title: Prevalence and clinical course in invasive infections with meningococcal endotoxin variants.
abstract: BACKGROUND
  Meningococci produce a penta-acylated instead of hexa-acylated lipid A when their lpxL1 gene is inactivated. Meningococcal strains with such lipid A endotoxin variants have been found previously in adult meningitis patients, where they caused less blood coagulopathy because of decreased TLR4 activation.
  
  
  METHODS
  A cohort of 448 isolates from patients with invasive meningococcal disease in the Netherlands were screened for the ability to induce IL-6 in monocytic cell Mono Mac 6 cells. The lpxL1 gene was sequenced of isolates, which show poor capacity to induce IL-6.. Clinical characteristics of patients were retrieved from hospital records.
  
  
  RESULTS
  Of 448 patients, 29 (6.5%) were infected with meningococci expressing a lipid A variant strain. Lipid A variation was not associated with a specific serogroup or genotype. Infections with lipid A variants were associated with older age (19.3 vs. 5.9 (median) years, p = 0.007) and higher prevalence of underlying comorbidities (39% vs. 17%; p = 0.004) compared to wild-type strains. Patients infected with lipid A variant strains had less severe infections like meningitis or shock (OR 0.23; 95%CI 0.09-0.58) and were less often admitted to intensive care (OR 0.21; 95%CI 0.07-0.60) compared to wild-type strains, independent of age, underlying comorbidities or strain characteristics.
  
  
  CONCLUSIONS
  In adults with meningococcal disease lipid A variation is rather common. Infection with penta-acylated lipid A variant meningococci is associated with a less severe disease course.
authors.affiliation: Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, The Netherlands. g.d.rodenburg@umcutrecht.nl
authors.forename: Gerwin D
authors.initials: GD
authors.lastname: Rodenburg
authors.forename: Floris
authors.initials: F
authors.lastname: Fransen
authors.forename: Debby
authors.initials: D
authors.lastname: Bogaert
authors.forename: Kim
authors.initials: K
authors.lastname: Schipper
authors.forename: Rolf H H
authors.initials: RH
authors.lastname: Groenwold
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Hamstra
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Westerhuis
authors.forename: Diederik
authors.initials: D
authors.lastname: van de Beek
authors.forename: Peter
authors.initials: P
authors.lastname: van der Ley
authors.forename: Elisabeth A M
authors.initials: EA
authors.lastname: Sanders
authors.forename: Arie
authors.initials: A
authors.lastname: van der Ende
mesh_terms: D000217:Acyltransferases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001426:Bacterial Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008050:Lipid A / Q000235:genetics* / Q000378:metabolism; D008589:Meningococcal Infections / Q000175:diagnosis / Q000453:epidemiology*; D008875:Middle Aged; D009154:Mutation; D009345:Neisseria meningitidis / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D015995:Prevalence; D012703:Serotyping; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D008050:Lipid A; D000217:Acyltransferases; C118473:LpxL protein, bacteria