Superfast Metagenomic Test Helps Diagnose Critically Ill Patients

According to a new study, the "metagenomic" test for neurological infections has a real clinical advantage.

In an badysis of the actual impact of an innovative test called Next Generation Metagenomic Sequencing (mNGS), developed by UCSF scientists to diagnose patients with mysterious inflammatory neurological conditions, this technique has been shown to identify infections better than any standard clinical method.

"The infectious cause of half the cases of meningitis and encephalitis is not diagnosed in the country's hospitals, and these critically ill patients urgently need a better test tool," said Charles Chiu, MD, PhD, professor of laboratory medicine and medicine at UCSF and lead author of the new study. Unlike conventional tests, which are often dictated by physicians 'insights, the mNGS test offers an unbiased approach to detect almost all possible pathogens – bacteria, viruses, fungi and parasites – present in patients' cerebrospinal fluid. . treatment.

The study, published in the New England Journal of Medicine, has been set up to deal only with the most difficult cases. To qualify, a patient had to be hospitalized for an acute neurological condition without definitive diagnosis. The study included 204 pediatric and adult patients, mainly from California, with meningitis (inflammation of the lining surrounding the brain), encephalitis (inflammation of the brain itself) or myelitis (inflammation of the spinal cord). spinal).

The test has highlighted many of the same infections identified by standard laboratory testing methods, which typically look for pathogens one by one and require doctors to know what they are looking for to succeed. But he also found 13 infections that were not detected by all conventional tests, such as a case of infection with the St. Louis encephalitis virus, not seen in California since 1986. And in more than half in these cases, the diagnosis of malignant meningitis was essential to guide the treatment of these patients. In the case of a hepatitis E virus infection that had not been tested by conventional tests, the successful diagnosis by nuclear hepatitis syndrome probably prevented the patient from having a liver transplant.

"The mNGS test is usually ordered as a last resort, and we ended up recruiting the most difficult patients to diagnose," said Chiu, also director of the UCSF-Abbott viral diagnostic and discovery center. "All conventional microbiology tests combine performance diagnostics in less than 50% of these patients, and we have shown that only one test, the mNGS, could have a significant impact on that number."

In total, the test identified 32 nervous system infections in 31 patients. In addition to the 13 diagnoses established by the MSnG alone, the new technology has confirmed 19 infections also diagnosed by conventional tests.

Less than half of the cases of meningitis and encephalitis are caused by infections. Most others are the result of autoimmune reactions, in which the patient's own body attacks the nervous system. However, both conditions require very different treatments – suppressing immunity in an infected patient can be harmful, and administering antibiotics in the case of an autoimmune disease is ineffective and may unnecessarily promote resistance Antimicrobials – that's the first thing the doctor needs to know when to treat such patients is what category of inflammatory disease they have.

"Patients with infectious and non-infectious encephalitis may be clinically indistinguishable," said Michael Wilson, MD, badociate professor of neurology at UCSF and co-lead author of the article, with the coordinator of the Hannah Sample study. "Having a broad test that governs the infection or excludes the infection can really help those cases that are in a gray area between infections and not."

However, the new test is not perfect and it has not been possible to diagnose 26 infections. In the majority of cases, the pathogen DNA was not present in cerebrospinal fluid, requiring badysis of another type of sample, such as brain abscess tissue, or use of an indirect test method, such as antibody testing. the diagnosis. West Nile virus infection, for example, is not identifiable by the sequencing of viral genetic material found in the cerebrospinal fluid, as it manifests itself very rapidly.

In some cases, meningitis has found traces of infections such as tuberculosis, which leave little trace in the cerebrospinal fluid. But even if these infections were not detected at a high enough level to be reported definitively, knowing that they were present, even in trace amounts, could still help doctors by ordering them to request another diagnostic test to confirm the presence of the pathogen.

Reference: Wilson et al. 2019. Clinical metagenomic sequencing for the diagnosis of meningitis and encephalitis. New England Journal of Medicine. DOI: 10.1056 / NEJMoa1803396.

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