title: Invasive infections with Haemophilus influenzae serotype a containing an IS1016-bexA partial deletion: possible association with virulence.
abstract: BACKGROUND
  Recent reports of invasive Haemophilus influenzae non-b capsular serotypes in the era since development of conjugate vaccines have prompted concern about serotype replacement. Unusual clusters of invasive infection due to H. influenzae serotype a with clinical features that resemble those of infection due to H. influenzae serotype b have been described. A unique feature often associated with more-virulent H. influenzae serotype a isolates is the IS1016-bexA partial deletion, which was previously identified in the capsule locus of H. influenzae serotype b strains. We report the clinical, epidemiologic, and molecular genetic features of 2 cases of severe disease caused by H. influenzae serotype a.
  
  
  METHODS
  Invasive H. influenzae isolates were serotyped with standard serological methods, and molecular typing was done with PCR. The capsular genotype of each isolate was characterized with PCR, partial sequencing, and Southern blot hybridization. Further strain typing was performed with pulsed-field gel electrophoresis.
  
  
  RESULTS
  We identified 2 children with severe invasive disease due to H. influenzae serotype a. Both H. influenzae serotype a isolates contained the identical pulsed-field gel electrophoresis pattern and capsular genotype. An IS1016-bexA partial deletion in the capsule gene locus similar to that found in H. influenzae serotype b was identified in both isolates by means of PCR and sequencing of the IS1016-bexA junction.
  
  
  CONCLUSIONS
  We describe 2 cases of severe invasive disease due to H. influenzae serotype a with the putative virulence-enhancing IS1016-bexA partial deletion and duplication of the capsule locus. Our data support the hypothesis that this mutation may be associated with virulence in non-b capsular serotypes of H. influenzae.
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Bill G
authors.initials: BG
authors.lastname: Kapogiannis
authors.forename: Sarah
authors.initials: S
authors.lastname: Satola
authors.forename: Harry L
authors.initials: HL
authors.lastname: Keyserling
authors.forename: Monica M
authors.initials: MM
authors.lastname: Farley
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics*; D005838:Genotype; D006192:Haemophilus Infections / Q000188:drug therapy / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D007223:Infant; D008297:Male; D017384:Sequence Deletion / Q000235:genetics*; D014774:Virulence / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C068101:bexA protein, Haemophilus influenzae