title: Increase in genetic diversity of Haemophilus influenzae serotype b (Hib) strains after introduction of Hib vaccination in The Netherlands.
abstract: Recently, there has been an increase in The Netherlands in the number of cases of invasive disease caused by Haemophilus influenzae serotype b (Hib). To study a possible change in the Hib population that could explain the rise in incidence, a multiple-locus variable number tandem repeats analysis (MLVA) was developed to genotype H. influenzae isolates. The MLVA enabled the differentiation of H. influenzae serotype b strains with higher discriminatory power than multilocus sequence typing (MLST). MLVA profiles of noncapsulated H. influenzae and H. influenzae serotype f strains were more heterogeneous than serotype b strains and were distinct from Hib, although some overlap occurred. The MLVA was used to genotype a collection of 520 H. influenzae serotype b strains isolated from patients in The Netherlands with invasive disease. The strains were collected from 1983 from 2002, covering a time period of 10 years before and 9 years after the introduction of the Hib vaccine in the Dutch national vaccination program. MLVA revealed a sharp increase in genetic diversity of Hib strains isolated from neonates to 4-year-old patients after 1993, when the Hib vaccine was introduced. Hib strains isolated from patients older than 4 years in age were genetically diverse, and no significant change in diversity was seen after the introduction of the vaccine. These observations suggest that after the introduction of the Hib vaccine young children no longer constitute the reservoir for Hib and that they are infected by adults carrying genetically diverse Hib strains.
authors.affiliation: Laboratory for Vaccine-Preventable Diseases, National Institute of Public Health and the Environment, P.O. Box 1, 3720 BA Bilthoven, The Netherlands. LM.Schouls@rivm.nl
authors.forename: Leo M
authors.initials: LM
authors.lastname: Schouls
authors.forename: Arie
authors.initials: A
authors.lastname: van der Ende
authors.forename: Ingrid
authors.initials: I
authors.lastname: van de Pol
authors.forename: Corrie
authors.initials: C
authors.lastname: Schot
authors.forename: Lodewijk
authors.initials: L
authors.lastname: Spanjaard
authors.forename: Paul
authors.initials: P
authors.lastname: Vauterin
authors.forename: Dorus
authors.initials: D
authors.lastname: Wilderbeek
authors.forename: Sandra
authors.initials: S
authors.lastname: Witteveen
mesh_terms: D000328:Adult; D016667:Bacterial Capsules; D002675:Child, Preschool; D014644:Genetic Variation; D005838:Genotype; D006192:Haemophilus Infections / Q000382:microbiology / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000008:administration & dosage*; D019741:Haemophilus influenzae type b / Q000145:classification* / Q000235:genetics / Q000276:immunology; D006801:Humans; D017589:Immunization Programs; D007223:Infant; D007231:Infant, Newborn; D018598:Minisatellite Repeats / Q000235:genetics; D009313:National Health Programs; D009426:Netherlands; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage*; D017422:Sequence Analysis, DNA; D012703:Serotyping; D014611:Vaccination
chemical_list: D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D011135:Polysaccharides, Bacterial