Norovirus

Updated: Sep 27, 2018
  • Author: Zartash Zafar Khan, MD, FACP; Chief Editor: Michael Stuart Bronze, MD  more...
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Overview

Practice Essentials

Norovirus, formerly referred to as Norwalk virus, is the most common cause of epidemic nonbacterial gastroenteritis in the world.

The image below depicts the norovirus genomic structure and capsid domains.

The norovirus genomic structure and capsid domains The norovirus genomic structure and capsid domains.

Signs and symptoms

Symptomatic norovirus gastroenteritis typically develops 24-48 hours after ingestion of contaminated food or water or after contact with an infected individual. The onset can be abrupt or gradual, but each episode is short-lived, lasting only 24-72 hours. Symptoms include the following:

  • Nausea and vomiting (profuse, nonbloody, nonbilious)

  • Watery diarrhea (nonbloody)

  • Abdominal cramps

  • Headaches

  • Low-grade fever is common: But temperatures may reach 38.9˚C

  • Myalgias and malaise

Focal tenderness and peritoneal signs are absent in abdominal examination. Vital signs in norovirus gastroenteritis include the following:

  • Low-grade fever

  • Tachycardia

  • Possible hypotension with volume depletion

See Clinical Presentation for more detail.

Diagnosis

Laboratory studies

Norovirus infection can be detected via the following studies:

  • Immune electron microscopy: Immune serum is used to aggregate virus in stool samples to aid detection

  • Antigen detection immunoassay: Has high sensitivity but low specificity because of reactivity with antigenic variants and homologous viruses

  • Nucleic acid amplification: Highly sensitive and specific [1]

Serum antibody titers can be detected within 2 weeks of illness. During norovirus infection, immunoglobulin M (IgM) to norovirus has been found to be more specific than IgG. [2]

Imaging studies

Imaging for isolated, uncomplicated gastroenteritis is not required. In patients with severe symptoms in whom acute abdomen is suspected and in those with preexisting disorders such as inflammatory bowel disease, abdominal radiography or computed tomography scanning should be performed.

New strain

In January 2013, the US Centers for Disease Control and Prevention (CDC) reported that a new norovirus strain, GII.4 Sydney, which was first detected in Australia, had spread to the United States. During the last 4 months of 2012, GII.4 Sydney accounted for 53% of 266 norovirus outbreaks in the United States, with roughly half of them having resulted from direct person-to-person transmission and another 20% having been foodborne. In general, GII.4 strains are associated with higher rates of hospitalization and death. [3, 4]

See Workup for more detail.

Management

Treatment of norovirus gastroenteritis includes the following:

  • Oral fluid and electrolyte replacement: Generally adequate for the treatment of norovirus infections

  • Intravenous fluid and electrolyte resuscitation: May be necessary in cases of severe volume depletion

  • Antiemetics: For relief of nausea and vomiting

  • Analgesics: For relief of myalgias and headache

  • Antiperistaltic agents: Should generally be avoided in cases of infectious diarrhea but can be considered in patients with severe diarrhea

See Treatment and Medication for more detail.

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Background

Norwalk virus was officially renamed norovirus by the International Committee on Taxonomy of Viruses in 2002. The virions contain a single-stranded RNA molecule in round to hexagonal capsids that are 35-39 nm in diameter, with icosahedral symmetry. The surface structure of the capsid is a regular pattern with distinctive features and 32 cup-shaped depressions. [5, 6]

Norovirus was first recognized as a cause of gastroenteritis in 1972, when it was detected in stool samples collected from infected elementary school students and contacts during an outbreak in Norwalk, Ohio, in 1968. It was declared a member of the Caliciviridae family of viruses in 1993. [7] It is now considered the most common cause of epidemic nonbacterial gastroenteritis in the world.

In the 1970s and 1980s, typing of Norwalk-like virus (NLV) relied solely on immunologic methods involving human clinical samples as the source of antigens and antibodies. These methods had serious limitations in accuracy and reproducibility and never provided a reliable scheme for antigenic classification of strains. In the 1990s, however, newer molecular techniques to amplify, sequence, and express the genome of NLV strains allowed researchers to genetically and antigenically characterize NLV strains. [8]

The Norovirus genus contains more than 40 different strains that are divided into 5 genogroups based on sequence similarity. Viruses in genogroups I, II, and IV are primarily human pathogens, although genogroup II contains a porcine-specific virus. Viruses in genogroup III and V infect bovine and murine species, respectively. Each genogroup is further subdivided into genoclusters based on sequence similarity. [9]

The genome consists of single-stranded RNA of 7.3-7.7 kilobases. It encodes 3 open reading frames (ORFs). ORF 1 is the largest (approximately 1700 amino acids) and expressed as a nonstructural polyprotein precursor that is cleaved by the viral 3C-like protease. ORF 2 encodes the viral capsid (550 amino acids) and contains the shell and protruding domains. ORF 3 encodes a small basic protein of unknown function. See the image below.

The norovirus genomic structure and capsid domains The norovirus genomic structure and capsid domains.
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Pathophysiology

Noroviruses are transmitted person to person via direct contact, exposure to aerosols, or fecal–oral routes. Noroviruses are highly contagious, with infection requiring fever than 10 virions (ID50 = 10 virions), leading to disease in 50% of inoculated individuals. The virus is extremely stable in the environment and resists freezing temperatures, heat (up to 60°C), disinfection with chlorine, acidic conditions, vinegar, alcohol, antiseptic hand solutions, and high sugar concentrations. The incubation period is approximately 1-2 days, and symptoms typically last 1-3 days (or longer in immunocompromised individuals). Viral shedding occurs for up to 3 weeks following infection. [10]

Noroviruses bind polymorphic histoblood group antigens (HBGAs) that putatively serve as receptors or cofactors for infection. Strains from different genoclusters bind various HBGAs: Genogroup I viruses preferentially bind blood group A and O antigens, while genogroup II viruses predominantly bind A and B antigens. [11] Individual norovirus strains may be capable of infecting only a subset of the human population, although the diverse binding profiles found within genogroup I and genogroup II viruses likely collectively make nearly all individuals susceptible to norovirus infection. [10] Recurrent infections can occur throughout life because of the great diversity of norovirus strains and the lack of cross-strain or long-term immunity.

Infection is characterized by damage to the microvilli in the small intestine. Upon microscopic investigation, villi are found to be blunted, although the mucosa and epithelium remain intact. [12] A recent study demonstrated increased epithelial cell apoptosis and damage to tight junction proteins. [13] Diarrhea is induced by D-xylose and fat malabsorption, with enzymatic dysfunction observed at the brush border, along with leak flux and anion secretion. [14, 13] Vomiting is related to virus-mediated changes in gastric motility and delayed gastric emptying. Notably, no histopathologic lesions can be identified in the gastric mucosa of infected patients. [15] Noroviruses do not invade the colon, so fecal leukocytes are typically absent, and hematochezia is rare.

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Epidemiology

Frequency

United States

According to a Centers for Disease Control and Prevention (CDC) report updated in December 2014, each year on average in the United States, norovirus causes 19-21 million cases of acute gastroenteritis (inflammation of the stomach or intestines or both), leads to 1.7-1.9 million outpatient visits and 400,000 emergency department visits (primarily in young children), and contributes to about 56,000-71,000 hospitalizations and 570-800 deaths (mostly among young children and elderly persons). [16]

Norovirus illness can be acquired at any time during the year, but it is most common in winter. In addition, there can be 50% more norovirus illness cases in years when a new strain of the virus is being circulated.

According to surveillance reports prepared by CDC's OutbreakNet team, in 2006, 1,270 reported foodborne outbreaks resulted in 27,634 illnesses and 11 deaths. Among these 1,270 outbreaks, 621 had a single confirmed cause that was most often norovirus (54% of outbreaks), followed by Salmonella species (18% of outbreaks). [17]

Outbreaks have been reported in restaurants, health care facilities, schools, resorts, cruise ships, military ships, and barracks. Viral transmission occurs year-round, with a higher incidence of disease in winter months in temperate climates. [18]

International

Data regarding outbreaks in developing nations are not well quantified, but the outbreak rate in other industrial nations is similar to that of the United States.

Mortality/Morbidity

Norovirus gastroenteritis typically lasts 24-72 hours, with remission occurring without sequelae. Death is extremely rare, except in individuals particularly vulnerable to profound volume depletion.

Age

Norovirus gastroenteritis can occur in individuals of all ages. Studies using norovirus recombinant antigen have suggested an increase in antibody prevalence with advancing age. In one study, the prevalence of norovirus immunoglobulin G (IgG) rose during school-aged years, reaching a peak of 70% in persons aged 11-16 years. [19] It should be noted, however, that not all infected individuals sustain detectable antibody responses.

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Prognosis

Norovirus gastroenteritis is a self-limiting disease with an excellent prognosis in otherwise healthy individuals.

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Patient Education

Patients with norovirus infection should be educated on personal and environmental hygiene, including avoiding/eliminating contaminated foods and water. Ill individuals should refrain from attending school or work.

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