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Prevalence and clinical course in invasive infections with meningococcal endotoxin variants

Gerwin D Rodenburg1, Floris Fransen, Debby Bogaert

  • 1Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, The Netherlands. g.d.rodenburg@umcutrecht.nl

Plos One
|December 5, 2012
PubMed
Abstract

Insights

Meningococcal lipid A variation, common in adults, leads to less severe disease. These penta-acylated endotoxin variants cause reduced inflammation and milder outcomes in invasive meningococcal disease.

Area of Science:

  • Microbiology
  • Immunology
  • Infectious Diseases

Background:

  • Neisseria meningitidis normally produces hexa-acylated lipid A.
  • Inactivation of the lpxL1 gene results in penta-acylated lipid A variants.
  • Previous studies linked these variants to reduced TLR4 activation and less coagulopathy in adult meningitis.

Purpose of the Study:

  • To investigate the prevalence of lipid A variants in invasive meningococcal disease (IMD).
  • To determine the clinical characteristics and disease severity associated with these variants.

Main Methods:

  • Screening of 448 meningococcal isolates from Dutch IMD patients for IL-6 induction in Mono Mac 6 cells.
  • Sequencing the lpxL1 gene in isolates with low IL-6 induction capacity.
  • Retrieval of clinical data from patient hospital records.

Main Results:

  • 6.5% of isolates (29/448) exhibited lipid A variation.
  • Lipid A variants were not linked to specific serogroups or genotypes.
  • Infections with lipid A variants were associated with older patients and more comorbidities.
  • Patients with lipid A variants experienced less severe disease, including lower rates of meningitis, shock, and intensive care unit admission.

Conclusions:

  • Lipid A variation in meningococci is relatively common in adult IMD.
  • Infection with penta-acylated lipid A variants is associated with a milder disease course.

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