DENVER — , results of a real-world analysis show.
Metagenomic next-generation sequencing (mNGS) of RNA and DNA from cerebrospinal fluid (CSF) simultaneously tests for a wide range of infectious agents and identifies individual pathogens, including viruses, bacteria, fungi, and parasites. About half of patients with a suspected central nervous system (CNS) infection may go undiagnosed due to a lack of tools that detect rare pathogens. Although mNGS is currently available only in specialized laboratories, expanding access to the diagnostic could address this problem, investigators noted.
“Our results justify incorporation of CSF mNGS testing as part of the routine diagnostic workup in hospitalized patients who present with potential central nervous system infections,” study investigator Charles Chiu, MD, PhD, professor in the Department of Laboratory Medicine as well as Medicine and Department of Medicine – Infectious Diseases and director of the Clinical Microbiology Laboratory, University of California San Fransisco (UCSF), said at a press conference.
The findings were presented at the 2024 annual meeting of the American Academy of Neurology (AAN).
‘Real-World’ Performance
Accurate diagnosis of CNS infections on the basis of CSF, imaging, patient history, and presentation is challenging, the researchers noted. “Roughly 50% of patients who present with a presumed central nervous system infection actually end up without a diagnosis,” Dr. Chiu said.
This is due to the lack of diagnostic tests for rare pathogens and because noninfectious conditions like cancer, autoantibody syndrome, or vasculitis can mimic an infection, he added.
CSF is “very limiting,” Dr. Chiu noted. “We are unable, practically, from a volume perspective, as well as a cost and turnaround time perspective, to be able to send off every possible test for every possible organism.”
The inability to rapidly pinpoint the cause of an infectious disease like meningitis or encephalitis can cause delays in appropriate treatment.
To assess the “real-world” performance of mNGS, researchers collected 4828 samples from mainly hospitalized patients across the United States and elsewhere from 2016 to 2023.
Overall, the test detected at least one pathogen in 16.6% of cases. More than 70% were DNA or RNA viruses, followed by bacteria, fungi, and parasites.
High Sensitivity
The technology was also able to detect novel or emerging neurotropic pathogens, including a yellow fever virus responsible for a transfusion-transmitted encephalitis outbreak and Fusarium solani, which caused a fungal meningitis outbreak.
Investigators also conducted a chart review on a subset of 1052 patients at UCSF to compare the performance of CSF nMGS testing with commonly used in-hospital diagnostic tests.
“We showed that as a single test, spinal fluid mNGS has an overall sensitivity of 63%, specificity of 99%, and accuracy of 90%,” said Dr. Chiu.
The sensitivity of mNGS was significantly higher compared with direct-detection testing from CSF (46%); direct-detection testing performed on samples other than CSF, such as blood (15%); and indirect serologic testing looking for antibodies (29%) (P < .001 for all).
This suggests that mNGS could potentially “detect the hundreds of different pathogens that cause clinically indistinguishable infections,” Dr. Chui said.
mNGS testing is currently confined to large specialized or reference laboratories. For greater access to the test, routine clinical labs or hospital labs would have to implement it, said Dr. Chiu.
“If you can bring the technology to the point of care, directly to the hospital lab that’s running the test, we can produce results that would have a more rapid impact on patients,” he said.