Serotype distribution of remaining pneumococcal meningitis in the mature PCV10/13 period : Findings from the PSERENADE Project

Funding Information: The PSERENADE project is funded by the Bill and Melinda Gates Foundation as part of the World Health Organization Pneumococcal Vaccines Technical Coordination Project, grant number INV-010429/OPP1189065. Publisher Copyright: © 2021 by the authors.Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5-7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites (N = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed.publishersversionPeer reviewe

Changes in invasive pneumococcal disease caused by streptococcus pneumoniae serotype 1 following introduction of pcv10 and pcv13 : Findings from the pserenade project

Funding Information: Funding: The PSERENADE project is funded by the Bill and Melinda Gates Foundation as part of the World Health Organization Pneumococcal Vaccines Technical Coordination Project, grant num‐ ber INV‐010429/OPP1189065. Funding Information: Conflicts of Interest: KH conducted the study and analyses while working at the Johns Hopkins School of Public Health but is an employee at Pfizer, Inc. as of 26 October 2020. MDK reports grants from Merck, personal fees from Merck, and grants from Pfizer, outside the submitted work. JCB reports funding from Pfizer in the past year, unrelated to the submitted work. JAS reports grants from the Bill & Melinda Gates Foundation, the Wellcome Trust, the UK MRC, National Institute of Health Research, outside the submitted work. MCB reports lectures fee from MSD outside from submitted work. AS reports grants and personal fees from Pfizer and personal fees from MSD and Sanofi Pasteur, outside the submitted work. ML has been a member of advisory boards and has received speakers honoraria from Pfizer and Merck. German pneumococcal surveillance has been supported by Pfizer and Merck. SD reports grant from Pfizer, outside the submitted work. KA re‐ ports a grant from Merck, outside the submitted work. AvG as received researching funding from Pfizer (last year 2017, Pfizer Investigator‐Initiated Research [IIR] Program IIR WI 194379); attended advisory board meetings for Pfizer and Merck. CMA reports grants and personal fees from Pfizer, Qiagen and BioMerieux and grants from Genomica SAU, outside the submitted work. AM‐research support to my institution from Pfizer and Merck; honoraria for advisory board membership from GlaxoSmithKline, Merck and Pfizer. SNL performs contract research for GSK, Pfizer, Sanofi Pasteur on behalf of St. George’s University of London, but receives no personal remuneration. IY stated she was a member of mRNA‐1273 study group and has received funding to her institution to conduct clinical research from BioFire, MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Novavax, Sanofi‐Pasteur, and Micron. RD has received grants/research support from Pfizer, Merck Sharp & Dohme and Medimmune; has been a scientific consultant for Pfizer, MeMed, Merck Sharp & Dohme, and Biondvax; had served on advisory boards of Pfizer, Merck Sharp & Dohme and Biondvax and has been a speaker for Pfizer. LLH reports research grants to her institution from GSK, Pfizer and Merck. JDK has received an unrestricted grant‐in‐aid from Pfizer Canada that sup‐ ports, in part, the CASPER invasive pneumococcal disease surveillance project. MH received an educational grant from Pfizer AG for partial support of this project. However, Pfizer AG had no role in the data analysis and content of the manuscript. MC has previously received a professional fee from Pfizer (Ireland), an unrestricted research grant from Pfizer Ireland (2007–2016) and an In‐ vestigator Initiated Reward from Pfizer Ireland in 2018 (W1243730). CLB, MD has intellectual prop‐ erty in BioFire Diagnostics and receives royalties through the University of Utah. CLB is an advisor to IDbyDNA. AK reports personal fees from Pfizer, outside the submitted work. MT reports grants from GlaxoSmithKline and grants from Pfizer Inc. to the Finnish Institute for Health and Welfare for research projects outside the submitted work, in which she has been a co‐investigator. JCS re‐ ports had received assistance from Pfizer for attending to scientific meetings outside the submitted work. SCGA received travel grant from Pfizer. BL had two research grants from Pfizer on Strepto‐ coccus pneumoniae. EV reports grants from French public health agency, during the conduct of the study; grants from Pfizer, grants from Merck, outside the submitted work. NBZ has received inves‐ tigator‐initiated research grants from GlaxoSmithKline, Takeda Pharmaceuticals, Merck and the Se‐ rum Institute of India, all unrelated to this research. CGS reports grant funding from Pfizer, Merck, and AstraZeneca in the past 3 years. NMvS reports grants and fee for service from Pfizer, fee for service from MSD and GSK, outside the submitted work; In addition, NMvS has a patent WO 2013/020090 A3 with royalties paid to University of California San Diego (inventors: Nina van Sorge/Victor Nizet). All other authors did not declare any conflicts of interest. The funders had no Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococ-cal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) con-taining ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERE‐ NADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) compar-ing the pre‐PCV10/13 period to each post‐PCV10/13 year by site using a Bayesian multi‐level, mixed-effects Poisson regression and all‐site IRRs using a linear mixed‐effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all‐site IRR was 0.05 (95% credibility interval 0.04–0.06) for all ages, 0.05 (0.04–0.05) for <5 years of age, 0.08 (0.06–0.09) for 5–17 years, 0.06 (0.05–0.08) for 18–49 years, 0.06 (0.05–0.07) for 50–64 years, and 0.05 (0.04–0.06) for ≥65 years. PCV10/13 use in infant immunization programs was followed by a 95% reduction in ST1 IPD in all ages after approximately 6 years. Limited data availability from the highest ST1 disease burden countries using a 3+0 schedule constrains generalizability and data from these settings are needed.publishersversionPeer reviewe

Changes in Invasive Pneumococcal Disease Caused by Streptococcus pneumoniae Serotype 1 Following Introduction of PCV10 and PCV13: Findings from the PSERENADE Project.

Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococcal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) containing ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) comparing the pre-PCV10/13 period to each post-PCV10/13 year by site using a Bayesian multi-level, mixed-effects Poisson regression and all-site IRRs using a linear mixed-effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all-site IRR was 0.05 (95% credibility interval 0.04–0.06) for all ages, 0.05 (0.04–0.05) for <5 years of age, 0.08 (0.06–0.09) for 5–17 years, 0.06 (0.05–0.08) for 18–49 years, 0.06 (0.05–0.07) for 50–64 years, and 0.05 (0.04–0.06) for ≥65 years. PCV10/13 use in infant immunization programs was followed by a 95% reduction in ST1 IPD in all ages after approximately 6 years. Limited data availability from the highest ST1 disease burden countries using a 3+0 schedule constrains generalizability and data from these settings are needed

Changes in Invasive Pneumococcal Disease Caused by Streptococcus pneumoniae Serotype 1 following Introduction of PCV10 and PCV13: Findings from the PSERENADE Project

Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococcal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) containing ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) comparing the pre-PCV10/13 period to each post-PCV10/13 year by site using a Bayesian multi-level, mixed-effects Poisson regression and all-site IRRs using a linear mixed-effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all-site IRR was 0.05 (95% credibility interval 0.04-0.06) for all ages, 0.05 (0.04-0.05) for <5 years of age, 0.08 (0.06-0.09) for 5-17 years, 0.06 (0.05-0.08) for 18-49 years, 0.06 (0.05-0.07) for 50-64 years, and 0.05 (0.04-0.06) for ≥65 years. PCV10/13 use in infant immunization programs was followed by a 95% reduction in ST1 IPD in all ages after approximately 6 years. Limited data availability from the highest ST1 disease burden countries using a 3+0 schedule constrains generalizability and data from these settings are needed

Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Project.

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon

Serotype distribution of remaining pneumococcal meningitis in the mature PCV10/13 period : Findings from the PSERENADE Project

Funding text The PSERENADE project is funded by the Bill and Melinda Gates Foundation as part of the World Health Organization Pneumococcal Vaccines Technical Coordination Project, grant number INV-010429/OPP1189065. Publisher Copyright: © 2021 by the authors.Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5-7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites (N = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed.Peer reviewe

Global landscape review of serotype-specific invasive pneumococcal disease surveillance among countries using PCV10/13 : The pneumococcal serotype replacement and distribution estimation (PSERENADE) project

Funding text The PSERENADE project is funded by the Bill and Melinda Gates Foundation as part of the World Health Organization Pneumococcal Vaccines Technical Coordination Project, grant number INV-010429/OPP1189065. Publisher Copyright: © 2021 by the authors.Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.Peer reviewe

Changes in invasive pneumococcal disease caused by streptococcus pneumoniae serotype 1 following introduction of pcv10 and pcv13 : Findings from the pserenade project

Funding text 1 Funding: The PSERENADE project is funded by the Bill and Melinda Gates Foundation as part of the World Health Organization Pneumococcal Vaccines Technical Coordination Project, grant num‐ ber INV‐010429/OPP1189065. Funding text 2 Conflicts of Interest: KH conducted the study and analyses while working at the Johns Hopkins School of Public Health but is an employee at Pfizer, Inc. as of 26 October 2020. MDK reports grants from Merck, personal fees from Merck, and grants from Pfizer, outside the submitted work. JCB reports funding from Pfizer in the past year, unrelated to the submitted work. JAS reports grants from the Bill & Melinda Gates Foundation, the Wellcome Trust, the UK MRC, National Institute of Health Research, outside the submitted work. MCB reports lectures fee from MSD outside from submitted work. AS reports grants and personal fees from Pfizer and personal fees from MSD and Sanofi Pasteur, outside the submitted work. ML has been a member of advisory boards and has received speakers honoraria from Pfizer and Merck. German pneumococcal surveillance has been supported by Pfizer and Merck. SD reports grant from Pfizer, outside the submitted work. KA re‐ ports a grant from Merck, outside the submitted work. AvG as received researching funding from Pfizer (last year 2017, Pfizer Investigator‐Initiated Research [IIR] Program IIR WI 194379); attended advisory board meetings for Pfizer and Merck. CMA reports grants and personal fees from Pfizer, Qiagen and BioMerieux and grants from Genomica SAU, outside the submitted work. AM‐research support to my institution from Pfizer and Merck; honoraria for advisory board membership from GlaxoSmithKline, Merck and Pfizer. SNL performs contract research for GSK, Pfizer, Sanofi Pasteur on behalf of St. George’s University of London, but receives no personal remuneration. IY stated she was a member of mRNA‐1273 study group and has received funding to her institution to conduct clinical research from BioFire, MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Novavax, Sanofi‐Pasteur, and Micron. RD has received grants/research support from Pfizer, Merck Sharp & Dohme and Medimmune; has been a scientific consultant for Pfizer, MeMed, Merck Sharp & Dohme, and Biondvax; had served on advisory boards of Pfizer, Merck Sharp & Dohme and Biondvax and has been a speaker for Pfizer. LLH reports research grants to her institution from GSK, Pfizer and Merck. JDK has received an unrestricted grant‐in‐aid from Pfizer Canada that sup‐ ports, in part, the CASPER invasive pneumococcal disease surveillance project. MH received an educational grant from Pfizer AG for partial support of this project. However, Pfizer AG had no role in the data analysis and content of the manuscript. MC has previously received a professional fee from Pfizer (Ireland), an unrestricted research grant from Pfizer Ireland (2007–2016) and an In‐ vestigator Initiated Reward from Pfizer Ireland in 2018 (W1243730). CLB, MD has intellectual prop‐ erty in BioFire Diagnostics and receives royalties through the University of Utah. CLB is an advisor to IDbyDNA. AK reports personal fees from Pfizer, outside the submitted work. MT reports grants from GlaxoSmithKline and grants from Pfizer Inc. to the Finnish Institute for Health and Welfare for research projects outside the submitted work, in which she has been a co‐investigator. JCS re‐ ports had received assistance from Pfizer for attending to scientific meetings outside the submitted work. SCGA received travel grant from Pfizer. BL had two research grants from Pfizer on Strepto‐ coccus pneumoniae. EV reports grants from French public health agency, during the conduct of the study; grants from Pfizer, grants from Merck, outside the submitted work. NBZ has received inves‐ tigator‐initiated research grants from GlaxoSmithKline, Takeda Pharmaceuticals, Merck and the Se‐ rum Institute of India, all unrelated to this research. CGS reports grant funding from Pfizer, Merck, and AstraZeneca in the past 3 years. NMvS reports grants and fee for service from Pfizer, fee for service from MSD and GSK, outside the submitted work; In addition, NMvS has a patent WO 2013/020090 A3 with royalties paid to University of California San Diego (inventors: Nina van Sorge/Victor Nizet). All other authors did not declare any conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococ-cal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) con-taining ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERE‐ NADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) compar-ing the pre‐PCV10/13 period to each post‐PCV10/13 year by site using a Bayesian multi‐level, mixed-effects Poisson regression and all‐site IRRs using a linear mixed‐effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all‐site IRR was 0.05 (95% credibility interval 0.04–0.06) for all ages, 0.05 (0.04–0.05) for <5 years of age, 0.08 (0.06–0.09) for 5–17 years, 0.06 (0.05–0.08) for 18–49 years, 0.06 (0.05–0.07) for 50–64 years, and 0.05 (0.04–0.06) for ≥65 years. PCV10/13 use in infant immunization programs was followed by a 95% reduction in ST1 IPD in all ages after approximately 6 years. Limited data availability from the highest ST1 disease burden countries using a 3+0 schedule constrains generalizability and data from these settings are needed.Peer reviewe

Serotype Distribution of Remaining Pneumococcal Meningitis in the Mature PCV10/13 Period: Findings from the PSERENADE Project

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5-7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites (N = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed

Global landscape review of serotype-specific invasive pneumococcal disease surveillance among countries using PCV10/13 : The pneumococcal serotype replacement and distribution estimation (PSERENADE) project

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.publishedVersionPeer reviewe