Norovirus, formerly referred to as Norwalk virus, is a very contagious virus that causes acute gastroenteritis. People of all ages can get infected and sick with norovirus. The most common symptoms of norovirus are diarrhea, vomiting, nausea, and stomach pain. Other symptoms include fever, headache, and body ache. About 50% of cases of foodborne gastroenteritis in United States are caused by norovirus. Worldwide, about 1 out of every 5 cases of acute gastroenteritis is caused by norovirus.
The image below depicts the norovirus genomic structure and capsid domains.
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The norovirus genomic structure and capsid domains.
Signs and symptoms
Symptomatic norovirus gastroenteritis typically develops 12-48 hours after ingestion of contaminated food or water or after contact with an infected individual. Symptoms typically last for 24-72 hours.
Symptoms include the following:
Nausea and vomiting (profuse, nonbloody, nonbilious)
Watery diarrhea (nonbloody)
Abdominal cramps
Headaches
Low-grade fever
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
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 now is 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.
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The norovirus genomic structure and capsid domains.
Noroviruses are transmitted person to person via direct contact, exposure to aerosols, or fecal–oral routes. Noroviruses are highly contagious, with infection requiring fewer 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.[13, 14] 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 typically are absent, and hematochezia is rare.
According to a Centers for Disease Control and Prevention (CDC) report updated in March 2021, most norovirus outbreaks in the United States happen from November to April. In years when there is a new strain of the virus, there can be 50% more norovirus illness.
Each year, on average in the United States, norovirus causes[41] :
900 deaths, mostly among adults aged 65 and older
109,000 hospitalizations
465,000 emergency department visits, mostly in young children
2,270,000 outpatient clinic visits annually, mostly in young children
19 to 21 million cases of vomiting and diarrhea illnesses
Multistate outbreak of norovirus illnesses linked to raw oysters from Texas has been reported as of April 11, 2023.[40] Another multistate outbreak of norovirus illnesses linked to raw oysters from British Columbia was reported as of June, 2022.
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 1 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.
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.
Symptomatic norovirus gastroenteritis typically develops 12-48 hours after ingestion of contaminated food or water or after contact with an infected individual. Symptoms typically last for 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 be higher as well)
Vectors for norovirus infection include the following:
Water sources include both potable water and lake or swimming pool water (when ingested); noroviruses are relatively resistant to inactivation by chlorine.
Food sources include shellfish (eg, oysters, clams), leafy greens such as lettuce, fruits, cake frosting, and meats. Spread can occur through undercooked contaminated foods or improper hand washing by an infected food handler.
Body fluid sources include vomitus and feces from infected individuals. Maximal viral shedding occurs during the first 48 hours of illness; however, viruses can be detected in stool up to 3 weeks after illness resolves.[20]
Significant electrolyte and blood chemistry abnormalities such as hypokalemia, hyponatremia, metabolic alkalosis, and elevated creatinine phosphokinase can occur in patients with pre-existing conditions such as inflammatory bowel disease, renal failure, immunocompromising conditions, and cardiovascular disease. Severe clinical features, including acute renal failure, arrhythmia, and signs of acute organ rejection in renal transplant patients were observed in a university hospital outbreak.[21]
One case of norovirus encephalopathy was reported in a 23-month-old child.[22]
Hemolytic uremic syndrome has been reported in association with norovirus gastroenteritis in a patient with chronic renal failure.[23]
Generally, routine laboratory studies are not helpful in suspected cases of norovirus gastroenteritis. In severe cases of gastroenteritis with volume depletion, electrolytes and blood urea nitrogen and creatinine should be monitored.
The peripheral white blood cell count usually is normal. There may be slight polymorphonuclear leucocytosis and lymphopenia.
The absence of fecal leucocytes and occult blood in stool is helpful in ruling out other enteroinvasive infectious diarrhea processes. Stool culture should be performed to exclude infection with bacterial organisms such as Yersinia, Shigella, Salmonella, and Campylobacter species.[24]
Detection methods include the following:
Immune electron microscopy: Immune serum is used to aggregate virus in stool samples to aid detection.
Antigen detection immune assay: This has high sensitivity but low specificity because of reactivity with antigenic variants and homologous viruses.
Nucleic acid amplification: This technique is highly sensitive and specific. The sensitivity of real-time polymerase chain reaction (RT-PCR) is more than 1000 times greater than that of standard enzyme-linked immunosorbent assays and approximately 10-fold greater than reverse-transcription PCR in detection of norovirus capsid proteins in stool and food samples.[1]
Norovirus is included on the multiplex testing panels for gastrointestinal pathogens. As of February 2023, FDA approved panels for norovirus are R-Biopharm AB and CEPHEID.
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 for isolated uncomplicated gastroenteritis is not required.
In patients with severe symptoms in whom acute abdomen is suspected and in those with pre-existing diseases such as inflammatory bowel disease or other comorbidities, abdominal radiography or CT scanning should be performed.
If the patient is an international traveler, stool testing for ova and parasites and stool culture should be considered.
If the patient is severely immunocompromised (eg, with AIDS), stool tests for Cyclospora, cytomegalovirus (CMV), Isospora, and Cryptosporidium may be considered.
The surface area of the villus is reduced (villus blunting), along with the appearance of a dense intraepithelial infiltrate of CD8+ T lymphocytes. An increase in polymononuclear cells in the lamina propria of the small intestine also is observed.
In one study, electrophysiological analyses of duodenal biopsies from patients with norovirus infection showed increased epithelial apoptosis and a reduction in tight junctional protein expression, leading to epithelial barrier dysfunction. This likely contributes to diarrhea during norovirus infection by a leak flux mechanism (ie, ions and water leak from subepithelial capillaries into the intestinal lumen by paracellular diffusion due to increased permeability of tight junctions). Increased anion secretion was another finding in the study.[13] See the image below.
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Hematoxylin and eosin stain of duodenal epithelium.
In all epidemic outbreaks (2 or more people who shared a common meal), the local and/or state health department should be contacted for investigation of potential sources.
In cases of norovirus outbreaks, several measures should be taken to prevent further transmission, as follows:
Contaminated sources should be identified and eliminated.
Strict hand hygiene is necessary. Food handlers should be thoroughly educated on the infectivity of norovirus, and updated hygienic codes should be maintained.[25] Although virucidal efficacy of alcohol against feline calicivirus is inferior to that of povidone-iodine, it is greatly variable depending on different formulations, concentrations, and contact times. In one study, only a 0.5-1 log10 reduction in virus titer was achieved after exposure to ethanol (62-99.5%) for 30 seconds. Another study showed a 2 and 3 log10 reduction in virus titer when 80% ethanol was used for 30 seconds and 1 minute, respectively. Successful control of a norovirus outbreak using 80% alcohol-based hand rubs was reported in an infirmary.[26] Hand washing with soap and water is necessary for hands that are visibly soiled.[27]
Environmental sanitization and disinfection should be performed.
Instruct individuals with viral gastroenteritis to self-quarantine.
Clinical trials are in progress for vaccine development. Currently no vaccines against norovirus are available due to wide genetic and antigenic diversity of noroviruses with multiple co-circulated variants of various genotypes.
Symptoms of norovirus infection usually are self-limited and resolve spontaneously within 24-48 hours. Antidiarrheal agents may be used with caution but should be avoided in children. Over-the-counter analgesics (eg, ibuprofen, acetaminophen) and antiemetics, if prescribed by a physician, can be used for symptomatic relief (drug-specific product labeling should be consulted). Fluid intake is recommended to maintain hydration.
Zartash Zafar Khan, MD, FACP, Infectious Disease Consultant
Disclosure: Nothing to disclose.
Coauthor(s)
Michelle A Jaworski, MD, Consulting Staff, Midland Orthopedic Associates
Disclosure: Nothing to disclose.
Todd S Wills, MD, Associate Professor, Department of Medicine, Division of Infectious Disease and International Medicine, Program Director, Infectious Disease Fellowship Program, University of South Florida College of Medicine
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Richard B Brown, MD, FACP, Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine
Disclosure: Nothing to disclose.
Chief Editor
Michael Stuart Bronze, MD, David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London
Disclosure: Nothing to disclose.
Additional Contributors
Joseph R Masci, MD, FACP, FCCP, Professor of Medicine, Professor of Preventive Medicine, Icahn School of Medicine at Mount Sinai; Director of Medicine, Elmhurst Hospital Center
Disclosure: Nothing to disclose.
Mark Martin Huycke, MD, Professor of Medicine, Infectious Diseases Section, University of Oklahoma Health Sciences Center; Chief, Medical Service, Department of Veterans Affairs Medical Center, Oklahoma City
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