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. 2021 Apr 1;9(4):738.
doi: 10.3390/microorganisms9040738.

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

Maria Garcia Quesada  1 , Yangyupei Yang  1 , Julia C Bennett  1 , Kyla Hayford  1 , Scott L Zeger  1 , Daniel R Feikin  2 , Meagan E Peterson  1 , Adam L Cohen  3 , Samanta C G Almeida  4 , Krow Ampofo  5 , Michelle Ang  6 , Naor Bar-Zeev  1   7 , Michael G Bruce  8 , Romina Camilli  9 , Grettel Chanto Chacón  10 , Pilar Ciruela  11   12 , Cheryl Cohen  13   14 , Mary Corcoran  15 , Ron Dagan  16 , Philippe De Wals  17 , Stefanie Desmet  18   19 , Idrissa Diawara  20   21 , Ryan Gierke  22 , Marcela Guevara  11   23 , Laura L Hammitt  1 , Markus Hilty  24 , Pak-Leung Ho  25 , Sanjay Jayasinghe  26 , Jackie Kleynhans  13   14 , Karl G Kristinsson  27 , Shamez N Ladhani  28 , Allison McGeer  29 , Jason M Mwenda  30 , J Pekka Nuorti  31   32 , Kazunori Oishi  33 , Leah J Ricketson  34 , Juan Carlos Sanz  35 , Larisa Savrasova  36   37 , Lena Petrova Setchanova  38 , Andrew Smith  39   40 , Palle Valentiner-Branth  41 , Maria Teresa Valenzuela  42 , Mark van der Linden  43 , Nina M van Sorge  44 , Emmanuelle Varon  45 , Brita A Winje  46 , Inci Yildirim  47 , Jonathan Zintgraff  48 , Maria Deloria Knoll  1 ; The Pserenade Team
Collaborators, Affiliations

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

Maria Garcia Quesada et al. Microorganisms. .

Abstract

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.

Keywords: PCV impact; global; meta-analysis; pneumococcal meningitis; serotype distribution.

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Conflict of interest statement

K.H. 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. M.D.K. reports grants from Merck, personal fees from Merck, and grants from Pfizer, outside the submitted work. J.C.B. reports funding from Pfizer in the past year, unrelated to the submitted work. M.L. has been a member of advisory boards and has received speaker’s honoraria from Pfizer and Merck. German pneumococcal surveillance has been supported by Pfizer and Merck. S.D. reports grant from Pfizer, outside the submitted work. J.C.S. had received assistance from Pfizer for attending scientific meetings outside the submitted work. K.A. reports a grant from Merck, outside the submitted work. M.C. has previously received a professional fee from Pfizer (Ireland), an unrestricted research grant from Pfizer Ireland (2007–2016), and an Investigator Initiated Reward from Pfizer Ireland in 2018 (W1243730). S.C.G.A. received travel grant from Pfizer. A.M. has received research support to their institution from Pfizer and Merck; honoraria for advisory board membership from GlaxoSmithKline, Merck and Pfizer. S.N.L. performs contract research for GSK, Pfizer, Sanofi Pasteur on behalf of St. George’s University of London but receives no personal remuneration. I.Y. 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. R.D. has received grants/research support from Pfizer, Merck Sharp and Dohme, and Medimmune; has been a scientific consultant for Pfizer, MeMed, Merck Sharp and Dohme, and Biondvax; had served on advisory boards of Pfizer, Merck Sharp and Dohme, and Biondvax and has been a speaker for Pfizer. L.L.H. reports research grants to her institution from GSK, Pfizer, and Merck. E.V. reports grants from the French public health agency, during the conduct of the study and grants from Pfizer and grants from Merck outside the submitted work. M.H. 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. N.B.Z. has received investigator-initiated research grants from GlaxoSmithKline, Takeda Pharmaceuticals, Merck, and the Serum Institute of India, all unrelated to this research. N.Mv.S. reports grants and fees for service from Pfizer, fees for service from MSD and GSK, outside the submitted work; in addition, N.Mv.S. has a patent WO 2013/020090 A3 with royalties paid to University of California San Diego (inventors: Nina van Sorge/Victor Nizet). M.C.B. reports lecture fees from MSD outside from submitted work. C.L.B., M.D., has intellectual property in BioFire Diagnostics and receives royalties through the University of Utah. C.L.B. is an advisor to IDbyDNA. M.T. 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. Av.G. as received researching funding from Pfizer (last year 2017, Pfizer Investigator-Initiated Research [IIR] Program IIR WI 194379); they have attended advisory board meetings for Pfizer and Merck. C.M.A. reports grants and personal fees from Pfizer, Qiagen, and BioMerieux and grants from Genomica SAU, outside the submitted work. BL had two research grants from Pfizer on Streptococcus pneumoniae. J.D.K. has received an unrestricted grant-in-aid from Pfizer Canada that supports, in part, the CASPER invasive pneumococcal disease surveillance project. C.G.S. reports grant funding from Pfizer, Merck, and AstraZeneca in the past 3 years. 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.

Figures

Figure 1
Figure 1
Number of serotyped cerebrospinal fluid positive (CSF+) pneumococcal meningitis cases per site in mature PCV10/13 years by UN region, pneumococcal conjugate vaccine (PCV) product used during years included in the analysis, and age group. Abbreviations: EU = Europe, NAm = North America, LAC = Latin America and Caribbean, SSA = Sub-Saharan Africa, NAf = Northern Africa and Western Asia, AS = Asia, OC = Oceania. PCV13 is Pfizer’s Prevnar13/Prevenar13; PCV10 is GSK’s Synflorix.
Figure 2
Figure 2
Percentage of CSF+ pneumococcal meningitis cases in the mature PCV10/13 period due to serotypes included in current and upcoming products. PCV13 is Pfizer’s Prevnar13/Prevenar13; PCV10 is GSK’s Synflorix. PCV13 results are modeled output. PCV10 results are a pooled distribution of 210 cases in Brazil and 43 cases in other PCV10 sites for <5 years of age and of 707 cases in Brazil and 181 cases in other PCV10 sites for ≥5 years of age. ST3 is illustrated separately in lighter purple in the bars corresponding to products that include ST3 due to the uncertain effectiveness against ST3 in current products [21,22,23]. ST6C is illustrated in grey above the bars where ST6A is included. Although ST6C is not included in PCV10 or PCV13, PCV13 offers cross-protection through ST6A [24]. ST6A also benefits from cross-protection with ST6B, included in both PCV10 and PCV13. Therefore, ST6A causes a very small fraction of disease in both settings and age groups, and it is not shown. Confidence intervals do not include ST6C, as this serotype is not included in PCV10/13.
Figure 3
Figure 3
Site-specific percentages of CSF+ pneumococcal meningitis in the mature PCV10/13 period due to serotypes included in current and upcoming products. Each site is represented by a dot, which are colored by region and sized proportionally to the number of cases contributed by that site. The black boxes illustrate the IQR for the site-specific percentages. For PCV13 sites, the modeled results shown in Figure 2 are shown here in red diamonds. Data from Singapore are not shown for confidentiality but contributed to the PCV13 modeled results. PCV13 is Pfizer’s Prevnar13/Prevenar13; PCV10 is GSK’s Synflorix.
Figure 4
Figure 4
Serotype-specific distribution of CSF+ pneumococcal meningitis in the mature PCV10/13 period. Serotypes are colored by the lowest valency PCV product they are included in. The “x” in the PCV legend represents the extra serotypes included in that product relative to the next lower product (i.e., PCV13x includes serotypes 3, 6A, and 19A not in PCV10). PCV13 is Pfizer’s Prevnar13/Prevenar13; PCV10 is GSK’s Synflorix. Serotype 6C is colored separately because, although it is not included in any product, it is covered through cross-protection with PCV13-type serotype 6A [24]. Morocco and Bulgaria were not included in the PCV10 distribution due to serotyping limitations. * Serotype distribution for PCV13 sites is modeled output for the top 25 serotypes based on a pooled ranking plus serotype 1. Serotype distribution for PCV10 sites is from pooling cases across sites.
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