Serotype-Specific Changes in Invasive Pneumococcal Disease after Pneumococcal Conjugate Vaccine Introduction: A Pooled Analysis of Multiple Surveillance Sites

Daniel R. Feikin, Eunice W. Kagucia, Jennifer D. Loo, Ruth Link-Gelles, Milo A. Puhan, Thomas Cherian, Orin S. Levine, Cynthia G. Whitney, Katherine L. O'Brien, Matthew R. Moore, Daniel R. Feikin, Ruth Link-Gelles, Thomas Cherian, Richard A. Adegbola, Mary Agocs, Krow Ampofo, Nick Andrews, Theresa Barton, Javier Benito, Claire V. BroomeMichael G. Bruce, Lisa R. Bulkow, Carrie L. Byington, Teresa Camou, Heather Cook, Suzanne Cotter, Ron Dagan, Philippe de Wals, Geneviève Deceuninck, Barbara Denham, Giles Edwards, Juhani Eskola, Margaret Fitzgerald, Emmanouil Galanakis, Gabriela Garcia-Gabarrot, Juan J. Garcia-Garcia, Amadeu Gene, Borja Gomez, Helen Heffernan, Thomas W. Hennessy, Sigrid Heuberger, Markus Hilty, Helene Ingels, Sanjay Jayasinghe, Eunice W. Kagucia, James D. Kellner, Nicola P. Klein, Andrea Kormann-Klement, Jana Kozakova, Vicki Krause, Paula Kriz, Lotte Lambertsen, Agnès Lepoutre, Orin S. Levine, Marc Lipsitch, Jennifer D. Loo, Mariana Lopez-Vega, Marguerite Lovgren, Sofia Maraki, Edward O. Mason, Peter B. McIntyre, Robert Menzies, Allison Messina, Elizabeth Miller, Santiago Mintegi, Matthew R. Moore, Jitka Motlova, Lawrence H. Moulton, Kathrin Mühlemann, Carmen Muñoz-Almagro, Katherine L. O'Brien, David R. Murdoch, Daniel E. Park, Milo A. Puhan, Arthur L. Reingold, Raquel Sa-Leao, Abanti Sanyal, Peter G. Smith, Lodewijk Spanjaard, Chonnamet Techasaensiri, Richard E. Thompson, Koh C. Thoon, Gregory J. Tyrrell, Palle Valentiner-Branth, Arie van der Ende, Otto G. Vanderkooi, Mark P.G. van der Linden, Emmanuelle Varon, Jan Verhaegen, Didrik F. Vestrheim, Imelda Vickers, Anne von Gottberg, Rüdiger von Kries, Pauline Waight, Robert Weatherholtz, Susanne Weiss, Cynthia G. Whitney, Arnold Yee, Anita K.M. Zaidi

Research output: Contribution to journalArticlepeer-review

353 Citations (Scopus)


Background:Vaccine-serotype (VT) invasive pneumococcal disease (IPD) rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Increases in non-vaccine-serotype (NVT) IPD rates occurred in some sites, presumably representing serotype replacement. We used a standardized approach to describe serotype-specific IPD changes among multiple sites after PCV7 introduction.Methods and Findings:Of 32 IPD surveillance datasets received, we identified 21 eligible databases with rate data ≥2 years before and ≥1 year after PCV7 introduction. Expected annual rates of IPD absent PCV7 introduction were estimated by extrapolation using either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates. To estimate whether changes in rates had occurred following PCV7 introduction, we calculated site specific rate ratios by dividing observed by expected IPD rates for each post-PCV7 year. We calculated summary rate ratios (RRs) using random effects meta-analysis. For children <5 years old, overall IPD decreased by year 1 post-PCV7 (RR 0·55, 95% CI 0·46-0·65) and remained relatively stable through year 7 (RR 0·49, 95% CI 0·35-0·68). Point estimates for VT IPD decreased annually through year 7 (RR 0·03, 95% CI 0·01-0·10), while NVT IPD increased (year 7 RR 2·81, 95% CI 2·12-3·71). Among adults, decreases in overall IPD also occurred but were smaller and more variable by site than among children. At year 7 after introduction, significant reductions were observed (18-49 year-olds [RR 0·52, 95% CI 0·29-0·91], 50-64 year-olds [RR 0·84, 95% CI 0·77-0·93], and ≥65 year-olds [RR 0·74, 95% CI 0·58-0·95]).Conclusions:Consistent and significant decreases in both overall and VT IPD in children occurred quickly and were sustained for 7 years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD occurred in most sites, with variable magnitude. These findings may not represent the experience in low-income countries or the effects after introduction of higher valency PCVs. High-quality, population-based surveillance of serotype-specific IPD rates is needed to monitor vaccine impact as more countries, including low-income countries, introduce PCVs and as higher valency PCVs are used.Please see later in the article for the Editors' Summary.

Original languageEnglish
Article numbere1001517
JournalPLoS Medicine
Issue number9
Publication statusPublished - Sept 2013

Bibliographical note

Funding Information:
We thank the GAVI Alliance, through AVI-Technical Assistance Consortium, for support of the dosing landscape analysis from which many of the datasets included here were identified. An expert consultation meeting for the study held at WHO in September 2011 was supported by the Bill and Melinda Gates Foundation. We thank the Serotype Replacement Study Group for providing feedback on the analysis at various points and contributing to the paper; the Group co-investigators for collecting and providing the site-specific data; and the Technical Advisory Group (TAG) members for their advice on the study design and data interpretation.


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