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Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study.
Lancet Infect Dis. 2019 07; 19(7):759-769.LI

Abstract

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.

Authors+Show Affiliations

Parasites and Microbes, Wellcome Sanger Institute, Hinxton, UK. Electronic address: stephanie.lo@sanger.ac.uk.Parasites and Microbes, Wellcome Sanger Institute, Hinxton, UK.Parasites and Microbes, Wellcome Sanger Institute, Hinxton, UK.Department of Microbiology, New York University School of Medicine, New York, NY, USA.Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Johannesburg, South Africa.The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.Rollins School Public Health, Emory University, Atlanta, GA, USA.Malawi-Liverpool-Wellcome-Trust, Blantyre, Malawi.NIHR Global Health Research Unit on Mucosal Pathogens, Division of Infection and Immunity, University College London, London, UK; WHO Collaborating Centre for New Vaccines Surveillance, Medical Research Council Unit The Gambia at The London School of Hygiene & Tropical Medicine, Fajara, The Gambia.Department of Microbiology and Carol Yu Centre for Infection, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.Department of Microbiology and Carol Yu Centre for Infection, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.WHO Collaborating Centre for New Vaccines Surveillance, Medical Research Council Unit The Gambia at The London School of Hygiene & Tropical Medicine, Fajara, The Gambia.Centre for Inflammation Research, Queens Research Institute, University of Edinburgh, Edinburgh, UK.The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Johannesburg, South Africa.Rollins School Public Health, Emory University, Atlanta, GA, USA.Centers for Disease Control and Prevention, Atlanta, GA, USA.Rollins School Public Health, Emory University, Atlanta, GA, USA; Emory Global Health Institute, Emory University, Atlanta, GA, USA.Parasites and Microbes, Wellcome Sanger Institute, Hinxton, UK.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

31196809

Citation

Lo, Stephanie W., et al. "Pneumococcal Lineages Associated With Serotype Replacement and Antibiotic Resistance in Childhood Invasive Pneumococcal Disease in the post-PCV13 Era: an International Whole-genome Sequencing Study." The Lancet. Infectious Diseases, vol. 19, no. 7, 2019, pp. 759-769.
Lo SW, Gladstone RA, van Tonder AJ, et al. Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study. Lancet Infect Dis. 2019;19(7):759-769.
Lo, S. W., Gladstone, R. A., van Tonder, A. J., Lees, J. A., du Plessis, M., Benisty, R., Givon-Lavi, N., Hawkins, P. A., Cornick, J. E., Kwambana-Adams, B., Law, P. Y., Ho, P. L., Antonio, M., Everett, D. B., Dagan, R., von Gottberg, A., Klugman, K. P., McGee, L., Breiman, R. F., & Bentley, S. D. (2019). Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study. The Lancet. Infectious Diseases, 19(7), 759-769. https://doi.org/10.1016/S1473-3099(19)30297-X
Lo SW, et al. Pneumococcal Lineages Associated With Serotype Replacement and Antibiotic Resistance in Childhood Invasive Pneumococcal Disease in the post-PCV13 Era: an International Whole-genome Sequencing Study. Lancet Infect Dis. 2019;19(7):759-769. PubMed PMID: 31196809.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study. AU - Lo,Stephanie W, AU - Gladstone,Rebecca A, AU - van Tonder,Andries J, AU - Lees,John A, AU - du Plessis,Mignon, AU - Benisty,Rachel, AU - Givon-Lavi,Noga, AU - Hawkins,Paulina A, AU - Cornick,Jennifer E, AU - Kwambana-Adams,Brenda, AU - Law,Pierra Y, AU - Ho,Pak Leung, AU - Antonio,Martin, AU - Everett,Dean B, AU - Dagan,Ron, AU - von Gottberg,Anne, AU - Klugman,Keith P, AU - McGee,Lesley, AU - Breiman,Robert F, AU - Bentley,Stephen D, AU - ,, Y1 - 2019/06/10/ PY - 2019/01/21/received PY - 2019/04/01/revised PY - 2019/04/10/accepted PY - 2019/6/15/pubmed PY - 2020/6/10/medline PY - 2019/6/15/entrez SP - 759 EP - 769 JF - The Lancet. Infectious diseases JO - Lancet Infect Dis VL - 19 IS - 7 N2 - 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. SN - 1474-4457 UR - https://www.unboundmedicine.com/medline/citation/31196809/Pneumococcal_lineages_associated_with_serotype_replacement_and_antibiotic_resistance_in_childhood_invasive_pneumococcal_disease_in_the_post_PCV13_era:_an_international_whole_genome_sequencing_study_ DB - PRIME DP - Unbound Medicine ER -