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

Cryptococcus Infection Network Cohort Study Working Group

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 : an official publication of the Infectious Diseases Society of America
Volume70
Issue number2
DOIs
StatePublished - Jan 2 2020

Fingerprint

Cryptococcosis
Longitudinal Studies
Cohort Studies
HIV
Hematologic Neoplasms
Confidence Intervals
Ventriculostomy
Spinal Puncture
Central Nervous System Diseases
Autoimmunity
Immunosuppression
Fever
Central Nervous System
Prospective Studies
Morbidity
Transplants
Therapeutics

Keywords

  • cryptococcosis
  • cryptococcus
  • outcomes
  • transplant

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

A Multicenter, Longitudinal Cohort Study of Cryptococcosis in Human Immunodeficiency Virus-negative People in the United States. / Cryptococcus Infection Network Cohort Study Working Group .

In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Vol. 70, No. 2, 02.01.2020, p. 252-261.

Research output: Contribution to journalArticle

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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.",
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author = "{Cryptococcus Infection Network Cohort Study Working Group} and Marr, {Kieren A.} and Yifei Sun and Andrej Spec and Na Lu and Anil Panackal and John Bennett and Peter Pappas and Darin Ostrander and Kausik Datta and Zhang, {Sean X.} and Williamson, {Peter R.}",
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AU - Cryptococcus Infection Network Cohort Study Working Group

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.

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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.

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