UC Davis researchers use data and computer statistics to create more individualized bacterial infection screening protocol
Doctors must often subject infant children to invasive medical tests when they are brought into the emergency room with a fever. One such test is called a lumbar puncture or a spinal tap. It involves sticking a needle in a baby’s spine and collecting bone marrow to test for dangerous bacteria. A new study, that combines advanced medical tests and computer statistics, might drastically decrease the number of babies who have to undergo the procedure. Researchers from UC Davis and doctors from across the United States used an algorithm to establish a better non-invasive screening protocol for babies with fevers.
Febrile babies are taken seriously because around ten percent of all infants younger than 60 days who arrive at the emergency room with a fever have a bacterial infection which could cause meningitis, a deadly condition that causes the brain to swell. A spinal tap allows doctors to try to grow bacterial cultures from a baby’s bone marrow and definitively diagnosis a baby with a bacterial infection. However, there are other non-invasive blood and urine tests that allow doctors to get some idea about whether a baby has a bacterial infection or not. These tests are used to identify infants that are at risk and need a spinal tap, and send home babies who clearly have less dangerous viral infections. The new protocol, published in JAMA Pediatrics, suggests which screening tests doctors should use, and the cutoff numbers for each test to maximize the number of babies who can safely be sent home without a spinal tap.
The new protocol is not the first clinical suggestion for how doctors should treat babies with fever. Prior research has suggested bacterial infection screening measures. However, according to Nathan Kuppermann the principal investigator on the study and a professor of Emergency Medicine and Pediatrics at UC Davis, those models were based on older and less precise medical tests like general white blood cell counts. As a result, many babies that did not need spinal taps or antibiotics were given them as a precautionary measure.
“Traditional blood counts are pretty sensitive at picking up kids with infections, but they are not specific, which means that babies who don’t have bacterial infections could still have positive screening tests,” Kuppermann said. “In the new era not only [are the tests] very sensitive, but [they are] also specific which means that kids who don’t have bacterial infections typically have normal screening tests.”
To create the protocol, the researchers who call themselves the Pediatric Emergency Care Applied Research Network, used an algorithm to determine which of these new screening tests were most effective and the cutoff numbers that could safely maximize the number of babies sent home without a spinal tap.
The group enrolled febrile infants at 26 distinct emergency rooms across the United States. The babies were treated normally, but doctors sent in the data from the tests they conducted to diagnose the babies. Then the researchers determined whether each baby was screened correctly. They recorded the results of spinal taps for babies that underwent the procedure, and followed up with parents of infants who were sent home. After the data collection, the team had a full set of numbers for many different potential screening tests, and a result; whether the baby had a bacterial infection or not.
Half of the data was computer analyzed using a statistical method called recursive partitioning. The computer determined which non-invasive tests could best predict whether a baby had a bacterial infection or not, and generated numerical thresholds for each test. In the end, the algorithm determined that only three tests were needed; a urine analysis, a neutrophil white blood cell count, and a procalcitonin test. Both the neutrophil white blood cell count and the procalcitonin test are newer screening tests that identify the prevalence of specific biomarkers commonly found in the body when fighting a bacterial infection. The researchers then tested the model against the other half of the data. They found their model would have been able to properly screen all but one of the 1266 babies in the data pool, and prevent 523 spinal taps.
Today, the way emergency rooms treat febrile infants is disparate. According to Deborah Levine a professor of Emergency Medicine and Pediatrics at Bellevue Hospital in New York, each emergency room and doctor develops its own way of practicing based on medical judgement and literature. This new study might impact how emergency rooms do things.
“The standard of care evolves with studies like this,” Levine said. “This may change the standard of care for many people.”
The new protocol was a byproduct of a much larger study that the Pediatric Emergency Care Applied Research Network is conducting on RNA biosignatures. It turns out that a viral or bacterial infection uniquely affects RNA gene expression. According to Nathan Kuppermann, RNA biosignatures might be more accurate at definitively diagnosing a baby than a spinal tap. If the researchers can speed up the test, the RNA biosignature test could act as screening test and the definitive test, essentially making the newly developed protocol obsolete.
“RNA biosignatures, that is really the holy grail,” Kuppermann said.
However, reliable quick RNA biosignature tests are years away. The new screening protocol is here today, and has the potential to spare infants from unnecessary invasive tests and improve medical care. It has already been implemented at the UC Davis Medical Center in Sacramento.
Written by: Peter Smith – science@theaggie.org
