Medicine Research Conference on March 30 featured two researchers from the Division of Infectious Diseases: Ephraim L. Tsalik, MD, PhD, and John Perfect, MD, presented information about their work in identifying and preventing everything from hospital acquired infections (HAIs) to cryptococcosis.
New Paradigms in Infectious Disease Diagnostics
Dr. Tsalik, assistant professor of medicine, said his current work is to “shine light into the black box of infectious disease diagnostics” – especially in the hospital setting. Novel diagnostic methods are important in emergency departments, Tsalik explained, because EDs are often the first points of contact for patients with serious and critical illness.
Despite using all currently available tools to diagnose sepsis, “15 to 25 percent of patients with suspected sepsis actually have non-infectious diseases,” he said. “So how do we improve diagnostic paradigms?”
Tsalik outlined two general approaches to infectious disease diagnostics: pathogen-based diagnostics, like cultures and mass spectroscopyto allow for rapid pathogen identification; and one that features host-based diagnostics, such as serological tests and new approaches such as host gene expression profiling in the face of infection.
Many of the pathogen-based diagnostics have been tested at Duke’s Acute Infectious Disease Clinical Research Unit; the unit has already enlisted 7,000 patients worldwide in observational studies. Using these cohorts, Tsalik and his collaborators have defined patterns of gene expression changes associated with various infectious pathogen classes including viral, gram positive, and gram negative. Most intriguingly, these host-response signatures can be identified early in the disease process, before the patient may even have a runny nose, said Tsalik. If doctors can use gene expression to identify factors, and make a diagnostic test for biomarkers for specific infection, the lag time between infection and diagnosis could be rapidly reduced.
The story of sweetness
John Perfect, MD, professor of medicine and interim chief of the Division of Infectious Diseases, attempted to fit 34 years of cryptococcosis research into a 30-minute presentation, and in the process explained to MRC attendees how a research platform around a specific infection developed.
Cryptococcosis, infection of the cryptococcus fungus, which Perfect joked needs a new PR person, is the third-leading cause of death in Sub-Saharan Africa, and recent American infections in the Pacific Northwest have raised concern that the disease could have a broader outbreak in the States. Unfortunately, the infection doesn’t get as much ink as SARs or West Nile, meaning patients and clinicians aren’t as savvy when it comes to diagnosis and treatment.
Dr. Perfect said Duke University Hospital sees two or three cases of cryptococcosis cases per month, with a mortality rate of 20 to 25 percent.
“That’s not good enough,” said Perfect.
Perfect – his delivery had been likened to a Baptist preacher’s, he said – outlined what’s next for the disease, which involved understanding cryptococcus’s trehalose pathway, and using the fungi’s protective sugar shell to destroy the pathogen.
“Cryptococcus with knocked-out trehalose pathways doesn’t survive,” said Perfect. “The trehalose pathway controls many of the fungi’s pathways.”
To do this, Perfect is attempting to identify the protein, or crystal structure, of cryptococcus, which has never been done before. He’s also working with zebra fish animal models to gain a real-time glimpse at the fungi’s infection in a transparent host. The latter work is being supported by the Department of Medicine’s Integrated Research RFA initiative.
“Our goal is to get cryptococcosis down to a five-percent mortality rate,” said Perfect.