Characterization of the Molecular Epidemiology of Neisseria meningitidis and Investigation of Two Potential Risk Factors Associated with Invasive Meningococcal Disease.

Abstract

The occurrence of invasive meningococcal disease (IMD) is the result of a complex interaction of host, agent, and environmental risk factors within both individuals and populations. The goal of this dissertation research was to better understand the epidemiology of its underlying organism, Neisseria meningitidis, and two potential risk factors associated with invasive disease. This dissertation is comprised of three projects. The first project better characterized invasive isolates of N. meningitidis recovered during peak and later periods of an epidemic of serogroup B IMD in Oregon using pulsed-field gel electrophoresis. The epidemic, characterized by increased occurrence of sporadic disease, rather than localized outbreaks, appears to have been due to the introduction and spread of a new clone within the population. Through amplification and detection of an integrated bacteriophage by polymerase chain reaction, the second project investigated whether this recently-proposed virulence factor was associated with IMD among a diverse collection of isolates from the United States. As the bacteriophage was associated with serogroup, but not isolate collection source, the results suggest it represents a genetic element acquired by certain clonal strains, rather than a virulence factor required for invasive disease. In the third project, an agent-based, simulation model was developed to represent the extent to which increasing population use of broad-spectrum antibiotics among children younger than five years of age may be having an impact on the epidemiology of IMD. By reducing the prevalence of colonizing organisms, the model demonstrated that increased population broad-spectrum antibiotic use among children younger than five years led to a lower proportion of children with acquired immunity and a higher population susceptibility to invasive disease. The results of this dissertation research argue for increased molecular characterization of circulating strains within IMD public health laboratory surveillance programs; underscore the continued need to identify new meningococcal virulence factors; and encourage additional research into the role of increasing population broad-spectrum antibiotic use as an environmental risk factor of IMD.