After a decade in development, a new genomic test developed at the University of California–San Francisco (UCSF) promises to rapidly and accurately diagnosis infections caused by almost any pathogen—whether a virus, bacterium, fungus, or parasite.
The tool uses a genomic sequencing technique, called metagenomic next-generation sequencing (mNGS), to quickly decipher if a bacterium, fungus, virus, or parasite is causing an infection. Instead of ruling out each pathogen in a process of elimination, mNGS analyzes all the nucleic acids, RNA and DNA, present in a sample simultaneously.
"Our technology is deceptively simple," said Charles Chiu, MD, PhD, professor of laboratory medicine and infectious diseases at UCSF and senior author of the study, in a university press release. "By replacing multiple tests with a single test, we can take the lengthy guesswork out of diagnosing and treating infections."
Chiu and his colleagues began work developing the test in the early 2010s, as a way to identify pathogens causing neurologic illnesses. The test was first used clinically in 2014, and has been used with increasing frequency at the UCSF Clinical Microbiology Laboratory.
The test works by separating human genetic sequences from cerebral spinal fluid samples, leaving behind only genetic material from the pathogens. Running the test on a sample costs about $3,000.
86% sensitivity
In a study published in Nature Medicine, Chiu's group says the UCSF team has analyzed nearly 5,000 cerebral spinal fluid samples with the test, 14.4% of which turned out to have an infection.
From 2016 through 2023, the sensitivity of mNGS testing increased to 86%, as testing increased from 116 samples in 2016 to 1,067 in 2022. The median turnaround times for UCSF and non-UCSF patients were 8.2 and 11.4 days, respectively, from sample collection to result, the authors said.
DNA viruses were most frequently detected (45.5%), followed by RNA viruses (26.4%), bacteria (16.6%), fungi (8.5%) and parasites (2.9%).
Our results indicate that mNGS testing should be viewed as a complementary yet essential part of the workup for patients with diagnostically challenging CNS infections.
"We found that mNGS testing was the most sensitive test for the detection of pathogens in a cohort of patients with clinically severe and diagnostically challenging CNS [central nervous system] infections and the only or first test to make the diagnosis in 67 (30.4%) of 220 infections," the authors wrote. "Our results indicate that mNGS testing should be viewed as a complementary yet essential part of the workup for patients with diagnostically challenging CNS infections."
In a companion study published in Nature Communications, the team used mNGS to identify pathogens in respiratory fluid that can cause pneumonia and automated it to get results faster.
