Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome...

• Autores: Lo, Stephanie W.; Gladstone, Rebecca A.; van Tonder, Andries J.; Lees, John A.; du Plessis, Mignon; Benisty, Rachel; Givon Lavi, Noga; Hawkins, Paulina A.; Cornick, Jennifer E.; Kwambana Adams, Brenda; Law, Pierra Y.; Ho, Pak Leung; Antonio, Martin; Everett, Dean B.; Dagan, Ron; Von Gottberg, Anne; Klugman, Keith P.; McGee, Lesley; Breiman, Robert F.; Bentley, Stephen D.; Brooks, Abdullah W.; Corso, Alejandra; Davydov, Alexander; Maguire, Alison; Pollard, Andrew; Kiran, Anmol; Skoczynska, Anna; Moiane, Benild; Beall, Bernard; Sigauque, Betuel; Aanensen, David; Lehmann, Deborah; Faccone, Diego Francisco
• Año de publicación: 2019
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: STREPTOCOCCAL; VACCINE; PCV13; RESISTANCE
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Background: Invasive pneumococcal disease remains an important health priority owing to increasing disease incidence caused by pneumococci expressing non-vaccine serotypes. We previously defined 621 Global Pneumococcal Sequence Clusters (GPSCs) by analysing 20 027 pneumococcal isolates collected worldwide and from previously published genomic data. In this study, we aimed to investigate the pneumococcal lineages behind the predominant serotypes, the mechanism of serotype replacement in disease, as well as the major pneumococcal lineages contributing to invasive pneumococcal disease in the post-vaccine era and their antibiotic resistant traits. Methods: We whole-genome sequenced 3233 invasive pneumococcal disease isolates from laboratory-based surveillance programmes in Hong Kong (n=78), Israel (n=701), Malawi (n=226), South Africa (n=1351), The Gambia (n=203), and the USA (n=674). The genomes represented pneumococci from before and after pneumococcal conjugate vaccine (PCV) introductions and were from children younger than 3 years. We identified predominant serotypes by prevalence and their major contributing lineages in each country, and assessed any serotype replacement by comparing the incidence rate between the pre-PCV and PCV periods for Israel, South Africa, and the USA. We defined the status of a lineage as vaccine-type GPSC (≥50% 13-valent PCV [PCV13] serotypes) or non-vaccine-type GPSC (>50% non-PCV13 serotypes) on the basis of its initial serotype composition detected in the earliest vaccine period to measure their individual contribution toward serotype replacement in each country. Major pneumococcal lineages in the PCV period were identified by pooled incidence rate using a random effects model. Findings: The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. These serotypes were associated with more than one lineage, except for serotype 5 (GPSC8). Serotype replacement was mainly mediated by expansion of non-vaccine serotypes within vaccine-type GPSCs and, to a lesser extent, by increases in non-vaccine-type GPSCs. A globally spreading lineage, GPSC3, expressing invasive serotypes 8 in South Africa and 33F in the USA and Israel, was the most common lineage causing non-vaccine serotype invasive pneumococcal disease in the PCV13 period. We observed that same prevalent non-vaccine serotypes could be associated with distinctive lineages in different countries, which exhibited dissimilar antibiotic resistance profiles. In non-vaccine serotype isolates, we detected significant increases in the prevalence of resistance to penicillin (52 [21%] of 249 vs 169 [29%] of 575, p=0·0016) and erythromycin (three [1%] of 249 vs 65 [11%] of 575, p=0·0031) in the PCV13 period compared with the pre-PCV period. Interpretation: Globally spreading lineages expressing invasive serotypes have an important role in serotype replacement, and emerging non-vaccine serotypes associated with different pneumococcal lineages in different countries might be explained by local antibiotic-selective pressures. Continued genomic surveillance of the dynamics of the pneumococcal population with increased geographical representation in the post-vaccine period will generate further knowledge for optimising future vaccine design. Funding: Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control.
Fil: Lo, Stephanie W.. Wellcome Sanger Institute; Reino Unido
Fil: Gladstone, Rebecca A.. Wellcome Sanger Institute; Reino Unido
Fil: van Tonder, Andries J.. Wellcome Sanger Institute; Reino Unido
Fil: Lees, John A.. University Of New York. School Of Medicine; Estados Unidos
Fil: du Plessis, Mignon. National Institute For Communicable Diseases; Sudáfrica
Fil: Benisty, Rachel. Ben Gurion University of the Negev; Israel
Fil: Givon Lavi, Noga. Ben Gurion University of the Negev; Israel
Fil: Hawkins, Paulina A.. University of Emory. Rollins School of Public Health; Estados Unidos
Fil: Cornick, Jennifer E.. Malawi liverpool wellcome trust; Malaui
Fil: Kwambana Adams, Brenda. University College London; Estados Unidos
Fil: Law, Pierra Y.. University of Hong Kong; China
Fil: Ho, Pak Leung. University of Hong Kong; China
Fil: Antonio, Martin. Medical Research Council Unit The Gambia; Gambia
Fil: Everett, Dean B.. University of Edinburgh; Reino Unido
Fil: Dagan, Ron. Ben Gurion University of the Negev; Israel
Fil: Von Gottberg, Anne. National Institute For Communicable Diseases; Sudáfrica
Fil: Klugman, Keith P.. University of Emory. Rollins School of Public Health; Estados Unidos
Fil: McGee, Lesley. Centers for Disease Control and Prevention; Estados Unidos
Fil: Breiman, Robert F.. University of Emory. Rollins School of Public Health; Estados Unidos
Fil: Bentley, Stephen D.. Wellcome Sanger Institute; Reino Unido
Fil: Brooks, Abdullah W.. The Global Pneumococcal Sequencing Consortium; Reino Unido
Fil: Corso, Alejandra. The Global Pneumococcal Sequencing Consortium; Reino Unido. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas. Área de Antimicrobianos; Argentina
Fil: Davydov, Alexander. The Global Pneumococcal Sequencing Consortium; Reino Unido
Fil: Maguire, Alison. The Global Pneumococcal Sequencing Consortium; Reino Unido
Fil: Pollard, Andrew. The Global Pneumococcal Sequencing Consortium; Reino Unido
Fil: Kiran, Anmol. The Global Pneumococcal Sequencing Consortium; Reino Unido
Fil: Skoczynska, Anna. The Global Pneumococcal Sequencing Consortium; Reino Unido
Fil: Moiane, Benild. The Global Pneumococcal Sequencing Consortium; Reino Unido
Fil: Beall, Bernard. The Global Pneumococcal Sequencing Consortium; Reino Unido
Fil: Sigauque, Betuel. The Global Pneumococcal Sequencing Consortium; Reino Unido
Fil: Aanensen, David. The Global Pneumococcal Sequencing Consortium; Reino Unido
Fil: Lehmann, Deborah. The Global Pneumococcal Sequencing Consortium; Reino Unido
Fil: Faccone, Diego Francisco. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Instituto Nacional de Enfermedades Infecciosas. Área de Antimicrobianos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina