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Abstract
Viruses are responsible for more than 50% of all health-care associated gastroenteritis. Of those, norovirus is the leading cause of viral gastroenteritis and adenovirus can cause a wide range of clinical diseases, including gastroenteritis, respiratory illnesses and conjunctivitis. Therefore, molecular surveillance of these viruses is essential to identify prevalent strains that are linked to epidemics.
In this thesis, two molecular epidemiological studies of norovirus were performed to characterise strains within Australia and New Zealand, between 2014 and 2017, by using both clinical and wastewater samples (Chapters 3 and 4). In chapter three, we identified a decline in the prevalence of the recent pandemic variant Sydney 2012 which was concomitant with the emergence of several novel recombinant viruses in both nations. Interestingly, two of these recombinants contained the GII.4 Sydney capsid which we hypothesised may have provided a higher epidemiological fitness to these noroviruses. In chapter 4, we sought to explore the potential mechanisms that could facilitate such a change. Analysis of full-length GII.4 Sydney 2012 capsid sequences revealed positive selection in residue 373 of epitope A in all three recombinant GII.4 Sydney 2012 strains. In addition, amino acid reversion to the predecessor New Orleans 2009 variant was observed in GII.P16/GII.4 Sydney 2012 capsid, an event likely to have facilitated the GII.4 Sydney capsid persistence observed.
In chapter 5, we investigated the diversity of adenovirus within the Australian population also using wastewater and clinical samples. We successfully sequenced a total of 20 serotypes and identified F-41 as the most prevalent serotype (average of 68.5%) in the Australian population during 2016-2017. Collectively in chapters 3-5 we showed that NGS of wastewater samples provides a more informative summary of viruses that cause asymptomatic and symptomatic infections and not just the latter which is commonly reported from clinical samples.
In summary, this is the first Australian study to assess population-level epidemiology of norovirus and adenovirus, highlighting the benefits of using both clinical and environmental samples for surveillance of viruses circulating within the population. A better understanding of the viral strains’ distribution will enhance the development of a successful vaccine.