University of Arizona Department of Emergency Medicine researchers have joined a nationwide, multicenter collaborative study to develop a quicker, more accurate diagnostic test to better treat “febrile” infants – babies 2 months or younger – with serious infections.
The goal of the study, which is through the federally funded national research consortium, Pediatric Emergency Care Applied Research Network (PECARN), is to validate a test that will rapidly determine if an infection is bacterial or non-bacterial, thereby sparing many newborns from unnecessary antibiotics, invasive procedures (such as lumbar punctures) and hospitalizations, said Aaron Leetch, MD, assistant professor of emergency medicine and pediatrics and the study’s principal investigator at the UA Health Sciences.
“The technology we are working to develop will help us shorten the hospital stay, avoid painful procedures and give a better answer for what is causing the fever. This will be the most important research on how to treat febrile infants with fever in the last 30 years,” said Dr. Leetch.
Annually, about 500,000 babies ages 2 months or younger with high fever are taken to emergency departments across the country. Only 6 to 10 percent of these febrile infants will have an invasive or serious bacterial illness, such as urinary tract infections, bacterial meningitis or sepsis. The majority of these infants will have non-bacterial infections.
Newborns are at risk of developing life-threatening infections because of their underdeveloped immune system, explained pediatric hospitalist Chan Lowe, MD, associate professor in the UA Department of Pediatrics, and one of the study’s researchers. Currently, the standard diagnostic method for a bacterial infection is microbial cultures, which take at least 48 hours to process and can be difficult to interpret, with six times the likelihood of getting a false positive than a true positive.
Because of the lengthy turnaround time and unreliability of the culture method – and the potential dangerous outcomes from untreated bacterial infections – febrile infants who are brought to the emergency department with high fever are subjected to additional invasive procedures. Current medical management guidelines include performing a lumbar puncture to test for meningitis, administering aggressive antibiotics and admission to the hospital for a minimum of 48 hours until culture results are available.
From previous studies, researchers have discovered it is possible to identify bacterial infections from non-bacterial infections from a genetic biosignature – a combination of thousands of signals from the baby’s immune response and the infecting organism itself. Researchers found that febrile infants with bacterial infections have distinct gene expression patterns characterized by over-expression of inflammatory genes, while those without bacterial infections consistently have over-expressed interferon genes.
By identifying these genetic biosignatures, researchers hope to develop a precise diagnostic test that, with a rapid turnaround of two to four hours, would allow for less invasive, more accurate and timely evaluation and diagnosis of young febrile infants in the emergency department.
The UA is one of 18 emergency medicine departments participating in the nationwide study, “Application of Transcriptional Signatures for Diagnosis of Febrile Infants within the PECARN Network (BioSigs).” Wayne State University in Detroit is principal site for the study, which is funded by a National Institutes of Health grant (1R01HD085233).
The University of Arizona Emergency Medicine Research Center (AEMRC) – Tucson at the UA Emergency Medicine Department recently was named one of six U.S. Research Node Centers (RNC) for PECARN, the nation’s first federally funded pediatric research network dedicated to the prevention and management of acute illnesses and injuries in children.
“We are thrilled to be included in this national pediatric network trial, which is one of several great research opportunities that are coming soon to our community as a result of being the Southwest Research Node Center for PECARN,” said SW-RNC principal investigator Kurt Denninghoff, MD, distinguished professor of emergency medicine and associate director of the AEMRC – Tucson.
About the University of Arizona Health Sciences
The University of Arizona Health Sciences is the statewide leader in biomedical research and health professions training. The UA Health Sciences includes the UA Colleges of Medicine (Phoenix and Tucson), Nursing, Pharmacy and Mel and Enid Zuckerman College of Public Health, with main campus locations in Tucson and the growing Phoenix Biomedical Campus in downtown Phoenix. From these vantage points, the UA Health Sciences reaches across the state of Arizona and the greater Southwest to provide cutting-edge health education, research, patient care and community outreach services. A major economic engine, the UA Health Sciences employs almost 5,000 people, has nearly 1,000 faculty members and garners more than $126 million in research grants and contracts annually. For more information: http://uahs.arizona.edu