The best magazine
Host Factors Associated With Populations in Healthcare Settings
Both host genetic factors and acquired immunity play a role in norovirus susceptibility. Genetic resistance to norovirus infection is related to human histo-blood group antigen (HBGA) genotype. Individuals who express HBGA on cell surfaces and in body fluids, termed secretors, are generally susceptible to a wider range of norovirus strains whereas nonsecretor individuals tend to be significantly more resistant to norovirus infections. However, susceptibility and resistance patterns differ according to norovirus strain. The ability of norovirus-specific antibodies to bind to norovirus capsid sites involved in attachment to HBGA is believed to correlate with protection.
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.
In immunocompromised patients, norovirus can cause chronic dehydrating diarrhea, leading to severe disease complications and sometimes mortality (reported to be up to 25%). The evolution of GII.4 strains within a long-term shedding immunocompromised patient has been observed to lead to the generation of antigenically distinct strains, supporting the hypotheses that long-term shedders in healthcare settings may serve as a source for the emergence of epidemic strains.
Although children have the highest incidence in the community, among hospital in-patients the elderly suffer a longer duration of illness with more severe symptoms, contributing to excess mortality. Immunosenescence may be one contributory factor; this consequence of aging is increasingly recognized as a major risk factor leading to increases in inflammation, autoimmunity, cancer, susceptibility to gastrointestinal infections, and poor response to vaccines, which is particularly acute among the elderly in residential care. Another risk factor may be ongoing statin use, which has been implicated as a risk factor for norovirus disease. Consistent with this are in-vitro and in-vivo experiments that have demonstrated that statins can increase norovirus pathogenicity and reduce the infectious dose required to cause disease in animal models. Considering the increasing and widespread use of these types of drugs in an aging population globally, a better understanding of the relationship between statins and the risk of norovirus infection and disease and of age related waning immunity is needed.
Another area gaining interest is the interaction between the gut microbiota and noroviruses. 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. 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. 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.
Other healthcare associated infections, such as Clostridium difficile diarrhea, are associated with altered microbiota composition characterized by a loss of diversity; repopulation of the gut environment with 'healthy' microbiota can reverse chronic C. difficile diarrhea. Recently, the acquisition of norovirus infection though fecal transplantation from an asymptomatic donor to a C. difficile chronically infected patient was reported, highlighting the risks of such therapies. However, new approaches using targeted gut colonization or bacteriotherapy show promise and may provide safer and adaptable future therapies for intestinal diseases and infections characterized by dysbiosis.
Source: ...