Karius Test data look promising

Redwood City, CA—Karius, a life sciences company specializing in infectious disease diagnostics with genomics and data through the innovative use of next-generation sequencing to analyze microbial cell-free DNA, recently announced the positive results of a clinical study using blood samples from patients with confirmed invasive fungal infections (IFI).

The study, entitled “Liquid biopsy for infectious diseases: sequencing of cell-free plasma to detect pathogen DNA in patients with invasive fungal disease,” showed that the Karius Test, a noninvasive blood test, was able to detect both Aspergillus and non-Aspergillus molds in patients with proven IFI, who were previously diagnosed by invasive samplings of infected tissue. The results were published in Diagnostic Microbiology and Infectious Disease, a peer-reviewed journal in clinical microbiology focused on the diagnosis and treatment of infectious disease. The study was also approved by the Stanford University Institutional Review Board.

Despite the availability of a number of new antifungal therapies, invasive fungal infections remain a major cause of morbidity and mortality, especially in immunocompromised patients. Although physicians traditionally rely on tissue biopsies for life-threatening deep-seated infections to provide a microbiologic diagnosis, an invasive procedure might not be an option in certain cases, and these procedures could lead to high morbidity and contribute to additional healthcare costs.

“There is a significant need for a non-invasive blood test that can aid in the diagnosis of deep infections, particularly when an invasive diagnostic procedure is not possible, or in immunocompromised patients where the number of potential pathogens is very large,” said David K. Hong, M.D., VP Medical Affairs and Clinical Development at Karius, and lead author of the study. Liquid biopsies have proven to be effective in oncology, and the technology is poised to have wider applications, particularly in infectious disease.

The Karius Test is a novel next-generation sequencing assay that was used to detect pathogen-derived cell-free DNA in patients with IFI. The study included nine adult patients at Stanford University Medical Center with diagnosed IFI, as confirmed by standard tissue biopsies. Patients had deep fungal infections in their lungs, heart, brain, sternum, small bowel or peri-pancreatic lymph nodes. Plasma samples were collected from these patients and the samples were sent to Karius’ laboratory in Redwood City for analysis.

According to the article, “In seven out of nine cases, plasma NGS testing detected the same fungus identified from the biopsy tissue at the genus level. In some cases, conventional microbiology identified molds only to the genus level (e.g. Rhizopus species). The fungi identified by plasma NGS included Aspergillus terreus and non-Aspergillus molds including Scedosporium, Rhizopus, and Cunninghamella. In one case, plasma NGS identified Aspergillus lentulus while conventional microbiology identified the organism as Aspergillus fumigatus species complex. A. lentulus is morphologically identical to A. fumigatus and shares 91% sequence homology, and both belong to the A. fumigatus species complex with A. lentulus showing decreased susceptibility to many azoles. This instance highlights the importance of species-level identification of invasive fungal infections.

“This technique identified molds at the species level from a variety of body locations, showing the ability of cell-free plasma to integrate information from many organs,” continues the article. “This approach, in conjunction with radiographic data and other clinical data, can help target antifungal therapy without the need for an invasive biopsy procedure and its associated morbidity. Furthermore, increased breadth of detection allows for identification of a wide range of pathogens including both Aspergillus and non-Aspergillus molds. Of note, this open-ended approach can also potentially identify organisms that can mimic IFIs such as Nocardia spp. and Toxoplasma gondii.”

“This is the first report of a plasma NGS test that can noninvasively identify the causal pathogen in proven IFI. This test may allow for earlier targeting of antifungal therapy and forestall an invasive biopsy, particularly when such a biopsy is delayed or could adversely affect the patient's condition. It may be possible in the future to identify antifungal resistance genes by plasma NGS to help further guide therapy.”