Precision Diagnosis of Acute Infectious Diseases
Charles Chiu, MD, PhD, Associate Professor of Laboratory Medicine and Medicine / Infectious Diseases, UC San Francisco
L to R, Front Row: Michael Geschwind, MD, PhD; Joe DeRisi, PhD; Michael Wilson, MD, MAS; Charles Chiu, MD, PhD; Steve Miller, MD, PhD; Kelsey Zorn, MHS; Back Row: Jeffrey Gelfand, MD, MAS; Hannah Sample, BS; Scot Federman, BA; Eric Chow, PhD; Wei Gu, MD, PhD; Allan Gopez, CLS; Walter Lorizio, CLS; Crystal Chan, CLS Specialist; Lydia Dang, CLS
Current tests in clinical microbiology laboratories fail to diagnose many life-threatening infections in a timely fashion, resulting in increased health care costs and likelihood of death. UCSF has pioneered the use of a state-of-the-art sequencing test, called metagenomic next-generation sequencing (NGS), to reveal the cause of unknown infections that routinely elude physicians. NGS allows for much faster “decoding” of genetic material than was previously possible.
UCSF researchers aim to provide the first-ever demonstration of precision medicine in infectious diseases by implementing this technology to diagnose brain and blood infections in 300 critically ill, hospitalized patients at three UC medical centers over 18 months.
They will validate the test in a licensed clinical laboratory to ensure sensitivity and accuracy, analyze the sequencing data using a secure cloud computing platform linked to the patient electronic medical record, and create a multidisciplinary "precision medicine" consult team to interpret results and guide treatment. Importantly, they will critically evaluate the impact of this test on overall costs and clinical outcomes. The immediate goal is to develop a clinically reimbursable, self-sustaining test that can be used for precision diagnosis of infectious diseases in hospitalized patients. Ultimately, the aim is to leverage nonprofit and industry partners to make this test widely accessible to patients in California and beyond.
Read a case study of a 14-year-old boy with encephalitis accurately diagnosed by Chiu’s technique.
The team will continue to expand precision diagnostic tests for infectious diseases by completing the CLIA standard confirmation of the test for diagnosing blood infections and by initiating a clinical study for patients with blood infections. Work is ongoing to increase the speed of the tests, attempt to study the determinants of antibiotic resistance, and to harness AI to better diagnose infectious or non-infectious causes of illness. Additionally, the team is working to complete an economic analysis to further demonstrate the value of their assays compared to the current standard of practice.
UC Team Members
UC San Francisco
- Steve Miller, MD/PhD, Associate Professor, Department of Laboratory Medicine; Director, UCSF Clinical Microbiology Laboratory
- Joseph DeRisi, PhD, Chair and Professor, Department of Biochemistry and Biophysics
- Eric Chow, Ph.D., Director, UCSF Center for Advanced Technology (CAT)
- Stephen Hauser, MD, Chair, Department of Neurology
- Michael Wilson, MD; Michael Geschwind, MD/PhD; Jeffrey Gelfand, MD; Felicia Chow, MD, Department of Neurology
- Hannah Sample, BS, Project Manager, Department of Neurology
- Chaz Langelier, MD/PhD, Assistant Professor, Department of Medicine / Infectious Diseases
- Kelsey Zorn, UCSF Clinical Research Coordinator
UC Los Angeles
- Romney Humphries, PhD/D(ABMM), Director, UCLA Clinical Microbiology Laboratory
- Jeffrey Klausner, MD/MPH; Tara Vijayan, MD; Paul Allyn III, MD, Department of Medicine / Infectious Diseases
- Paul Vespa, MD, Department of Neurology
- UCLA Coordinators: Jamie Murkey, Chelsea Shannon
- Christopher Polage, MD, Director, UCD Clinical Microbiology Laboratory
- Stuart Cohen, MD, Professor and Chief, Infectious Diseases
- Lara Zimmerman, MD, Department of Neurology
- Muzna Naqvi, MD, Clinical Site Coordinator, UC Davis Medical Center
- UCD Coordinators: Nicolle Ocampo, Fatemeh Memar, Czarina Ganzon
- Brent Fulton, PhD/MBA, Assistant Adjunct Professor of Health Economics and Policy; Associate Director, Nicholas C. Petris Center on Health Care Markets
Private and Nonprofit Partners
- Jonathan Hirsch, PhD (President)
- Laurie Gomer, MBA
- David Shaywitz, MD/PhD (Chief Executive Officer)
- Omar Serang, BS (Chief Technology Officer)
- Sri Madabushi, PhD (Business Head, Google Genomics)
Quest Diagnostics, Inc.
- Rick Pesano, MD/PhD (Vice President)
- John Leake, MD/MPH (Medical Director, Infectious Diseases)
California Department of Public Health (CDPH)
- James Watt, MD
- Dongxiang Xia, MD/PhD
- Sharon Messenger, PhD
- Debra Wadford, PhD
- Mostafa Ronaghi, PhD (Chief Technology Officer)
Children’s National Medical Center
- Brittany Goldberg, MD, Division of Pediatric Infectious Diseases
- Joseph Campos, PhD, D(ABMM), Division of Laboratory Medicine
St. Jude’s Children Research Hospital
- Randall Hayden, MD, Medical Microbiology and Pathology
Children’s Hospital Los Angeles
- Jeffrey Bender, MD, Division of Pediatric Infectious Diseases
- Grace Aldrovandi, MD, Division of Pediatric Infectious Diseases
- Jennifer Dien Bard, PhD, D(ABMM)
- Samia Naccache, PhD
Children’s Hospital Colorado / University of Colorado
- Kevin Messacar, MD, Division of Pediatric Infectious Diseases
- Samuel Dominguez, MD/PhD, Division of Pediatric Infectious Diseases
Zuckerberg San Francisco General Hospital and Trauma Center
- Lisa Winston, MD, Division of Infectious Diseases
- Barbara Haller, MD, PhD, Chief, Microbiology
In order to achieve its goals, the PDAID project requires additional funds beyond those provided by CIAPM. The state’s contribution to the project is significantly leveraged by generous donations from the Sandler and the William F. Bowes, Jr., foundations for a total of $2.4 million, and by additional funding from the Charles and Helen Schwab foundation and a $400,000 award from the Marcus Program in Precision Medicine Innovation at UCSF. In addition, PDAID is funded by research awards that, together, amount to close to $400,000.
- UCSF provided in-kind support through administrative fees and faculty time.
- In-kind contributions from Quest, CDPH and UCSF in the form of patient samples for the validation of the sequencing assay.