Cryptococcus: Emerging host risk factors for infection

Author: mycolabadmin
11/5/2025
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Summary

This scientific review examines why some people without HIV are getting serious Cryptococcus infections and becoming very sick. Researchers found that people with liver problems, kidney disease, diabetes, cancer, and autoimmune diseases face much higher risk. The review also identifies new drugs and therapies that can surprisingly increase infection risk, highlighting the importance of understanding individual patient factors when treating these dangerous fungal infections.

Background

Invasive cryptococcal disease caused by Cryptococcus neoformans has historically been a rare opportunistic infection primarily seen in patients with hematologic malignancies, but became a significant cause of life-threatening infections during the HIV pandemic. While HIV-positive individuals remain the primary population affected, there is growing recognition of invasive Cryptococcus infections in non-HIV infected hosts with potentially worse outcomes.

Objective

This review examines emerging host risk factors for invasive cryptococcal disease in non-HIV infected populations, including hepatic dysfunction, renal disease, diabetes mellitus, autoimmune diseases, primary immunodeficiencies, solid organ transplantation, hematologic malignancies, and novel immunomodulatory therapies.

Results

Multiple studies identified hepatic dysfunction, renal disease, diabetes mellitus, hematologic malignancies, and autoimmune diseases as significant risk factors for invasive cryptococcosis in non-HIV hosts. Decompensated liver cirrhosis conveyed the second highest risk after advanced HIV infection with an adjusted odds ratio of 8.5. Novel therapies including tyrosine kinase inhibitors and fingolimod were associated with increased cryptococcal disease risk.

Conclusion

Non-HIV infected hosts with invasive cryptococcosis often have worse outcomes than HIV-positive patients despite historically being considered lower risk. Understanding emerging host risk factors, including metabolic disorders, iatrogenic immunosuppression, and host genetic susceptibility, is essential for developing novel prevention and treatment strategies in this expanding patient population.

Published in:PLoS Pathogens,
Study Type:Review,
Source: PMID: 41191707, DOI: 10.1371/journal.ppat.1013602