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.
Bibliographical noteFunding 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 2014 Elsevier B.V., All rights reserved.
- Streptococcus pneumoniae