title: Pneumococcal conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk Indigenous infants (PREV-IX_COMBO): protocol of a randomised controlled trial.
abstract: BACKGROUND
  Otitis media (OM) starts within weeks of birth in almost all Indigenous infants living in remote areas of the Northern Territory (NT). OM and associated hearing loss persist from infancy throughout childhood and often into adulthood. Educational and social opportunities are greatly compromised. Pneumococcus and non-typeable Haemophilus influenzae (NTHi) are major OM pathogens that densely colonise the nasopharynx and infect the middle ear from very early in life. Our hypothesis is that compared to current single vaccine schedules, a combination of vaccines starting at 1 month of age, may provide earlier, broadened protection.
  
  
  METHODS
  This randomised outcome assessor, blinded controlled trial will recruit 425 infants between 28 and 38 days of age and randomly allocate them (1:1:1) to one of three pneumococcal conjugate vaccine (PCV) schedules: Synflorix at 2, 4, 6 months of age, Prevenar13 at 2, 4 and 6 months of age, or an investigational schedule of Synflorix at 1, 2 and 4 months plus Prevenar13 at 6 months of age. The blinded primary outcomes at 7 months of age are immunogenicity of specific vaccine antigens (geometric mean concentration (GMC) and proportion of participants with above threshold GMC of 0.35 µg/L). Secondary outcomes at all timepoints are additional immunogenicity measures and proportion of participants with nasopharyngeal carriage of vaccine-type pneumococci and NTHi, and any OM, including any tympanic membrane perforation. Parental interviews will provide data on common risk factors for OM.
  
  
  BACKGROUND
  Ethical approval has been obtained from NT Department of Health and Menzies HREC (EC00153), Central Australian HREC (EC00155) and West Australian Aboriginal Health Ethics Committee (WAAHEC- 377-12/2011). Final trial results, data analyses, interpretation and conclusions will be presented in appropriate written and oral formats to parents and guardians, participating communities, local, national and international conferences, and published in peer-reviewed open access journals.
  
  
  BACKGROUND
  ACTRN12610000544077 and NCT01174849.
authors.affiliation: Child Health Division, Menzies School of Heath Research, Darwin, Northern Territory, Australia.
authors.forename: Amanda Jane
authors.initials: AJ
authors.lastname: Leach
authors.affiliation: Centre for International Child Health, Murdoch Childrens Research Institute, University of Melbourne, Melbourne, Victoria, Australia London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Edward Kim
authors.initials: EK
authors.lastname: Mulholland
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Mathu
authors.initials: M
authors.lastname: Santosham
authors.affiliation: Prince Alfred Hospital, Sydney, New South Wales, Australia University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Paul John
authors.initials: PJ
authors.lastname: Torzillo
authors.affiliation: National Aboriginal Community Controlled Health Organisation, Canberra, Australian Capital Territory, Australia.
authors.forename: Ngiare Joy
authors.initials: NJ
authors.lastname: Brown
authors.affiliation: National Centre for Immunization Research and Surveillance, Sydney, New South Wales, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: McIntyre
authors.affiliation: Child Health Division, Menzies School of Heath Research, Darwin, Northern Territory, Australia.
authors.forename: Heidi
authors.initials: H
authors.lastname: Smith-Vaughan
authors.affiliation: University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Sue
authors.initials: S
authors.lastname: Skull
authors.affiliation: Murdoch Childrens Research Institute, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Balloch
authors.affiliation: Child Health Division, Menzies School of Heath Research, Darwin, Northern Territory, Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: Andrews
authors.affiliation: Telethon Kids Institute, Perth, Western Australia, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Carapetis
authors.affiliation: Strijen, The Netherlands.
authors.forename: Joseph
authors.initials: J
authors.lastname: McDonnell
authors.affiliation: Northern Territory Department of Health & Families, Darwin, Northern Territory, Australia.
authors.forename: Vicki
authors.initials: V
authors.lastname: Krause
authors.affiliation: Child Health Division, Menzies School of Heath Research, Darwin, Northern Territory, Australia Department of Paediatrics, Royal Darwin Hospital, Darwin, Northern Territory, Australia.
authors.forename: Peter Stanley
authors.initials: PS
authors.lastname: Morris
mesh_terms: D001315:Australia; D002985:Clinical Protocols; D005260:Female; D006192:Haemophilus Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D006193:Haemophilus influenzae; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009305:Nasopharynx / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000276:immunology*; D012107:Research Design; D012306:Risk; D013296:Streptococcus pneumoniae / Q000276:immunology; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: C538862:13-valent pneumococcal vaccine; C547294:PHiD-CV vaccine; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate
keywords: IMMUNOLOGY; MICROBIOLOGY; PUBLIC HEALTH