title: Invasive serotype a Haemophilus influenzae infections with a virulence genotype resembling Haemophilus influenzae type b: emerging pathogen in the vaccine era?
abstract: OBJECTIVE
  Haemophilus influenzae type b causes severe disease in nonimmune infants and young children; other serotypes are uncommon pathogens and thought to have low virulence. Some have hypothesized that with the virtual elimination of H influenzae type b, other serotypes might acquire virulence traits and emerge as important pathogens of children. We describe the clinical, epidemiologic, and molecular biologic features of 5 cases of severe disease attributable to Haemophilus influenzae type a.
  
  
  METHODS
  After observing 4 cases of invasive disease caused by H influenzae type a, we reviewed microbiology records at 3 reference laboratories that perform all serotyping in Utah and surveillance databases. Strains of H influenzae type a and control strains were examined by Southern blotting with the use of the cap probe pUO38 and by pulsed-field gel electrophoresis. The putative virulence mutation, the IS1016-bexA deletion, was detected by polymerase chain reaction amplification and sequencing.
  
  
  RESULTS
  During a 10-month period, we observed 5 children with severe invasive disease caused by H influenzae type a. No isolates of H influenzae type a had been submitted to the reference laboratories between 1992 and 1998. The median age of patients was 12 months (range: 6-48 months). Four of 5 had meningitis and bacteremia; 1 had purpura fulminans. Three isolates, representing 1 of 2 pulsed-field gel electrophoresis patterns, contained the IS1016-bexA deletion and were associated with particularly severe disease.
  
  
  CONCLUSIONS
  We describe an unusual cluster of severe disease caused by H influenzae type a that resembles the clinical and epidemiologic features of H influenzae type b disease. Our data support the hypothesis that the IS1016-bexA deletion may identify more virulent strains of H influenzae. Haemophilus influenzae, epidemiology, virulence, serotyping, pathogenicity.
authors: Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, USA.
authors: E E
authors: EE
authors: Adderson
authors: C L
authors: CL
authors: Byington
authors: L
authors: L
authors: Spencer
authors: A
authors: A
authors: Kimball
authors: M
authors: M
authors: Hindiyeh
authors: K
authors: K
authors: Carroll
authors: S
authors: S
authors: Mottice
authors: E K
authors: EK
authors: Korgenski
authors: J C
authors: JC
authors: Christenson
authors: A T
authors: AT
authors: Pavia
mesh_terms: D001483:Base Sequence; D015139:Blotting, Southern; D004269:DNA, Bacterial / Q000032:analysis; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D005838:Genotype; D006192:Haemophilus Infections / Q000382:microbiology*; D018073:Haemophilus Vaccines; D006193:Haemophilus influenzae / Q000145:classification* / Q000472:pathogenicity; D019741:Haemophilus influenzae type b / Q000472:pathogenicity*; D006801:Humans; D011695:IgA Vasculitis / Q000175:diagnosis / Q000382:microbiology* / Q000628:therapy; D007223:Infant; D008583:Meningitis, Haemophilus / Q000175:diagnosis / Q000382:microbiology* / Q000628:therapy; D008969:Molecular Sequence Data; D012307:Risk Factors; D012703:Serotyping
chemical_list: D004269:DNA, Bacterial; D018073:Haemophilus Vaccines