Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: Randomised, double-blind, placebo-controlled trial

F. T. Cutts, S. M.A. Zaman, G. Enwere, S. Jaffar, O. S. Levine, J. B. Okoko, C. Oluwalana, A. Vaughan, S. K. Obaro, A. Leach, K. P. McAdam, E. Biney, M. Saaka, U. Onwuchekwa, F. Yallop, N. F. Pierce, B. M. Greenwood, R. A. Adegbola

Research output: Contribution to journalArticle

694 Citations (Scopus)

Abstract

Background: Pneumonia is estimated to cause 2 million deaths every year in children. Streptococcus pneumoniae is the most important cause of severe pneumonia. We aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children. Methods: We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause admissions. Analyses were per protocol and intention to treat. Findings: 529 children assigned vaccine and 568 allocated placebo were not included in the per-protocol analysis. Results of per-protocol and intention-to-treat analyses were similar. By per-protocol analysis, 333 of 8189 children given vaccine had an episode of radiological pneumonia compared with 513 of 8151 who received placebo. Pneumococcal vaccine efficacy was 37% (95% CI 27-45) against first episode of radiological pneumonia. First episodes of clinical pneumonia were reduced overall by 7% (95% CI 1-12). Efficacy of the conjugate vaccine was 77% (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50% (21-69) against disease caused by all serotypes, and 15% (7-21) against all-cause admissions. We also found an efficacy of 16% (3-28) against mortality. 110 serious adverse events arose in children given the pneumococcal vaccine compared with 131 in those who received placebo. Interpretation: In this rural African setting, pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and invasive pneumococcal disease, and can substantially reduce admissions and improve child survival. Pneumococcal conjugate vaccines should be made available to African infants.

Original languageEnglish (US)
Pages (from-to)1139-1146
Number of pages8
JournalLancet
Volume365
Issue number9465
DOIs
StatePublished - Mar 26 2005

Fingerprint

Gambia
Pneumococcal Pneumonia
Conjugate Vaccines
Pneumococcal Vaccines
Placebos
Pneumonia
Vaccines
Intention to Treat Analysis
Streptococcus pneumoniae
Mortality

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia : Randomised, double-blind, placebo-controlled trial. / Cutts, F. T.; Zaman, S. M.A.; Enwere, G.; Jaffar, S.; Levine, O. S.; Okoko, J. B.; Oluwalana, C.; Vaughan, A.; Obaro, S. K.; Leach, A.; McAdam, K. P.; Biney, E.; Saaka, M.; Onwuchekwa, U.; Yallop, F.; Pierce, N. F.; Greenwood, B. M.; Adegbola, R. A.

In: Lancet, Vol. 365, No. 9465, 26.03.2005, p. 1139-1146.

Research output: Contribution to journalArticle

Cutts, FT, Zaman, SMA, Enwere, G, Jaffar, S, Levine, OS, Okoko, JB, Oluwalana, C, Vaughan, A, Obaro, SK, Leach, A, McAdam, KP, Biney, E, Saaka, M, Onwuchekwa, U, Yallop, F, Pierce, NF, Greenwood, BM & Adegbola, RA 2005, 'Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: Randomised, double-blind, placebo-controlled trial', Lancet, vol. 365, no. 9465, pp. 1139-1146. https://doi.org/10.1016/S0140-6736(05)71876-6
Cutts, F. T. ; Zaman, S. M.A. ; Enwere, G. ; Jaffar, S. ; Levine, O. S. ; Okoko, J. B. ; Oluwalana, C. ; Vaughan, A. ; Obaro, S. K. ; Leach, A. ; McAdam, K. P. ; Biney, E. ; Saaka, M. ; Onwuchekwa, U. ; Yallop, F. ; Pierce, N. F. ; Greenwood, B. M. ; Adegbola, R. A. / Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia : Randomised, double-blind, placebo-controlled trial. In: Lancet. 2005 ; Vol. 365, No. 9465. pp. 1139-1146.
@article{f64bbabe3fee481c9244a900b825ba4d,
title = "Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: Randomised, double-blind, placebo-controlled trial",
abstract = "Background: Pneumonia is estimated to cause 2 million deaths every year in children. Streptococcus pneumoniae is the most important cause of severe pneumonia. We aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children. Methods: We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause admissions. Analyses were per protocol and intention to treat. Findings: 529 children assigned vaccine and 568 allocated placebo were not included in the per-protocol analysis. Results of per-protocol and intention-to-treat analyses were similar. By per-protocol analysis, 333 of 8189 children given vaccine had an episode of radiological pneumonia compared with 513 of 8151 who received placebo. Pneumococcal vaccine efficacy was 37{\%} (95{\%} CI 27-45) against first episode of radiological pneumonia. First episodes of clinical pneumonia were reduced overall by 7{\%} (95{\%} CI 1-12). Efficacy of the conjugate vaccine was 77{\%} (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50{\%} (21-69) against disease caused by all serotypes, and 15{\%} (7-21) against all-cause admissions. We also found an efficacy of 16{\%} (3-28) against mortality. 110 serious adverse events arose in children given the pneumococcal vaccine compared with 131 in those who received placebo. Interpretation: In this rural African setting, pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and invasive pneumococcal disease, and can substantially reduce admissions and improve child survival. Pneumococcal conjugate vaccines should be made available to African infants.",
author = "Cutts, {F. T.} and Zaman, {S. M.A.} and G. Enwere and S. Jaffar and Levine, {O. S.} and Okoko, {J. B.} and C. Oluwalana and A. Vaughan and Obaro, {S. K.} and A. Leach and McAdam, {K. P.} and E. Biney and M. Saaka and U. Onwuchekwa and F. Yallop and Pierce, {N. F.} and Greenwood, {B. M.} and Adegbola, {R. A.}",
year = "2005",
month = "3",
day = "26",
doi = "10.1016/S0140-6736(05)71876-6",
language = "English (US)",
volume = "365",
pages = "1139--1146",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "9465",

}

TY - JOUR

T1 - Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia

T2 - Randomised, double-blind, placebo-controlled trial

AU - Cutts, F. T.

AU - Zaman, S. M.A.

AU - Enwere, G.

AU - Jaffar, S.

AU - Levine, O. S.

AU - Okoko, J. B.

AU - Oluwalana, C.

AU - Vaughan, A.

AU - Obaro, S. K.

AU - Leach, A.

AU - McAdam, K. P.

AU - Biney, E.

AU - Saaka, M.

AU - Onwuchekwa, U.

AU - Yallop, F.

AU - Pierce, N. F.

AU - Greenwood, B. M.

AU - Adegbola, R. A.

PY - 2005/3/26

Y1 - 2005/3/26

N2 - Background: Pneumonia is estimated to cause 2 million deaths every year in children. Streptococcus pneumoniae is the most important cause of severe pneumonia. We aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children. Methods: We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause admissions. Analyses were per protocol and intention to treat. Findings: 529 children assigned vaccine and 568 allocated placebo were not included in the per-protocol analysis. Results of per-protocol and intention-to-treat analyses were similar. By per-protocol analysis, 333 of 8189 children given vaccine had an episode of radiological pneumonia compared with 513 of 8151 who received placebo. Pneumococcal vaccine efficacy was 37% (95% CI 27-45) against first episode of radiological pneumonia. First episodes of clinical pneumonia were reduced overall by 7% (95% CI 1-12). Efficacy of the conjugate vaccine was 77% (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50% (21-69) against disease caused by all serotypes, and 15% (7-21) against all-cause admissions. We also found an efficacy of 16% (3-28) against mortality. 110 serious adverse events arose in children given the pneumococcal vaccine compared with 131 in those who received placebo. Interpretation: In this rural African setting, pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and invasive pneumococcal disease, and can substantially reduce admissions and improve child survival. Pneumococcal conjugate vaccines should be made available to African infants.

AB - Background: Pneumonia is estimated to cause 2 million deaths every year in children. Streptococcus pneumoniae is the most important cause of severe pneumonia. We aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children. Methods: We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause admissions. Analyses were per protocol and intention to treat. Findings: 529 children assigned vaccine and 568 allocated placebo were not included in the per-protocol analysis. Results of per-protocol and intention-to-treat analyses were similar. By per-protocol analysis, 333 of 8189 children given vaccine had an episode of radiological pneumonia compared with 513 of 8151 who received placebo. Pneumococcal vaccine efficacy was 37% (95% CI 27-45) against first episode of radiological pneumonia. First episodes of clinical pneumonia were reduced overall by 7% (95% CI 1-12). Efficacy of the conjugate vaccine was 77% (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50% (21-69) against disease caused by all serotypes, and 15% (7-21) against all-cause admissions. We also found an efficacy of 16% (3-28) against mortality. 110 serious adverse events arose in children given the pneumococcal vaccine compared with 131 in those who received placebo. Interpretation: In this rural African setting, pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and invasive pneumococcal disease, and can substantially reduce admissions and improve child survival. Pneumococcal conjugate vaccines should be made available to African infants.

UR - http://www.scopus.com/inward/record.url?scp=20144367956&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20144367956&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(05)71876-6

DO - 10.1016/S0140-6736(05)71876-6

M3 - Article

C2 - 15794968

AN - SCOPUS:20144367956

VL - 365

SP - 1139

EP - 1146

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9465

ER -