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. 2025 Mar;90(3):106426.
doi: 10.1016/j.jinf.2025.106426. Epub 2025 Jan 27.

Global impact of 10- and 13-valent pneumococcal conjugate vaccines on pneumococcal meningitis in all ages: The PSERENADE project

Yangyupei Yang  1 , Maria Deloria Knoll  2 , Carly Herbert  3 , Julia C Bennett  4 , Daniel R Feikin  5 , Maria Garcia Quesada  4 , Marissa K Hetrich  4 , Scott L Zeger  4 , Eunice W Kagucia  6 , Melody Xiao  4 , Adam L Cohen  7 , Mark van der Linden  8 , Mignon du Plessis  9 , Inci Yildirim  10 , Brita A Winje  11 , Emmanuelle Varon  12 , Maria Teresa Valenzuela  13 , Palle Valentiner-Branth  14 , Anneke Steens  15 , J Anthony Scott  6 , Larisa Savrasova  16 , Juan Carlos Sanz  17 , Aalisha Sahu Khan  18 , Kazunori Oishi  19 , Néhémie Nzoyikorera  20 , J Pekka Nuorti  21 , Jolita Mereckiene  22 , Kimberley McMahon  23 , Allison McGeer  24 , Grant A Mackenzie  25 , Laura MacDonald  26 , Shamez N Ladhani  27 , Karl G Kristinsson  28 , Jackie Kleynhans  29 , James D Kellner  30 , Sanjay Jayasinghe  31 , Pak-Leung Ho  32 , Markus Hilty  33 , Laura L Hammitt  34 , Marcela Guevara  35 , Charlotte Gilkison  36 , Ryan Gierke  37 , Stefanie Desmet  38 , Philippe De Wals  39 , Ron Dagan  40 , Edoardo Colzani  41 , Pilar Ciruela  42 , Urtnasan Chuluunbat  43 , Guanhao Chan  44 , Romina Camilli  45 , Michael G Bruce  46 , Maria-Cristina C Brandileone  47 , Krow Ampofo  48 , Katherine L O'Brien  4 , Kyla Hayford  4 ; PSERENADE Team
Affiliations

Global impact of 10- and 13-valent pneumococcal conjugate vaccines on pneumococcal meningitis in all ages: The PSERENADE project

Yangyupei Yang et al. J Infect. 2025 Mar.

Abstract

Background: Pneumococcal conjugate vaccines (PCVs) introduced in childhood national immunization programs lowered vaccine-type invasive pneumococcal disease (IPD), but replacement with non-vaccine-types persisted throughout the PCV10/13 follow-up period. We assessed PCV10/13 impact on pneumococcal meningitis incidence globally.

Methods: The number of cases with serotyped pneumococci detected in cerebrospinal fluid and population denominators were obtained from surveillance sites globally. Site-specific meningitis incidence rate ratios (IRRs) comparing pre-PCV incidence to each year post-PCV10/13 were estimated by age (<5, 5-17 and ≥18 years) using Bayesian multi-level mixed effects Poisson regression, accounting for pre-PCV trends. All-site weighted average IRRs were estimated using linear mixed-effects regression stratified by age, product (PCV10 or PCV13) and prior PCV7 impact (none, moderate, or substantial). Changes in pneumococcal meningitis incidence were estimated overall and for product-specific vaccine-types and non-PCV13-types.

Results: Analyses included 10,168 cases <5 y from PCV13 sites and 2849 from PCV10 sites, 3711 and 1549 for 5-17 y and 29,187 and 5653 for ≥18 y from 42 surveillance sites (30 PCV13, 12 PCV10, 2 PCV10/13) in 30 countries, primarily high-income (84%). Six years after PCV10/PCV13 introduction, pneumococcal meningitis declined 48-74% across products and PCV7 impact strata for children <5 y, 35-62% for 5-17 y and 0-36% for ≥18 y. Impact against PCV10-types at PCV10 sites, and PCV13-types at PCV13 sites was high for all age groups (<5 y: 96-100%; 5-17 y: 77-85%; ≥18 y: 73-85%). After switching from PCV7 to PCV10/13, increases in non-PCV13-types were generally low to none for all age groups.

Conclusion: Pneumococcal meningitis declined in all age groups following PCV10/PCV13 introduction. Plateaus in non-PCV13-type meningitis suggest less replacement than for all IPD. Data from meningitis belt and high-burden settings were limited.

Keywords: Incidence; Indirect protection; Pneumococcal conjugate vaccines; Pneumococcal meningitis; Serotype replacement; Serotypes; Vaccine impact.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KH conducted the study and analyses while working at the Johns Hopkins School of Public Health but became an employee at Pfizer, Inc. on 26 October 2020. MDK reports grants from Merck, personal fees from Merck, and grants from Pfizer, outside 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. 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 reports a grant from Merck, outside the submitted work. AM reports research support to her institution from Pfizer and Sanofi and personal fees for advisory board membership and webinar presentations from AstraZeneca, GSK, Merck, Moderna, Novavax Pfizer, Seqirus. 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, Biondvax and GSK; had served on advisory boards of Pfizer, Merck Sharp & Dohme Biondvax and GXRD has received grants/research support from Pfizer, Merck Sharp & Dohme and Medimmune; has been a scientific consultant for Pfizer, MeMed, Merck Sharp & Dohme, Biondvax and GSK; and has been a speaker for Pfizer, Astra-Zeneca, GSK. LLH reports research grants to her institution from GSK, Pfizer and Merck. JDK has received an unrestricted grant-inaid from Pfizer Canada that supports, 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. JCS reports had received assistance from Pfizer for attending to scientific meetings outside the submitted work. EV reports grants from French public health agency, during the conduct of the study; grants from Pfizer, grants from Merck, outside the submitted work. KGK reports grants from GlaxoSmithKline Biologicals SA, outside of the submitted work. KA reports a grant from Merck, outside the submitted work. SCGA received travel grant from Pfizer. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
All-site weighted average incidence rate ratios for all serotype pneumococcal meningitis and vaccine/serotype-specific pneumococcal meningitis, comparing the annual post-PCV10/13 incidence rate to the average pre-PCV incidence rate, among children <5 years of age. Footnotes: Y-axis scales differ between figures. PCV10-types include serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F; PCV13-types include PCV10-types plus serotypes 3, 6A and 19A. Shaded areas indicate the year of PCV10/13 rollout. Estimates at year 0 indicate the change in incidence after the first year of PCV10/13 use. The size of the symbols in the figures reflects the number of sites contributing data to each time point, with larger symbols representing more sites.
Fig. 2
Fig. 2
All-site weighted average incidence rate ratios for all serotype pneumococcal meningitis and vaccine/serotype-specific pneumococcal meningitis, comparing the annual post-PCV10/13 pneumococcal meningitis incidence rate to the average pre-PCV incidence rate, among children 5–17 years of age. Footnotes: Y-axis scales differ between figures. PCV10-types include serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F; PCV13-types include PCV10-types plus serotypes 3, 6A and 19A. Shaded areas indicate the year of PCV10/13 rollout. Estimates at year 0 indicate the change in incidence after the first year of PCV10/13 use. The size of the symbols in the figures reflects the number of sites contributing data to each time point, with larger symbols representing more sites.
Fig. 3
Fig. 3
All-site weighted average incidence rate ratios for all serotype pneumococcal meningitis and vaccine/serotype-specific pneumococcal meningitis, comparing the annual post-PCV10/13 pneumococcal meningitis incidence rate to the average pre-PCV incidence rate, among adults ≥18 years of age. Footnotes: Y-axis scales differ between figures. PCV10-types include serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F; PCV13-types include PCV10-types plus serotypes 3, 6A and 19A. Shaded areas indicate the year of PCV10/13 rollout. Estimates at year 0 indicate the change in incidence after the first year of PCV10/13 use. In adults, the model that best fit the data was the one with one year time lag as compared to the year of PCV roll out as for children aged <5 years. For sites with moderate or substantial PCV7 impact, the time lag started at PCV7 introduction (not shown). For sites with no PCV7 impact, the start of the time lag was from year −1, indicating the pre-PCV period (i.e., IRR=1) for children aged <5 years and from year 0 for all other age groups. The size of the symbols in the figures reflects the number of sites contributing data at each time point, with larger symbols representing more sites.
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