TY - JOUR
T1 - A multicenter, longitudinal cohort study of cryptococcosis in human immunodeficiency virus-negative people in the United States
AU - Marr, Kieren A.
AU - Sun, Yifei
AU - Spec, Andrej
AU - Lu, Na
AU - Panackal, Anil
AU - Bennett, John
AU - Pappas, Peter
AU - Ostrander, Darin
AU - Datta, Kausik
AU - Zhang, Sean X.
AU - Williamson, Peter R.
N1 - Publisher Copyright:
© The Author(s) 2019.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/1/15
Y1 - 2020/1/15
N2 - 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.
AB - 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.
KW - Cryptococcosis
KW - Cryptococcus
KW - Outcomes
KW - Transplant
UR - http://www.scopus.com/inward/record.url?scp=85077460476&partnerID=8YFLogxK
U2 - 10.1093/cid/ciz193
DO - 10.1093/cid/ciz193
M3 - Article
C2 - 30855688
AN - SCOPUS:85077460476
VL - 70
SP - 252
EP - 261
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
IS - 2
ER -