<i>Cryptococcus gattii</i> complex infections in southern Brazil: epidemiology, clinical features, management and outcomes from a 33-year cohort

Cryptococcus gattii complex has emerged as an important cause of invasive fungal disease in both immunocompetent and immunocompromised hosts, yet robust clinical and epidemiological data remain limited, particularly in Latin America. An observational study was conducted to describe and analyze the clinical characteristics and outcomes of all proven and probable cases of C. gattii complex infection managed at a tertiary referral center in southern Brazil from 1992-2025. A total of 39 cases were identified. The median age was 54 years, and 61.5% were male. Most patients (61.5%) were considered immunocompetent, although comorbidities were common. Headache (61.5%), altered mental status (33.3%), and fever (30.8%) were the most frequent symptoms overall. Pulmonary disease was the predominant clinical form (76.9%), but meningitis/meningoencephalitis was also common (69.2%). Nearly half (46.2%) had both pulmonary and neurological disease. Cryptococcomas were frequent (76.9%); the majority were managed without surgical intervention. Severe impairment of consciousness at presentation and cerebrospinal fluid protein levels above 92.15 mg/dL were significantly associated with mortality. Amphotericin B (AmB) deoxycholate plus fluconazole was the most prescribed induction regimen, with a median duration of 3 weeks. The overall mortality was 20.5%. Immune reconstitution inflammatory syndrome (IRIS) occurred only among patients with cryptococcomas and was managed with glucocorticoids in most cases. The performance of the cryptococcal antigen test (CrAg) was excellent in both neurological and pulmonary diseases. This study highlights the clinical spectrum of C. gattii complex infection and supports the potential utility of shorter induction regimens (< 4 weeks), as well as the role of CrAg as a valuable diagnostic tool.