Pneumococcal Population Dynamics in the Conjugate Vaccine Era

Abstract

The introduction of pneumococcal conjugate vaccines (PCVs) in the early years of the 21st century have led to significant changes in pneumococcal epidemiology. Using transmission modeling and genomics based approaches, this dissertation evaluates alterations to the pneumococcal population through the PCV era. Chapter 1 presents a transmission model designed to examine factors that may influence the potential of a previously rare antibiotic resistant lineages to emerge following the introduction of a vaccine targeting more common resistant types, finding that such emergence is more likely in settings with high antibiotic use, high carriage burden, and frequent multiple carriage. Chapter 2 examines the population genomics of pediatric pneumococcal carriage before and after the introduction of PCV-13, finding that the non-vaccine type population composition experienced changes immediately following vaccine introduction but moved back towards its pre-vaccination state over time. Additionally, there is evidence that serotype 3, which is included in PCV-13, has persisted following vaccine introduction, though there are genetic differences between the pre- and post-vaccination population of this serotype. Chapter 3 compares isolates of a single non-vaccine serotype, 33F, collected from carriage and invasive disease, finding evidence that the invasive capacity of this serotype may have declined following the introduction of PCV-13 and that very closely related pairs isolates are disproportionately likely to both be from either carriage or disease. Together, these projects contribute to our understanding of how the pneumococcal population has and will continue to change as PCV use expands.