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 RESEARCH ARTICLE 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 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 Matthias Horn1*, Christian Theilacker2, Ralf Sprenger2, Christof von Eiff2, Ernestine Mahar2, Julia Schiffner-Rohe2, Mathias W. Pletz ID3, Mark van der Linden4, Markus Scholz ID1 1 Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany, 2 Pfizer Pharma GmbH, Berlin, Germany, 3 Institute for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany, 4 Institute of Medical Microbiology, German National Reference Centre for Streptococci, University Hospital RWTH Aachen, Aachen, Germany * OPEN ACCESS Citation: Horn M, Theilacker C, Sprenger R, von Eiff C, Mahar E, Schiffner-Rohe J, et al. (2023) Mathematical modeling of pneumococcal transmission dynamics in response to PCV13 infant vaccination in Germany predicts increasing IPD burden due to serotypes included in nextgeneration PCVs. PLoS ONE 18(2): e0281261. https://doi.org/10.1371/journal.pone.0281261 Editor: Joel Mossong, Health Directorate, LUXEMBOURG Abstract Introduction Two next-generation pneumococcal conjugate vaccines (PCVs), a 15- and a 20-valent PCV (PCV15 and PCV20), have recently been licensed for use in adults, and PCV15 has also been licensed in children. We developed a dynamic transmission model specific for Germany, with the aim to predict carriage prevalence and invasive pneumococcal disease (IPD) burden for serotypes included in these vaccines. Received: February 24, 2022 Accepted: January 18, 2023 Published: February 15, 2023 Copyright: © 2023 Horn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This study was sponsored by Pfizer Pharma GmbH, Germany. The co-authors employed by Pfizer (CT, RS, CvE, EM, and JSR) supported MH and MS regarding study design, data collection and analysis, and preparation of the manuscript. Pfizer had no role in the decision to Methods The model allows to follow serotype distributions longitudinally both in the absence and presence of PCV vaccinations. We considered eight age cohorts and seven serotype groups according to the composition of different pneumococcal vaccines. This comprises the additional serotypes contained in PCV15 and PCV20 but not in PCV13. Results The model predicted that by continuing the current vaccine policy (standard vaccination with PCV13 in children and with PPSV23 in adults) until 2031, IPD case counts due to any serotype in children <2 years of age will remain unchanged. There will be a continuous decrease of IPD cases in adults aged 16-59y, but a 20% increase in adults �60y. Furthermore, there will be a steady decrease of the proportion of carriage and IPD due to serotypes included in PCV7 and PCV13 over the model horizon and a steady rise of non-PCV13 serotypes in carriage and IPD. The highest increase for both pneumococcal carriage and absolute IPD case counts was predicted for serotypes 22F and 33F (included in both PCV15 and PCV20) and PLOS ONE | https://doi.org/10.1371/journal.pone.0281261 February 15, 2023 1 / 23 PLOS ONE publish. Epidemiological modeling was also supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the project PROGNOSIS (grant number #031L0296A). The BMBF had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Mathematical modeling of pneumococcal transmission dynamics in Germany serotypes 8, 10A, 11A, 12F, and 15B (included in PCV20 only), particularly in older adults. Between 2022 and 2031, serotypes included in PCV20 only are expected to cause 19.7– 25.3% of IPD cases in adults �60y. Conclusions We conclude that introduction of next-generation PCVs for adults may prevent a substantial and increasing proportion of adult IPDs, with PCV20 having the potential to provide the broadest protection against pneumococcal disease. Introduction Streptococcus pneumoniae is among the most frequent causes of vaccine-preventable morbidity and mortality both in children and adults globally [1]. It causes invasive infections, such as bacteremic pneumonia, meningitis, or primary sepsis, and non-invasive infections, such as non-bacteremic pneumonia, otitis media or sinusitis [2]. In adults, non-bacteremic pneumonia is by far the most common clinical presentation of pneumococcal disease, and more than 80% of pneumococcal pneumonia is non-bacteremic [3]. The pneumococcus primarily resides in the nasopharynx of young children, from which it transmits by respiratory droplets to other individuals [4]. Upper airway carriage of the pneumococcus is a prerequisite to cause disease. With a carriage prevalence between 20–60% among healthy children, this young population is considered the main reservoir for spreading infection to other children as well as to adults [4, 5]. The pneumococcal polysaccharide capsule is the most common virulence factor of S. pneumoniae, and with 100 known capsular serotypes it is also highly diverse [6]. Serotypes differ in propensity to cause disease and case fatality [7–9]. Currently, two pneumococcal vaccines are recommended for use in adults in Germany: a 23-valent pneumococcal polysaccharide vaccine (PPSV23; containing serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F) and a 13-valent pneumococcal conjugate vaccine (PCV13; containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) for immunocompromised individuals. Vaccines recommended for pneumococcal disease prevention in children are PCV13 and a 10-valent pneumococcal conjugate vaccine (PCV10; containing serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, 23F). PPSV23 has been recommended for adults �60y in Germany since 1998 [10]. In children, PCV7 (containing serotypes 4, 6B, 9V, 14, 18C, 19F, 23F) was first universally recommended in 2006 and replaced by either PCV10 or PCV13 in 2009, with PCV13 being used almost exclusively in recent years [11]. Pneumococcal vaccination is also recommended for all individuals with underlying chronic conditions as well as for individuals with congenital or acquired immunodeficiency [12]. Vaccination rates for PCVs in children <2y are suboptimal with 90% and 75% for the primary and booster dose, respectively [13]. The uptake of pneumococcal vaccination among older adults has been low, with only 22.5% of adults aged 60-7 (...truncated)