title: Comparing Haemophilus influenzae type b conjugate vaccine schedules: a systematic review and meta-analysis of vaccine trials.
abstract: BACKGROUND
  The optimal schedule and the need for a booster dose are unclear for Haemophilus influenzae type b (Hib) conjugate vaccines. We systematically reviewed relative effects of Hib vaccine schedules.
  
  
  METHODS
  We searched 21 databases to May 2010 or June 2012 and selected randomized controlled trials or quasi-randomized controlled trials that compared different Hib schedules (3 primary doses with no booster dose [3p+0], 3p+1 and 2p+1) or different intervals in primary schedules and between primary and booster schedules. Outcomes were clinical efficacy, nasopharyngeal carriage and immunological response. Results were combined in random-effects meta-analysis.
  
  
  RESULTS
  Twenty trials from 15 countries were included; 16 used vaccines conjugated to tetanus toxoid (polyribosylribitol phosphate conjugated to tetanus toxoid). No trials assessed clinical or carriage outcomes. Twenty trials examined immunological outcomes and found few relevant differences. Comparing polyribosylribitol phosphate conjugated to tetanus toxoid 3p+0 with 2p+0, there was no difference in seropositivity at the 1.0 μg/mL threshold by 6 months after the last primary dose (combined risk difference -0.02; 95% confidence interval: -0.10, 0.06). Only small differences were seen between schedules starting at different ages, with different intervals between primary doses, or with different intervals between primary and booster doses. Individuals receiving a booster were more likely to be seropositive than those at the same age who did not.
  
  
  CONCLUSIONS
  There is no clear evidence from trials that any 2p+1, 3p+0 or 3p+1 schedule of Hib conjugate vaccine is likely to provide better protection against Hib disease than other schedules. Until more data become available, scheduling is likely to be determined by epidemiological and programmatic considerations in individual settings.
authors.affiliation: From the *Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; †Center for Aging Sciences (Ce.S.I.), G. d'Annunzio University, Chieti, Italy; ‡Institute of General Practice and Health Services Research, University of Zürich, Zürich, Switzerland; §Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University Foundation, Chieti, Italy; and ¶Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Nicola
authors.initials: N
authors.lastname: Low
authors.forename: Shelagh M
authors.initials: SM
authors.lastname: Redmond
authors.forename: Anne W S
authors.initials: AW
authors.lastname: Rutjes
authors.forename: Nahara A
authors.initials: NA
authors.lastname: Martínez-González
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
authors.forename: Marcello
authors.initials: M
authors.lastname: di Nisio
authors.forename: Pippa
authors.initials: P
authors.lastname: Scott
mesh_terms: D006192:Haemophilus Infections / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D019741:Haemophilus influenzae type b / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D007231:Infant, Newborn; D016032:Randomized Controlled Trials as Topic; D018074:Vaccines, Conjugate / Q000008:administration & dosage
chemical_list: D018073:Haemophilus Vaccines; D018074:Vaccines, Conjugate