A Multicenter, Longitudinal Cohort Study of Cryptococcosis in Human Immunodeficiency Virus–negative People in the United States
Author:
Marr Kieren A1, Sun Yifei2, Spec Andrej3, Lu Na1, Panackal Anil4, Bennett John4, Pappas Peter5, Ostrander Darin1, Datta Kausik1, Zhang Sean X6, Williamson Peter R4, Lyons Jennifer, Bhimraj Adarsh, Trotman Robin, Health Cox, Perfect John, Lyon G Marshall, Vazquez Jose, Piwoz Julia, Marr Kieren, Hopkins Johns, Spindel Steven, Wray Dannah, Bennett John, Garcia-Diaz Julia, Nolt Dawn, Subramanian Aruna, Pappas Peter, Schaenman Joanna, Taplitz Randy, Diego San, Miceli Marisa, Lee Samuel A, Nguyen Hong, Pannaraj Pia, Hasbun Rodrigo, Limaye Ajit, Powderly William, Spec Andrej,
Affiliation:
1. Department of Medicine, Johns Hopkins University, Baltimore, Maryland 2. Department of Biostatistics, Columbia University, New York 3. Department of Medicine, Washington University, St. Louis, Missouri 4. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 5. Department of Medicine, University of Alabama at Birmingham 6. Department of Pathology, Johns Hopkins University, Baltimore, Maryland
Abstract
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.
Funder
National Institute of Allergy and Infectious Diseases
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Microbiology (medical)
Cited by
62 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|