Noroviruses are a highly diverse group of single-stranded RNA viruses. There are two genogroups (I and II), comprising 9 and 22 genotypes, respectively , that principally cause disease in humans. Despite this great diversity, norovirus outbreaks in healthcare settings are caused overwhelmingly by GII.4 strains. These viruses also are associated with more severe outcomes, even after accounting for the more vulnerable case-mix that they tend to infect in healthcare settings . The emergence of particular GII.4 variants correlates with periodic increases in the number of outbreaks and the overall magnitude of the annual norovirus epidemic wave. This phenomenon, similar to the antigenic shift seen with influenza viruses, is thought to be due to the emergence of antigenic variants for which there is little or no population immunity [27–31].
Although the role of ward closures, specific cleaning regimes and case isolation in controlling norovirus in healthcare institutions continues to be debated, the evidence to date suggests that the best strategy for preventing the spread of norovirus infections in hospitals is likely to be by preventing direct contact between infected and susceptible patients. The introduction of norovirus into the hospital environment from the community may be practically inevitable; curtailing spread in the hospital could be significantly curtailed through the isolation of patients in single occupancy rooms while receiving care. As proximity to a symptomatic case is a driver of norovirus outbreaks, transmission of norovirus infections is likely to be promoted in an environment in which care is provided in wards with high patient density with limited physical barriers and shared toilet facilities, coupled with patient movement between assessment units and final inpatient destination wards. In nursing homes, density of room occupancy is likely less of a driver of transmission; residents are more mobile and self-sufficient and gather in communal use rooms, all of which can facilitate norovirus transmission.
Predominance of GII.4 strains may be related to both the ability of this genotype to evade herd immunity through continuous evolution, but also because of its ability to attach to a wider range of cellular host receptors that are present in the majority of the population .
Another area gaining interest is the interaction between the gut microbiota and noroviruses [63▪]. Disruption of the gut microbiota following norovirus infection has been described in some patients independent of age, resulting in a loss of diversity and increased Proteobacteria, which may potentially lead to an increased risk of complications, such as postinfection irritable bowel syndrome [7,64]. Microbiota composition changes significantly with age ; a decrease of bifidobacteria, which are thought to play an immune-modulatory role and represent important components of a ‘healthy’ gut microbiota, is known to be associated with the aging process. Among the elderly, the microbiota associated with those in long-term care is less diverse than among those that remain in the community, and that the loss of the ‘community’-like microbiota is associated with ill-health . Kuss et al. demonstrated that the gut flora directly impacts on infectivity and pathogenicity of viruses by facilitating entry and infection through direct virus-bacteria interactions, and the recent observation that norovirus can bind to HBGA-like molecules present in certain gut bacteria provide an interesting avenue to explore the relationship between microbiota composition and norovirus infection, with a potential to inform new therapeutic approaches [63▪]. Therefore, nutritional status, immunosenescence, inflammation, the microbiome and even whether an individual lives in the community or in an institution may all be associated with aging and susceptibility to norovirus. As such, a holistic approach may be required to better understand host factors associated with norovirus disease, and ultimately to inform the design of therapy and prevention.
Significant progress has been made in developing nonreplicating VLP-based vaccines against norovirus. These have shown to be immunogenic and to confer a significant degree of protection (48% against disease and 26% against infection) to challenge in volunteer studies . Multivalent vaccines can induce broad mucosal and systemic blocking antibodies [75,76]. These promising results may, in the near future, lead to phase III clinical trials in different target populations . One of the challenges that any norovirus vaccine must overcome is the need to elicit cross-reactive protection against the diverse population of norovirus genotypes and variant strains within genotypes. Norovirus GII.4 strains are the most prevalent, and their constant evolution is associated with epidemic waves every 2–4 years because of the emergence of antigenically novel strains that escape herd immunity [29–31]. Therefore, an efficacious norovirus vaccine must be able to protect against a variety of antigenically diverse variants of GII.4 noroviruses. If the strategy of employing consensus VLPs to provide protection against the evolving blockade epitopes is not successful, vaccines may need to be reformulated regularly, as is done for influenza vaccines, to incorporate novel antigens [53,77]. However, consensus or chimeric VLP approaches that require only the mutation of certain epitopes may provide a system that is more amenable for rapid production of vaccines that can adapt to emerging strains.
Papers of particular interest, published within the annual period of review, have been highlighted as:
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