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 - Funding Information:
Financial support. This work was supported by the National Institutes of Health (intramural–extramural grant number U01 AI109657 and extramural grant numbers AI001123-01 and AI001124-01; to A. P.’s institution).
Funding Information:
Potential conflicts of interest. K. A. M. reports personal fees from Cidara and Merck outside the submitted work; A. P. reports being employed as Director at Merck & Co., Inc., since April 2017. A. S. reports grants and personal fees from Astellas Pharma, Inc.; grants from Scynexis; grants from IMMY; grants and personal fees from Mayne Pharma; and grants and personal fees from Minnetronix outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Publisher Copyright:
© The Author(s) 2019.
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 -