title: PneuMum: Impact from a randomised controlled trial of maternal 23-valent pneumococcal polysaccharide vaccination on middle ear disease amongst Indigenous infants, Northern Territory, Australia.
abstract: BACKGROUND
  We assessed maternal 23-valent pneumococcal polysaccharide (23vPPV) vaccine efficacy (VE) against middle ear disease and pneumococcal carriage amongst Australian Indigenous infants.
  
  
  METHODS
  In an open label, allocation concealed, outcome-assessor blinded, community stratified, randomised controlled trial, healthy pregnant Indigenous women aged 17-39 years in the Northern Territory of Australia received the 23vPPV (1:1:1) at: 30-36 weeks gestation, birth, or were unvaccinated (ClinicalTrials.gov NCT00714064). Co-primary outcomes were the point prevalences of infant middle ear disease and 23vPPV-type carriage at age 7 months.
  
  
  RESULTS
  The consent rate was 50% (313/632). Among 227 eligible participants randomised, retention rates were 86% (66/77) controls; 89% (67/75) pregnancy vaccinees; 88% (66/75) birth vaccinees. At infant age 7 months, ear disease prevalence was: 71% (47/66) controls, 63% (42/67) pregnancy vaccinees, 76% (50/66) birth vaccinees; and 23vPPV-type carriage was: 26% (17/66) controls, 18% (12/67) pregnancy vaccinees, 18% (12/66) birth vaccinees. For pregnancy vaccinees, VE was 12% (95% CI -12% to 31%) against infant ear disease and 30% (95% CI -34% to 64%) against 23vPPV-type carriage. In a post-hoc analysis, VE against infant ear disease concurrent with carriage of 23vPPV or related types was 51% (95% CI -2% to 76%). There were no serious adverse effects following receipt of the 23vPPV in pregnancy or at birth.
  
  
  CONCLUSIONS
  In a high risk population, our study was unable to demonstrate efficacy of 23vPPV in pregnancy against the co-primary outcomes of either all-cause infant ear disease or 23vPPV-type nasopharyngeal carriage at age 7 months. Efficacy against ear disease concurrent with carriage of vaccine-related serotypes (a more specific outcome) suggests 23vPPV in pregnancy may complement childhood pneumococcal vaccination programs.
authors.affiliation: Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia. Electronic address: Michael.Binks@menzies.edu.au.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Binks
authors.affiliation: Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Moberley
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, VIC, Australia; University of Melbourne, Melbourne, VIC, Australia; Royal Children's Hospital, Melbourne, VIC, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Balloch
authors.affiliation: Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Leach
authors.affiliation: Department of Health and Families, Darwin, NT, Australia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Nelson
authors.affiliation: Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Hare
authors.affiliation: Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia.
authors.forename: Cate
authors.initials: C
authors.lastname: Wilson
authors.affiliation: Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Morris
authors.affiliation: Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia.
authors.forename: Jane
authors.initials: J
authors.lastname: Nelson
authors.affiliation: Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Chatfield
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, VIC, Australia; University of Melbourne, Melbourne, VIC, Australia; Royal Children's Hospital, Melbourne, VIC, Australia.
authors.forename: Mimi L K
authors.initials: ML
authors.lastname: Tang
authors.affiliation: Royal Prince Alfred Hospital, Sydney, NSW, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Torzillo
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Carapetis
authors.affiliation: Murdoch Childrens Research Institute, Melbourne, VIC, Australia; University of Melbourne, Melbourne, VIC, Australia; Royal Children's Hospital, Melbourne, VIC, Australia.
authors.forename: E Kim
authors.initials: EK
authors.lastname: Mulholland
authors.affiliation: Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia.
authors.forename: Ross M
authors.initials: RM
authors.lastname: Andrews
mesh_terms: D000293:Adolescent; D000328:Adult; D002353:Carrier State / Q000453:epidemiology* / Q000276:immunology / Q000517:prevention & control; D005260:Female; D006801:Humans; D007112:Immunity, Maternally-Acquired; D007223:Infant; D009305:Nasopharynx / Q000382:microbiology*; D015876:Northern Territory / Q000453:epidemiology; D010033:Otitis Media / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011247:Pregnancy; D015995:Prevalence; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000302:isolation & purification*; D014611:Vaccination; D055815:Young Adult; D000095283:Australian Aboriginal and Torres Strait Islander Peoples
chemical_list: C414006:23-valent pneumococcal capsular polysaccharide vaccine; D022242:Pneumococcal Vaccines
keywords: 23-valent pneumococcal polysaccharide vaccine; Australia; Indigenous; Otitis media; Pneumococcus; Pregnancy