Children who have suffered an infection for meningococcus should receive a workup for animmunodeficiency (specifically a terminal complement disorder)

Children who have suffered an infection for meningococcus should receive a workup for animmunodeficiency (specifically a terminal complement disorder): Excerpt from Avoiding Common Pediatric Errors

Author: Lindsey Albrecht, MD

What to Do - Gather Appropriate Data

The complement pathways make up an important part of the body's innate immunesystem.Complementproteinsplayakeyroleindefenseagainstpyogenic organisms, and most congenital and acquired complement deficiencies are associated with an increased risk of infection. The complement system has three pathways: classical, alternative, and lectin. These are triggered separately but converge at complement protein C3. Activated C3 can itself activate more C3, generating amplification of this process. Clusters of C3b are ultimately deposited on the particular target, which allows the formation ofamembraneattackcomplexcomprisedofcomponentsC5bthrough9.The membrane attack complex then creates perforations in cellular membranes, thus exerting killing power over certain invading organisms.

Deficiencies in the terminal complement proteins (C5–C9) are associated with an increased risk of Neisseria meningitides infection. One pediatric study performed in New York showed that 18% of pediatric patients with a first episode of systemic meningococcal infection had an underlying complement deficiency; other estimates range between 1% and 15%. Patients with recurrent disease, a family history of disease, or disease caused by an uncommon meningococcal serotype are considered more likely to have a complement deficiency. Of patients who are known to be homozygous for terminal complement mutations (with resultant deficiencies in C5, C6, C7, C8 or C9), 50% to 60% will develop systemic meningococcal infection. This indicates that the membrane attack complex is critical for host defense against meningococcal infection. Interestingly, bacterial meningitis or septicemia caused by N. meningitides may be the first and only manifestation of an underlying congenital terminal complement deficiency. Late complement deficiencies are generally transmitted in an autosomal recessive manner.

In addition to terminal complement protein deficiencies, systemic Neisseria infection may more rarely be associated with properidin deficiency.

Properidin is a serum protein that promotes activation of the alternate complementpathway.Unlikethecomplementdeficiencies,properidindeficiency is frequently transmitted in an X-linked fashion. Given this, patients often have a family history of male members with a history of meningococcal infection.

Becauseofthesignificantassociationofterminalcomplementdeficiency withsystemicN.meningitidesinfection,screeningisindicatedinpatientswith systemic meningococcal infection. Screening for late complement deficiencies can be performed with a CH50 assay, a test that primarily evaluates the classical pathway of the complement cascade. Reduction of the CH50 occurs when individual complement components are deficient; a reduced CH50 is an indication for testing of individual complement components. Because properidin activates the alternative pathway, properidin deficiency will result in a normal CH50. The AP50 screening test of the alternative pathway may be abnormal, but often is in the low normal range. If this diagnosis is suspected, specialized testing of properidin is indicated.

Diagnosis of terminal complement deficiencies and properidin deficiency is important because it allows for counseling of the patient and the patient's physician with respect to management of future febrile illnesses. It also allows for the identification of other family members who might be affected and at risk for systemic meningococcal infection. Even if unaffected, family members may be carriers of a disease causing mutation and may pass this mutation on to their offspring. Genetic counseling is certainly appropriate in these families. The administration of the currently available quadrivalent meningococcal vaccine will likely reduce the morbidity and mortality associated with systemic meningococcal disease in these patients. In conclusion, systemic meningococcal infection in children calls for an evaluation of the complement cascade. Diagnosis of complement or properidindeficiency allows forimproved care of theaffectedpatient andthe potential identification of family members at risk for meningococcal disease.

Suggested Readings

Leggiadro RJ, Winkelstein JA. Prevalence of complement deficiencies in children with systemic meningococcal infections. Pediatr Infect Dis J. 1987;6(1):75–76.
Linton SM, Morgan BP. Properdin deficiency and meningococcal disease–identifying those most at risk. Clin Exp Immunol. 1999;118(2):189–191.
Mathew S, Overturf GD. Complement and properidin deficiencies in meningococcal disease. Pediatr Infect Dis J. 2006;25(3):255–256.
Overturf GD. Indications for the immunological evaluation of patients with meningitis. Clin Infect Dis. 2003;36(2):189–194.

Book Source Details

• Book Title: Avoiding Common Pediatric Errors
• Author(s): Anthony D Slonim MD, DrPH; Lisa Marcucci MD
• Year of Publication: 2008
• Copyright Details: Avoiding Common Pediatric Errors, Copyright © 2008 Lippincott Williams & Wilkins.

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• Back to disease: Meningococcal disease: Introduction
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

More About This Book: Title: Avoiding Common Pediatric Errors Authors: Anthony D Slonim MD, DrPH; Lisa Marcucci MD Publisher: Lippincott Williams & Wilkins Copyright: 2008 ISBN: 0-7817-7489-6

 » Next page: Remember that A comes before B and C. If you haven't protected the airway, you haven't effectively cared for the patient (Avoiding Common Pediatric Errors)

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