Meta-Analysis of the Efficacy of Conjugate Vaccines against Invasive Pneumococcal Disease

This chapter reviews the results of four trials to study efficacy of pneumococcal conjugate vaccine against invasive pneumococcal disease (IPD) and explores the protection achieved against aggregate and individual serotypes using the common end point of invasive pneumococcal disease (IPD) in all the four trials. It also discusses these results in terms of the different populations at risk and the schedules of vaccination. Children initially randomized in California received oral polio vaccines and diphtheria-tetanus whole-cell pertussis (DTwP) vaccines, while children randomized later received inactivated polio and diphtheria-tetanus-acellular pertussis (DTaP) vaccines; children in an American Indian trial received inactivated or oral polio and DTaP vaccines. Meta-analyses of results were performed from intent-to-treat analyses, modified to include children who received at least one dose of vaccine or placebo. The demonstration of substantial conjugate pneumococcal vaccine efficacy in large clinical trials in four disparate regions of the world encourages the view that the vaccine is likely to prevent IPD in most countries in which vaccine serotypes are an important cause of IPD among infants. Pneumococcal conjugate vaccine has been considered as a probe to determine the burden of disease due to pneumococci in contexts such as pneumonia, and has greatly reduced the burden of IPD due to vaccine serotypes in the United States. The introduction of vaccine requires well-designed surveillance studies to understand the impact of the vaccine on the range of disease in populations in which it is introduced.