Elsevier

The Lancet

Volume 365, Issue 9465, 26 March–1 April 2005, Pages 1139-1146
The Lancet

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

https://doi.org/10.1016/S0140-6736(05)71876-6Get rights and content

Summary

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.

Introduction

Pneumonia causes an estimated 19% of the 10 million childhood deaths worldwide.1 Up to half of all cases of severe childhood pneumonia are caused by pneumococcus in developing countries.2 In The Gambia3 and other African countries,4, 5 invasive pneumococcal disease rates are up to tenfold higher than in industrialised countries, and the disease is a major cause of admissions and deaths.5 The high burden of pneumococcal disease in The Gambia prompted studies to assess pneumococcal vaccines. Conjugate vaccines were shown to be safe, immunogenic, and induce immunological memory in Gambian infants.6, 7, 8 In view of these findings, we aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine against radiological pneumonia in rural areas of The Gambia.

Section snippets

Study setting

We undertook a randomised, double-blind, placebo-controlled trial in the Upper River Division and Central River Division of The Gambia, covering an area of 5000 km2. The estimated population of this area was 380 000 in 2000.9

The prevalence of HIV-1 infection among antenatal clinic attendees in this region has remained stable at about 1% since 1993.10 In background studies from 1989–93, the mortality rate in infants was 80 per 1000 child-years, and in children age 1–4 years it was 19 per 1000

Results

We recruited children from August, 2000, to February, 2003. Vaccination ended in April, 2003, and clinical follow-up ended in April, 2004. 22 170 children were screened for eligibility, of whom 17 437 (79%) participated in the study (figure). Table 1 shows characteristics of children in the per-protocol analysis. Median age at receipt of the first dose of vaccine or placebo was 11 weeks (IQR 8–16) and for the third dose it was 24 weeks (19–32). Median length of follow-up was 103 weeks (84–116)

Discussion

We have shown that pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and substantially reduces admissions and improves child survival. Similar to findings from the USA19, 20 and South Africa,21 we found that conjugate pneumococcal vaccine is efficacious against invasive pneumococcal disease. We have confirmed and defined more precisely vaccine efficacy against pneumonia with consolidation, and shown that the preventable burden of pneumococcal-related pneumonia is

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