Johns Hopkins team diagnoses brain infections using next-gen sequencing

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Pinpointing the cause of brain infections and inflammation is challenging, with more than half of cases going undiagnosed. But a Johns Hopkins University team is aiming to change that with next-generation sequencing.

The researchers, including bioinformatics experts and physicians, sequenced brain tissue samples from 10 patients with symptoms of brain infection. They took biopsies of brain lesions identified by MRI. Using a computer, they removed the human DNA sequences and analyzed the remaining DNA against a database containing bacterial, viral and single-cell pathogen genomes, the team said in a statement.

"Identifying organisms involved in brain infections is critical for establishing adequate treatments and, in the case of tuberculosis or viral infections, is a major challenge in clinical practice," said Dr. Pardo-Villamizar, an associate professor of neurology at the Johns Hopkins University School of Medicine, in the statement.

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They found Mycobacterium tuberculosis in three patients, Epstein-Barr virus in another, and JC polyomavirus in a fifth patient. In other patients, they were unable to identify a specific cause, but found bacteria species related to a known bacterium that is treatable with antibiotics. While the approach didn't successfully diagnose the cause of infection for all patients, ruling out particular pathogens could suggest that brain infection is not present and that other treatment may be appropriate.

"If someone has an infection, then you don't necessarily want to give them steroids to reduce inflammation. You'll make the infection worse by knocking down the immune system," Pardo-Villamizar said in the statement. "Having a correct diagnosis is the only way to ensure the best, individualized precision treatment."

The team said the tool will only become more useful as more pathogens' genomes are sequenced and added to the database. In fact, the sample from one patient for whom results were inconclusive was tested again the following year. The researchers found that it matched the genome for Elizabethkingia, a previously unknown bacterium that had been sequenced since the initial testing.

Next-gen sequencing could be a cost-effective addition to pathology labs, the team said. It takes a few days and costs less than $500 to sequence each sample, according to the statement. Comparing the sample to other species takes less than two hours. But more research is needed before this method can be brought into widespread use, including identifying what organisms can be found in healthy brains, Pardo-Villamizar said. They will also need a large study of patients with an established diagnosis to calculate the rate of false positive or false negative results.

- here's the statement
- and here is the study abstract

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