title: Association of chronic meningococcemia with infection by meningococci with underacylated lipopolysaccharide.
abstract: OBJECTIVE
  Chronic meningococcemia is an uncommon manifestation of meningococcal disease. Our objective was to asses whether a bacterial factor, a mutation in the lpxL1 gene resulting in underacylated lipopolysaccharide, might be important in chronic meningococcemia.
  
  
  METHODS
  We identified 15 patients with chronic meningococcemia over a 50-year period. Chronic meningococcemia episodes were defined by a febrile episode of at least one week and presence of meningococci in blood and/or cerebrospinal fluid (CSF). Meningococcal isolates from these patients were characterised by serogrouping, multi-locus sequence typing, and in vitro interleukin 6 inducing capacity. lpxL1 gene mutations were determined by direct sequencing.
  
  
  RESULTS
  The median age was 21 years (range, 2-62) and median duration of symptoms before diagnosis was four weeks (range, 1-12). Of the 15 isolates, seven (47%) strains had a reduced interleukin 6 inducing capacity and were found to have a mutation in lpxL1 resulting in penta-acylated lipid A. This frequency is higher than previously reported among adult patients with meningococcal meningitis (7%; p < 0.0001) and invasive meningococcal disease (9%; p = 0.001).
  
  
  CONCLUSIONS
  We conclude that chronic meningococcemia patients are often infected with meningococci with a mutation in lpxL1 resulting in underacylated lipid A. The lpxL1 mutations may well explain the protracted and benign clinical course in these patients.
authors: Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, The Netherlands.
authors: Matthijs C
authors: MC
authors: Brouwer
authors: Lodewijk
authors: L
authors: Spanjaard
authors: Jan M
authors: JM
authors: Prins
authors: Peter
authors: P
authors: van der Ley
authors: Diederik
authors: D
authors: van de Beek
authors: Arie
authors: A
authors: van der Ende
mesh_terms: D000215:Acylation; D000217:Acyltransferases / Q000172:deficiency / Q000235:genetics; D000293:Adolescent; D000328:Adult; D016470:Bacteremia / Q000382:microbiology* / Q000473:pathology*; D001426:Bacterial Proteins / Q000235:genetics; D015373:Bacterial Typing Techniques; D001769:Blood / Q000382:microbiology; D002555:Cerebrospinal Fluid / Q000382:microbiology; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004731:Endotoxins / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008589:Meningococcal Infections / Q000382:microbiology* / Q000473:pathology*; D008875:Middle Aged; D058885:Multilocus Sequence Typing; D009154:Mutation; D009345:Neisseria meningitidis / Q000201:enzymology / Q000276:immunology / Q000302:isolation & purification* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D012703:Serotyping; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004731:Endotoxins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000217:Acyltransferases; C118473:LpxL protein, bacteria