Earlier Meningitis Detection

MU research team suggests neutrophil ratios should be analyzed in addition to counting white blood cells

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Though doctors take a watchful waiting approach with fever more often than not, Michael Cooperstock, MD, University of Missouri School of Medicine, has seen children with meningitis go "from well to dead in 8-12 hours."

It's only about one out of every 1,000 children with a fever who are diagnosed with meningitis. While meningococcal infection is relatively rare, affecting approximately 2,500 people per year in the U.S., it is a devastating disease. Meningitis kills 7 to 15% of those who acquire the infection, and often causes permanent complications for survivors, such as brain damage and hearing loss. Many patients also require amputation of limbs because the disease can cause severe tissue damage to extremities.

With all this in mind, Cooperstock said, "It's so darn serious, you don't want to miss a clue."

Dissecting Neurophils
Cooperstock's recent study provides just one more key to the meningitis mystery. In their study of 216 cases from the U.S. Multicenter Meningococcal Surveillance Study, MU researchers found that 33% of the patients with active infections had total white blood cell counts that appeared normal. After examining the patients' blood tests more closely, the researchers found that a better indicator of infection was not the total white blood cell count but rather abnormalities in two particular types of white blood cells called neutrophils.

White blood cell differentials have been studied for a century, but this is the first time researchers have included neutrophils in the equation.

"When we looked at the neutrophil counts of each patient, we examined not only the total number of neutrophils, but also the number of immature neutrophils and the ratio of immature to total neutrophil cells," Cooperstock said. "We found that 94% of the patients showed an abnormality of one or more of these three tests, indicating a serious infection might be present. Reliance on the total white blood cell count alone, however, would have given false reassurance that infection was not present in more than 30% of those cases."

Neutrophils are the most abundant type of white blood cells, acting as first responders to help fight infection, particularly bacterial infections. Mature neutrophil cells are called segmented neutrophils, and immature cells are known as band neutrophils.

"Our study suggests that physicians should look not at the total white cell count but at the total number of neutrophils, the total number of band neutrophils and the ratio of band to total neutrophils as an indicator that could lead to a suspicion of meningococcal infection," Cooperstock said. "If any of the three neutrophil indicators are outside a certain range, there is a possibility that the patient has a serious bacterial infection, including the possibility of meningococcal disease, and would need careful attention."

In the study, which was recently published in the Pediatric Infectious Disease Journal, Cooperstock concluded that without an immature-to-total neutrophil ratio, 37% of cases would've been missed. Neutrophil was associated with a poor prognosis.

"Our purpose with the publication of this study is to point out the best way to evaluate neutrophil counts when ordering blood analysis," Cooperstock said. "That's especially important for children with fever, who often may not present with typical meningococcal symptoms."

Manual Testing
One critical aspect of this new study is the use of manual testing methods to count band neurtrophils.

Most emergency departments use automated white blood cell counts, which provide a quicker diagnosis but leave more room for error.

"Up until recently, these machines don't count band neutrophils."Cooperstock explained. "It's crucial because the white blood count can still look totally normal and you may miss a meningitis diagnosis."

The manual procedure is rarely used anymore, but offers accurate results and can be performed in a clinic setting. The procedure involves diluting blood in a diluents that lyes the red cells to remove them from view. A hemocytomer is charged with the diluted blood and nuclei are counted in the appropriate areas of the grid with a light microscope.

Cooperstock and his team are in the process of assembling a control group of pediatric patients with fever and high white blood cell counts who don't have meningitis.

"Our thesis suggests if you look at these criteria prospectively, you might find other serious infections that meet these criteria," he said. "It's possible that we might uncover bacterial infections or kidney infections in children who might be thought to have a urinary tract infection."

Though the chances of a meningitis diagnosis are extremely low, Cooperstock advocates for more blood testing when children present with fever.

"Every hour matters," he said. "It's like we tell our residents: a fever you see in the first few hours is different than one you see after a few days. You need to worry more if the fever's evolving quickly."

Robin Hocevar is on staff at ADVANCE. Contact rhocevar@advanceweb.com


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