A novel metagenomic sequencing (mNGS) test developed at UC San Francisco (UCSF) offers a rapid and accurate method for diagnosing a wide range of neurological infections. The test sequences all genetic material in cerebrospinal fluid (CSF) to identify bacteria, viruses, fungi, or parasites, providing results in as little as 48 hours. This breakthrough promises to expedite treatment and improve outcomes for patients with difficult-to-diagnose infections.
The mNGS test was developed by Charles Chiu, MD, PhD, and colleagues at UCSF in the early 2010s. It has since become a routine diagnostic tool at UCSF, with hospitals and clinics nationwide sending samples for analysis. Between 2016 and 2023, the UCSF team analyzed nearly 5,000 CSF samples, identifying infections in 14.4% of cases. In those samples with confirmed infections, the test accurately identified the pathogen 86% of the time.
Clinical Impact and Advantages
"Our mNGS test performs better than any other category of test for neurologic infections," said Chiu. "The results support its use as a critical part of the diagnostic armamentarium for physicians who are working up patients with infectious diseases."
The mNGS test offers several advantages over traditional diagnostic methods, particularly in cases where the causative pathogen is rare or unknown. Traditional methods often involve a lengthy series of individual tests, delaying diagnosis and treatment. The mNGS test, in contrast, provides a comprehensive analysis of all genetic material in the sample, identifying even unexpected or novel pathogens.
In one notable case, the mNGS test was used to diagnose a young boy with leptospirosis, a rare bacterial infection, after a long series of tests had failed to identify the cause of his illness. The rapid diagnosis allowed doctors to administer penicillin, leading to the boy's full recovery.
Expansion to Respiratory Pathogen Detection
Recognizing the potential of mNGS for pandemic preparedness, Chiu and his team have adapted the technology for use with respiratory fluids. This adaptation significantly reduces processing time, with the goal of achieving same-day or next-day results. The researchers demonstrated that the respiratory test could detect viruses with pandemic potential, including SARS-CoV-2, influenza A and B, and RSV, even when present in low amounts.
Regulatory Status and Commercialization
Both the CSF and respiratory versions of the mNGS test have received breakthrough device designation from the U.S. Food and Drug Administration (FDA). To increase access to the technology, Chiu, along with Joe DeRisi, PhD, Michael Wilson, MD, and others, founded Delve Bio, which is now the exclusive provider of the mNGS CSF test developed at UCSF.
"These findings support including mNGS as a core tool in the clinical workup for CNS infections," said Steve Miller, MD, PhD, chief medical officer of Delve Bio. "mNGS offers the single most unbiased, complete and definitive tool for pathogen detection. Thanks to its ability to quickly diagnose an infection, mNGS helps guide management decisions and treatment for patients with meningitis and encephalitis, potentially reducing healthcare costs down the line."
