title: Effects of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine on nasopharyngeal bacterial colonization in young children: a randomized controlled trial.
abstract: BACKGROUND
  This study evaluated the effects of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) on nasopharyngeal bacterial colonization compared with the 7-valent pneumococcal conjugate vaccine (7vCRM) in young children.
  
  
  METHODS
  A randomized controlled trial in the Netherlands, initiated 2 years after 7vCRM introduction, was conducted between 1 April 2008 and 1 December 2010. Infants (N = 780) received either PHiD-CV or 7vCRM (2:1) at 2, 3, 4, and 11-13 months of age. Nasopharyngeal samples taken at 5, 11, 14, 18, and 24 months of age were cultured to detect Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus. Polymerase chain reaction assays quantified H. influenzae and S. pneumoniae and confirmed H. influenzae as nontypeable (NTHi). Primary outcome measure was vaccine efficacy (VE) against NTHi colonization.
  
  
  RESULTS
  In both groups, NTHi colonization increased with age from 33% in 5-month-olds to 65% in 24-month-olds. Three months postbooster, VE against colonization was 0.5% (95% confidence interval [CI], -21.8% to 18.4%) and VE against acquisition 10.9% (95% CI, -31.3% to 38.9%). At each sampling moment, no differences between groups in either NTHi prevalence or H. influenzae density were detected. Streptococcus pneumoniae (range, 39%-57%), M. catarrhalis (range, 63%--69%), and S. aureus (range, 9%-30%) colonization patterns were similar between groups.
  
  
  CONCLUSIONS
  PHiD-CV had no differential effect on nasopharyngeal NTHi colonization or H. influenzae density in healthy Dutch children up to 2 years of age, implying that herd effects for NTHi are not to be expected. Other bacterial colonization patterns were also similar.
authors.affiliation: Department of Pediatric Immunology and Infectious Diseases,  Wilhelmina Children's Hospital, University Medical Center Utrecht.
authors.forename: Menno R
authors.initials: MR
authors.lastname: van den Bergh
authors.forename: Judith
authors.initials: J
authors.lastname: Spijkerman
authors.forename: Kristien M
authors.initials: KM
authors.lastname: Swinnen
authors.forename: Nancy A
authors.initials: NA
authors.lastname: François
authors.forename: Thierry G
authors.initials: TG
authors.lastname: Pascal
authors.forename: Dorota
authors.initials: D
authors.lastname: Borys
authors.forename: Lode
authors.initials: L
authors.lastname: Schuerman
authors.forename: Ed P F
authors.initials: EP
authors.lastname: Ijzerman
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Bruin
authors.forename: Arie
authors.initials: A
authors.lastname: van der Ende
authors.forename: Reinier H
authors.initials: RH
authors.lastname: Veenhoven
authors.forename: Elisabeth A M
authors.initials: EA
authors.lastname: Sanders
mesh_terms: D000367:Age Factors; D015373:Bacterial Typing Techniques; D002675:Child, Preschool; D005260:Female; D006192:Haemophilus Infections / Q000517:prevention & control*; D006193:Haemophilus influenzae / Q000145:classification / Q000302:isolation & purification*; D054884:Host-Pathogen Interactions; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D008297:Male; D009305:Nasopharynx / Q000382:microbiology*; D011008:Pneumococcal Infections / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage*; D013296:Streptococcus pneumoniae / Q000302:isolation & purification
chemical_list: C538863:10-valent pneumococcal vaccine; C547294:PHiD-CV vaccine; D022242:Pneumococcal Vaccines