Current epidemiology and clinical features of Cryptococcus infection in patients without HIV infection: a multicentre study in 46 hospitals from Australia and New Zealand

Clin Infect Dis. 2023 May 26;ciad321. doi: 10.1093/cid/ciad321. Online ahead of print.


Introduction: Patients without HIV infection are increasingly recognised to be at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete.

Methods: We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV, and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included.

Results: Of 475 patients with cryptococcosis, 90% were HIV-negative (426/475) with the marked predominance of HIV-negative cases evident in both Cryptococcus neoformans (88.7%) and C. gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n=91), organ transplantation (n=81), other immunocompromising condition (n=97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70/426). The serum cryptococcal antigen test was positive in 85.1 % of tested patients (319/375); high titres independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titre and/or fungaemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (p=0.89).

Conclusion: The present study revealed 90% of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii cases, respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV.

Keywords: Cryptococcus gattii; Cryptococcus neoformans; cancer; cryptococcosis; transplantation.