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Next-generation sequencing test identifies pathogens quickly in stem cell transplant patients

NEW ORLEANS — A novel, next-generation sequencing plasma assay identified a broad range of infections more quickly than conventional tests in stem cell transplant patients, researchers said.

The findings suggest that the Karius Digital Culture test, which uses a standard blood draw and identifies cell-free DNA fragments of bacteria, viruses, fungi and other eukaryotic pathogens, can be used to accurately diagnose difficult-to-detect infections, monitor them and provide earlier initiation of targeted therapy in these high-risk patients. According to the manufacturer, the Karius test can detect more than 1,250 pathogens.

Peter Chin-Hong
Peter Chin-Hong

“Our current methods of testing can only detect a narrow range of pathogens and may require invasive biopsies,” Peter Chin-Hong, MD, professor of medicine at the University of California, San Francisco School of Medicine, and an Infectious Disease News Editorial Board member, said in a press release.

Diagnosis remains challenging for patients undergoing stem-cell transplant (SCT) because they are at increased risk of becoming infected by numerous pathogens. Therefore, researchers enrolled 10 patients in a prospective, observational pilot study to evaluate whether the next-generation sequencing (NGS) test could be used to rapidly and accurately detect infections in SCT patients.

The researchers drew plasma samples from patients at baseline and then collected samples at regular intervals during engraftment and when patients became febrile. The samples were tested using NGS and results were compared with those of conventional tests.

The most common organism identified by NGS, cytomegalovirus (CMV), was seen in six of 10 participants. The researchers observed a significant correlation between the NGS plasma assay and CMV PCR for five of six patients with detectable viral loads (P < .01). NGS also simultaneously discovered other viruses including Epstein-Barr virus, human herpesvirus 6B, BK virus and torque teno viruses. The assay detected Staphylococcus aureus 1 day before blood culture in one patient and Chlamydia trachomatis 30 days before diagnosis using targeted testing in another. These findings suggest that NGS can detect dangerous pathogens in immunocompromised patients early when used as a monitoring tool, the researchers said.

“In our study of stem-cell transplant patients, this next-generation sequencing approach showed a high correlation in the detection of cytomegalovirus compared to standard methods, and also identified other underlying infections earlier than traditional methods,” Chin-Hong said. “This ability to identify pathogens broadly and quickly, and monitor infection in high-risk patients, holds the potential to allow doctors to develop precise and effective treatment plans for patients.”

The study was one of four presented at ASM Microbe that focused on the performance of the Karius test. – by Savannah Demko

References:

Chin-Hong P, et al. The DISCOVER Trial: Application of a Novel Plasma Next-Generation Sequencing Assay to Detect Cell-Free Microbial DNA in Stem-Cell Transplant Patients. Presented at: ASM Microbe; June 1-5, 2017; New Orleans.

Hong D, et al. Liquid Biopsy for Infectious Diseases: Application of a Next-Generation Sequencing Cell-Free Plasma Assay to Detect Invasive Fungal Infections. Presented at: ASM Microbe; June 1-5, 2017; New Orleans.

Singer MN, et al. Detection of Nocardia cyriacigeorgica from a Deep Pulmonary Infection Using a Novel Plasma-Based Next Generation Sequencing Assay. Presented at: ASM Microbe; June 1-5, 2017; New Orleans.

Thair S, et al. The SEP-SEQ Trial - A Pilot Study Characterizing the Performance of a Novel Plasma Next-Generation Sequencing Assay to Detect Cell-Free Microbial DNA in Patients with Sepsis. Presented at: ASM Microbe; June 1-5, 2017; New Orleans.

Disclosure: Chin-Hong is a research contractor for Karius.

NEW ORLEANS — A novel, next-generation sequencing plasma assay identified a broad range of infections more quickly than conventional tests in stem cell transplant patients, researchers said.

The findings suggest that the Karius Digital Culture test, which uses a standard blood draw and identifies cell-free DNA fragments of bacteria, viruses, fungi and other eukaryotic pathogens, can be used to accurately diagnose difficult-to-detect infections, monitor them and provide earlier initiation of targeted therapy in these high-risk patients. According to the manufacturer, the Karius test can detect more than 1,250 pathogens.

Peter Chin-Hong
Peter Chin-Hong

“Our current methods of testing can only detect a narrow range of pathogens and may require invasive biopsies,” Peter Chin-Hong, MD, professor of medicine at the University of California, San Francisco School of Medicine, and an Infectious Disease News Editorial Board member, said in a press release.

Diagnosis remains challenging for patients undergoing stem-cell transplant (SCT) because they are at increased risk of becoming infected by numerous pathogens. Therefore, researchers enrolled 10 patients in a prospective, observational pilot study to evaluate whether the next-generation sequencing (NGS) test could be used to rapidly and accurately detect infections in SCT patients.

The researchers drew plasma samples from patients at baseline and then collected samples at regular intervals during engraftment and when patients became febrile. The samples were tested using NGS and results were compared with those of conventional tests.

The most common organism identified by NGS, cytomegalovirus (CMV), was seen in six of 10 participants. The researchers observed a significant correlation between the NGS plasma assay and CMV PCR for five of six patients with detectable viral loads (P < .01). NGS also simultaneously discovered other viruses including Epstein-Barr virus, human herpesvirus 6B, BK virus and torque teno viruses. The assay detected Staphylococcus aureus 1 day before blood culture in one patient and Chlamydia trachomatis 30 days before diagnosis using targeted testing in another. These findings suggest that NGS can detect dangerous pathogens in immunocompromised patients early when used as a monitoring tool, the researchers said.

“In our study of stem-cell transplant patients, this next-generation sequencing approach showed a high correlation in the detection of cytomegalovirus compared to standard methods, and also identified other underlying infections earlier than traditional methods,” Chin-Hong said. “This ability to identify pathogens broadly and quickly, and monitor infection in high-risk patients, holds the potential to allow doctors to develop precise and effective treatment plans for patients.”

The study was one of four presented at ASM Microbe that focused on the performance of the Karius test. – by Savannah Demko

References:

Chin-Hong P, et al. The DISCOVER Trial: Application of a Novel Plasma Next-Generation Sequencing Assay to Detect Cell-Free Microbial DNA in Stem-Cell Transplant Patients. Presented at: ASM Microbe; June 1-5, 2017; New Orleans.

Hong D, et al. Liquid Biopsy for Infectious Diseases: Application of a Next-Generation Sequencing Cell-Free Plasma Assay to Detect Invasive Fungal Infections. Presented at: ASM Microbe; June 1-5, 2017; New Orleans.

Singer MN, et al. Detection of Nocardia cyriacigeorgica from a Deep Pulmonary Infection Using a Novel Plasma-Based Next Generation Sequencing Assay. Presented at: ASM Microbe; June 1-5, 2017; New Orleans.

Thair S, et al. The SEP-SEQ Trial - A Pilot Study Characterizing the Performance of a Novel Plasma Next-Generation Sequencing Assay to Detect Cell-Free Microbial DNA in Patients with Sepsis. Presented at: ASM Microbe; June 1-5, 2017; New Orleans.

Disclosure: Chin-Hong is a research contractor for Karius.

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