The Epidemiologic and Clinical Importance of Norovirus Infection

The Virus

Caliciviruses (family Caliciviridae) are a group of nonenveloped, icosahedral viruses with a single-stranded, positive sense RNA genome [7]. Four genera are recognized in the Caliciviridae family: Norovirus, Sapovirus, Lagovirus, and Vesivirus. Viruses in the latter two genera infect only animals. The Norovirus and Sapovirus genera contain human and animal virus strains, but cross-species transmission of strains within these genera has not been recognized to occur. Human noroviruses cannot be

Epidemiology

Noroviruses infect persons of all ages. Previously, these viruses were believed to infect only school-aged children and adults, but recent studies indicate that they also infect young children and are second to rotaviruses in causing infants to be hospitalized. Noroviruses cause infection throughout the year, although there is a peak incidence during the cold-weather months [13]. Mead and colleagues [14] estimated that there are 23 million norovirus infections per year in the United States,

Transmission

Noroviruses are transmitted primarily by the fecal–oral route. Fecal contamination of food, water, and fomites, as well as direct person-to-person spread, accounts for most outbreaks. Contamination of food may occur at any point during its production. For example, shellfish and raspberries that were contaminated at the site where these foods are harvested or produced have been implicated in outbreaks, whereas other foods, such as salads, cold foods, and sandwiches, have caused outbreaks after

Clinical Manifestations

Norovirus infection is characterized by the sudden onset of vomiting or diarrhea or both symptoms. Human experimental infection studies with Norwalk virus show that the predominant symptom can vary from person to person; in one person it may be vomiting without diarrhea, whereas in another person it may be diarrhea without vomiting [4], [59]. Emesis is a characteristic finding in outbreaks that are associated with norovirus infection (Table 3), but this symptom is less common in children who

Pathogenesis

The pathogenesis of norovirus infections has been explored in experimental human infection studies. Biopsies obtained at the duodenojejunal junction from infected persons showed broadening and blunting of intestinal villi, epithelial cell disarray, crypt cell hyperplasia, cytoplasmic vacuolization, and infiltration of inflammatory cells into the lamina propria [75], [76]. These histologic changes can be noted a few hours before the onset of symptomatic illness as well as in asymptomatically

Diagnosis

RT-PCR assays are the most common approach for establishing a diagnosis of norovirus infection [36]. Virus-specific primers are used to amplify conserved regions of the genome (usually in the polymerase or VP1 genes). Specificity of the amplification is established by hybridization with a virus-specific probe or by direct sequencing of the amplicons. No single primer pair can detect all norovirus strains because of the high sequence diversity, but more than 90% of strains can be detected using

Treatment and Prevention

Generally, norovirus-associated illness is mild and self-limited, so treatment is supportive (eg, rehydration, analgesics, antiemetics). Some patients become ill enough to require hospitalization for fluid and electrolyte replacement. Mortality is rare, but it has occurred as a result of aspiration or because of increased debility in chronically ill patients.

Prevention is based upon avoidance of contaminated foodstuffs and water, disinfection of virus-contaminated areas, and handwashing by

Current Questions and Future Prospects

Recognition of the major importance of noroviruses as a cause of gastroenteritis in many different populations has increased significantly in the past decade. As rapid diagnostic assays become accessible in the near future, it will be important to determine if noroviruses cause chronic infections (as do animal caliciviruses) that are associated with arthritis, encephalitis, hepatitis, and myocarditis in addition to acute or chronic gastroenteritis. There is a great need for the development of

Acknowledgments

We thank Anne Hutson for help in preparation of Fig. 2. Norovirus research in our laboratories is supported by funding (N01-AI-25465, P01-AI-057788, and M01-RR-000188) from the National Institutes of Health.