Date of Award

4-12-2009

Document Type

Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Kirsten Bechtel

Abstract

The purpose of this study is to identify the utility of serum S-100B levels as a marker for meningitis in febrile infants younger than 3 months of age. All infants younger than 3 months of age who presented to the Pediatric Emergency Department (PED) of Yale-New Haven Children's Hospital and required both a lumbar puncture and venipuncture due to either a confirmed rectal temperature ≥38.0°C or an overall presentation that concerned the responsible physician for possible meningitis and required a lumbar puncture as part of their PED evaluation, were prospectively enrolled. A total of 111 patients participated after a 1.5-year recruitment period or about 40% of the 260 subjects calculated a priori to be required over 3 years in order to achieve 80% power. After informed written consent, approximately 1 mL of blood was obtained for the analysis of the serum level of S-100B, in addition to the volume normally drawn for standard laboratory analysis. Patients with confirmed meningitis as defined by a positive viral or bacterial culture, a positive polymerase chain reaction (PCR) for enterovirus or herpes simplex virus, and/or cerebrospinal fluid (CSF) pleocytosis, were compared with those subjects without meningitis. S-100B levels for 101 subjects were available for interim analysis, of which 27 (26.7%)met the criteria for meningitis and 74 (73.3%) did not. The median S-100B level in infants with meningitis was 247.0 ng/L (95% CI: 103.5, 804), as compared to 199.1 ng/L (142.5, 384.0) in those without meningitis (p>0.05). Receiver operating characteristic analysis revealed an area under the curve of 0.4917 (0.3940, 0.5863). Ad hoc power calculations demonstrated a 57% probability of detecting a difference of 390 ng/L between the two groups when using this sample size. At this time, this interim analysis of this ongoing study suggests that a larger sample size will still be required to determine if serum S-100B is a useful marker for meningitis in febrile young infants. Because CSF fluid analysis and the associated risks of lumbar puncture remain the only means by which to identify infants with meningitis, the search for a simple serum test for to determine the likelihood of meningitis will continue to be worthwhile.

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