The team of infectious disease and genomics experts at Duke
has developed what they call gene signatures, patterns that reflect which of a
patient’s genes are turned on or off, to indicate whether someone is fighting
infection from a virus or bacteria. Results can be derived from a small sample
of the patient’s blood.
The signatures were tested in an observational study described
in the January 20 issue of Science Translational Medicine. They were
found to be 87 percent accurate in classifying more than 300 patients with flu
viruses, rhinovirus, several strep bacteria and other common infections, as
well as showing when no infection was present.
With these findings, Duke researchers are a significant step
closer to developing a rapid blood test that could be used in clinics to
distinguish bacterial and viral infections and to guide appropriate treatment.
“A respiratory infection is one of the most common reasons
people come to the doctor,” said lead author Ephraim
L. Tsalik, M.D., Ph.D., assistant professor of medicine at Duke and
emergency medicine provider at the Durham VA Medical Center.
“We use a lot of information to make a diagnosis, but there’s
not an efficient or highly accurate way to determine whether the infection is
bacterial or viral. About three-fourths of patients end up on antibiotics to
treat a bacterial infection despite the fact that the majority have viral
infections. There are risks to excess antibiotic use, both to the patient and
to public health.”
Participants with respiratory problems were enrolled during
visits to emergency departments at five hospitals, including Duke, the Durham
VA Medical Center and UNC Hospital in Chapel Hill. The technique is more
accurate than other tests that look for the presence of specific microbes, the
authors report.
More precise ways of distinguishing infections could not only
reduce unnecessary use of antibiotics, but also lead to more precise treatments
of viruses, said senior author Geoffrey S. Ginsburg, M.D., Ph.D., director of Duke’s
Center for Applied Genomics & Precision Medicine.
“Right now, we can give patients Tamiflu to help them recover
from an influenza infection, but for most viral infections, the treatment is
fluids and rest until it resolves,” Ginsburg said.
“In the next five to 10 years, we will likely see new
antiviral medications for common bugs like respiratory syncytial virus (RSV)
and even rhinovirus, (the predominant cause of the common cold), and guiding
treatment choices will be even more important.”
Ginsburg and colleagues at Duke have been studying gene
signatures in respiratory infections for nearly a decade, but only recently has
technology allowed scientists to analyze a person’s genetic makeup, 25,000
genes at a time, he said.
The team had previously identified gene signatures associated
with viral infections, but this is the first study to distinguish
non-infectious illnesses and viral from bacterial infections at the patient’s
molecular level.
Still, with current technology, measuring a person’s gene
expression profile from blood could take as long as 10 hours. Study authors are
currently working with developers to create a one-hour test that could be used
in clinics.
“The ideal scenario, should this test ultimately be approved
for broad use, is you would go to the doctor’s office and receive your results
by the time you meet with your provider,” said senior author Christopher W. Woods, M.D., professor of medicine and
associate director of Duke’s genomics center.
“We are working to develop a test that could be run in most
clinical labs on existing equipment. We believe this could have a real impact
on the appropriate use of antibiotics and guide the use of antiviral treatments
in the future.”
In addition to Tsalik, Ginsburg and Woods, study authors
include Ricardo Henao; Marshall Nichols; Thomas Burke; Emily R. Ko; Micah T.
McClain; Lori L. Hudson; Anna Mazur; Debra H. Freeman; Tim Veldman; Raymond J.
Langley; Eugenia B. Quackenbush; Seth W. Glickman; Charles B. Cairns; Anja K.
Jaehne; Emanuel P. Rivers; Ronny M. Otero; Aimee K. Zaas; Stephen F. Kingsmore;
Joseph Lucas; Vance G. Fowler; and Lawrence Carin.
This research was supported by the U.S. Defense Advanced
Research Projects Agency (contracts N66001-07-C-2024; N66001-09-C-2082), by the
National Institutes of Health (U01AI066569; P20RR016480; HHSN266200400064C;
K24-AI093969), the Agency for Healthcare Research and Quality, the U.S.
Department of Veterans Affairs Office of Research and Development
(1IK2CX000530; 1IK2CX000611), and an in-kind contribution bioMérieux, Inc.
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