV-positive patients who have successfully completed a course of initial therapy, remain asymptomatic, and have a sustained increase (i.e., >6 months) in the CD4 count to ≥200 cells/mm³ after potent ART.[1][9][11]

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