Publicação
Molecular epidemiology of Streptococcus pneumoniae : impact of PCV7 in the Pneumococcal population responsible for invasive pediatric infections
| Resumo: | Streptococcus pneumoniae is considered to be one of the major pathogens worldwide in the pediatric care setting. A variety of antimicrobial agents is used to treat pneumococcal infections, but the recent increase and worldwide dissemination of strains resistant to the main antimicrobials used, namely -lactams and macrolides, is difficulting the treatment of infections. With the purpose of reducing the burden of invasive pneumococcal disease (IPD) and the dissemination of resistant strains, a seven-valent conjugate vaccine (PCV7), containing the polysaccharides of the seven most prevalent serotypes in the USA, was licensed first in USA and then in other countries. The efficacy of this vaccine has been demonstrated in the USA, but due to significant variations in terms of prevalence of infection, serotype distribution and antimicrobial resistance, the usefulness of this vaccine in other countries is compromised. The aim of this work was to evaluate the potential impact of PCV7 in Portugal, which has been administered since late 2001 through the private sector. In order to achieve this, a collection of 475 S. pneumoniae isolates recovered between 2003 and 2008, from invasive infection in children and adolescents (<18 yrs), was characterized by serotyping, antimicrobial susceptibility testing, pulsed field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). The data was then compared with previous studies in order to infer the possible changes in the pneumococcal population after vaccine availability. The results obtained in this study revealed a significant reduction of the overall proportion of IPD caused by serotypes covered by PCV7. Yet this decrease was accompanied by an increase of non-vaccine serotypes such as serotypes 1, 19A and 7F. Due to the considerable variation in terms of genetic lineages within the same serotype it was important to determine which clones were associated with the expansion of these non-vaccine types. Furthermore, it was essential to establish if the lineages identified in the post-vaccine period were genetically related to the pre-vaccine clones. Overall, the molecular typing of the invasive isolates demonstrated that the clones identified in the emerging serotypes were already in circulation before vaccine availability. One of the main serotypes associated with IPD and antimicrobial resistance after PCV7 availability was serotype 19A. This serotype became increasingly important in several countries but the different studies performed in several geographic regions indicated that the genetic lineages associated with its expansion were unrelated. While in Portugal, the main lineage in expansion was represented by the clone Denmark14-ST230, the one found increasing in the USA was represented by ST320 and ST199. To determine if the clone increasing in Portugal was restricted to the invasive population we performed a study concerning all serotype 19A strains recovered from IPD, non-invasive infections and asymptomatic carriers between 2001 and 2006 in Portugal. Indeed, certain lineages were found to be more associated with carriage (ST1151 and ST416) while others were associated with invasive disease (ST193) but the main lineage associated with 19A expansion, represented by ST230, was found in all three populations. PCV7, along with the more recent vaccines PCV10 and PCV13, cover a restricted number of serotypes, and taking into consideration that the introduction of the first pneumococcal conjugate vaccine led to the increase of non-vaccine serotypes, the need for new, non-serotype based, vaccines persists. Several proteins have already been proposed but none of them seem to improve the coverage of the already available vaccines. Nevertheless, a recently discovered set of proteins, which compose pilus-like structures, were suggested to be used in a new vaccine formulation. To evaluate the potential use of pili in vaccine and to determine their possible role as virulence factors in S. pneumoniae, we determined the prevalence of the two known pili (PI-1 and PI-2) in a collection of invasive isolates recovered from children and adolescents (<18 years) between 1999 and 2008. Overall, only 17% of the invasive pneumococcal strains presented PI-1 while PI-2 was found in 33% of the population. An association between pili and serotype and PFGE clone was identified yet, all piliated strains presented one of the capsular types covered by the recent PCV13. Since only a small proportion of invasive pneumococcal strains presented pili and because all piliated pneumococci harbored capsular types covered by the most recent conjugate vaccines we consider that pili-based vaccines might not be the appropriate choice for prevention of pneumococcal infection. The results obtained in this study indicate that the pneumococcal population has an extraordinary ability to adapt to stressful situations, such as the introduction of a vaccine, due to the extensive diversity of capsular types and genetic lineages found worldwide. Furthermore, taking into consideration the changes observed after PCV7, the new conjugate vaccines will most probably face the same problem which enhances the need for continuous surveillance of IPD. |
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| Autores principais: | Aguiar, Sandra I. |
| Assunto: | Microbiologia Streptococcus pneumoniae Fímbrias bacterianas Vacinas pneumocócicas Vacinas conjugadas Criança Avaliação Portugal Teses de doutoramento - 2011 |
| Ano: | 2011 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Streptococcus pneumoniae is considered to be one of the major pathogens worldwide in the pediatric care setting. A variety of antimicrobial agents is used to treat pneumococcal infections, but the recent increase and worldwide dissemination of strains resistant to the main antimicrobials used, namely -lactams and macrolides, is difficulting the treatment of infections. With the purpose of reducing the burden of invasive pneumococcal disease (IPD) and the dissemination of resistant strains, a seven-valent conjugate vaccine (PCV7), containing the polysaccharides of the seven most prevalent serotypes in the USA, was licensed first in USA and then in other countries. The efficacy of this vaccine has been demonstrated in the USA, but due to significant variations in terms of prevalence of infection, serotype distribution and antimicrobial resistance, the usefulness of this vaccine in other countries is compromised. The aim of this work was to evaluate the potential impact of PCV7 in Portugal, which has been administered since late 2001 through the private sector. In order to achieve this, a collection of 475 S. pneumoniae isolates recovered between 2003 and 2008, from invasive infection in children and adolescents (<18 yrs), was characterized by serotyping, antimicrobial susceptibility testing, pulsed field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). The data was then compared with previous studies in order to infer the possible changes in the pneumococcal population after vaccine availability. The results obtained in this study revealed a significant reduction of the overall proportion of IPD caused by serotypes covered by PCV7. Yet this decrease was accompanied by an increase of non-vaccine serotypes such as serotypes 1, 19A and 7F. Due to the considerable variation in terms of genetic lineages within the same serotype it was important to determine which clones were associated with the expansion of these non-vaccine types. Furthermore, it was essential to establish if the lineages identified in the post-vaccine period were genetically related to the pre-vaccine clones. Overall, the molecular typing of the invasive isolates demonstrated that the clones identified in the emerging serotypes were already in circulation before vaccine availability. One of the main serotypes associated with IPD and antimicrobial resistance after PCV7 availability was serotype 19A. This serotype became increasingly important in several countries but the different studies performed in several geographic regions indicated that the genetic lineages associated with its expansion were unrelated. While in Portugal, the main lineage in expansion was represented by the clone Denmark14-ST230, the one found increasing in the USA was represented by ST320 and ST199. To determine if the clone increasing in Portugal was restricted to the invasive population we performed a study concerning all serotype 19A strains recovered from IPD, non-invasive infections and asymptomatic carriers between 2001 and 2006 in Portugal. Indeed, certain lineages were found to be more associated with carriage (ST1151 and ST416) while others were associated with invasive disease (ST193) but the main lineage associated with 19A expansion, represented by ST230, was found in all three populations. PCV7, along with the more recent vaccines PCV10 and PCV13, cover a restricted number of serotypes, and taking into consideration that the introduction of the first pneumococcal conjugate vaccine led to the increase of non-vaccine serotypes, the need for new, non-serotype based, vaccines persists. Several proteins have already been proposed but none of them seem to improve the coverage of the already available vaccines. Nevertheless, a recently discovered set of proteins, which compose pilus-like structures, were suggested to be used in a new vaccine formulation. To evaluate the potential use of pili in vaccine and to determine their possible role as virulence factors in S. pneumoniae, we determined the prevalence of the two known pili (PI-1 and PI-2) in a collection of invasive isolates recovered from children and adolescents (<18 years) between 1999 and 2008. Overall, only 17% of the invasive pneumococcal strains presented PI-1 while PI-2 was found in 33% of the population. An association between pili and serotype and PFGE clone was identified yet, all piliated strains presented one of the capsular types covered by the recent PCV13. Since only a small proportion of invasive pneumococcal strains presented pili and because all piliated pneumococci harbored capsular types covered by the most recent conjugate vaccines we consider that pili-based vaccines might not be the appropriate choice for prevention of pneumococcal infection. The results obtained in this study indicate that the pneumococcal population has an extraordinary ability to adapt to stressful situations, such as the introduction of a vaccine, due to the extensive diversity of capsular types and genetic lineages found worldwide. Furthermore, taking into consideration the changes observed after PCV7, the new conjugate vaccines will most probably face the same problem which enhances the need for continuous surveillance of IPD. |
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