Conference Coverage

Next-generation sequencing test detects pathogens with high sensitivity



– A next-generation sequencing (NGS) test for pathogen detection demonstrated higher sensitivity than conventional testing methods in a cohort of diverse pediatric patients, according to researchers.

The NGS test, which detects sequences of circulating cell-free DNA in plasma, detected pathogens with 92% sensitivity, compared with 64% sensitivity for all conventional testing methods combined (P less than .01).

Dr. Jenna Rossoff of Ann & Robert H. Lurie Children's Hospital of Chicago Jennifer Smith/MDedge News

Dr. Jenna Rossoff

Specificity, however, was 64% with the NGS test and 89% with the conventional methods (P less than .01).

“While I think we can all recognize that specificity is important, I think sensitivity is more important to be able to get at sources of infection,” said Jenna Rossoff, MD, of Ann & Robert H. Lurie Children’s Hospital of Chicago.

Dr. Rossoff and her colleagues conducted this study and presented the results in a poster at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Lurie Children’s Hospital began using a commercially available NGS pathogen test, the Karius test, in 2016. Dr. Rossoff and her colleagues set out to evaluate how the test affected patient care by conducting a retrospective analysis of tests performed from December 2016 through August 2018.

The researchers studied 100 NGS tests performed for 79 pediatric patients. The patients had a median age of 11 years (range, 0.5-24 years).

Most patients (n = 60) were immunocompromised, largely due to a hematologic malignancy (n = 16), primary immune deficiency (n = 13), hematopoietic cell transplant (n = 10), or solid organ transplant (n = 7).

The remaining 19 patients were immunocompetent, and 9 of them had no underlying diagnosis. The most common diagnosis for this group was neurologic disorder (n = 6).


Of the 100 NGS tests evaluated, 70 were positive for any organism, and 56 of these were deemed clinically relevant.

“What I think is quite remarkable is that, of those clinically relevant organisms, tests on 14, which is 25% of those, were able to identify clinically relevant or pathogenic organisms when no other conventional testing modality was able to identify them,” Dr. Rossoff said. “And these were often in patients who underwent invasive procedures to try to get at the source of their infectious disease.”

In fact, the study included 42 patients who underwent 54 invasive diagnostic procedures, and 32 of those procedures could have been avoided based on positive NGS results, according to Dr. Rossoff and her colleagues.

Dr. Rossoff noted that the most common sites of infection were the bloodstream and respiratory tract, but the NGS test was able to identify pathogens in the bone, skin, cerebrospinal fluid, and urinary tract. She also pointed out that NGS results were available “in a fairly timely manner,” as 86% of test results were available within 48 hours of sample receipt.

Dr. Rossoff and her colleagues did not receive any funding for this study, but they were previously involved in a study funded by Karius, the company that commercialized the NGS test.

SOURCE: Rossoff J et al. ASPHO 2019. Abstract 439.

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