Efficacy of different pneumococcal conjugate vaccine schedules against pneumonia, hospitalisation, and mortality: Re-analysis of a randomised trial in The Gambia

Grant A. Mackenzie; Christian Bottomley; Albert Jan Van Hoek; David Jeffries; Martin Ota; Syed M.A. Zaman; Brian Greenwood; Felicity Cutts

doi:10.1016/j.vaccine.2014.02.081

Efficacy of different pneumococcal conjugate vaccine schedules against pneumonia, hospitalisation, and mortality: Re-analysis of a randomised trial in The Gambia

Grant A. Mackenzie^*, Christian Bottomley, Albert Jan Van Hoek, David Jeffries, Martin Ota, Syed M.A. Zaman, Brian Greenwood, Felicity Cutts

^*Corresponding author for this work

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

8 Citations (Scopus)

Abstract

Background: Pneumococcal conjugate vaccines (PCV) reduce disease due to Streptococcus pneumoniae. We aimed to determine the efficacy of different PCV schedules in Gambian children. Methods: We reanalysed data from a randomised placebo-controlled trial. Infants aged 6-51 weeks were allocated to three doses of nine-valent PCV (n= 8718) or placebo (n= 8719) and followed until age 30 months. We categorised participants to compare: (a) a first dose at age 6 or 10 weeks, (b) intervals of 1 or 2 months between doses, and (c) different intervals between second and third doses. The primary endpoint was first episode of radiologic pneumonia; other endpoints were hospitalisation and mortality. Using the placebo group as the reference population, Poisson regression models were used with follow-up after the first dose to estimate the efficacy of each schedule and from age 6 weeks to estimate the incidence rate difference between schedules. Results: Predicted efficacy in the groups aged 6 weeks (n= 2467, 154 events) or 10 weeks (n= 2420, 106 events) at first dose against radiologic pneumonia were 32% (95% CI 19-43%) and 33% (95% CI 21-44%), against hospitalisation 14% (95% CI 3-23%) and 17% (95% CI 7-26%), and against mortality 17% (95% CI -3 to 33%) and 16% (95% CI -3 to 32%) respectively. Predicted efficacy in the groups with intervals of 1 month (n= 2701, 133 events) or 2 months (n= 1351, 58 events) between doses against radiologic pneumonia were 33% (95% CI 20-44%) and 36% (95% CI 24-46%), against hospitalisation 15% (95% CI 5-24%) and 18% (95% CI 8-27%), and against mortality 17% (95% CI -2 to 33%) and 13% (95% CI -8 to 29%) respectively. Efficacy did not differ by interval between second and third doses, nor did the incidence rate difference between schedules. Conclusions: We found no evidence that efficacy or effectiveness of PCV9 differed when doses were given with modest variability around the scheduled ages or intervals between doses.

Original language	English
Pages (from-to)	2493-2500
Number of pages	8
Journal	Vaccine
Volume	32
Issue number	21
DOIs	https://doi.org/10.1016/j.vaccine.2014.02.081
Publication status	Published - 1 May 2014

Bibliographical note

Funding Information:
The original trial was supported by grants from the National Institute of Allergy and Infectious Diseases at the USA National Institutes of Health ( N01-AI-25477 ); WHO ( V23/181/127 ); the Children's Vaccine Programme at PATH ; and US Agency for International Development. Wyeth Vaccines donated study vaccine and placebo, Tetramune for all children in the Upper and Central River Divisions, and PCV7 for children who received placebo, after the trial results were reviewed. No additional funding was required for this analysis. No funding body had a role in the conception of this reanalysis, the interpretation, writing of the report, or the decision to submit for publication. The corresponding author had full access to all the data and had final responsibility for the decision to submit for publication.

Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.

Keywords

Mortality
Pneumonia
Schedule
Streptococcus pneumoniae
Vaccine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.vaccine.2014.02.081

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title = "Efficacy of different pneumococcal conjugate vaccine schedules against pneumonia, hospitalisation, and mortality: Re-analysis of a randomised trial in The Gambia",

abstract = "Background: Pneumococcal conjugate vaccines (PCV) reduce disease due to Streptococcus pneumoniae. We aimed to determine the efficacy of different PCV schedules in Gambian children. Methods: We reanalysed data from a randomised placebo-controlled trial. Infants aged 6-51 weeks were allocated to three doses of nine-valent PCV (n= 8718) or placebo (n= 8719) and followed until age 30 months. We categorised participants to compare: (a) a first dose at age 6 or 10 weeks, (b) intervals of 1 or 2 months between doses, and (c) different intervals between second and third doses. The primary endpoint was first episode of radiologic pneumonia; other endpoints were hospitalisation and mortality. Using the placebo group as the reference population, Poisson regression models were used with follow-up after the first dose to estimate the efficacy of each schedule and from age 6 weeks to estimate the incidence rate difference between schedules. Results: Predicted efficacy in the groups aged 6 weeks (n= 2467, 154 events) or 10 weeks (n= 2420, 106 events) at first dose against radiologic pneumonia were 32% (95% CI 19-43%) and 33% (95% CI 21-44%), against hospitalisation 14% (95% CI 3-23%) and 17% (95% CI 7-26%), and against mortality 17% (95% CI -3 to 33%) and 16% (95% CI -3 to 32%) respectively. Predicted efficacy in the groups with intervals of 1 month (n= 2701, 133 events) or 2 months (n= 1351, 58 events) between doses against radiologic pneumonia were 33% (95% CI 20-44%) and 36% (95% CI 24-46%), against hospitalisation 15% (95% CI 5-24%) and 18% (95% CI 8-27%), and against mortality 17% (95% CI -2 to 33%) and 13% (95% CI -8 to 29%) respectively. Efficacy did not differ by interval between second and third doses, nor did the incidence rate difference between schedules. Conclusions: We found no evidence that efficacy or effectiveness of PCV9 differed when doses were given with modest variability around the scheduled ages or intervals between doses.",

keywords = "Mortality, Pneumonia, Schedule, Streptococcus pneumoniae, Vaccine",

author = "Mackenzie, {Grant A.} and Christian Bottomley and {Van Hoek}, {Albert Jan} and David Jeffries and Martin Ota and Zaman, {Syed M.A.} and Brian Greenwood and Felicity Cutts",

note = "Funding Information: The original trial was supported by grants from the National Institute of Allergy and Infectious Diseases at the USA National Institutes of Health ( N01-AI-25477 ); WHO ( V23/181/127 ); the Children's Vaccine Programme at PATH ; and US Agency for International Development. Wyeth Vaccines donated study vaccine and placebo, Tetramune for all children in the Upper and Central River Divisions, and PCV7 for children who received placebo, after the trial results were reviewed. No additional funding was required for this analysis. No funding body had a role in the conception of this reanalysis, the interpretation, writing of the report, or the decision to submit for publication. The corresponding author had full access to all the data and had final responsibility for the decision to submit for publication. Copyright: Copyright 2014 Elsevier B.V., All rights reserved.",

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T1 - Efficacy of different pneumococcal conjugate vaccine schedules against pneumonia, hospitalisation, and mortality

T2 - Re-analysis of a randomised trial in The Gambia

AU - Mackenzie, Grant A.

AU - Bottomley, Christian

AU - Van Hoek, Albert Jan

AU - Jeffries, David

AU - Ota, Martin

AU - Zaman, Syed M.A.

AU - Greenwood, Brian

AU - Cutts, Felicity

N1 - Funding Information: The original trial was supported by grants from the National Institute of Allergy and Infectious Diseases at the USA National Institutes of Health ( N01-AI-25477 ); WHO ( V23/181/127 ); the Children's Vaccine Programme at PATH ; and US Agency for International Development. Wyeth Vaccines donated study vaccine and placebo, Tetramune for all children in the Upper and Central River Divisions, and PCV7 for children who received placebo, after the trial results were reviewed. No additional funding was required for this analysis. No funding body had a role in the conception of this reanalysis, the interpretation, writing of the report, or the decision to submit for publication. The corresponding author had full access to all the data and had final responsibility for the decision to submit for publication. Copyright: Copyright 2014 Elsevier B.V., All rights reserved.

PY - 2014/5/1

Y1 - 2014/5/1

N2 - Background: Pneumococcal conjugate vaccines (PCV) reduce disease due to Streptococcus pneumoniae. We aimed to determine the efficacy of different PCV schedules in Gambian children. Methods: We reanalysed data from a randomised placebo-controlled trial. Infants aged 6-51 weeks were allocated to three doses of nine-valent PCV (n= 8718) or placebo (n= 8719) and followed until age 30 months. We categorised participants to compare: (a) a first dose at age 6 or 10 weeks, (b) intervals of 1 or 2 months between doses, and (c) different intervals between second and third doses. The primary endpoint was first episode of radiologic pneumonia; other endpoints were hospitalisation and mortality. Using the placebo group as the reference population, Poisson regression models were used with follow-up after the first dose to estimate the efficacy of each schedule and from age 6 weeks to estimate the incidence rate difference between schedules. Results: Predicted efficacy in the groups aged 6 weeks (n= 2467, 154 events) or 10 weeks (n= 2420, 106 events) at first dose against radiologic pneumonia were 32% (95% CI 19-43%) and 33% (95% CI 21-44%), against hospitalisation 14% (95% CI 3-23%) and 17% (95% CI 7-26%), and against mortality 17% (95% CI -3 to 33%) and 16% (95% CI -3 to 32%) respectively. Predicted efficacy in the groups with intervals of 1 month (n= 2701, 133 events) or 2 months (n= 1351, 58 events) between doses against radiologic pneumonia were 33% (95% CI 20-44%) and 36% (95% CI 24-46%), against hospitalisation 15% (95% CI 5-24%) and 18% (95% CI 8-27%), and against mortality 17% (95% CI -2 to 33%) and 13% (95% CI -8 to 29%) respectively. Efficacy did not differ by interval between second and third doses, nor did the incidence rate difference between schedules. Conclusions: We found no evidence that efficacy or effectiveness of PCV9 differed when doses were given with modest variability around the scheduled ages or intervals between doses.

AB - Background: Pneumococcal conjugate vaccines (PCV) reduce disease due to Streptococcus pneumoniae. We aimed to determine the efficacy of different PCV schedules in Gambian children. Methods: We reanalysed data from a randomised placebo-controlled trial. Infants aged 6-51 weeks were allocated to three doses of nine-valent PCV (n= 8718) or placebo (n= 8719) and followed until age 30 months. We categorised participants to compare: (a) a first dose at age 6 or 10 weeks, (b) intervals of 1 or 2 months between doses, and (c) different intervals between second and third doses. The primary endpoint was first episode of radiologic pneumonia; other endpoints were hospitalisation and mortality. Using the placebo group as the reference population, Poisson regression models were used with follow-up after the first dose to estimate the efficacy of each schedule and from age 6 weeks to estimate the incidence rate difference between schedules. Results: Predicted efficacy in the groups aged 6 weeks (n= 2467, 154 events) or 10 weeks (n= 2420, 106 events) at first dose against radiologic pneumonia were 32% (95% CI 19-43%) and 33% (95% CI 21-44%), against hospitalisation 14% (95% CI 3-23%) and 17% (95% CI 7-26%), and against mortality 17% (95% CI -3 to 33%) and 16% (95% CI -3 to 32%) respectively. Predicted efficacy in the groups with intervals of 1 month (n= 2701, 133 events) or 2 months (n= 1351, 58 events) between doses against radiologic pneumonia were 33% (95% CI 20-44%) and 36% (95% CI 24-46%), against hospitalisation 15% (95% CI 5-24%) and 18% (95% CI 8-27%), and against mortality 17% (95% CI -2 to 33%) and 13% (95% CI -8 to 29%) respectively. Efficacy did not differ by interval between second and third doses, nor did the incidence rate difference between schedules. Conclusions: We found no evidence that efficacy or effectiveness of PCV9 differed when doses were given with modest variability around the scheduled ages or intervals between doses.

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KW - Pneumonia

KW - Schedule

KW - Streptococcus pneumoniae

KW - Vaccine

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Efficacy of different pneumococcal conjugate vaccine schedules against pneumonia, hospitalisation, and mortality: Re-analysis of a randomised trial in The Gambia

Abstract

Bibliographical note

Keywords

UN SDGs

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