RNA Biosignatures May Be a Faster, More Accurate Way to Detect Infant Bacterial Infection

RNA expression could hold the key to diagnosing bacterial infections in infants as young as two months with greater accuracy, lower costs, less time lost, as well as reduced pain and stress for parents and patients alike. A research team comprised of physicians from Children’s Hospital of Michigan, Wayne State University, UC Davis Medical Center, and Nationwide Children’s Hospital recently established a “proof of principle” for measuring RNA expression in the bloodstream and will now move on to testing the process in a larger study population. The diagnostic test uses RNA biosignatures to determine whether a bacterial infection is the root cause of fevers in very young children. The test would enable clinicians to distinguish bacterial infections from other causes of fever without having to wait 24 to 48 hours for bacterial cultures and without having to use painful procedures associated with these cultures, such as drawing samples of cerebrospinal fluid or blood.

The team conducted the study on a cohort of 279 infants 60 days of age or younger with rectal temperatures of at least 38°C/100.4 °F. The study also used a control group of 19 healthy infants with no fever. Eighty-nine of the febrile infants were determined to have bacterial infections. In the infants with bacteremia, or bacteria in the blood, the RNA test results matched those of the bacterial cultures 94% of the time. When the infants did not have bacteremia, the results matched those of the cultures 95% of the time. Furthermore, in cases of more serious bacterial infections like bacteremia, meningitis, and urinary tract infections, the RNA biosignatures test had an 87% sensitivity for detecting infection and an 88% specificity for ruling it out. “It may be that in the cases of disagreement between RNA biosignatures and standard cultures, the RNA biosignatures are more reflective of the true type of infection,” the researchers noted. The team added that the test is also “much more accurate” than the Yale Observation Scale, which is used to identify potential bacterial infections based on infant behavior.

Current evaluative processes that require bacterial cultures have several problematic issues, including that collecting samples can be somewhat risky, costly, and painful or stressful for the patients and their parents. Additionally, growing the cultures themselves takes time, 24 to 48 hours in most cases, and there is a risk of receiving false negatives if not enough blood is taken (a common issue with extremely young children), as well as a risk for false positives if bacteria are picked up from the skin during the blood draw. “These findings are potentially paradigm-changing,” said principal investigator Prashant Mahajan, MD, a professor of pediatrics and emergency medicine at Wayne State University and chief of pediatric emergency medicine at Children’s Hospital of Michigan. Nathan Kupperman, MD, MPH, professor and chair of the department of Emergency Medicine at UC Davis School of Medicine added, “An accurate but less invasive method to determine if babies with fevers have infections is the ‘holy grail’ for emergency department physicians.”

The team will move on to validate the study’s findings on a larger patient population and evaluate whether RNA biosignatures are sufficiently stable for use in diagnostics at two different time points. The researchers will also use the new study to determine if the biosignatures can be used to detect the presence of simultaneous bacterial and viral infections.