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

doi:10.1186/s12887-021-02552-z

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

Child Health

Research output: Contribution to journal › Article › peer-review

177 Downloads (Pure)

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 language	English
Article number	117
Pages (from-to)	1-14
Number of pages	14
Journal	BMC Pediatrics
Volume	21
Issue number	1
DOIs	https://doi.org/10.1186/s12887-021-02552-z
Publication status	Published - 8 Mar 2021

Access to Document

10.1186/s12887-021-02552-z

36241016-oaFinal published version, 979 KBLicence: Other

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this

Leach, A. J., Mulholland, E. K., Santosham, M., Torzillo, P. J., McIntyre, P., Smith-Vaughan, H., Wilson, N., Arrowsmith, B., Beissbarth, J., Chatfield, M. D., Oguoma, V. M., & Morris, P. S. (2021). 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. BMC Pediatrics, 21(1), 1-14. [117]. https://doi.org/10.1186/s12887-021-02552-z

@article{8872490b87d24ce1bb77c2acc9ffb5e3,

title = "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",

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{\texttrademark} (PHiD-CV10, with protein D of NTHi) and Prevenar13{\texttrademark} (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{\texttrademark} (P) at 2–4-6 months (_PPP), Synflorix{\texttrademark} (S) at 2–4-6 months (_SSS), or Synflorix{\texttrademark} at 1–2-4 months plus Prevenar13{\texttrademark} 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.",

keywords = "3-arm randomised controlled trial, Aboriginal, Combination schedule, Head-to-head, Infant, Otitis media, PCV13, PHiD-CV10, Pneumococcal conjugate vaccines",

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

note = "Funding Information: Australian National Health and Medical Research Council (GNT605810). AJL was supported by a NHMRC Senior Research Fellowship (GNT1020561). PVL was supported by a NHMRC Career Development Fellowship (GNT1146198). Financial Markets for Children (Grant number 2012–057) funded opsonophagocytic activity (OPA) assays and GSK provided protein D and reference sera for immunogenicity and reviewed protein D results prior to publication but had no influence on analysis or publication (published elsewhere). Funding Information: Between 2010 and 2012, AJL received research funds Pfizer (manufacturers of Prevenar13{\texttrademark}). In 2013, AJL received financial support from GSK and Pfizer to attend conferences. In 2018 AJL served on an advisory board for GSK. KM has served on an advisory board for GSK. GSK provided in-kind support for the Vietnam Pneumococcal trial, of which KM is the PI. MS served on the scientific advisory boards of Pfizer and GSK. MS also received research grants from Pfizer and GSK. PT and PMcI have no financial or other competing interests. Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = mar,

day = "8",

doi = "10.1186/s12887-021-02552-z",

language = "English",

volume = "21",

pages = "1--14",

journal = "BMC Pediatrics",

issn = "1471-2431",

publisher = "BioMed Central",

number = "1",

}

Leach, AJ, Mulholland, EK, Santosham, M, Torzillo, PJ, McIntyre, P, Smith-Vaughan, H, Wilson, N, Arrowsmith, B, Beissbarth, J, Chatfield, MD, Oguoma, VM & Morris, PS 2021, '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', BMC Pediatrics, vol. 21, no. 1, 117, pp. 1-14. https://doi.org/10.1186/s12887-021-02552-z

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. / Leach, Amanda Jane; Mulholland, Edward Kim; Santosham, Mathuram et al.
In: BMC Pediatrics, Vol. 21, No. 1, 117, 08.03.2021, p. 1-14.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

T2 - PREVIX_COMBO, a 3-arm randomised controlled trial

AU - Leach, Amanda Jane

AU - Mulholland, Edward Kim

AU - Santosham, Mathuram

AU - Torzillo, Paul John

AU - McIntyre, Peter

AU - Smith-Vaughan, Heidi

AU - Wilson, Nicole

AU - Arrowsmith, Beth

AU - Beissbarth, Jemima

AU - Chatfield, Mark D.

AU - Oguoma, Victor M.

AU - Morris, Peter Stanley

N1 - Funding Information: Australian National Health and Medical Research Council (GNT605810). AJL was supported by a NHMRC Senior Research Fellowship (GNT1020561). PVL was supported by a NHMRC Career Development Fellowship (GNT1146198). Financial Markets for Children (Grant number 2012–057) funded opsonophagocytic activity (OPA) assays and GSK provided protein D and reference sera for immunogenicity and reviewed protein D results prior to publication but had no influence on analysis or publication (published elsewhere). Funding Information: Between 2010 and 2012, AJL received research funds Pfizer (manufacturers of Prevenar13™). In 2013, AJL received financial support from GSK and Pfizer to attend conferences. In 2018 AJL served on an advisory board for GSK. KM has served on an advisory board for GSK. GSK provided in-kind support for the Vietnam Pneumococcal trial, of which KM is the PI. MS served on the scientific advisory boards of Pfizer and GSK. MS also received research grants from Pfizer and GSK. PT and PMcI have no financial or other competing interests. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/3/8

Y1 - 2021/3/8

N2 - 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.

AB - 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.

KW - 3-arm randomised controlled trial

KW - Aboriginal

KW - Combination schedule

KW - Head-to-head

KW - Infant

KW - Otitis media

KW - PCV13

KW - PHiD-CV10

KW - Pneumococcal conjugate vaccines

UR - http://www.scopus.com/inward/record.url?scp=85102716544&partnerID=8YFLogxK

U2 - 10.1186/s12887-021-02552-z

DO - 10.1186/s12887-021-02552-z

M3 - Article

C2 - 33685411

AN - SCOPUS:85102716544

SN - 1471-2431

VL - 21

SP - 1

EP - 14

JO - BMC Pediatrics

JF - BMC Pediatrics

IS - 1

M1 - 117

ER -

Leach AJ, Mulholland EK, Santosham M, Torzillo PJ, McIntyre P, Smith-Vaughan H et al. 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. BMC Pediatrics. 2021 Mar 8;21(1):1-14. 117. doi: 10.1186/s12887-021-02552-z

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this