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Opening the Door to New Diagnostic Tools
CHORI Scientists Identify Novel Marker of Bacterial Infection in Children

In an exciting new translational study just published in the American Journal of Emergency Medicine, CHORI clinical scientists Karim M. Mansour, MD, Frans A. Kuypers, PhD, Claudia R. Morris, MD, and their colleagues have shown that type IIa secretory phospholipase A2 (sPLA2) – an enzyme released by cells during inflammation – is significantly elevated in bacterial infections compared with viral infections in children. Although elevated sPLA2 levels have already been associated with infection in adults and with chronic inflammatory diseases, this is the first time they have been associated with bacterial infections in children, opening the door for sPLA2 to become a novel tool in helping diagnose children with fevers.

"Unfortunately, we have yet to discover the ideal test to determine if a child who presents to an emergency department with a fever has a self-limiting viral infection, or a more serious bacterial infection, which requires aggressive treatment," says Dr. Mansour.

“While I don't think we will end up with one test that can provide the answer, our study shows that sPLA2 has incredible utility as a marker for bacterial infection.”

Fever is one of the most common reasons that young children are taken to emergency rooms (ERs) – yet physicians still do not have a precise tool for identifying the cause of such fevers. The advent of pneumococcal vaccines and broad-spectrum antibiotics has dramatically changed the landscape of bacterial infections, significantly reducing the prevalence of bacterial infections. However, significant bacterial infections do still occur, and there is great urgency to sorting out such infections from the rest. 
“The younger the child, the more worried we are about bacterial infection. Because the young infant has a much less developed immune system, they are at risk for some pretty bad outcomes.”
"We may not see these infections in the same numbers we used to, but we do still see them, and it can have significant consequences if not diagnosed," says Dr. Mansour.

Because young children's immune systems are less developed, often the only symptom of a bacterial infection is fever. Older patients present with additional symptoms that would lead a physician to identify the type of infection more easily, but without such clues, physicians have to tease out the type of infection a child may have. While currently there is a battery of screening tests doctors can use, none of them, either alone or in concert, do the trick.

As Dr. Mansour explains, "How sensitive a test is is really critical in determining whether or not a result from that test is abnormal or not. Total white blood cell, or WBC, count, for example, is what is most universally accepted, but when you look at studies showing its true sensitivity, it is actually very low.
"In short, if the WBC value is high, we worry, and if it is low we worry, but if it is in between, we really don't know what it means. It definitely can't tell us whether this patient is infected with a bacterial pathogen or not."

What Dr. Mansour and his colleagues' latest study shows, however, is that sPLA2 levels are significantly increased in patients with bacterial infections rather than viral infections, suggesting that sPLA2 could provide a much more precise tool than currently exists for diagnosing bacterial infections in the ER.

"The results of the study really were striking," says Dr. Mansour. "While there were only two patients in a group of over sixty kids who had pneumococcal bacteremia, sPLA2 identified both. Their sPLA2 numbers were significantly higher than those patients with viral infection."

In addition to identifying the two patients with pneumococcal infection, elevated levels of sPLA2 also identified all the children who had bacterial urinary tract infections as well – the most common bacterial infection in the ER since the advent of vaccines and antibiotics. But the study also revealed another surprising result: the highest sPLA2 levels of all were found in two patients who were subsequently diagnosed with Kawasaki disease (KD), a multi-system disease in which the blood vessels of various systems in the body become inflamed.

"This may be an important finding because currently there are no good biomarkers for the disease, and KD is almost exclusively a clinical diagnosis," says Dr. Mansour.

While additional testing is required, the study suggests that in addition to helping identify bacterial infections, sPLA2 could in fact be an incredibly sensitive marker for KD diagnosis. In the mean time, however, Dr. Mansour and his colleagues have confirmed that sPLA2 is a viable marker for bacterial inflammation.

"While it is universally accepted in the emergency department that there is no consensus on how you manage a febrile child older than 28 days, this hopefully takes us one step further in coming up with a decision rule for approaching the management of the febrile child at risk for serious bacterial infection" says Dr. Mansour.


“This study clearly shows that bacterial processes may cause more inflammation than viral infections, and that measuring sPLA2 levels can differentiate between the two.”

Tuesday, May 17, 2011 8:19 AM

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