BACKGROUND: Pneumococcal conjugate vaccines (PCVs) that are ten-valent (PCV10) and 13-valent (PCV13) became available in 2010. We evaluated their global impact on invasive pneumococcal disease (IPD) incidence in all ages. METHODS: Serotype-specific IPD cases and population denominators were obtained directly from surveillance sites using PCV10 or PCV13 in their national immunisation programmes and with a primary series uptake of at least 50%. Annual incidence rate ratios (IRRs) were estimated comparing the incidence before any PCV with each year post-PCV10 or post-PCV13 introduction using Bayesian multi-level, mixed-effects Poisson regressions, by site and age group. All site-weighted average IRRs were estimated using linear mixed-effects regression, stratified by product and previous seven-valent PCV (PCV7) effect (none, moderate, or substantial). FINDINGS: Analyses included 32 PCV13 sites (488 758 cases) and 15 PCV10 sites (46 386 cases) in 30 countries, primarily high income (39 sites), using booster dose schedules (41 sites). By 6 years after PCV10 or PCV13 introduction, IPD due to PCV10-type serotypes and PCV10-related serotype 6A declined substantially for both products (age <5 years: 83-99% decline; ≥65 years: 54-96% decline). PCV7-related serotype 19A increases before PCV10 or PCV13 introduction were reversed at PCV13 sites (age <5 years: 61-79% decline relative to before any PCV; age ≥65 years: 7-26% decline) but increased at PCV10 sites (age <5 years: 1·6-2·3-fold; age ≥65 years: 3·6-4·9-fold). Serotype 3 IRRs had no consistent trends for either product or age group. Non-PCV13-type IPD increased similarly for both products (age <5 years: 2·3-3·3-fold; age ≥65 years: 1·7-2·3-fold). Despite different serotype 19A trends, all-serotype IPD declined similarly between products among children younger than 5 years (58-74%); among adults aged 65 years or older, declines were greater at PCV13 (25-29%) than PCV10 (4-14%) sites, but other differences between sites precluded attribution to product. INTERPRETATION: Long-term use of PCV10 or PCV13 reduced IPD substantially in young children and more moderately in older ages. Non-vaccine-type serotypes increased approximately two-fold to three-fold by 6 years after introduction of PCV10 or PCV13. Continuing serotype 19A increases at PCV10 sites and declines at PCV13 sites suggest that PCV13 use would further reduce IPD at PCV10 sites. FUNDING: Bill & Melinda Gates Foundation as part of the WHO Pneumococcal Vaccines Technical Coordination Project.

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

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

Centre for Global Health Research Kenya Medical Research Institute Kisumu Kenya

Centre for Infectious Disease Control National Institute for Public Health and the Environment Bilthoven Netherlands

Centre for International Child Health WHO Collaborating Centre for Research and Training in Child and Neonatal Health University of Melbourne Parkville VIC Australia; Murdoch Children's Research Institute Parkville VIC 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

Child Health Research Foundation Dhaka Bangladesh

CIBER Epidemiology and Public Health Madrid Spain; Public Health Institute of Navarre IdiSNA Pamplona Spain

CIBER Epidemiology and Public Health Madrid Spain; Surveillance and Public Health Emergency Response Public Health Agency of Catalonia Barcelona Spain

Communicable Diseases Centre National Institute of Public Health Ljubljana Slovenia

Department for Vaccine Preventable Diseases National Public Health Organization Athens Greece

Department of Clinical Microbiology Landspitali The National University Hospital Reykjavik Iceland

Department of Communicable Disease and Control and Health Protection Public Health Agency of Sweden Solna Sweden

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 Immunizations Vaccines and Biologicals WHO Geneva Switzerland

Department of Immunizations Vaccines and Biologicals WHO Geneva Switzerland; Division of Bacterial Diseases National Center for Immunizations and Respiratory Diseases Centers for Disease Control and Prevention Atlanta GA USA

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 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; New Vaccines Group Murdoch Children's Research Institute Parkville VIC Australia

Department of Pediatrics University of Calgary Calgary AB Canada

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

Department of Social and Preventive Medicine Laval University Quebec QC Canada

Division of Bacterial Diseases National Center for Immunizations and Respiratory Diseases 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 Wellington New Zealand

European Centre for Disease Prevention and Control Solna Sweden

Faculty of Health Sciences Oslo Metropolitan University Oslo Norway

French Public Health Agency Saint Maurice France

Health Protection Surveillance Centre Dublin Ireland

Immunisation and Countermeasures Division UK Health Security Agency London UK

Infectious Disease Center and Department of Clinical Research National Hospital Organization Mie Hospital Tsu Japan

Infectious Disease Epidemiology and Prevention Statens Serum Institut Copenhagen Denmark

Institute of Public Health Riga Stradins University Riga Latvia

Instituto de Salud Pública de Chile Santiago Chile

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

Malawi Liverpool Wellcome Programme Blantyre Malawi; NIHR Global Health Research Unit on Mucosal Pathogens Division of Infection and Immunity University College London London UK

Mohammed 6 University of Sciences and Health Mohammed 6 Higher Institute of Biosciences and Biotechnologies Rabat Morocco

National Center of Communicable Diseases Ministry of Health Ulaanbaatar Mongolia

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 Reference Centre for Bacterial Meningitis National Medicines Institute Warsaw Poland

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

Public Health Scotland Glasgow UK

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

Regional Public Health Laboratory General Directorate of Public Health Madrid Spain

Singapore Ministry of Health Communicable Diseases Division Singapore

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

UMass Chan Medical School Worcester MA USA

Vaccine Study Center Kaiser Permanente Oakland CA USA

Erratum v

Lancet Infect Dis. 2025 Mar;25(3):e137. doi: 10.1016/S1473-3099(25)00032-5. PubMed

Zobrazit více v PubMed

Wahl B, O'Brien KL, Greenbaum A, et al. Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000–15. Lancet Glob Health. 2018;6:e744–e757. PubMed PMC

Troeger C, Blacker B, Khalil IA, et al. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect Dis. 2018;18:1191–1210. PubMed PMC

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

View-hub by IVAC Pneumococcal conjugate vaccine (PCV) https://view-hub.org/vaccine/pcv

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

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

Ladhani SN, Collins S, Djennad A, et al. Rapid increase in non-vaccine serotypes causing invasive pneumococcal disease in England and Wales, 2000–17: a prospective national observational cohort study. Lancet Infect Dis. 2018;18:441–451. PubMed

Moore MR, Link-Gelles R, Schaffner W, et al. Impact of 13-valent pneumococcal conjugate vaccine used in children on invasive pneumococcal disease in children and adults in the United States: analysis of multisite, population-based surveillance. Lancet Infect Dis. 2015;15:301–309. PubMed PMC

Lewnard JA, Hanage WP. Making sense of differences in pneumococcal serotype replacement. Lancet Infect Dis. 2019;19:e213–e220. PubMed

Weinberger DM, Warren JL, Dalby T, et al. Differences in the impact of pneumococcal serotype replacement in individuals with and without underlying medical conditions. Clin Infect Dis. 2019;69:100–106. 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

Savulescu C, Krizova P, Lepoutre A, et al. Effect of high-valency pneumococcal conjugate vaccines on invasive pneumococcal disease in children in SpIDnet countries: an observational multicentre study. Lancet Respir Med. 2017;5:648–656. PubMed

Hanquet G, Krizova P, Valentiner-Branth P, et al. Effect of childhood pneumococcal conjugate vaccination on invasive disease in older adults of 10 European countries: implications for adult vaccination. Thorax. 2019;74:473–482. PubMed PMC

Palmu AA, De Wals P, Toropainen M, et al. Similar impact and replacement disease after pneumococcal conjugate vaccine introduction in hospitalised children with invasive pneumococcal disease in Europe and North America. Vaccine. 2021;39:1551–1555. PubMed

Carstairs KL, Tanen DA, Johnson AS, Kailes SB, Riffenburgh RH. Pneumococcal bacteremia in febrile infants presenting to the emergency department before and after the introduction of the heptavalent pneumococcal vaccine. Ann Emerg Med. 2007;49:772–777. PubMed

Wilkinson M, Bulloch B, Smith M. Prevalence of occult bacteremia in children aged 3 to 36 months presenting to the emergency department with fever in the postpneumococcal conjugate vaccine era. Acad Emerg Med. 2009;16:220–225. PubMed

Zeretzke CM, McIntosh MS, Kalynych CJ, Wylie T, Lott M, Wood D. Reduced use of occult bacteremia blood screens by emergency medicine physicians using immunization registry for children presenting with fever without a source. Pediatr Emerg Care. 2012;28:640–645. PubMed

Hadfield JD. MCMC methods for multi-response generalized linear mixed models: the MCMCglmm R package. J Stat Softw. 2010;33:1–22. PubMed

UN Methodology: geographic regions. https://unstats.un.org/unsd/methodology/m49/#geo-regions

The World Bank World Bank country and lending groups. https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups

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

US Centers for Disease Control and Prevention Direct and indirect effects of routine vaccination of children with 7-valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease—United States, 1998–2003. Morb Mortal Wkly Rep. 2005;54:893–897. PubMed

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

Kwambana-Adams BA, Asiedu-Bekoe F, Sarkodie B, et al. An outbreak of pneumococcal meningitis among older children (≥5 years) and adults after the implementation of an infant vaccination programme with the 13-valent pneumococcal conjugate vaccine in Ghana. BMC Infect Dis. 2016;16:575. 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

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

Blyth CC, Jayasinghe S, Andrews RM. A rationale for change: an increase in invasive pneumococcal disease in fully vaccinated children. Clin Infect Dis. 2020;70:680–683. PubMed

Ben-Shimol S, Greenberg D, Givon-Lavi N, et al. Early impact of sequential introduction of 7-valent and 13-valent pneumococcal conjugate vaccine on IPD in Israeli children <5 years: an active prospective nationwide surveillance. Vaccine. 2014;32:3452–3459. PubMed

Ciruela P, Izquierdo C, Broner S, et al. The changing epidemiology of invasive pneumococcal disease after PCV13 vaccination in a country with intermediate vaccination coverage. Vaccine. 2018;36:7744–7752. PubMed

Picazo J, Ruiz-Contreras J, Casado-Flores J, et al. Effect of the different 13-valent pneumococcal conjugate vaccination uptakes on the invasive pneumococcal disease in children: analysis of a hospital-based and population-based surveillance study in Madrid, Spain, 2007–2015. PLoS One. 2017;12 PubMed PMC

van der Linden M, Falkenhorst G, Perniciaro S, Imöhl M. Effects of infant pneumococcal conjugate vaccination on serotype distribution in invasive pneumococcal disease among children and adults in Germany. PLoS One. 2015;10 PubMed PMC

Harboe ZB, Dalby T, Weinberger DM, et al. Impact of 13-valent pneumococcal conjugate vaccination in invasive pneumococcal disease incidence and mortality. Clin Infect Dis. 2014;59:1066–1073. PubMed

Steens A, Bergsaker MAR, Aaberge IS, et al. Effects of vaccination on invasive pneumococcal disease in South Africa. N Engl J Med. 2014;371:1889–1899. PubMed

Broome CV, Facklam RR, Fraser DW. Pneumococcal disease after pneumococcal vaccination: an alternative method to estimate the efficacy of pneumococcal vaccine. N Engl J Med. 1980;303:549–552. PubMed

Sings HL, Gessner BD, Wasserman MD, Jodar L. Pneumococcal conjugate vaccine impact on serotype 3: a review of surveillance data. Infect Dis Ther. 2021;10:521. PubMed PMC

Savulescu C, Krizova P, Valentiner-Branth P, et al. Effectiveness of 10 and 13-valent pneumococcal conjugate vaccines against invasive pneumococcal disease in European children: SpIDnet observational multicentre study. Vaccine. 2022;40:3963–3974. PubMed

Deceuninck G, Brousseau N, Lefebvre B, et al. Effectiveness of thirteen-valent pneumococcal conjugate vaccine to prevent serotype 3 invasive pneumococcal disease in Quebec in children, Canada. Vaccine. 2023;41:5486–5489. PubMed

De Serres G, Pilishvili T, Link-Gelles R, et al. Use of surveillance data to estimate the effectiveness of the 7-valent conjugate pneumococcal vaccine in children less than 5 years of age over a 9 year period. Vaccine. 2012;30:4067–4072. PubMed

Prymula R, Peeters P, Chrobok V, et al. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study. Lancet. 2006;367:740–748. PubMed

Poolman J, Kriz P, Feron C, et al. Pneumococcal serotype 3 otitis media, limited effect of polysaccharide conjugate immunisation and strain characteristics. Vaccine. 2009;27:3213–3222. PubMed

Kieninger DM, Kueper K, Steul K, et al. Safety, tolerability, and immunologic noninferiority of a 13-valent pneumococcal conjugate vaccine compared to a 7-valent pneumococcal conjugate vaccine given with routine pediatric vaccinations in Germany. Vaccine. 2010;28:4192–4203. PubMed

Yeh SH, Gurtman A, Hurley DC, et al. Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine in infants and toddlers. Pediatrics. 2010;126:e493–e505. PubMed

Snape MD, Klinger CL, Daniels ED, et al. Immunogenicity and reactogenicity of a 13-valent-pneumococcal conjugate vaccine administered at 2, 4, and 12 months of age: a double-blind randomized active-controlled trial. Pediatr Infect J. 2010;29:e80–e90. PubMed

Dagan R, Patterson S, Juergens C, et al. Comparative immunogenicity and efficacy of 13-valent and 7-valent pneumococcal conjugate vaccines in reducing nasopharyngeal colonization: a randomized double-blind trial. Clin Infect Dis. 2013;57:952–962. 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

Garcia Quesada M, Peterson ME, Bennett JC, et al. Serotype distribution of remaining invasive pneumococcal disease after extensive use of ten-valent and 13-valent pneumococcal conjugate vaccines (the PSERENADE project): a global surveillance analysis. Lancet Infect Dis. 2024 doi: 10.1016/S1473-3099(24)00588-7. published online Dec 17. PubMed DOI PMC

Cherian T, Cohen M, de Oliveira L, et al. Report to Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization. World Health Organization; 2017. Pneumococcal Conjugate Vaccine (PCV) Review of Impact Evidence (PRIME): summary of findings from systematic review; pp. 1–215.

Hammitt LL, Etyang AO, Morpeth SC, et al. Effect of ten-valent pneumococcal conjugate vaccine on invasive pneumococcal disease and nasopharyngeal carriage in Kenya: a longitudinal surveillance study. Lancet. 2019;393:2146–2154. PubMed PMC

Hanage WP, Kaijalainen TH, Syrjänen RK, et al. Invasiveness of serotypes and clones of Streptococcus pneumoniae among children in Finland. Infect Immun. 2005;73:431–435. PubMed PMC

Yildirim I, Hanage WP, Lipsitch M, et al. Serotype specific invasive capacity and persistent reduction in invasive pneumococcal disease. Vaccine. 2010;29:283–288. PubMed PMC

Horn M, Theilacker C, Sprenger R, et al. Mathematical modeling of pneumococcal transmission dynamics in response to PCV13 infant vaccination in Germany predicts increasing IPD burden due to serotypes included in next-generation PCVs. PLoS One. 2023;18 PubMed PMC

Flasche S, Le Polain de Waroux O, O'Brien KL, et al. Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data. Lancet Digit Health. 2021;3:e360–e370. PubMed PMC

Serotype distribution of remaining invasive pneumococcal disease after extensive use of ten-valent and 13-valent pneumococcal conjugate vaccines (the PSERENADE project): a global surveillance analysis