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Altered Neutrophil Counts at Diagnosis of Invasive Meningococcal Infection in Children

Demissie, Dawit E. BA, BS*; Kaplan, Sheldon L. MD; Romero, Jose R. MD; Leake, John A. D. MD, MPH§; Barson, William J. MD; Halasa, Natasha B. MD, MPH; Byington, Carrie L. MD**; Shetty, Avinash K. MD††; Tan, Tina Q. MD‡‡; Hoffman, Jill A. MD§§; Lin, Philana L. MD, MSc¶¶; Edwards, Kathryn M. MD; Mason, Edward O. Jr. PhD‖‖; Cooperstock, Michael S. MD, MPH***

Pediatric Infectious Disease Journal: October 2013 - Volume 32 - Issue 10 - p 1070–1072
doi: 10.1097/INF.0b013e31829e31f1
Original Studies

Background: Invasive meningococcal infections can be devastating. Substantial endotoxemia releases mature and immature neutrophils. Endothelial margination of mature neutrophils may increase the immature-to-total neutrophil ratio (ITR). These changes have not been previously well-described in invasive meningococcal disease.

Methods: Using 2001 to 2011 data from the US Multicenter Meningococcal Surveillance Study, the diagnostic sensitivity and clinical correlates of white blood cell count, absolute neutrophil count (ANC), immature neutrophil count (INC) and ITR were evaluated alone and in combination at the time of diagnosis of invasive meningococcal disease.

Results: Two hundred sixteen patients were evaluated: meningococcemia (65), meningitis (145) and other foci (6). ANC ≤1000/mm3 or ≥10,000/mm3 was present in 137 (63%), INC ≥500/mm3 in 170 (79%) and ITR ≥0.20 in 139 (64%). One or more of these 3 criteria were met in 204 of the 216 (94%). Results were similar for meningococcemia and meningitis subgroups. All 13 cases with mildest disease met 1 or more of the 3 criteria. Eight children presented with ANCs <1000/mm3: 3 of them died and a fourth required partial amputation in all 4 limbs.

Conclusions: Invasive meningococcal disease is characterized by striking abnormalities in ANC, INC and/or ITR. Neutropenia was associated with a poor prognosis. Notably, without INCs, 37% of cases would have been missed. Automated methods not measuring immature white blood cells should be avoided when assessing febrile children. Serious infection should be considered when counts meet any of the 3 criteria.

From the *University of Missouri School of Medicine, Columbia, MO; Department of Pediatrics, Pediatric Infectious Disease Section, Baylor College of Medicine, Houston, TX; ‡Department of Pediatrics, University of Arkansas of Medical Sciences, Little Rock, AR; §Department of Pediatrics, Children’s Hospital San Diego, San Diego, CA; Department of Pediatrics, Ohio State University College of Medicine and Public Health, Columbus, OH; Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN; **Department of Pediatrics, University of Utah Health Sciences Center, Salt Lake City, UT; ††Department of Pediatrics, Wake Forest University School of Medicine, Winston-Salem, NC; ‡‡Department of Pediatrics, Northwestern University Medical School, Chicago, IL; §§Department of Pediatrics, University of Southern California School of Medicine, Los Angeles, CA; ¶¶Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA; ‖‖Department of Pediatrics, Pediatric Infectious Disease Section, Baylor College of Medicine, Houston, TX; and ***Department of Child Health, Division of Infectious Disease and Rheumatology, University of Missouri School of Medicine, Columbia, MO.

Accepted for publication May 30, 2013.

Sanofi-pasteur supported the surveillance study from which the data for this study originated. The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: Michael S. Cooperstock, MD, MPH, Department of Child Health, Women’s and Children’s Hospital, University of Missouri Health Care, 404 Keene Street, Columbia, MO 65201. E-mail:

© 2013 by Lippincott Williams & Wilkins, Inc.