title: Invasive Haemophilus influenzae disease in the vaccine era in Rio de Janeiro, Brazil.
abstract: BACKGROUND
  Haemophilus influenzae (Hi) serotype b (Hib) conjugate vaccine was incorporated into the infant immunisation schedule in Brazil in 1999, where Hib was one of the major etiologic sources of community-acquired bacterial meningitis.
  
  
  OBJECTIVE
  The purpose of this study is to describe the molecular epidemiology of invasive Hi disease in Rio de Janeiro state, Brazil, before and after vaccine introduction.
  
  
  METHODS
  Surveillance data from 1986 to 2014 were analysed. Hi isolates recovered from cerebrospinal fluid (CSF) or blood from 1993 to 2014 were serotyped by slide agglutination, genotyped by multilocus sequence typing (MLST), and the capsule type evaluation, differentiation of serologically non-typeable isolates, and characterisation of the capsule (cap) locus was done by polymerase chain reaction. Antimicrobial susceptibility testing was performed using E-test.
  
  
  RESULTS
  From 1986 to 1999 and from 2000 to 2014, 2580 and 197 (42% without serotype information) confirmed cases were reported, respectively. The case fatality rate was 17% and did not correlate with the strain. Hib and b- variant isolates belonged to ST-6, whereas serotype a isolates belonged to the ST-23 clonal complex. Serotype a appeared to emerge during the 2000s. Non-encapsulated isolates were non-clonal and distinct from the encapsulated isolates. Ampicillin-resistant isolates were either of serotype b or were non-encapsulated, and all of them were β-lactamase-positive but amoxicillin-clavulanic acid susceptible.
  
  
  CONCLUSIONS
  Although Hi meningitis became a relatively rare disease in Rio de Janeiro after the introduction of the Hib conjugate vaccine, the isolates recovered from patients have become more diverse. These results indicate the need to implement an enhanced surveillance system to continue monitoring the impact of the Hib conjugate vaccine.
authors.affiliation: Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Epidemiologia e Sistemática Molecular, Rio de Janeiro, RJ, Brasil.|Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Rio de Janeiro, RJ, Brasil.
authors.forename: Mari
authors.initials: M
authors.lastname: Tuyama
authors.affiliation: Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Epidemiologia e Sistemática Molecular, Rio de Janeiro, RJ, Brasil.
authors.forename: Jessica
authors.initials: J
authors.lastname: Corrêa-Antônio
authors.affiliation: University of Pittsburgh, School of Medicine and Graduate School of Public Health, Infectious Diseases Epidemiology Research Unit, Pittsburgh, PA, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Schlackman
authors.affiliation: University of Pittsburgh, School of Medicine and Graduate School of Public Health, Infectious Diseases Epidemiology Research Unit, Pittsburgh, PA, United States of America.
authors.forename: Jane W
authors.initials: JW
authors.lastname: Marsh
authors.affiliation: Secretaria de Estado de Saúde do Rio de Janeiro, Assessoria de Meningites, Rio de Janeiro, RJ, Brasil.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Rebelo
authors.affiliation: Secretaria de Estado de Saúde do Rio de Janeiro, Assessoria de Meningites, Rio de Janeiro, RJ, Brasil.
authors.forename: Elaine O
authors.initials: EO
authors.lastname: Cerqueira
authors.affiliation: Fundação Oswaldo Cruz-Fiocruz, Instituto Fernandes Figueira, Rio de Janeiro, RJ, Brasil.
authors.forename: Márcio
authors.initials: M
authors.lastname: Nehab
authors.affiliation: Fundação Oswaldo Cruz-Fiocruz, Instituto Fernandes Figueira, Rio de Janeiro, RJ, Brasil.
authors.forename: Fabíola
authors.initials: F
authors.lastname: Kegele
authors.affiliation: CientíficaLab, Rio de Janeiro, RJ, Brasil.
authors.forename: Getúlio F
authors.initials: GF
authors.lastname: Carmo
authors.affiliation: CientíficaLab, Rio de Janeiro, RJ, Brasil.
authors.forename: Dominique Ca
authors.initials: DC
authors.lastname: Thielmann
authors.affiliation: Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Rio de Janeiro, RJ, Brasil.
authors.forename: Paulo F
authors.initials: PF
authors.lastname: Barroso
authors.affiliation: University of Pittsburgh, School of Medicine and Graduate School of Public Health, Infectious Diseases Epidemiology Research Unit, Pittsburgh, PA, United States of America.
authors.forename: Lee H
authors.initials: LH
authors.lastname: Harrison
authors.affiliation: Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Epidemiologia e Sistemática Molecular, Rio de Janeiro, RJ, Brasil.
authors.forename: David E
authors.initials: DE
authors.lastname: Barroso
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016667:Bacterial Capsules; D001938:Brazil / Q000453:epidemiology; D005838:Genotype; D006192:Haemophilus Infections / Q000453:epidemiology* / Q000382:microbiology; D018073:Haemophilus Vaccines; D006193:Haemophilus influenzae / Q000187:drug effects / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D017589:Immunization Programs; D008583:Meningitis, Haemophilus / Q000453:epidemiology / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine