title: Clinical and Molecular Epidemiology of Childhood Invasive Nontypeable Haemophilus influenzae Disease in England and Wales.
abstract: BACKGROUND
  In countries with established Haemophilus influenzae type b (Hib) immunization programs, nontypeable H. influenzae (NTHi) is now responsible for nearly all invasive H. influenzae cases across all age groups.
  
  
  METHODS
  Public Health England (PHE) conducts enhanced national surveillance of invasive H. influenzae disease in England and Wales. Invasive NTHi isolates submitted to Public Health England from children of ages 1 month to 10 years during 2003-2010 were characterized by multilocus sequence typing (MLST). Detailed clinical information was obtained for all laboratory-confirmed cases of invasive NTHi disease in children during 2009-2013.
  
  
  RESULTS
  In England and Wales, there were 7797 cases of invasive H. influenzae disease diagnosed during 2000-2013 and 1585 (20%) occurred in children aged 1 month to 10 years, where NTHi was responsible for 31-51 cases (incidence, 0.53-0.92/100,000) annually. Detailed clinical follow-up of 214 confirmed NTHi cases diagnosed in this age-group during 2009-2013 revealed that 52% (n = 111) occurred in <2-year-old and 52% (n=110) had comorbidity. Bacteremic pneumonia was the most common clinical presentation (n = 99, 46%), 16% (n = 34) required intensive care and 11% (n = 23) died. Characterization by biotyping and MLST of 316 NTHi strains from children with invasive disease during 2003-2010 revealed a genetically heterogeneous population (155 MLSTs) with diverse biotypes and no association with comorbidity status, clinical disease or outcome.
  
  
  CONCLUSIONS
  The high level of genetic diversity in invasive NTHi strains highlights the difficulties in developing an effective vaccine against this pathogen.
authors.affiliation: From the *Immunisation, Hepatitis and Blood Safety Department (IHBSD), †Respiratory and Vaccine Preventable Bacterial Reference Unit (RVPBRU), §Infectious Disease Informatics, Public Health England, London, United Kingdom; ‡Paediatric Infectious Diseases Research Group, St. George's University of London, London, United Kingdom; ¶Institute for Hygiene and Microbiology, University of Wuerzburg, Wuerzburg, Germany; and ‖School of Medicine, Griffith University Gold Coast Campus, Queensland, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Collins
authors.forename: Anna
authors.initials: A
authors.lastname: Vickers
authors.forename: Shamez N
authors.initials: SN
authors.lastname: Ladhani
authors.forename: Sally
authors.initials: S
authors.lastname: Flynn
authors.forename: Steven
authors.initials: S
authors.lastname: Platt
authors.forename: Mary E
authors.initials: ME
authors.lastname: Ramsay
authors.forename: David J
authors.initials: DJ
authors.lastname: Litt
authors.forename: Mary P E
authors.initials: MP
authors.lastname: Slack
mesh_terms: D002648:Child; D002675:Child, Preschool; D004739:England / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006192:Haemophilus Infections / Q000453:epidemiology* / Q000266:history / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D049674:History, 21st Century; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D017720:Molecular Epidemiology; D058885:Multilocus Sequence Typing; D010802:Phylogeny; D011159:Population Surveillance; D065288:Serogroup; D014852:Wales / Q000453:epidemiology