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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

M. Garcia Quesada, ME. Peterson, JC. Bennett, K. Hayford, SL. Zeger, Y. Yang, MK. Hetrich, DR. Feikin, AL. Cohen, A. von Gottberg, M. van der Linden, NM. van Sorge, LH. de Oliveira, S. de Miguel, I. Yildirim, DF. Vestrheim, JR. Verani, E. Varon,...

. 2025 ; 25 (4) : 445-456. [pub] 20241217

Language English Country United States

Document type Journal Article

Grant support
001 World Health Organization - International

E-resources Online Full text

NLK ProQuest Central from 2001-08-01 to 2 months ago
Nursing & Allied Health Database (ProQuest) from 2001-08-01 to 2 months ago
Health & Medicine (ProQuest) from 2001-08-01 to 2 months ago
Public Health Database (ProQuest) from 2001-08-01 to 2 months ago

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

CIBER de Enfermedades Respiratorias Madrid Spain

CIBER Epidemiología y Salud Pública Madrid 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 Bacteria Parasites and Fungi Statens Serum Institut Copenhagen Denmark

Department of Clinical Microbiology Landspitali The National University Hospital Reykjavik Iceland

Department of Health Security Finnish Institute for Health and Welfare Helsinki 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

Department of Microbiology Public Health Agency of Sweden Solna Sweden

Department of Paediatrics University of Melbourne Parkville VIC Australia

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 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 Dirección General de Salud Pública Madrid Spain

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

Faculty of Infectious and Tropical Diseases London School of Hygiene and Tropical Medicine London UK

Health Sciences Unit Faculty of Social Sciences Tampere University Tampere Finland

Immunisation and Countermeasures Division UK Health Security Agency London UK

Infectious Disease Epidemiology and Prevention Statens Serum Institut Copenhagen Denmark

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

Institute of Infection Veterinary and Ecological Sciences University of Liverpool Liverpool UK

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

Johns Hopkins Bloomberg School of Public Health Baltimore MD USA

Malawi Liverpool Wellcome Programme Blantyre Malawi

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

Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine Banjul The Gambia

Medicine Department International University of Catalunya Barcelona Spain

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

Molecular Microbiology Department Hospital Sant Joan de Déu Research Institute Barcelona Spain

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

National Reference Centre for Streptococcus Pneumoniae University Hospitals Leuven Leuven Belgium

Navarre Institute for Health Research Pamplona Spain

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

Pan American Health Organization WHO Washington DC USA

Public Health Institute of Navarre Pamplona Spain

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

Royal College of Surgeons in Ireland Dublin Ireland

School of Pathology Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa

School of Public Health Faculty of Health Sciences University of the Witwatersrand Johannesburg South Africa

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

References provided by Crossref.org

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$a Garcia Quesada, Maria $u Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. Electronic address: mgarci64@jhmi.edu
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$a 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 / $c M. Garcia Quesada, ME. Peterson, JC. Bennett, K. Hayford, SL. Zeger, Y. Yang, MK. Hetrich, DR. Feikin, AL. Cohen, A. von Gottberg, M. van der Linden, NM. van Sorge, LH. de Oliveira, S. de Miguel, I. Yildirim, DF. Vestrheim, JR. Verani, E. Varon, P. Valentiner-Branth, G. Tzanakaki, N. Sinkovec Zorko, LP. Setchanova, F. Serhan, KJ. Scott, JA. Scott, C. Savulescu, L. Savrasova, R. Reyburn, K. Oishi, JP. Nuorti, D. Napoli, JM. Mwenda, C. Muñoz-Almagro, E. Morfeldt, K. McMahon, A. McGeer, L. Mad'arová, GA. Mackenzie, M. Eugenia León, SN. Ladhani, KG. Kristinsson, J. Kozakova, J. Kleynhans, NP. Klein, JD. Kellner, S. Jayasinghe, PL. Ho, M. Hilty, MA. Harker-Jones, LL. Hammitt, M. Grgic-Vitek, C. Gilkison, R. Gierke, N. French, I. Diawara, S. Desmet, P. De Wals, T. Dalby, R. Dagan, M. Corcoran, E. Colzani, G. Chanto Chacón, J. Castilla, R. Camilli, M. Ang, K. Ampofo, SCG. Almeida, P. Alarcon, KL. O'Brien, M. Deloria Knoll, PSERENADE Team
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$a 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.
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$a Peterson, Meagan E $u Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
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$a van der Linden, Mark $u Reference Laboratory for Streptococci, Department of Medical Microbiology, University Hospital RWTH Aachen, Aachen, Germany
700    1_
$a van Sorge, Nina M $u Medical Microbiology and Infection Prevention, Netherlands Reference Laboratory for Bacterial Meningitis, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
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$a de Oliveira, Lucia H $u Pan American Health Organization, WHO, Washington, DC, USA
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$a de Miguel, Sara $u CIBER de Enfermedades Respiratorias, Madrid, Spain; Epidemiology Department, Dirección General de Salud Pública, Madrid, Spain
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$a Yildirim, Inci $u Department of Pediatrics, Yale New Haven Children's Hospital, New Haven, CT, USA
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$a Varon, Emmanuelle $u National Reference Centre for Pneumococci, Data Research Department, Intercommunal Hospital of Créteil, Créteil, France
700    1_
$a Valentiner-Branth, Palle $u Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark
700    1_
$a Tzanakaki, Georgina $u National Meningitis Reference Laboratory, Department of Public Health Policy, School of Public Health, University of West Attica, Athens, Greece
700    1_
$a Sinkovec Zorko, Nadja $u Communicable Diseases Centre, National Institute of Public Health, Ljubljana, Slovenia
700    1_
$a Setchanova, Lena P $u University Multiprofile Hospital for Active Treatment Saint Ivan Rilski, Clinical Microbiology Laboratory, Sofia, Bulgaria
700    1_
$a Serhan, Fatima $u WHO, Geneva, Switzerland
700    1_
$a Scott, Kevin J $u Bacterial Respiratory Infection Service, Scottish Microbiology Reference Laboratory, NHS Greater Glasgow and Clyde, Glasgow, UK
700    1_
$a Scott, J Anthony $u Epidemiology and Demography Department, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Coast, Kilifi, Kenya
700    1_
$a Savulescu, Camelia $u Epidemiology Department, Epiconcept, Paris, France
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$a Savrasova, Larisa $u Institute of Public Health, Riga Stradiņš University, Riga, Latvia
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$a Reyburn, Rita $u Murdoch Children's Research Institute, Parkville, VIC, Australia
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$a Oishi, Kazunori $u Toyama Institute of Health, Toyama, Japan
700    1_
$a Nuorti, J Pekka $u Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland; Health Sciences Unit, Faculty of Social Sciences, Tampere University, Tampere, Finland
700    1_
$a Napoli, Daniela $u Clinical Bacteriology Service, Department of Bacteriology, National Institute for Infectious Diseases (INEI-ANLIS) "Dr Carlos G Malbrán", Buenos Aires, Argentina
700    1_
$a Mwenda, Jason M $u WHO Regional Office for Africa, Brazzaville, Republic of the Congo
700    1_
$a Muñoz-Almagro, Carmen $u 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
700    1_
$a Morfeldt, Eva $u Department of Microbiology Public Health Agency of Sweden, Solna, Sweden
700    1_
$a McMahon, Kimberley $u Centre for Disease Control, Department of Health and Community Services, Darwin, NT, Australia
700    1_
$a McGeer, Allison $u Toronto Invasive Bacterial Diseases Network and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
700    1_
$a Mad'arová, Lucia $u National Reference Centre for Pneumococcal and Haemophilus Diseases, Regional Authority of Public Health, Banská Bystrica, Slovakia
700    1_
$a Mackenzie, Grant A $u 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 & Tropical Medicine, London, UK; Medical Research Council Unit The Gambia at London School of Hygiene & Tropical Medicine, Banjul, The Gambia
700    1_
$a Eugenia León, Maria $u Central Laboratory of Public Health, Asunción, Paraguay
700    1_
$a Ladhani, Shamez N $u Immunisation and Countermeasures Division, UK Health Security Agency, London, UK
700    1_
$a Kristinsson, Karl G $u Department of Clinical Microbiology, Landspitali-The National University Hospital, Reykjavik, Iceland
700    1_
$a Kozakova, Jana $u National Institute of Public Health, Prague, Czech Republic
700    1_
$a Kleynhans, Jackie $u Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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$a Klein, Nicola P $u Vaccine Study Center, Kaiser Permanente, Oakland, CA, USA
700    1_
$a Kellner, James D $u Department of Pediatrics, University of Calgary and Alberta Health Services, Calgary, AB, Canada
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$a Jayasinghe, Sanjay $u 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
700    1_
$a Ho, Pak-Leung $u Department of Microbiology and Carol Yu Centre for Infection, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region, China
700    1_
$a Hilty, Markus $u Swiss National Reference Centre for Invasive Pneumococci, Institute for Infectious Diseases, University of Bern, Bern, Switzerland
700    1_
$a Harker-Jones, Marcella A $u 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
700    1_
$a Hammitt, Laura L $u 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
700    1_
$a Grgic-Vitek, Marta $u Communicable Diseases Centre, National Institute of Public Health, Ljubljana, Slovenia
700    1_
$a Gilkison, Charlotte $u Epidemiology Team, Institute of Environmental Science and Research, Porirua, New Zealand
700    1_
$a Gierke, Ryan $u Division of Bacterial Diseases, National Center for Immunizations and Respiratory Diseases, US Centers for Disease Control and Prevention, Atlanta, GA, USA
700    1_
$a French, Neil $u Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK; Malawi Liverpool Wellcome Programme, Blantyre, Malawi
700    1_
$a Diawara, Idrissa $u Infectious Diseases Research Unit, Mohammed VI Center for Research & Innovation (CM6RI), Rabat, Morocco; Mohammed VI University of Sciences and Health, Mohammed VI Higher Institute of Biosciences and Biotechnologies (UM6SS), Casablanca, Morocco
700    1_
$a Desmet, Stefanie $u Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium; National Reference Centre for Streptococcus Pneumoniae, University Hospitals Leuven, Leuven, Belgium
700    1_
$a De Wals, Philippe $u Department of Social and Preventive Medicine, Laval University, Québec, QC, Canada
700    1_
$a Dalby, Tine $u Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark; Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark
700    1_
$a Dagan, Ron $u The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
700    1_
$a Corcoran, Mary $u Irish Meningitis and Sepsis Reference Laboratory, Children's Health Ireland at Temple Street, Dublin, Ireland; Royal College of Surgeons in Ireland, Dublin, Ireland
700    1_
$a Colzani, Edoardo $u European Centre for Disease Prevention and Control, Solna, Sweden
700    1_
$a Chanto Chacón, Grettel $u Costa Rican Institute for Research and Teaching in Nutrition and Health, Tres Ríos, Costa Rica
700    1_
$a Castilla, Jesús $u CIBER Epidemiología y Salud Pública, Madrid, Spain; Public Health Institute of Navarre, Pamplona, Spain; Navarre Institute for Health Research, Pamplona, Spain
700    1_
$a Camilli, Romina $u Department of Infectious Diseases, Italian National Institute of Health, Rome, Italy
700    1_
$a Ang, Michelle $u National Public Health Laboratory, National Centre for Infectious Diseases, Singapore
700    1_
$a Ampofo, Krow $u Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Utah Health Sciences Center, Salt Lake City, UT, USA
700    1_
$a Almeida, Samanta C G $u National Laboratory for Meningitis and Pneumococcal Infections, Center of Bacteriology, Institute Adolfo Lutz, São Paulo, Brazil
700    1_
$a Alarcon, Pedro $u Instituto de Salud Pública de Chile, Santiago, Chile
700    1_
$a O'Brien, Katherine L $u Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; WHO, Geneva, Switzerland
700    1_
$a Deloria Knoll, Maria $u Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
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