A Multicenter, Longitudinal Cohort Study of Cryptococcosis in HIV-Negative People in the United States
Abstract
BACKGROUND
Cryptococcosis is increasingly recognized in people without HIV.
METHODS
A multicenter, prospective cohort study was performed in 25 U.S. centers. Consenting patients were prospectively followed for up to 2 years. Neurologic morbidities were assessed with longitudinal event depiction and functional scores (Montreal Cognitive Assessment, MoCA). Risks for death were analyzed using Cox regression.
RESULTS
145 subjects were enrolled. Most were male (95, 65.5%) and had immunosuppression (120, 82.8%), including solid organ transplant (SOT, 33.8%), autoimmunity (15.9%), and hematologic malignancies (11.7%). Disease involved the central nervous system (CNS) in 71 subjects (49%). Fever was uncommon, documented in 40 (27.8%) subjects, and absence was associated with diagnostic delay (mean 48.2 vs. 16.5 days, p=0.007). Abnormal MoCA scores (1 lumbar puncture and eight (11.3%) required ventriculostomies. In multivariable models, older age (>60 years) was associated with higher risks for death (HR 2.14, 95% CI 1.05-4.38, p=0.036), and lower risks were noted with underlying hematologic malignancy (HR 0.29, 95% CI 0.09-0.98, p=0.05) and prior SOT (HR 0.153, 95% CI 0.05-0.44, p=0.001).
CONCLUSION
Despite aggressive antifungal therapies, outcomes of CNS cryptococcosis in people who don't have HIV is characterized by substantial long-term neurologic sequelae. Studies are needed to understand mechanism(s) of cognitive decline and to enable better treatment algorithms.
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 145 participants or records.
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