A multicenter, longitudinal cohort study of cryptococcosis in human immunodeficiency virus-negative people in the United States

Kieren A. Marr, Yifei Sun, Andrej Spec, Na Lu, Anil Panackal, John Bennett, Peter Pappas, Darin Ostrander, Kausik Datta, Sean X. Zhang, Peter R. Williamson

Research output: Contribution to journalArticle

Abstract

Background. Cryptococcosis is increasingly recognized in people without human immunodeficiency virus (HIV). Methods. A multicenter, prospective cohort study was performed in 25 US centers. Consenting patients were prospectively followed for ≤2 years. Neurological morbidities were assessed with longitudinal event depiction and functional scores (Montreal Cognitive Assessment [MoCA]). Risks of death were analyzed using Cox regression. Results. One hundred forty-five 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 = .007). Abnormal MoCA scores (<26) were predictive of CNS disease; low scores (<22) were associated with poor long-term cognition. Longitudinal event depiction demonstrated frequent complications in people with CNS disease; 25 subjects (35.2%) required >1 lumbar puncture and 8 (11.3%) required ventriculostomies. In multivariable models, older age (>60 years) was associated with higher risks of death (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.05-4.38; P = .036), and lower risks were noted with underlying hematologic malignancy (HR, 0.29; 95% CI, 0.09-0.98; P = .05) and prior SOT (HR, 0.153; 95% CI, 0.05-0.44; P = .001). Conclusions. Despite aggressive antifungal therapies, outcomes of CNS cryptococcosis in people without HIV are characterized by substantial long-term neurological sequelae. Studies are needed to understand mechanism(s) of cognitive decline and to enable better treatment algorithms.

Original languageEnglish (US)
Pages (from-to)252-261
Number of pages10
JournalClinical Infectious Diseases
Volume70
Issue number2
DOIs
StatePublished - Jan 15 2020

Keywords

  • Cryptococcosis
  • Cryptococcus
  • Outcomes
  • Transplant

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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