Precision Diagnosis of Acute Infectious Diseases; Neuroinflammatory Cohort

Study Overview
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Brief Summary
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This study aims to use a clinically validated metagenomic next-generation sequencing (mNGS) assay to provide a demonstration of precision medicine for diagnosis of acute infectious disease in hospitalized patients. From June 2016 to June 2017, 200 patients will be enrolled from multiple hospitals in California and outside of California. Patients will be evaluated to determine the impact on the mNGS assay on diagnostic yield, hospital costs and clinical outcomes.

Detailed Description
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This study aims to use a clinically validated metagenomic next-generation sequencing (mNGS) assay to provide a demonstration of precision medicine for diagnosis of acute infectious disease in hospitalized patients, with the goal of directly impacting clinical care and improving patient mortality. This diagnostic test has been previously validated in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, the University of California, San Francisco Clinical Microbiology Laboratory. From June 2016 to June 2017, investigators will prospectively enroll 200 patients from multiple hospitals in California (University of California, San Francisco; University of California, Los Angeles; University of California, Davis; Children's Hospital Los Angeles) and outside California (Children's National Medical Center, Children's Hospital Colorado, St. Jude Children's Research Hospital) for mNGS testing, and evaluate the impact on the assay on diagnostic yield, hospital costs and clinical outcomes.

Official Title
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Clinical Implementation of Metagenomic Next-Generation Sequencing for Precision Diagnosis of Acute Infectious Diseases; Neuroinflammatory Cohort

Conditions
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Encephalitis, Meningitis

Intervention / Treatment
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* Device: mNGS for pathogen detection


Participation Criteria
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Eligibility Criteria
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Exclusions: Patients on a 5150 or 5250 psychiatric hold Prisoners University of California employees / students or close associates of any of the key personnel on the study Outpatients and/or patients with chronic illness Inclusion: Demographic Criteria Age: any (no age limit) Language: any (with the use of interpreting services for obtaining consent) For the following, the infectious syndromes include meningitis, encephalitis, fever, sepsis, and pneumonia: Clinical Criteria Hospital admission or transfer with diagnosis of an presumed infectious syndrome or clinical presentation consisting with an infectious syndrome, as defined below: Meningitis: fever >38°C and abnormal imaging or CSF pleocytosis (CSF white blood cell count (WBC) > 5 /mm^3) +/- stiff neck, +/- headache, +/- seizure Encephalitis: pleocytosis and at least one of the following: altered mental status, seizures, new onset of focal neurologic findings, abnormal EEG, acute brain abnormalities on neuroimaging No known diagnosis of non-infectious etiology responsible for symptoms Time of enrollment: within 7 days of onset of symptoms, either initial presentation or acute exacerbation of presumed infectious syndrome. Specimen Criteria cerebrospinal fluid available within 7 days of symptom onset AND within 3 days of hospital admission or transfer unless evidence for acute exacerbation as defined by abrupt decline in clinical status, worsening pleocytosis or other laboratory parameters Minimum of 600 microliters (uL) of clinical sample, stored at 4 degrees Celsius (C) no more than 5 days (ideally frozen in -70 degrees Celsius within 24 hours of collection) No more than 3 freeze-thaw cycles

Ages Eligible for Study
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Minimum Age: 1 Minute
Maximum Age: 110 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: patients enrolled for mNGS testing<br>Patients with meningitis and/or encephalitis will be enrolled in this study in order to analyze the clinical utility of mNGS for pathogen detection. There is no control group for this study (Investigators will identify historical controls by retrospective chart review and clinical reimbursement documents). | Device: mNGS for pathogen detection<br>* This assay is a laboratory-validated metagenomic test for comprehensive detection of viruses, bacteria, fungi, and parasites in clinical samples.<br>* Other names: UCSF metagenomic next-generation sequencing testing;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number of Cases With at Least One Provider Response | Investigators will evaluate impact of mNGS assay by clinician surveys and Clinical Microbial Sequencing Board (CMSB) feedback and discussion as measured by at least 1 provider response per case. | within 1 month of patient enrollment in study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Outcomes: Time From Cerebrospinal Fluid Collection to mNGS Results | Investigators will review medical records to determine time of initial presentation and measure the time to mNGS results. | from admission to 1 month post discharge for each patient during the enrollment period of study | 
| Clinical Outcomes: Length of Stay | Investigators will review medical records to determine length of stay including discharge to rehab facilities. | from admission to 1 month post discharge for each patient during the enrollment period of study | 
| Clinical Outcomes: Final Diagnosis Category | Investigators will review medical records to determine final diagnosis after all diagnostic testing has been performed including metagenomic Next-Gen sequencing and autopsy where applicable. | from admission to time of final case review (1 month post discharge or up to one year) | 
| Clinical Outcomes: Concordance of mNGS With Other Molecular Testing on Cerebrospinal Fluid Pathogens | mNGS findings were compared to conventional testing for concordance. Conventional testing included both tests that were ordered as part of each patients workup and those order to confirm mNGS findings on cerebrospinal fluid (CSF). | from admission to 1 month post discharge for each patient during the enrollment period of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metagenomic next-generation sequencing, microbiological diagnosis, bacterial infections, viral infections, fungal infections, parasitic infections