Genomic Epidemiology and Transmission Dynamics of Healthcare-Associated Pathogens

Abstract

Healthcare-associated infections are important causes of morbidity and mortality and are associated with a substantial increase in health care costs each year. They are often caused by opportunistic pathogens such as Staphylococcus aureus that colonize healthy individuals and it is within this context that the majority of transmission occurs. This dissertation presents some of the challenges and opportunities associated with the identification and control of pathogens both inside and outside of healthcare facilities. Chapter One characterizes the impact of host heterogeneity on infection control interventions to reduce S. aureus carriage, finding that failure to take into account multiple carrier types including hosts resistant to colonization, which make up 50% of the population, results in an underestimation of pathogen transmissibility and overestimation of the effectiveness of intervention strategies. Chapter Two evaluates the potential for genome sequencing in routine hospital surveillance by comparing the accuracy of existing approaches in distinguishing between infections acquired through patient-to-patient transmission and those acquired prior to admission and identifying transmission clusters and outbreaks. Using simulated epidemiological and pathogen genomic data, we find that sequencing-based methods may not always provide additional benefit particularly when individuals are screened at time of admission. However, in order to successfully detect transmission clusters and outbreaks, genomes substantially improve the resolution to link connected cases. Chapter Three examines the population genomics of sequence type (ST) 22 community-acquired methicillin-resistant S. aureus (MRSA) in the Gaza strip, where a high carriage prevalence of MRSA has been previously reported. ST22 is the genotype of EMRSA-15, a pandemic clone that recently emerged and became widespread in hospitals across Europe. However, we find that the Gaza strains are more closely related to the diverse methicillin-susceptible ST22 population from which the hospital-associated clade emerged. We also find evidence for two clones, resulting from two separate acquisitions of resistance as well as diversification of additional genetic determinants. Together, these projects contribute to our understanding of how efforts to control pathogens both inside and outside healthcare settings are challenged by their diversity, diversity in the population that hosts them, and the methods and tools used in their surveillance.