Norovirus infection overview

# Overview
Noroviruses (Norwalk) infection is the most common cause of acute gastroenteritis. Norovirus is a single-stranded RNA, non-enveloped virus. Norovirus  is a highly contagious virus. It is often transmitted via contaminated food or water, or by touching contaminated surfaces. Norovirus  gastroenteritis results in abdominal pain (usually diffuse, stabbing pain), nausea, diarrhea (usually watery), and vomiting. There is no age or gender predisposition to the development of norovirus infection. Risk factors for norovirus infection include close contact with infected individuals, particularly those in the same household, poor food-handling hygiene, and consumption of contaminated shellfish and/or raw vegetables. Symptoms of norovirus infection start within 12 to 48 hours of exposure to the virus and usually last 24 to 72 hours. Patients usually recover completely without treatment (only hydration) and without any serious long-term sequalae. Young children, elderly, and immunocompromised patients are at a higher risk of complications. In rare cases, norovirus illness can be serious, especially for young children and older adults. Lab findings are usually non-specific and may only be remarkable for signs of dehydration, such as elevated BUN and creatinine, relative polycythemia, and metabolic alkalosis. Real-time PCR is the optimal method for the diagnosis of norovirus infection. Supportive care is the mainstay of therapy for norovirus infection. Treatment includes oral/IV fluid administration to replace fluids lost from vomiting and diarrhea and to electrolyte disturbances. Other pharmacologic agents, such as anti-motility and anti-emetic agents may be administered among adults only (controversial efficacy), whereas anti-diarrheal agents are usually not recommended. Preventive measures include avoidance of exposure, proper hand washing, and adequate handling of food products.

# Historical Perspective
Originally called the "Norwalk agent" after Norwalk, Ohio, Norovirus was first discovered after an outbreak in an elementary school in 1968. The first documentation of the virus on electron microscopy was in 1972.

# Classification
Norovirus constitutes a genus of genetically diverse single-stranded RNA, non-enveloped viruses belonging to the Caliciviridae family. The Norwalk virus is the only species belonging to that genus; however, several strains have been identified including: Hawaii virus, Mexico virus, and Desert Shield virus. These strains can genetically be classified into five different genogroups (GI, GII, GIII, GIV, and GV).

# Pathophysiology
Noroviruses are highly contagious, given that as few as 10 particles are enough to cause the disease, transmission is via the fecal-oral route and peaks during the period when symptoms are most severe, and up to 3 days after recovery. As many strains of noroviruses exist, immunity is not gained following an infection. A non-functional fucosyltransferase FUT2 mutation has been associated with protection against the most common norovirus strains as FUT2 is required for viral transport in the small intestine.

# Causes
Norovirus is the cause of norovirus infection. Noroviruses (genus Norovirus) are a group of related, single-stranded RNA, nonenveloped viruses that cause acute gastroenteritis in humans. Noroviruses belong to the family Caliciviridae.

# Differentiating Norovirus from other Diseases
Norovirus should be differentiated from other causes of infectious vomiting and diarrhea, including other causes of viral gastroenteritis (sapovirus, adenovirus, rotavirus), bacterial gastroenteritis (yersinia, vibrio, shigella, salmonella, escherichia coli), and parasitic infections (amoebiasis, cryptosporidiosis).

# Epidemiology and Demographics
Norovirus is the leading cause of acute gastroenteritis and foodborne illness in all age groups in the United States. It causes approximately 21 million cases of gastroenteritis yearly. The genogroup II, genotype 4 strain is most commonly involved in large outbreaks of norovirus.

# Risk Factors
Risk factors for norovirus infection include close contact with infected individuals, particularly those in the same household, poor food-handling hygiene, and consumption of contaminated shellfish and/or raw vegetables.

# Natural History, Complications and Prognosis
Symptoms of norovirus infection start within 12 to 48 hours of exxposure to the virus and usually last 24 to 72 hours. Patients usually recover completely without treatment (only hydration) and without any serious long-term sequalae. Young children, elderly, and immunocompromised patients are at a higher risk of complications.

# Diagnosis

## History and Symptoms
Symptoms of norovirus infection include malaise, fever, stabbing diffuse abdominal pain, diarrhea, vomiting, and anorexia. Parents of infected children may often report easy irritability and oliguria/anuria.

## Physical Examination
Physical examination of patients with norovirus infection may be remarkable for low-grade fever, tachycardia, abdominal tenderness, and signs of dehydration (reduced skin turgor, sunken fontanelles, sunken eyes, dry mucous membranes). Physical examination in severe cases may be remarkable for hypotension and altered mental status.

## Laboratory Findings
Laboratory findings of norovirus infection include elevated concentration of inflammatory markers, hypokalemia, and chloride-sensitive metabolic alkalosis. Signs of dehydration may be present, such as relative polycythemia, elevated BUN, and elevated creatinine (pre-renal acute kidney injury). RT-qPCR assay is the optimal test for the diagnosis of norovirus infection. Enzyme immunoassays to detect norovirus have been developed but are less useful due to low sensitivity. Norovirus is not usually grown on culture.

# Treatment

## Medical Therapy
Supportive care is the mainstay of therapy for norovirus infection. Treatment includes oral/IV fluid administration to replace fluids lost from vomiting and diarrhea and to electrolyte disturbances. Over the counter oral rehydration solutions (ORS) are usually available, but home-made ORS may be prepared by mixing 1 liter of clean drinking water, 0.5 teaspoon of salt, and 6 teaspoons of sugar. Anti-motility and anti-emetic agents may be administered for symptomatic relief among adults only (controversial efficacy). Antimicrobial agents, including antiviral agents, are generally not recommended to treat norovirus infection.

## Primary Prevention
There is no vaccine to prevent norovirus infection. Prevention of foodborne norovirus disease is based on the provision of safe food and water.  Noroviruses are relatively resistant to temperature changes and have been associated with illness after eating steamed shellfish.  Moreover, noroviruses can survive in up to 10 ppm chlorine, well in excess of levels routinely present in public water systems.  Despite these features, it is likely that relatively simple measures, such as correct handling of cold foods, strict hand washing after using the bathroom and before handling food items, and paid sick leave, may substantially reduce foodborne transmission of noroviruses.  Prevention of norovirus disease spread via droplets from vomitus (person to person transmission) should focus on methods that limit transmission including: isolation precautions (e.g. isolating sick patients in a healthcare facility) and environmental disinfection.

## Secondary Prevention
The CDC currently does not conduct active surveillance to monitor outbreaks of gastroenteritis caused by noroviruses. The National Outbreak Reporting System (NORS) is a web-based system that was launched by the CDC in 2009 to collect information on outbreaks of foodborne, waterborne, and enteric diseases that spread from person-to-person, animals, environmental surfaces, and other or unknown ways. Public health agencies can report all outbreaks of gastroenteritis, including norovirus illness. The CDC also developed CaliciNet in 2009. It is a network of public health and food regulatory laboratories that submit norovirus sequences identified from outbreaks into a national database.