The epidemiology and evolution of norovirus in Australia

Noroviruses are considered the leading cause of non-bacterial gastroenteritis in humans worldwide, and have been linked to a significant disease burden in both developed and developing countries. This has focused attention towards prevention strategies, especially the development of a norovirus vaccine. However, there first needs to be a clear understanding of the molecular epidemiology of noroviruses, and how they evolve to escape herd immunity. This thesis examines these two key issues. The molecular epidemiology of noroviruses is complex, with new epidemic variants usually emerging every 2 to 4 years. This thesis shows that the delay from the first detection of an epidemic variant to the first peak in incidence caused by that variant ranged from 2 to 7 months. The implication of this finding is that once norovirus vaccines are introduced, the delay period would be the time that pharmaceutical companies would have to formulate, produce and distribute a revised norovirus vaccine.In this thesis, an examination of the incidence and prevalence of norovirus genotypes revealed that while GII.4 norovirus is the predominant genotype seen in all settings, it had a much lower incidence in community-based outbreaks and sporadic cases (70%) than in outbreaks occurring in healthcare settings (94%). On account of the limited cross-over protection against genotypes not included in the vaccine formula, the implication of this finding is that a vaccine targeted against only GII.4 norovirus would leave the vaccinated population vulnerable to a large portion of genotypes, especially in community settings. The finding that GII.b/GII.3 norovirus is particularly prevalent in young children further highlights the importance of documenting demographics associated with particular virus genotypes, so that vaccines can be tailored to specific target groups.In this thesis, an analysis of the evolution of different norovirus strains revealed that not all strains evolve in the same manner. Some strains displayed a temporal progression, while others circulated concurrently. However, one singular finding emerged; changes occur in both structural and non-structural regions of the genome accompanying a major shift in norovirus prevalence. This has never been explicitly stated before for the noroviruses, as many studies focus on the structural portion of the genome. From the study of the emergence of the current epidemic strain GII.e/GII.4_2012, the apparent order of change appears to be: first a change in the structural region, then a change in the non-structural regions. Change occurring in both parts of the norovirus genome may prove valuable in predicting the emergence of new epidemic variant/strains of norovirus. The findings of this thesis indicated that the molecular epidemiology of norovirus is complex and dynamic, providing a challenge in the development of an effective norovirus vaccine. It is important to gain sufficient and continual understanding of the molecular epidemiology and evolution of noroviruses so that effective vaccines can be developed and maintained despite the rapid evolution the virus can undergo.