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CSF Leukocyte Aggregation to Identify Bacterial Meningitis



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Am Fam Physician. 2000 May 1;61(9):2806-2809.

Bacterial meningitis is a life-threatening condition that has more serious sequelae in children than viral meningitis. Unfortunately, current laboratory tests cannot effectively distinguish bacterial from viral meningitis. Bacterial cultures of blood and cerebrospinal fluid (CSF) have been the most useful diagnostic technique, despite a delay of at least 24 hours for bacteria to grow in CSF. Several studies have shown that leukocytes tend to aggregate spontaneously in the blood in a variety of infectious conditions and in noninfectious inflammatory conditions, including osteomyelitis, postimmunization conditions and myocardial infarction. The biologic mechanism for this phenomenon is poorly understood. Aggregate formation appears to play a role in the immune response by drawing white blood cells to the site of inflammation. Use of a simple bedside test may be helpful in earlier diagnosis of meningitis, thus avoiding unnecessary antibiotic treatment and prolonged hospitalization. Michelow and associates evaluated the efficacy of a bedside test to accurately identify children with bacterial meningitis.

All children undergoing lumbar puncture for suspected meningitis were enrolled in the prospective study provided there was ample CSF available for slide preparation and culture. Classic culture criteria were used to classify the types of meningitis. Medical staff were instructed in slide preparation. Testing was easily standardized; white blood cells with nuclei less than one-cell diameter apart were considered aggregated. A leukocyte aggregation score (LAS) was determined using an air-dried, fixed smear of the CSF with the proportion of aggregated leukocytes expressed as a percentage of total leukocytes.

Of the 113 children enrolled in the study, 67 had bacterial meningitis, 23 had viral meningitis, 19 had culture-negative (undefined) meningitis, three had tuberculous meningitis and one patient had neurocysticercosis. Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type B accounted for most of the bacterial cases. Patients with bacterial meningitis had a significantly higher median LAS than patients with viral or culture-negative meningitis. There was a substantial overlap in scores between patients with bacterial and aseptic meningitis. The bottom of the stained CSF slide appeared to be the optimal location to evaluate aggregation.

The authors conclude that among the conventional tests used to identify the cause of meningitis, LAS has the most favorable odds ratio for arriving at the correct diagnosis. The technique is simple but susceptible to technical difficulties and requires extensive cell counts. Although LAS appears to have promise as a helpful adjunct in the timely diagnosis of bacterial meningitis in children, further validation of its clinical usefulness is needed.

Michelow IC, et al. Value of cerebrospinal fluid leukocyte aggregation in distinguishing the causes of meningitis in children. Pediatr Infect Dis J. January 2000;19:66–72.


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