10 Dec Point of Care Platform Aims To Detect Sepsis in 90 Minutes
MedicalResearch.com Interview with:
Leo McHugh, Ph.D.
Medical Research: What is the background for this study? What are the main findings?
Dr. McHugh: Sepsis is the leading cause of child mortality in the world, and in developing countries kills more adults than breast cancer, prostate cancer and HIV combined. Approximately 30% of people admitted to ICU have sepsis, and up to 50% of these patients die. It’s a major cost burden also, costing the US health system $17 billion per year. The best way to reduce costs and improve patient outcomes is to detect sepsis early and with confidence, so that appropriate treatments can be applied. Each hour delay in the detection of sepsis has been reported to correspond to an 8% increase in mortality. So the need for a rapid and accurate diagnostic is recognized. Traditional methods rely on detection of the specific pathogen causing the infection, and these methods often take more than 24 hours, and find a pathogen in only 30% of clinically confirmed cases because they’re trying to detect a minuscule amount of pathogen or pathogenic product in the blood. Our approach was to use the host’s own immune system, which is highly tuned to respond to the presence of pathogens. Around 30% of all genes are dysregulated in sepsis, so there is a huge signal base to draw from. The trick with using multi marker host response is to pick out the specific combination of gene expression patterns that cover the broad range of patients that present with sepsis and who may present either early or late in the episode, thus with different gene activation patterns.
This paper describes a simple combination of such genes that can be used to detect sepsis and performs over the full range of patients irrespective of stage of infection or severity of infection. In it’s current format, the test is manual and takes 4-6 hours, and is a great advance on the current tools, however the methods we’ve used are specifically designed to meet requirements to port this assay onto a fully automated Point of Care platform that could deliver a result in under 90 minutes.
Medical Research: What should clinicians and patients take away from your report?
Dr. McHugh: This is a new class of test that gives physicians insights into their patient’s state in a way that was never previously possible, by getting a direct snapshot of what’s happening at the genetic level in that patient. It needs to be appreciated that this test is highly complementary to all of the pathogen detection tests out there because a pathogen detection only tells you that the pathogen is present, it doesn’t say anything about the current state of your patient, whereas host response is a direct measure of the patient’s state. It’s important to note that genetic changes happen before the they manifest into clinical changes, so there’s an education opportunity here for physicians in learning about these new classes of gene expression tests for acute care. Multi-marker gene expression tests have been around and trusted in cancer for some time, but it’s now entering into acute care and bringing with it the clinical benefits already established in cancer diagnostics. From a patient advocacy standpoint, these types of tests use methods that herald the age of personalized medicine. Use of a single biomarker for diagnosis of a complex disease like sepsis is already recognized to be inadequate, and multi-marker tests such as SeptiCyte Lab provide the opportunity take a more nuanced approach to diagnosis.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. McHugh: The obvious next step is to do a large prospective, dedicated clinical trial using the kit that we’re manufacturing. This is exactly what we’re currently doing at multiple sites in the Netherlands and the US. These results are expected to support regulatory clearance in 2016. The present study was done in adult Intensive Care Units, but the SeptiCyte Lab signature may also be found to be useful in other populations, most notably in children, and we are also running trials at the moment to gather this information.
McHugh L, Seldon TA, Brandon RA, Kirk JT, Rapisarda A, Sutherland AJ, et al. A Molecular Host Response Assay to Discriminate Between Sepsis and Infection-Negative Systemic Inflammation in Critically Ill Patients: Discovery and Validation in Independent Cohorts. PLoS Med, 2015; 12 (12): e1001916 DOI: 10.1371/journal.pmed.1001916
Leo McHugh, Ph.D. (2015). Point of Care Platform Aims To Detect Sepsis in 90 Minutes