BACKGROUND: Widespread use of pneumococcal conjugate vaccines (PCVs) has reduced vaccine-type invasive pneumococcal disease (IPD). We describe the serotype distribution of IPD after extensive use of ten-valent PCV (PCV10; Synflorix, GSK) and 13-valent PCV (PCV13; Prevenar 13, Pfizer) globally. METHODS: IPD data were obtained from surveillance sites participating in the WHO-commissioned Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project that exclusively used PCV10 or PCV13 (hereafter PCV10 and PCV13 sites, respectively) in their national immunisation programmes and had primary series uptake of at least 70%. Serotype distribution was estimated for IPD cases occurring 5 years or more after PCV10 or PCV13 introduction (ie, the mature period when the serotype distribution had stabilised) using multinomial Dirichlet regression, stratified by PCV product and age group (<5 years, 5-17 years, 18-49 years, and ≥50 years). FINDINGS: The analysis included cases occurring primarily between 2015 and 2018 from 42 PCV13 sites (63 362 cases) and 12 PCV10 sites (6806 cases) in 41 countries. Sites were mostly high income (36 [67%] of 54) and used three-dose or four-dose booster schedules (44 [81%]). At PCV10 sites, PCV10 serotypes caused 10·0% (95% CI 6·3-12·9) of IPD cases in children younger than 5 years and 15·5% (13·4-19·3) of cases in adults aged 50 years or older, while PCV13 serotypes caused 52·1% (49·2-65·4) and 45·6% (40·0-50·0), respectively. At PCV13 sites, PCV13 serotypes caused 26·4% (21·3-30·0) of IPD cases in children younger than 5 years and 29·5% (27·5-33·0) of cases in adults aged 50 years or older. The leading serotype at PCV10 sites was 19A in children younger than 5 years (30·6% [95% CI 18·2-43·1]) and adults aged 50 years or older (14·8% [11·9-17·8]). Serotype 3 was a top-ranked serotype, causing about 9% of cases in children younger than 5 years and 14% in adults aged 50 years or older at both PCV10 and PCV13 sites. Across all age and PCV10 or PCV13 strata, the proportion of IPD targeted by higher-valency PCVs beyond PCV13 was 4·1-9·7% for PCV15, 13·5-36·0% for PCV20, 29·9-53·8% for PCV21, 15·6-42·0% for PCV24, and 31·5-50·1% for PCV25. All top-ten ranked non-PCV13 serotypes are included in at least one higher-valency PCV. INTERPRETATION: The proportion of IPD due to serotypes included in PCVs in use was low in mature PCV10 and PCV13 settings. Serotype distribution differed between PCV10 and PCV13 sites and age groups. Higher-valency PCVs target most remaining IPD and are expected to extend impact. FUNDING: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

Arctic Investigations Program Division of Preparedness and Emerging Infections National Center for Emerging and Zoonotic Infectious Diseases US Centers for Disease Control and Prevention Anchorage AK USA

Bacterial Respiratory Infection Service Scottish Microbiology Reference Laboratory NHS Greater Glasgow and Clyde Glasgow UK

Central Laboratory of Public Health Asunción Paraguay

Centre for Disease Control Department of Health and Community Services Darwin NT Australia

Centre for Respiratory Diseases and Meningitis National Institute for Communicable Diseases of the National Health Laboratory Service Johannesburg South Africa; School of Pathology Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa

Centre for Respiratory Diseases and Meningitis National Institute for Communicable Diseases of the National Health Laboratory Service Johannesburg South Africa; School of Public Health Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa

CIBER de Enfermedades Respiratorias Madrid Spain; Epidemiology Department Dirección General de Salud Pública Madrid Spain

CIBER Epidemiología y Salud Pública Madrid Spain; Medicine Department International University of Catalunya Barcelona Spain; Molecular Microbiology Department Hospital Sant Joan de Déu Research Institute Barcelona Spain

CIBER Epidemiología y Salud Pública Madrid Spain; Public Health Institute of Navarre Pamplona Spain; Navarre Institute for Health Research Pamplona Spain

Clinical Bacteriology Service Department of Bacteriology National Institute for Infectious Diseases Dr Carlos G Malbrán Buenos Aires Argentina

Communicable Diseases Centre National Institute of Public Health Ljubljana Slovenia

Costa Rican Institute for Research and Teaching in Nutrition and Health Tres Ríos Costa Rica

Department of Clinical Microbiology Landspitali The National University Hospital Reykjavik Iceland

Department of Health Security Finnish Institute for Health and Welfare Helsinki Finland; Health Sciences Unit Faculty of Social Sciences Tampere University Tampere Finland

Department of Infectious Diseases Italian National Institute of Health Rome Italy

Department of Microbiology and Carol Yu Centre for Infection Queen Mary Hospital The University of Hong Kong Hong Kong Special Administrative Region China

Department of Microbiology Immunology and Transplantation KU Leuven Leuven Belgium; National Reference Centre for Streptococcus Pneumoniae University Hospitals Leuven Leuven Belgium

Department of Microbiology Public Health Agency of Sweden Solna Sweden

Department of Pediatrics University of Calgary and Alberta Health Services Calgary AB Canada

Department of Pediatrics Yale New Haven Children's Hospital New Haven CT USA

Department of Public Health Ministry of Health and Care Services Oslo Norway

Department of Social and Preventive Medicine Laval University Québec QC Canada

Division of Bacterial Diseases National Center for Immunizations and Respiratory Diseases US Centers for Disease Control and Prevention Atlanta GA USA

Division of Global Health Protection Center for Global Health Centers for Disease Control and Prevention Nairobi Kenya; Division of Bacterial Diseases National Center for Immunizations and Respiratory Diseases US Centers for Disease Control and Prevention Atlanta GA USA

Division of Pediatric Infectious Diseases Department of Pediatrics University of Utah Health Sciences Center Salt Lake City UT USA

Epidemiology and Demography Department KEMRI Wellcome Trust Research Programme Centre for Geographic Medicine Coast Kilifi Kenya

Epidemiology Department Epiconcept Paris France

Epidemiology Team Institute of Environmental Science and Research Porirua New Zealand

European Centre for Disease Prevention and Control Solna Sweden

Immunisation and Countermeasures Division UK Health Security Agency London UK

Infectious Disease Epidemiology and Prevention Statens Serum Institut Copenhagen Denmark

Infectious Disease Epidemiology and Prevention Statens Serum Institut Copenhagen Denmark; Department of Bacteria Parasites and Fungi Statens Serum Institut Copenhagen Denmark

Infectious Diseases Research Unit Mohammed 6 Center for Research and Innovation Casablanca Morocco

Institute of Infection Veterinary and Ecological Sciences University of Liverpool Liverpool UK; Malawi Liverpool Wellcome Programme Blantyre Malawi

Institute of Public Health Riga Stradiņš University Riga Latvia

Instituto de Salud Pública de Chile Santiago Chile

Irish Meningitis and Sepsis Reference Laboratory Children's Health Ireland at Temple Street Dublin Ireland; Royal College of Surgeons in Ireland Dublin Ireland

Johns Hopkins Bloomberg School of Public Health Baltimore MD USA

Johns Hopkins Bloomberg School of Public Health Baltimore MD USA; Epidemiology and Demography Department KEMRI Wellcome Trust Research Programme Centre for Geographic Medicine Coast Kilifi Kenya

Johns Hopkins Bloomberg School of Public Health Baltimore MD USA; WHO Geneva Switzerland

Medical Microbiology and Infection Prevention Netherlands Reference Laboratory for Bacterial Meningitis Amsterdam UMC University of Amsterdam Amsterdam Netherlands

Murdoch Children's Research Institute Parkville VIC Australia

National Centre for Immunisation Research and Surveillance and Discipline of Child and Adolescent Health Children's Hospital Westmead Clinical School Faculty of Medicine and Health University of Sydney Westmead NSW Australia

National Institute of Public Health Prague Czech Republic

National Laboratory for Meningitis and Pneumococcal Infections Center of Bacteriology Institute Adolfo Lutz São Paulo Brazil

National Meningitis Reference Laboratory Department of Public Health Policy School of Public Health University of West Attica Athens Greece

National Public Health Laboratory National Centre for Infectious Diseases Singapore

National Reference Centre for Pneumococcal and Haemophilus Diseases Regional Authority of Public Health Banská Bystrica Slovakia

National Reference Centre for Pneumococci Data Research Department Intercommunal Hospital of Créteil Créteil France

New Vaccines Group Murdoch Children's Research Institute Parkville VIC Australia; Department of Paediatrics University of Melbourne Parkville VIC Australia; Faculty of Infectious and Tropical Diseases London School of Hygiene and Tropical Medicine London UK; Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine Banjul The Gambia

Pan American Health Organization WHO Washington DC USA

Reference Laboratory for Streptococci Department of Medical Microbiology University Hospital RWTH Aachen Aachen Germany

Swiss National Reference Centre for Invasive Pneumococci Institute for Infectious Diseases University of Bern Bern Switzerland

The Shraga Segal Department of Microbiology Immunology and Genetics Faculty of Health Sciences Ben Gurion University of the Negev Beer Sheva Israel

Toronto Invasive Bacterial Diseases Network and Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON Canada

Toyama Institute of Health Toyama Japan

University Multiprofile Hospital for Active Treatment Saint Ivan Rilski Clinical Microbiology Laboratory Sofia Bulgaria

Vaccine Study Center Kaiser Permanente Oakland CA USA

WHO Geneva Switzerland

WHO Regional Office for Africa Brazzaville Republic of the Congo

Erratum v

Lancet Infect Dis. 2025 Feb;25(2):e68. doi: 10.1016/S1473-3099(25)00002-7. PubMed

Zobrazit více v PubMed

GBD 2019 Antimicrobial Resistance Collaborators Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2022;400:2221–2248. PubMed PMC

Johnson HL, Deloria-Knoll M, Levine OS, et al. Systematic evaluation of serotypes causing invasive pneumococcal disease among children under five: the Pneumococcal Global Serotype project. PLoS Med. 2010;7 PubMed PMC

International Vaccine Access Center. Johns Hopkins Bloomberg School of Public Health VIEW-hub by IVAC: pneumococcal conjugate vaccine (PCV) access and coverage. https://view-hub.org/vaccine/pcv/access

WHO Pneumococcal conjugate vaccine for childhood immunization—WHO position paper. Wkly Epidemiol Rec. 2007;82:93–104. PubMed

Cherian T, Cohen M, de Oliveira L, et al. Pneumococcal Conjugate Vaccine (PCV) Review of Impact Evidence (PRIME): summary of findings from systematic review. 2017. https://terrance.who.int/mediacentre/data/sage/SAGE_Docs_Ppt_Oct2017/9_session_PCV/Oct2019_session9_PCV_PRIMEsummary.pdf

Feikin DR, Kagucia EW, Loo JD, et al. Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites. PLoS Med. 2013;10 PubMed PMC

PATH New pneumococcal vaccine from Serum Institute of India achieves WHO prequalification. 2019. https://www.path.org/our-impact/media-center/new-pneumococcal-vaccine-serum-institute-india-achieves-who-prequalification/

Merck US FDA approves Merck's VAXNEUVANCE™ (pneumococcal 15-valent conjugate vaccine) for the prevention of invasive pneumococcal disease in infants and children. 2022. https://www.merck.com/news/u-s-fda-approves-mercks-vaxneuvance-pneumococcal-15-valent-conjugate-vaccine-for-the-prevention-of-invasive-pneumococcal-disease-in-infants-and-children/

Merck European Commission expands Merck's VAXNEUVANCE™ (pneumococcal 15-valent conjugate vaccine) indication to include infants, children and adolescents. 2022. https://www.merck.com/news/european-commission-expands-mercks-vaxneuvance-pneumococcal-15-valent-conjugate-vaccine-indication-to-include-infants-children-and-adolescents/

Pfizer US FDA approves PREVNAR 20, Pfizer's 20-valent pneumococcal conjugate vaccine for infants and children. 2023. https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-prevnar-20r-pfizers-20-valent-pneumococcal

European Medicines Agency Prevenar 20 (previously Apexxnar) https://www.ema.europa.eu/en/medicines/human/EPAR/prevenar-20-previously-apexxnar

US Food and Drug Administration CAPVAXIVE. 2024. https://www.fda.gov/vaccines-blood-biologics/capvaxive

McGuinness D, Kaufhold RM, McHugh PM, et al. Immunogenicity of PCV24, an expanded pneumococcal conjugate vaccine, in adult monkeys and protection in mice. Vaccine. 2021;39:4231–4237. PubMed

Vaxcyte Pipeline. https://vaxcyte.com/pipeline/

GSK Pipeline. https://www.gsk.com/en-gb/innovation/pipeline/

Inventprise New Inventprise pneumococcal vaccine enters phase 1/2 clinical evaluation. 2022. https://inventprise.com/2022/11/10/new-inventprise-pneumococcal-vaccine-enters-phase-1-2-clinical-evaluation/

Datta AK, Kapre SV. Preclinical results for a 25-valent pneumococcal conjugate vaccine using a novel linker platform technology. 2022. https://inventprise.com/wp-content/uploads/2023/02/INVENT_ISPPD-2022-PRECLINICAL-RESULTS-FOR-A-25-VALENT-PNEUMOCOCCAL-CONJUGATE-VACCINE-1.pdf

Deloria-Knoll M, Bennett JC, Garcia Quesada M, et al. Global landscape review of serotype-specific invasive pneumococcal disease surveillance among countries using PCV10/13: the Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project. Microorganisms. 2021;9:742. PubMed PMC

Garcia Quesada M, Yang Y, Bennett JC, et al. Serotype distribution of remaining pneumococcal meningitis in the mature PCV10/13 period: findings from the PSERENADE Project. Microorganisms. 2021;9:738. PubMed PMC

Merck Merck announces US FDA has granted breakthrough therapy designation for V116, the company's investigational 21-valent pneumococcal conjugate vaccine, for the prevention of invasive pneumococcal disease and pneumococcal pneumonia in adults. 2022. https://www.merck.com/news/merck-announces-u-s-fda-has-granted-breakthrough-therapy-designation-for-v116-the-companys-investigational-21-valent-pneumococcal-conjugate-vaccine-for-the-prevention-of-invasive-pneumococ/

Bennett JC, Deloria Knoll M, Kagucia EW, et al. Global impact of ten-valent and 13-valent pneumococcal conjugate vaccines on invasive pneumococcal disease in all ages (the PSERENADE project): a global surveillance analysis. Lancet Infect Dis. 2024 doi: 10.1016/S1473-3099(24)00665-0. published online Dec 17. PubMed DOI PMC

van Selm S, vac Cann LM, Kolkman MAB, van der Zeijst BAM, van Putten JPM. Genetic basis for the structural difference between Streptococcus pneumoniae serotype 15B and 15C capsular polysaccharides. Infect Immun. 2003;71:6192–6198. PubMed PMC

Yee TW. Springer; 2015. Vector generalized linear and additive models.

Cooper D, Yu X, Sidhu M, Nahm MH, Fernsten P, Jansen KU. The 13-valent pneumococcal conjugate vaccine (PCV13) elicits cross-functional opsonophagocytic killing responses in humans to Streptococcus pneumoniae serotypes 6C and 7A. Vaccine. 2011;29:7207–7211. PubMed PMC

Grant LR, Slack MPE, Theilacker C, et al. Distribution of serotypes causing invasive pneumococcal disease in children from high-income countries and the impact of pediatric pneumococcal vaccination. Clin Infect Dis. 2023;76:e1062–e1070. PubMed PMC

Grant LR, Slack MPE, Theilacker C, et al. Distribution of serotypes causing invasive pneumococcal disease in older adults from high-income countries and impact of pediatric and adult vaccination policies. Vaccine. 2023;41:5662–5669. PubMed

Hanquet G, Krizova P, Dalby T, et al. Serotype replacement after introduction of 10-valent and 13-valent pneumococcal conjugate vaccines in 10 countries, Europe. Emerg Infect Dis. 2022;28:137–138. PubMed PMC

Løchen A, Croucher NJ, Anderson RM. Divergent serotype replacement trends and increasing diversity in pneumococcal disease in high income settings reduce the benefit of expanding vaccine valency. Sci Rep. 2020;10 PubMed PMC

Soeters HM, Kambiré D, Sawadogo G, et al. Impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis, Burkina Faso, 2016–2017. J Infect Dis. 2019;220(suppl 4):S253–S262. PubMed PMC

Ousmane S, Kobayashi M, Seidou I, et al. Characterization of pneumococcal meningitis before and after introduction of 13-valent pneumococcal conjugate vaccine in Niger, 2010–2018. Vaccine. 2020;38:3922–3929. PubMed

Bozio CH, Abdul-Karim A, Abenyeri J, et al. Continued occurrence of serotype 1 pneumococcal meningitis in two regions located in the meningitis belt in Ghana five years after introduction of 13-valent pneumococcal conjugate vaccine. PLoS One. 2018;13 PubMed PMC

Agossou J, Ebruke C, Noudamadjo A, et al. Declines in pediatric bacterial meningitis in the Republic of Benin following introduction of pneumococcal conjugate vaccine: epidemiological and etiological findings, 2011–2016. Clin Infect Dis. 2019;69:S140–S147. PubMed PMC

Libwea JN, Fletcher MA, Ndombo PK, et al. Impact of 13-valent pneumococcal conjugate vaccine on laboratory-confirmed pneumococcal meningitis and purulent meningitis among children >5 years in Cameroon, 2011–2018. PLoS One. 2021;16 PubMed PMC

Bennett JC, Hetrich MK, Garcia Quesada M, et al. Changes in invasive pneumococcal disease caused by Streptococcus pneumoniae serotype 1 following introduction of PCV10 and PCV13: findings from the PSERENADE project. Microorganisms. 2021;9:696. PubMed PMC

Korbal P, Wysocki J, Jackowska T, et al. Phase 3 safety and immunogenicity study of a three-dose series of twenty-valent pneumococcal conjugate vaccine in healthy infants and toddlers. Pediatr Infect Dis J. 2024;43:587–595. PubMed PMC

Martinon-Torres F, Wysocki J, Szenborn L, et al. A phase III, multicenter, randomized, double-blind, active comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of V114 compared with PCV13 in healthy infants (PNEU-PED-EU-1) Vaccine. 2023;41:3387–3398. PubMed

Ladhani SN, Andrews N, Ramsay ME. Summary of evidence to reduce the two-dose infant priming schedule to a single dose of the 13-valent pneumococcal conjugate vaccine in the national immunisation programme in the UK. Lancet Infect Dis. 2021;21:e93–102. PubMed

Andrews NJ, Waight PA, Burbidge P, et al. Serotype-specific effectiveness and correlates of protection for the 13-valent pneumococcal conjugate vaccine: a postlicensure indirect cohort study. Lancet Infect Dis. 2014;14:839–846. PubMed

US Centers for Disease Control and Prevention Grading of Recommendations, Assessment, Development, and Evaluation (GRADE): 20-valent pneumococcal conjugate vaccine (PCV20) for children aged <2 years. 2023. https://www.cdc.gov/vaccines/acip/recs/grade/PCV20-child.html

US Centers for Disease Control and Prevention GRADE: PCV15 use in children aged <2 years. 2022. https://www.cdc.gov/vaccines/acip/recs/grade/pneumo-PCV15-child.html

Bertran M, Amin-Chowdhury Z, Sheppard CL, et al. Increased incidence of invasive pneumococcal disease among children after COVID-19 pandemic, England. Emerg Infect Dis. 2022;28:1669–1672. PubMed PMC

Perniciaro S, van der Linden M, Weinberger DM. Reemergence of invasive pneumococcal disease in Germany during the spring and summer of 2021. Clin Infect Dis. 2022;75:1149–1153. PubMed PMC

Amin-Chowdhury Z, Aiano F, Mensah A, et al. Impact of the coronavirus disease 2019 (COVID-19) pandemic on invasive pneumococcal disease and risk of pneumococcal coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): prospective national cohort study, England. Clin Infect Dis. 2021;72:e65–e75. PubMed PMC

Danino D, Ben-Shimol S, van der Beek BA, et al. Decline in pneumococcal disease in young children during the coronavirus disease 2019 (COVID-19) pandemic in Israel associated with suppression of seasonal respiratory viruses, despite persistent pneumococcal carriage: a prospective cohort study. Clin Infect Dis. 2022;75:e1154–e1164. PubMed PMC

Global impact of ten-valent and 13-valent pneumococcal conjugate vaccines on invasive pneumococcal disease in all ages (the PSERENADE project): a global surveillance analysis