Norovirus and Other Human Calicivirus Infections

Caliciviridae is a family of viruses that is divided into at least 5 genera, with noroviruses and sapoviruses being the 2 that are often termed human caliciviruses. The cause of a condition first described in 1929 as the “winter vomiting disease” because of its predilection for wintertime outbreaks, norovirus was initially named in 1968 as the Norwalk virus because it was discovered in Norwalk, OH. Noroviruses are single-stranded RNA viruses, with many genotypes capable of causing human disease. The primary genotypes responsible for disease in humans are G-I (∼15% of cases), G-II (∼85% of cases), and G-IV (<1% of cases). The viral capsid is composed of 2 primary proteins: VP1 and VP2. The P-domain can undergo antigenic drift and shift, thereby allowing immune evasion and giving the virus potential for pandemic spread.In the United States, noroviruses are responsible for more than 50,000 hospitalizations each year and 500 to 800 deaths. With more than 1 million doctor visits annually, norovirus is now the #1 cause of pediatric gastroenteritis since the introduction of the rotavirus vaccines. Sapovirus infections have also been recognized in the past as a substantial cause of sporadic cases of acute pediatric gastroenteritis and more recently of outbreaks of diarrheal illness. Worldwide, norovirus is responsible for 685 million episodes of gastroenteritis annually, with 200 million of these cases among children younger than age 5 years. These infections lead to the deaths of an estimated 50,000 children every year, nearly all of which occur in developing countries. Periodically a pandemic strain arises and the number of deaths more than doubles. Just how often norovirus is the cause of travelers’ diarrhea is not known, but some studies indicate the incidence may be as high as 65% of cases.Shedding of norovirus and sapovirus can be asymptomatic, most often among children, which makes closed populations (schools, child care centers, long-term care facilities, and cruise ships) particularly susceptible to the development of outbreaks. Viral transmission is most commonly fecal-oral, either directly from contaminated food or by touching surfaces harboring the virus and then from hand to mouth. Currently, in fact, norovirus is the #1 cause of foodborne illnesses in the United States. Contagious vomitus has also been the source of individual infections and several outbreaks.Several factors contribute to the ease of norovirus spread: it has a very low infectious dose of fewer than 100 viral particles, it can live a long time on contaminated surfaces, large numbers of viral particles are excreted with infection, and shedding can persist for weeks after symptoms resolve.Infections occur throughout the year but have an increased incidence during the cooler months. The incubation period is 12 to 48 hours, after which symptomatic patients may develop the abrupt onset of nausea and vomiting with watery diarrhea, abdominal cramps, and loss of appetite. Most typically, symptoms last for 1 to 3 days, but the very young and the elderly as well as patients weakened by underlying illness may have more prolonged illness. Beyond the gastrointestinal tract, patients may experience fever, muscle aches, and headache. Rarely, norovirus infection has been associated with hemolytic-uremic syndrome, elevations in liver function tests, and influenzalike symptoms. Some studies have suggested a possible link between norovirus infection and the development of inflammatory bowel disease.Several diagnostic tests can identify norovirus: a multiplex nucleic acid-based assay, an enzyme immunoassay kit, and real-time reverse transcriptase-polymerase chain reaction. These tests, however, are not widely available in clinical laboratories; they are primarily used for public health reasons rather than for the care of individual patients for whom symptoms are usually of short duration and self-resolving with supportive care.Maintenance of hydration, either orally or intravenously, is the mainstay of treatment. Vaccines against norovirus are in the early stages of development, but for now at least, meticulous handwashing with soap and running water remains the key to prevention and is more effective than the use of alcohol gels. Within the hospital setting, regular control measures as well as contact precautions should be taken for patients admitted with norovirus infection.COMMENT: In the age of probiotics and prebiotics, monoclonal antibodies, fifth-generation antimicrobials, stem cell transplants, even fecal transplants, how ironic that our best defense against norovirus is running water and soap! Is it comic or tragic that our best tools against malaria (and, for that matter, Zika) remain bug spray and mosquito netting? Yes, to paraphrase Frost, the world is lovely, dark and deep, but we have promises to keep, and miles to go before we sleep.

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