Otitis media outcomes of a combined 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine and 13-valent pneumococcal conjugate vaccine schedule at 1-2-4-6 months: PREVIX_COMBO, a 3-arm randomised controlled trial

Amanda Jane Leach, Edward Kim Mulholland, Mathuram Santosham, Paul John Torzillo, Peter McIntyre, Heidi Smith-Vaughan, Nicole Wilson, Beth Arrowsmith, Jemima Beissbarth, Mark D. Chatfield, Victor M. Oguoma, Peter Stanley Morris

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Abstract

Background: Aboriginal children living in Australian remote communities are at high risk of early and persistent otitis media, hearing loss, and social disadvantage. Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are the primary pathogens. We compared otitis media outcomes in infants randomised to either a combination of Synflorix™ (PHiD-CV10, with protein D of NTHi) and Prevenar13™ (PCV13, with 3, 6A, and 19A), withrecommended schedules for each vaccine alone. We previously reported superior broader overall immunogenicityof the combination schedule at 7 months, and early superiority of PHiD-CV10 compared to PCV13 at 4 months.
Methods: In an open-label superiority trial, we randomised (1:1:1) Aboriginal infants at 28 to 38 days of age, to either Prevenar13™ (P) at 2–4-6 months (_PPP), Synflorix™ (S) at 2–4-6 months (_SSS), or Synflorix™ at 1–2-4 months plus Prevenar13™ at 6 months (SSSP). Ears were assessed using tympanometry at 1 and 2 months, combined with otoscopy at 4, 6, and 7 months. A worst ear diagnosis was made for each child visit according to a severityhierarchy of normal, otitis media with effusion (OME), acute otitis media without perforation (AOMwoP), AOM with perforation (AOMwiP), and chronic suppurative otitis media (CSOM)
Results: Between September 2011 and September 2017, 425 infants were allocated to _PPP(143), _SSS(141) or SSSP(141). Ear assessments were successful in 96% scheduled visits. At 7 months prevalence of any OM was 91, 86,and 90% in the _PPP, _SSS, and SSSP groups, respectively. There were no significant differences in prevalence ofany form of otitis media between vaccine groups at any age. Combined group prevalence of any OM was 43, 57,82, 87, and 89% at 1, 2, 4, 6, and 7 months of age, respectively. Of 388 infants with ear assessments at 4, 6 and 7months, 277 (71.4%) had OM that met criteria for specialist referral; rAOM, pOME, or CSOM. 
Conclusions: Despite superior broader overall immunogenicity of the combination schedule at 7 months, and early superiority of PHiD-CV10 compared to PCV13 at 4 months, there were no significant differences in prevalence of otitis media nor healthy ears throughout the first months of life.
Original languageEnglish
Article number117
Pages (from-to)1-14
Number of pages14
JournalBMC Pediatrics
Volume21
Issue number1
DOIs
Publication statusPublished - 8 Mar 2021

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