Limiting comparisons to the latest pre-introduction years limited our ability to incorporate pre-introduction temporal trends. Conversely, abstraction of only the earliest full post-introduction year for data points in those <5 years of age, to maintain a “pure” non-targeted group, resulted in exclusion of later data points

when the PCV impact would be greater. Finally, we did not assess indirect effects in vaccinated children. Because direct protection from vaccination is imperfect and vaccinated children remain at some risk for disease, some component of their protection is likely due to indirect effects. Ruxolitinib This is supported by declines in all-cause pneumonia in vaccinated age groups after introduction significantly exceeding those found in pre-licensure efficacy trials [79]. Additionally, although pneumonia is by far the most common clinical syndrome associated with pneumococcal infection, most cases of pneumococcal pneumonia are not microbiologically identified and thus not represented here. However, the included pneumonia data are

consistent with the relationships described. In spite of these limitations, the consistent association between PCV introduction and subsequent declines in both VT-carriage and VT-IPD in non-target age-groups supports reduction of NP carriage and transmission as a key element Selleckchem MDV3100 in the overall public health impact of PCV, offering a unique contribution for licensing decisions for pneumococcal vaccines. The authors gratefully acknowledge the work of Jennifer

Loo for provision of the literature search results. This study is part of the research of the PneumoCarr Consortium funded by the Grand Challenges in Global Health Initiative which is supported by the Bill & Melinda Gates Foundation, the Foundation for the National Institutes of Health, the Wellcome Trust and the Canadian Institutes of Health Research. We gratefully acknowledge the Pneumococcal Conjugate Vaccine Dosing Landscape project, a project of the Accelerated Vaccine Initiative, Technical Assistance Consortium-Special Studies. Support for the Pneumococcal unless Conjugate Vaccine Dosing Landscape Project, was provided by Program for Appropriate Technology in Health (PATH) through funding from the Global Alliance for Vaccines and Immunization (GAVI). The views expressed by the authors do not necessarily reflect the views of the GAVI Alliance and/or PATH. Conflict of interest statement: KOB has had research grant support related to pneumococcus from Pfizer, and GlaxoSmithKline and has served on pneumococcal external expert committees convened by Merck, Aventis-pasteur, and GlaxoSmithKline. MDK serves on a Data and Safety Monitoring Board for Novartis for vaccines unrelated to pneumococcus.