Publicação
Evolution and adaptation of Streptococcus pneumoniae population in the era of expanded conjugate vaccines
| Resumo: | Streptococcus pneumoniae (or pneumococcus) is one of the most important causes of bacterial infections mainly in young children, immunocompromised individuals of all ages and the elderly. It is responsible for meningitis, bacteremia and pneumonia, as well as sinusitis and otitis media. Besides this, the natural way of living of this bacterium is through asymptomatic nasopharyngeal colonization. Colonization rates are generally high among young children, the major reservoir and source of transmission of pneumococci. Once colonization is the first step for pneumococcal disease and is essential for bacteria spreading between individuals, this has been an important focus of research. Most pneumococcus have a polysaccharide capsule that is responsible for the existence of close to 100 variants (or serotypes) and that is considered its main virulence factor. For this reason, the capsule has been the main target for pneumococcal vaccine design. In Portugal, pneumococcal conjugate vaccines (PCVs) were only introduced in the Nacional Immunization Program in 2015. In the era of multivalent pneumococcal conjugated vaccines, epidemiological and surveillance studies are of major importance to obtain information that will help our understanding of serotype and clonal replacement changes occurring in carriage and disease as a consequence of vaccination. To obtain this information, microbial typing tools are fundamental to provide data about the evolution of bacterial population. Serotyping tools are widely used to address the effectiveness of pneumococcal vaccination. However, it is known that capsular type alone may not give the full picture regarding vaccine impact. The aim of this study was to address the clonal evolution and adaptation of the pneumococcus after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Portugal. For that, we used multilocus sequence typing (MLST), the ‘gold standard’ of molecular typing for the pneumococcus. We analyzed close to 700 nasopharyngeal isolates from children attending day-care centers, collected before introduction of PCV13 (2009 – 2010) and in the years afterwards (2011 – 2016) in two regions of Portugal. Our focus turned into answering main questions regarding the clonal evolution leading to persistence of some vaccine-types and emergence of non-vaccine types, overtime. The results showed that, regarding the few vaccine-types that are still in circulation, for most cases it is one major clone, that was already in circulation before vaccine introduction, that is responsible for the persistence of that serotype, as it is the case of the clonal complex (CC) 179 associated with serotype 19F. Besides that, whenever there is high clonal diversity and the presence of antimicrobial resistant clones before vaccine introduction, in most cases it is the resistant clone that is maintained overtime. Regarding non-vaccine types we detected clonal expansion associated with clones that were already in circulation and the emergence of novel, previously undetected clones. In this group of serotypes, antimicrobial resistance did not have such an important role as the one detected for the vaccine-type clones. We found few capsular switch events, but we could not correlate this phenomenon with vaccine impact. With this study we could conclude that PCV13 impacts on the pneumococcal population beyond capsular type and that this population is able to genetically adapt and evolve to this pressure. |
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| Autores principais: | Candeias, Catarina Isabel Brandão |
| Assunto: | Streptococcus pneumoniae Colonization PCV13 MLST Clones Teses de mestrado - 2018 |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Streptococcus pneumoniae (or pneumococcus) is one of the most important causes of bacterial infections mainly in young children, immunocompromised individuals of all ages and the elderly. It is responsible for meningitis, bacteremia and pneumonia, as well as sinusitis and otitis media. Besides this, the natural way of living of this bacterium is through asymptomatic nasopharyngeal colonization. Colonization rates are generally high among young children, the major reservoir and source of transmission of pneumococci. Once colonization is the first step for pneumococcal disease and is essential for bacteria spreading between individuals, this has been an important focus of research. Most pneumococcus have a polysaccharide capsule that is responsible for the existence of close to 100 variants (or serotypes) and that is considered its main virulence factor. For this reason, the capsule has been the main target for pneumococcal vaccine design. In Portugal, pneumococcal conjugate vaccines (PCVs) were only introduced in the Nacional Immunization Program in 2015. In the era of multivalent pneumococcal conjugated vaccines, epidemiological and surveillance studies are of major importance to obtain information that will help our understanding of serotype and clonal replacement changes occurring in carriage and disease as a consequence of vaccination. To obtain this information, microbial typing tools are fundamental to provide data about the evolution of bacterial population. Serotyping tools are widely used to address the effectiveness of pneumococcal vaccination. However, it is known that capsular type alone may not give the full picture regarding vaccine impact. The aim of this study was to address the clonal evolution and adaptation of the pneumococcus after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Portugal. For that, we used multilocus sequence typing (MLST), the ‘gold standard’ of molecular typing for the pneumococcus. We analyzed close to 700 nasopharyngeal isolates from children attending day-care centers, collected before introduction of PCV13 (2009 – 2010) and in the years afterwards (2011 – 2016) in two regions of Portugal. Our focus turned into answering main questions regarding the clonal evolution leading to persistence of some vaccine-types and emergence of non-vaccine types, overtime. The results showed that, regarding the few vaccine-types that are still in circulation, for most cases it is one major clone, that was already in circulation before vaccine introduction, that is responsible for the persistence of that serotype, as it is the case of the clonal complex (CC) 179 associated with serotype 19F. Besides that, whenever there is high clonal diversity and the presence of antimicrobial resistant clones before vaccine introduction, in most cases it is the resistant clone that is maintained overtime. Regarding non-vaccine types we detected clonal expansion associated with clones that were already in circulation and the emergence of novel, previously undetected clones. In this group of serotypes, antimicrobial resistance did not have such an important role as the one detected for the vaccine-type clones. We found few capsular switch events, but we could not correlate this phenomenon with vaccine impact. With this study we could conclude that PCV13 impacts on the pneumococcal population beyond capsular type and that this population is able to genetically adapt and evolve to this pressure. |
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