A Multicenter, Longitudinal Cohort Study of Cryptococcosis in Human Immunodeficiency Virus-negative People in the United States Article

Full Text via DOI: 10.1093/cid/ciz193 PMID: 30855688 Web of Science: 000506801400013
Industry Collaboration

Cited authors

  • Marr, Kieren A.; Sun, Yifei; Spec, Andrej; Lu, Na; Panackal, Anil; Bennett, John; Pappas, Peter; Ostrander, Darin; Datta, Kausik; Zhang, Sean X.; Williamson, Peter R.; Lyons, Jennifer; Bhimraj, Adarsh; Trotman, Robin; Perfect, John; Lyon, G. Marshall; Vazquez, Jose; Piwoz, Julia; Marr, Kieren; Spindel, Steven; Wray, Dannah; Garcia-Diaz, Julia; Strasfeld, Lynne; Nolt, Dawn; Subramanian, Aruna; Schaenman, Joanna; Taplitz, Randy; Miceli, Marisa; Lee, Samuel A.; Hong Nguyen; Pannaraj, Pia; Hashun, Rodrigo; Limaye, Ajit; Powderly, William


  • 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.

Publication date

  • 2020

Published in

International Standard Serial Number (ISSN)

  • 1058-4838

Start page

  • 252

End page

  • 261


  • 70


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