Clinical and Economic Burden of Pneumococcal Disease Due to Serotypes Contained in Current and Investigational Pneumococcal Conjugate Vaccines in Children Under Five Years of Age

Abstract

Introduction The widespread implementation of pneumococcal conjugate vaccines (PCVs) has significantly reduced the burden of pneumococcal disease around the world. Although licensed 10-valent (PCV10) and 13-valent (PCV13) vaccines have considerably reduced mortality and morbidity, a sizeable disease burden attributable to serotypes not contained in these PCVs remains. This study aimed to estimate the annual clinical and economic burden of pneumococcal disease attributable to licensed (PCV10 and PCV13) and investigational PCVs, notably 15-valent (PCV15) and 20-valent (PCV20) vaccines, in 13 countries in children under 5 years of age. Methods A decision-analytic model was created to aggregate total cases [inclusive of invasive pneumococcal disease (IPD), pneumonia, and otitis media (OM)], deaths, and direct costs in each country of interest [stratified by PCV10/PCV13 countries, depending on national immunization programs (NIPs)] over 1 year, using up to the three most recent years of available serotype coverage data. Data inputs were sourced from local databases, surveillance reports, and published literature. Results In 5 PCV10 NIPs (Austria, Finland, Netherlands, New Zealand, Sweden), most remaining PCV20-type disease was due to PCV13-unique serotypes (30–85%), followed by PCV20-unique (9–50%), PCV15-unique (4–15%), and PCV10-unique (2–14%) serotypes. In 8 PCV13 NIPs (Australia, Canada, France, Germany, Italy, South Korea, Spain, United Kingdom), most remaining PCV20-type disease was caused by PCV20-unique serotypes (16–69%), followed by PCV13-unique (11–54%), PCV15-unique (2–33%), and PCV10-unique serotypes (3–19%). Across all countries, PCV20 serotypes caused 3000 to 345,000 cases of disease and cost between $1.3 and $44.9 million USD annually with variability driven by population size, NIP status, and epidemiologic inputs. In aggregate, PCV20 serotypes caused 1,234,000 cases and $213.5 million in annual direct medical costs in children under 5 years of age. Conclusion Despite the success of PCV10 and PCV13 in reducing pneumococcal disease, a substantial clinical and economic burden remains due to serotypes contained in investigational vaccines. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00544-1.

Modeling of pneumococcal serogroup 10 capsular polysaccharide molecular conformations provides insight into epitopes and observed cross-reactivity

“…Widespread introduction of PCVs has significantly reduced the burden of invasive pneumococcal disease (IPD) due to vaccine serotypes ( Wahl et al, 2018 ). However, increased prevalence of non-vaccine serotypes (due to serotype replacement as well as different geographical and socio-economic vaccination programs and prevalence of serotypes) means that IPD is still a leading cause of lower respiratory infection morbidity and mortality ( GBD 2016 Lower Respiratory Infections Collaborators, 2018 ; Balsells et al, 2017 ; Wasserman et al, 2021 ). This necessitated the development of the third generation of PCVs, with higher serotype valency and protection against the emerging serotypes ( Klugman and Rodgers, 2021 ).…”

NCCN Guidelines® Insights: Survivorship, Version 1.2022

“…140,141 Furthermore, the added serotype coverage is expected to have a large impact on disease burden in the United States and globally. 142,143 At the time of the panel meeting, the CDC's Advisory Committee on Immunization Practices (ACIP) had not yet released recommendations regarding the new vaccines. Panel members brought up possible issues of accessibility, cost, and insurance coverage, but the panel consensus was to follow ACIP's recommendations when they were available.…”

Letter to the Editor Regarding “Clinical and Economic Burden of Pneumococcal Disease Due to Serotypes Contained in Current and Investigational Pneumococcal Conjugate Vaccines in Children Under Five Years of Age”

“…The model used by Wasserman et al utilized recent data on the serotype-specific burden of invasive pneumococcal disease (IPD) from countries where either the 10-valent PCV (PCV10) or 13-valent PCV (PCV13) are already widely in use. The authors state ''we only considered the most recent serotype coverage and burden of disease to characterize the remaining burden of vaccine-preventable pneumococcal disease rather than historical estimates'' [1]. We argue that this approach does not acknowledge the potential for newer vaccines to have reduced serotype-specific immunogenicity compared with PCV10 or PCV13, which could result in an increase in the disease burden caused by the serotypes shared with these two PCVs.…”

“…In a recent article, Wasserman et al. used a decision-analytic model to estimate the clinical and economic burden of pneumococcal disease attributable to Streptococcus pneumoniae serotypes contained in current and investigational pneumococcal conjugate vaccines (PCVs) in children ≤ 5 years of age [ 1 ]. We would like to highlight some methodological limitations that may affect interpretation of the model results.…”