Precision Diagnosis of Acute Infectious Diseases; Neuroinflammatory Cohort
Precision Diagnosis of Acute Infectious Diseases; Neuroinflammatory Cohort
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.
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.
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

 1. Age: any (no age limit)

 2. 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

 1. 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

 2. No known diagnosis of non-infectious etiology responsible for symptoms

 3. Time of enrollment: within 7 days of onset of symptoms, either initial presentation or
 acute exacerbation of presumed infectious syndrome.

 Specimen Criteria

 1. 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

 2. 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)

 3. No more than 3 freeze-thaw cycles