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.
More About Non-Specific Urethritis
More Medical Textbooks Online about Non-Specific Urethritis
Review other book chapters online related to Non-Specific Urethritis:
Medical Books Excerpts
- Urethral Discharge
- "The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter" (2000)
- [ read ]
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: Gonococcal Infections (The 5-Minute Pediatric Consult)
Rate This Website
What do you think about the features of this website?
Take our user survey and have your say:
Website User Survey
Medical Tools & Articles:
Next articles:
Tools & Services:
Medical Articles:
Forums & Message Boards
- Ask or answer a question at the Boards:
