A genome sequencing test developed at UC San Francisco that can rapidly pinpoint the cause of a bacterial, viral, fungal or parasitic infection from among a huge range of possibilities is now available to help physicians nationwide diagnose mysterious cases of neurological infection in acutely ill patients.
Scientists at UCSF have already used the test on a trial basis to diagnose a number of patients, including the well-known case of a 14-year-old boy who was near death with swelling in his brain. The boy had undergone months of unsuccessful attempts to identify the cause of his illness with conventional lab tests, expensive imaging technologies and invasive procedures, including a brain biopsy. By sequencing his cerebrospinal fluid (CSF), UCSF scientists found that he had a bacterial infection called leptospirosis, and he rapidly recovered after receiving targeted treatment with penicillin.
The test has now been validated in UCSF’s Clinical Laboratory Improvement Amendments (CLIA)-licensed clinical microbiology laboratory and is approved for clinical use.
Pinpointing Genomic Signatures of Pathogens
Over the last year, UCSF physicians and researchers have examined the utility of the test using CSF collected from more than 200 patients enrolled in a nationwide study of eight hospitals, including three University of California medical centers. All of these patients suffered from acute neurological illnesses, including meningitis (inflammation of the coverings around the brain and spinal cord), encephalitis (inflammation of the brain), and myelitis (inflammation of the spinal cord).
Doctors often have trouble figuring out why these tissues become inflamed, as these conditions can have many causes, including infection, cancer and autoimmune disease. This can lead to inappropriate treatment. For example, steroids and immunosuppressive agents that are commonly used to treat autoimmune diseases make it harder for the body to fight infection.
The new sequencing test can help overcome this uncertainty by pinpointing the genomic signatures of a wide range of pathogens – including fungi, bacteria, viruses and parasites – all at once. If no pathogen is detected using this comprehensive test, doctors can also be more confident in pursuing other non-infectious causes of the illness. While the test does not always establish the cause of inflammation, it has the potential to speed up the diagnostic process significantly, and to spare patients from having to undergo a large number of diagnostic tests and invasive procedures.
Starting with Neurological Illnesses
The technique, known as metagenomic next-generation sequencing, or mNGS, is a “shotgun” approach in which all of the DNA and RNA in a clinical sample are sequenced at very high depth, with the generation of 10 to 20 million reads per sample. Currently, only testing of CSF for patients with neurological illnesses is available in the clinical lab. UCSF is actively working on making clinical mNGS testing available for other sample types including blood for patients with sepsis and lung fluid for patients with pneumonia. The testing process in the diagnostic laboratory takes about 72 hours, and results are generally available within one or two weeks.
Making a clinical test like this available to physicians everywhere is a paradigm shift in infectious disease diagnostics.
More information on the test and how to order it is available at the Center for Next-Gen Precision Diagnostics. The center serves as a reference lab to help doctors make diagnoses, but it does not provide consulting services directly to patients. The mNGS test must be ordered by a licensed provider authorized to order clinical laboratory tests and results are reported to the provider’s referring laboratory.
“Making a clinical test like this available to physicians everywhere is a paradigm shift in infectious disease diagnostics,” said Charles Chiu, MD, PhD, an associate professor of laboratory medicine at UCSF and principal investigator of the mNGS study. “Too many patients die or suffer unnecessarily because the cause of their illness cannot be determined in a timely fashion. We now have a single diagnostic tool that can be used to comprehensively diagnose or exclude infections in hospitalized patients with mysterious illnesses.”
The test was developed with support from the California Initiative to Advance Precision Medicine (CIAPM), UCSF Medical Center, the National Institutes of Health, the UC Center for Accelerated Innovation, and the Sandler, Bowes, and Charles and Helen Schwab foundations.
UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences; and a preeminent biomedical research enterprise. It also includes UCSF Health, which comprises three top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospitals in San Francisco and Oakland, and other partner and affiliated hospitals and healthcare providers throughout the Bay Area.