This competing renewal application builds on the success and productivity of our current project investigating changes in the pneumococcal population in the conjugate vaccine era, and seeks to continue surveillance and analysis during the introduction of PCV13. Our work to date has substantially increased our understanding of how this pathogen responds to the potent selective pressure of a vaccine. As PCV7 vaccine serotypes have virtually disappeared from the nasopharynx, they have been quickly and completely replaced by non-vaccine serotypes. Clinically, these non-vaccine serotypes have become responsible for the great majority of invasive pneumococcal disease. Now, a new 13-valent pneumococcal conjugate vaccine (PCV13) that includes 6 additional serotypes (1, 3, 5, 6A, 7F, 19A), will be introduced in 2010. This research will provide data needed to understand the clinical implications of PCV13 use, test specific hypotheses we have developed about bacterial adaptation, and serve as a template for understanding the evolution of other pathogens. Given our team of collaborators, the ongoing commitment of community partners, and our access to state-of-the-art genetic sequencing resources, we are uniquely positioned to address the following specific aims: 1. To examine trends in pneumococcal colonizing and invasive disease isolates, with regard to serotype and antibiotic resistance, host risk factors, and invasive potential, before and after introduction of PCV13. 2. To assess shifts in pneumococcal population structure (by MLST) and evaluate potential factors associated with successful spread of pneumococcal clones in Massachusetts in the context of PCV13 introduction. 3. To use whole genome sequencing to identify potential genetic determinants associated with serotype switching and invasiveness among clones that have emerged under selective vaccine pressure. To achieve these goals, we will collect new nasopharyngeal specimens from 2,250 children as they present for routine pediatric care (in 2011 and 2014) in nine distinct Massachusetts communities, and analyze them in the context of previous collections available for comparison from 2001, 2004, 2007, and 2009. In addition we will simultaneously analyze invasive disease isolates collected from children in Massachusetts as part of an enhanced statewide surveillance program in Massachusetts since 2001. In total, this continuing project provides an unprecedented opportunity to assess bacterial evolution in real time, and connect changes in carriage to those in invasive disease.

Public Health Relevance

The introduction of PCV13 will allow us to test specific hypotheses about the sequence and mechanisms of bacterial evolution in response to the potent selective pressure of immunization and continuing pressure of high rates of antibiotic use. Specifically, we will better understand the roles of antibiotic resistance, and other specific adaptations (e.g. the presence of pilus), as well as the clinical implications (for invasive disease) of inclusion of 19A, currently the most invasive and rapidly expanding serotype. These results will inform development and implementation of future vaccines, for pneumococcus and other organisms, by providing data on possible responses of bacterial populations that may blunt their intended clinical impact. Relevance The introduction of PCV13 will allow us to test specific hypotheses about the sequence and mechanisms of bacterial evolution in response to the potent selective pressure of immunization and continuing pressure of high rates of antibiotic use. Specifically, we will better understand the roles of antibiotic resistance, and other specific adaptations (e.g. the presence of pilus), as well as the clinical implications (for invasive disease) of inclusion of 19A, currently the most invasive and rapidly expanding serotype. These results will inform development and implementation of future vaccines, for pneumococcus and other organisms, by providing data on possible responses of bacterial populations that may blunt their intended clinical impact.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01AI066304-09
Application #
8705345
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Taylor, Christopher E,
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Harvard Pilgrim Health Care, Inc.
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02215
Lee, Grace M; Kleinman, Ken; Pelton, Stephen I et al. (2014) Impact of 13-Valent Pneumococcal Conjugate Vaccination on Streptococcus pneumoniae Carriage in Young Children in Massachusetts. J Pediatric Infect Dis Soc 3:23-32
Li, Yuan; Weinberger, Daniel M; Thompson, Claudette M et al. (2013) Surface charge of Streptococcus pneumoniae predicts serotype distribution. Infect Immun 81:4519-24
Croucher, Nicholas J; Finkelstein, Jonathan A; Pelton, Stephen I et al. (2013) Population genomics of post-vaccine changes in pneumococcal epidemiology. Nat Genet 45:656-63
Hsu, K K; Rifas-Shiman, S L; Shea, K M et al. (2013) Do community-level predictors of pneumococcal carriage continue to play a role in the conjugate vaccine era? Epidemiol Infect :1-9
Wroe, Peter C; Lee, Grace M; Finkelstein, Jonathan A et al. (2012) Pneumococcal carriage and antibiotic resistance in young children before 13-valent conjugate vaccine. Pediatr Infect Dis J 31:249-54
Calix, Juan J; Dagan, Ron; Pelton, Stephen I et al. (2012) Differential occurrence of Streptococcus pneumoniae serotype 11E between asymptomatic carriage and invasive pneumococcal disease isolates reflects a unique model of pathogen microevolution. Clin Infect Dis 54:794-9
Hanage, William P; Bishop, Cynthia J; Huang, Susan S et al. (2011) Carried pneumococci in Massachusetts children: the contribution of clonal expansion and serotype switching. Pediatr Infect Dis J 30:302-8
Hanage, W P; Bishop, C J; Lee, G M et al. (2011) Clonal replacement among 19A Streptococcus pneumoniae in Massachusetts, prior to 13 valent conjugate vaccination. Vaccine 29:8877-81
Regev-Yochay, Gili; Hanage, William P; Trzcinski, Krzysztof et al. (2010) Re-emergence of the type 1 pilus among Streptococcus pneumoniae isolates in Massachusetts, USA. Vaccine 28:4842-6
Weinberger, Daniel M; Harboe, Zitta B; Sanders, Elisabeth A M et al. (2010) Association of serotype with risk of death due to pneumococcal pneumonia: a meta-analysis. Clin Infect Dis 51:692-9

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