title: The Epidemiology of Invasive Haemophilus influenzae Non-Serotype B Disease in Ontario, Canada from 2004 to 2013.
abstract: BACKGROUND
  Since the widespread use of Haemophilus influenzae (Hi) type b (Hib) vaccines among children aged <5 years, an increase in invasive non-Hib disease incidence has been reported internationally. We sought to describe the epidemiology of invasive non-Hib disease in Ontario, Canada (population ~13.5 million).
  
  
  METHODS
  Confirmed invasive non-Hib cases (non-typeable [NTHi] and serotypes a, c, d, e, and f) were obtained from the provincial laboratory data system from 2004-2013. Data were deterministically linked to the provincial reportable disease system to provide further case information. Antibiotic resistance data were analysed separately from 2010-2014. Descriptive analyses included incidence rates, age group, serotype, site of specimen collection and resistance patterns; ethnicity data were not available. Temporal trends were evaluated by Poisson regression and p-values <0.05 were considered significant.
  
  
  RESULTS
  A total of 1307 cases of invasive non-Hib disease were included, increasing from 0.67 cases to 1.60 cases /100,000 from 2004 to 2013. Significant increases in the incidence of NTHi (0.50 to 1.28 cases/100 000 population), Hia (0.02 to 0.08 cases/100, 000) and Hif (0.13 to 0.18 cases/100, 000 population) were seen. Among persons aged 40-64 years, 3 Hi strains significantly increased over time; NTHi (0.22 to 0.99 cases/100, 000), Hia (0.00 to 0.06 cases/100, 000) and Hif (0.05 to 0.21 cases/100, 000). Among persons aged 65-84 years, there was a significant increase of NTHi (1.62 to 3.14 cases/100, 000) and Hia (0.00 to 0.34 cases/100, 000). Among persons aged 85+ years, only NTHi significantly increased from 4.89 to 10.28 cases/100, 000). Antimicrobial resistance (AMR) to ampicillin and clarithromycin was seen in greater than 25% of isolates but AMR did not increase over the duration of this study.
  
  
  CONCLUSIONS
  The incidence of invasive non-Hib disease has increased over time; NTHi, Hif and Hia are emerging pathogens, and should be monitored.
authors.affiliation: Immunization and Vaccine Preventable Diseases Division, Public Health Ontario, Toronto, ON, Canada.
authors.forename: Shalini
authors.initials: S
authors.lastname: Desai
authors.affiliation: Public Health Ontario Laboratories, Public Health Ontario, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Frances B
authors.initials: FB
authors.lastname: Jamieson
authors.affiliation: Public Health Ontario Laboratories, Public Health Ontario, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Samir N
authors.initials: SN
authors.lastname: Patel
authors.affiliation: Immunization and Vaccine Preventable Diseases Division, Public Health Ontario, Toronto, ON, Canada.
authors.forename: Chi Yon
authors.initials: CY
authors.lastname: Seo
authors.affiliation: Public Health Ontario Laboratories, Public Health Ontario, Toronto, ON, Canada.
authors.forename: Vica
authors.initials: V
authors.lastname: Dang
authors.affiliation: Immunization and Vaccine Preventable Diseases Division, Public Health Ontario, Toronto, ON, Canada.
authors.forename: Jill
authors.initials: J
authors.lastname: Fediurek
authors.affiliation: Immunization and Vaccine Preventable Diseases Division, Public Health Ontario, Toronto, ON, Canada.
authors.forename: Debeka
authors.initials: D
authors.lastname: Navaranjan
authors.affiliation: Immunization and Vaccine Preventable Diseases Division, Public Health Ontario, Toronto, ON, Canada.|Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
authors.forename: Shelley L
authors.initials: SL
authors.lastname: Deeks
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000667:Ampicillin / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D017291:Clarithromycin / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial; D005260:Female; D006192:Haemophilus Infections / Q000453:epidemiology* / Q000382:microbiology*; D018073:Haemophilus Vaccines / Q000276:immunology; D019741:Haemophilus influenzae type b; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D020128:Inhibitory Concentration 50; D008297:Male; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D016012:Poisson Distribution; D065288:Serogroup; D012703:Serotyping; D055815:Young Adult
chemical_list: D018073:Haemophilus Vaccines; D000667:Ampicillin; D017291:Clarithromycin