$5.7 million NIH grant to Wayne State offers new hope for more accurately diagnosing infants with serious infections
DETROIT – Prashant Mahajan, M.D., professor of Pediatrics and Emergency Medicine, chief of the Division of Emergency Medicine in the Department of Pediatrics at Wayne State University and Children’s Hospital of Michigan, has been awarded a five-year, $5.76 million grant (1R01HD085233) by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health. Dr. Mahajan and his collaborators will study how febrile infants – babies 2 months or younger who are brought to emergency rooms with invasive bacterial infections – can avoid invasive procedures such as lumbar punctures, overuse of antibiotics and unnecessary hospitalizations through a new, rapid and more accurate testing to be developed by their research team.
The researchers will investigate whole genome RNA expression profiles to define RNA biosignatures that allow precise diagnosis of isolated bacterial infections, isolated viral infections and bacterial-viral co-infections. The investigators will also validate the RNA biosignatures on a novel, PCR-based platform that has a rapid turnaround time of two to four hours, as opposed to current methods of bacterial cultures that often take up to 48 hours for results.
The evaluation of well-appearing febrile infants continues to be challenging and controversial for clinicians. Their immune system is immature and even otherwise normal infants are unable to protect themselves from invasive bacterial diseases such as meningitis, bacteremia and urinary tract infections. Fever is the most common reason for infants to be brought to emergency departments and approximately 250,000 very young febrile infants are taken to emergency rooms across the United States annually. In addition, many more are brought to pediatricians and other health care settings and thus, this continues to be one of the most vexing issues in pediatrics.
Dr. Mahajan said that less than 5 percent of febrile infants will have an invasive or serious bacterial illness. These infants are clinically indistinguishable from the majority of the febrile infants with non-bacterial illness. However, the outcomes, such as bacterial meningitis, severe sepsis and potentially death, are devastating. More importantly, the current standard use of bacterial cultures for diagnosis is suboptimal. In particular, culture results are reported after 24 to 48 hours are not helpful for clinical decision-making at the patient’s bedside.
Dr. Mahajan and his collaborators, Dr. Octavio Ramilo of Nationwide Children’s Hospital, The Ohio State University, and Dr. Nathan Kuppermann of the University of California, Davis Medical Center, have been researching the evaluation of the febrile infant for 15 years and have been continuously funded in their efforts since 2008. The investigative team initially received a $600,000 Targeted Issues Grant (H34MC08509) from Heath Resources Services Administration (HRSA) as part of the Emergency Medical Services for Children to create an infrastructure to study febrile infants in U.S. emergency departments through a federally supported network of approximately 20 pediatric emergency departments called Pediatric Emergency Care Applied Research Network. After establishing the infrastructure, Dr. Mahajan and his collaborators were awarded $3.15 million (R01HD062477) from the NICHD to further define and validate the bacterial and non-bacterial biosignatures of febrile infants. Their findings demonstrated that it is possible to identify bacterial infections from non-bacterial infections by RNA biosignatures in emergency departments with 95 percent accuracy.
“This award will aid in the development of a potentially paradigm-shifting approach of a new, more precise, efficient and rapid laboratory diagnostic strategies,” Dr. Mahajan said. “This would allow for a less-invasive, quicker and more accurate cost-effective evaluation of young febrile infants while bringing this exciting technology to patient’s bedside. If successful, it will substantially impact the care of thousands of febrile infants across the world.”
"Dr. Mahajan's research is highly timely and translational in nature in that it will allow for greater accuracy and enhance antibiotic stewardship among the most vulnerable of all children, very young infants," said Steven E. Lipshultz, M.D., chair of Pediatrics at Wayne State University’s School of Medicine and pediatrician-in-chief of Children's Hospital of Michigan.
“Dr. Mahajan’s research offers much promise to very sick infants, their parents and health care professionals,” said Gloria Heppner, Ph.D., associate vice president for Research at Wayne State University. “His work will assist in quickly and accurately diagnosing them, and ultimately will aid in determining the best treatment method, with potentially lower costs and better results.”
About Wayne State University, www.wayne.edu
Wayne State University is a premier urban research institution offering more than 400 academic programs through 13 schools and colleges to nearly 32,000 students. Its School of Medicine is the largest single-campus medical school in the nation with more than 1,200 medical students. In addition to undergraduate medical education, the school offers master’s degree, Ph.D. and M.D.-Ph.D. programs in 14 areas of basic science to about 400 students annually.
About the Children’s Hospital of Michigan, www.childrensdmc.org
For more than 125 years, the Children’s Hospital of Michigan is the first hospital in the state dedicated exclusively to the treatment of children. With more than 40 pediatric medical and surgical specialties and services, the hospital is a national leader in cancer, cardiology and heart surgery, gastroenterology and gastroenterology surgery, neurology and neurosurgery, nephrology, orthopedics, pulmonology and urology. It is ranked one of America’s best hospitals for children and sees more children than any hospital in the state. More Michigan pediatricians are trained at the Children’s Hospital of Michigan than at any other facility. Children’s Hospital of Michigan is one of eight hospitals operated by the Detroit Medical Center (DMC).