Nathan Kuppermann, professor of emergency medicine and pediatrics at UC Davis School of Medicine, is one of three principal investigators who will share in a five-year, $3.4 million grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. He and two colleagues are investigating the use of novel technologies for distinguishing between bacterial and viral infections in infants with fevers, a process that could lead to more rapid and accurate diagnoses and treatment for serious bacterial infections such as bacteremia and meningitis.
The multi-site study will explore whether arming clinicians with the latest in molecular diagnostic tools is effective. Researchers will make use of RNA biosignatures — biological indicators that can be indentified from a blood test — to distinguish febrile infants (infants with fever) who have bacterial infections from those infected with non-bacterial, or viral, pathogens.
The evaluation and management of febrile infants, especially those younger than 60 days of age, remains a challenge, particularly in hospital emergency departments. Six to 10 percent of such infants arrive with serious, bacterial infections. Current tests to distinguish infants with these infections from those with benign viral illnesses can be invasive, inaccurate and time consuming, sometimes yielding false positive or false negative results. In addition, urine, blood and spinal fluid cultures typically take several days for final results.
“By bringing together an experienced and multidisciplinary team of investigators, we plan to determine the host response to infection using RNA biosignatures to address some very challenging problems when evaluating these young, vulnerable infants,” said Kuppermann. “This investigation could significantly improve the care we can provide the youngest of patients when they arrive in the emergency department with a fever by providing physicians and families with precise information more quickly and thus avoiding unnecessary tests and hospitalizations.”
Kuppermann is leading the study along with Prashant Mahajan of Children’s Hospital of Michigan and Wayne State University, and Octavio Ramilo of Nationwide Children’s Hospital and Ohio State University. They are collaborating with colleagues at medical centers around the country as part the Pediatric Emergency Care Applied Research Network (PECARN).
“Bacterial infections likely carry very distinct biological signatures because they induce different host responses than nonbacterial pathogens,” said Kuppermann, who plans to use a type of molecular bar-coding technology to enable physicians to identify the specific markers in bacterial infections. He and the research team also plan to determine whether such tests are feasible and practical within an emergency-room setting.
“There is a clear need for developing less invasive, highly accurate and timelier diagnostic strategies for febrile infants,” said Kuppermann. “Making use of new molecular tools, especially in emergency care, ultimately can improve the care we provide to this vulnerable population.”
The new study will be conducted through PECARN, which is funded by the Emergency Medical Services for Children Program, part of the Maternal and Child Health Bureau of the U.S. Health Resources and Services Administration. In addition to UC Davis, the following sites also are participating in the study:
- Children’s Hospital of Michigan and Wayne State University
- Nationwide Children’s Hospital and Ohio State University
- Helen DeVos Children's Hospital
- Jacobi Medical Center
- Johns Hopkins University
- Columbia University Medical Center
- University of Colorado at Denver
- University of Maryland at Baltimore
- University of Michigan
- University of Utah
- Washington University
- Women's and Children's Hospital of Buffalo
- Cincinnati Children's Hospital
- Baylor Research Institute
- Bellevue Hospital Center, NYU
- Children's Hospital of Boston
- Children's Hospital of Philadelphia
- Medical College of Wisconsin
- Children's Memorial Hospital, Chicago
- Children’s Research Institute, Washington, D.C.