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Characterization of Norovirus strains and a seroprevalence study to understand the fluctuation of outbreak activity in Alberta, Canada

  • Author / Creator
    Hasing Rodriguez, Maria E
  • Norovirus (NoV) is recognized as the leading agent causing gastroenteritis among individuals of all ages. Historical data of NoV outbreak surveillance in Alberta, Canada, from the period July 2000 to June 2008 demonstrated a biennial pattern of NoV outbreak activity, in which peaks of high outbreak activity appeared to be driven by the emergence of new phylogenetic clusters of NoV within genotype GII.4 (GII.4 variants). The work in this thesis aimed to analyze the outbreak activity of NoV in Alberta between July 2008 and June 2015 and examine novel NoV GII.4 variants as well as immune responses at the population level. Norovirus outbreak surveillance data since July 2008, showed that GII.4 continued to be the most predominant genotype in Alberta, and was responsible for 47.6% to 80.2% of all NoV outbreaks per year. The overall number of NoV outbreaks observed per year demonstrated a loss of the biennial pattern since July 2011 as well as a gradual decline in the number of NoV outbreaks. Two novel GII.4 variants emerged in the 7-year period, New Orleans 2009 and Sydney 2012. Genotype GII.17 was also detected in November 2014. Unlike previous years, peaks of high outbreak activity were not always associated with the emergence of novel GII.4 variants, suggesting that, in addition to antigenic change of NoV GII.4, other factors also contributed to the high levels of NoV outbreak activity in Alberta. Since NoV strain genotyping for outbreak surveillance in the province has been performed based on a small 320bp region within the major capsid gene (ORF2) that provides limited information about the genetic diversity of NoV, a near-full length genome characterization was performed on a group of NoV strains representing 7 different GII.4 variants that have circulated in the province since 2002. A phylogenetic comparison demonstrated that most of the strains found in Alberta were similar to strains that had been described in global pandemics. Furthermore, recombination detection analysis as well as an assessment of the intra-host genetic diversity of NoV during chronic infection suggested that genetic changes in other genes besides the major capsid gene (ORF2), such as p22 (ORF1) and VP2 (ORF3) might improve the fitness of NoV GII.4. In order to examine if waning of herd immune response over time could be a factor in the annual fluctuations of outbreak activity levels, archived sera collected in 2008 and 2012-2014 from two different populations of Alberta, pregnant women and individuals receiving virology-serology testing, were tested for anti-NoV GII.4 IgG in a cross-sectional study. A high seroprevalence of 84.2% and 76.7%, respectively, were observed in each group. No significant differences in prevalence or geometric mean titers were identified across time points in these populations. In summary, the findings from this study suggest that, in addition to antigenic change of NoV at ORF2, other factors also affect the outbreak activity in Alberta and that ORF1 and ORF3 phylogenetic analysis should be included while monitoring the evolution of pandemic NoV strains. The results from this study provide useful data regarding the seroprevalence of NoV GII.4 in Alberta and the variability of anti-NoV GII.4 IgG responses within a large group of individuals, including pregnant women, providing a framework for further studies of immune responses at the population level.

  • Subjects / Keywords
  • Graduation date
    2016-06
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3NV99J91
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Medical Sciences-Laboratory Medicine and Pathology
  • Supervisor / co-supervisor and their department(s)
    • Pang, Xiaoli (Laboratory Medicine and Pathology)
    • Hazes, Bart (Medical Microbiology and Immunology)
  • Examining committee members and their departments
    • Koopmans, Marion (Virology)
    • Robinson, Joan (Pediatrics)
    • Preiksaitis, Jutta (Medicine)
    • Lee, Bonita (Pediatrics)