Norovirus

Norovirus (was "Norwalk-like viruses"), an RNA virus of the Caliciviridae taxonomic family, causes approximately 90% of epidemic non-bacterial outbreaks of gastroenteritis around the world, and is responsible for 50% of all foodborne outbreaks  of gastroenteritis  in the US. Norovirus affects people of all ages. The viruses are transmitted by faecally contaminated food or water and by person-to-person contact.

After infection, immunity to norovirus is not complete nor long-lasting. There is an inherited predisposition to infection and people whose blood type can be detected in their saliva are more often infected.

Outbreaks of norovirus disease often occur in closed or semi-closed communities, such as long-term care facilities, hospitals, prisons, dormitories, and cruise ships where once the virus has been introduced, the infection spreads very rapidly by either person-to-person transmission or through contaminated food. Many norovirus outbreaks have been traced to food that was handled by one infected person.

Norovirus is rapidly killed by chlorine-based disinfectants, but because the virus particle does not have a lipid envelope, it is less susceptible to alcohols and detergents.

There are different genogroups of norovirus and the majority of noroviruses that infect humans are classified into genogroup G1 and G2.

History
Originally, norovirus was named after Norwalk, Ohio, where an outbreak of acute gastroenteritis occurred among children at an elementary school in November 1968. In 1972, immune electron microscopy on stored stool samples identified a virus, which was given the name Norwalk virus. Numerous outbreaks with similar symptoms have been reported since. The cloning and sequencing of the Norwalk virus genome showed that these viruses have a genomic organization consistent with viruses belonging to the family Caliciviridae. The name norovirus (Norovirus for the genus) was approved by the International Committee on Taxonomy of Viruses in 2002.

Common names of the illness caused by noroviruses are winter vomiting disease, viral gastroenteritis and acute non-bacterial gastroenteritis, also colloquially known as "stomach flu" (a broad name which can also refer to gastric inflammation caused by other viruses and bacteria).

Some previously used names which can be used for PubMed and other internet searches are Norwalk virus, Norwalk-like virus, SRSVs (Small Round Structured Viruses), Sapporo virus and Snow Mountain.

Signs and symptoms
The disease is usually self-limiting, and characterised by nausea, vomiting, diarrhea, and abdominal pain. General lethargy, weakness, muscle aches, headache, and low-grade fever may occur. Symptoms may persist for several days and may become life-threatening in the young, the elderly, and the immune-compromised if dehydration is ignored or not treated.

Diagnosis
Specific diagnosis of norovirus is routinely made by polymerase chain reaction (PCR) assays or real-time PCR assays, which give results within a few hours. These assays are very sensitive and can detect concentrations as low as 10 virus particles.

Tests such as EIA that use antibodies against a mixture of norovirus strains are available commercially but lack specificity and sensitivity.

Prevention and infection control
Hand washing remains an effective method to reduce the spread of norovirus pathogens. Norovirus can be aerosolized when those stricken with the illness vomit. Surface sanitizing is recommended in areas where the Norovirus may be present on surfaces.

In health care environments, the prevention of nosocomial infections involves routine and terminal cleaning. Nonflammable alcohol vapor in CO2 systems are used in health care environments where medical electronics would be adversely affected by aerosolized chlorine or other caustic compounds.

Ligocyte is working on a vaccine and has already started phase 1 trials. http://www.ligocyte.com/pdf/norovirus.pdf

Associated foods
Noroviruses are transmitted directly via person to person or indirectly via contaminated water and foods. A CDC study of eleven outbreaks in New York State lists the suspected mode of transmission as person-to-person in seven outbreaks, foodborne in two, waterborne in one, and one unknown. The source of waterborne outbreaks may include water from municipal supplies, wells, recreational lakes, swimming pools and ice machines.

Shellfish and salad ingredients are the foods most often implicated in Norwalk outbreaks. Ingestion of raw or insufficiently steamed clams and oysters poses a high risk for infection with the Norwalk virus. Foods other than shellfish are contaminated by ill food handlers.

Relative frequency of disease
Only the common cold is reported more frequently than viral gastroenteritis as a cause of illness in the U.S. Although viral gastroenteritis is caused by a number of viruses, it is estimated that noroviruses are responsible for about 1/3 of the cases over the 6-to-24-month age group. In developing countries the percentage of individuals who have developed immunity at an early age is very high. In the U.S. the percentage increases gradually with age, reaching 50% in the population over 18 years of age. Immunity, however, is not permanent and reinfection can occur. Recent studies demonstrate that blood types B and AB confer partial protection against symptomatic infection.

Course of disease and complications
Norovirus causes acute gastroenteritis that develops between 24 and 48 hours after exposure with a median of 33-36 hours, and lasts for 24-60 hours. Severe illness is rare: although people are frequently treated in emergency rooms/A&E, they are rarely admitted to the hospital. The number of deaths from norovirus in the US is estimated to be around 300 each year, with most of these occurring in the very young, elderly and persons with weakened immune systems.

Detection of norovirus in foods
Routine protocols to detect norovirus (norovirus RNA) in clams and oysters by RT-PCR (reverse transcription polymerase chain reaction) are being employed by governmental laboratories such as the FDA in the USA. However, routine methods to detect the virus on other food items are not readily available due to the variable nature of different food items affecting concentration and extraction of the virus and presence of factors that make PCR (Polymerase chain reaction) analysis techniques ineffective.

Outbreaks

 * In November 2006, 679 (17%) out of 3,970 passengers and crew members aboard the trans-Atlantic Carnival Cruise Lines' Carnival Liberty, one of the world's largest cruise ships, contracted the virus.

Classification


Noroviruses (NoV) are a genetically diverse group of single stranded RNA, nonenveloped viruses belonging to the Caliciviridae family. According to the International Committee on Taxonomy of Virus, the genus Norovirus has one species which is called "Norwalk virus" and assigned the abbreviation "NV". Serotypes, strains and isolates include:
 * Desert Shield virus [U04469] 	(Hu/NLV/DSV395/1990/SR)
 * Lordsdale virus [X86557] 	(Hu/NLV/LD/1993/UK)
 * Mexico virus [U22498] 	(Hu/NLV/MX/1989/MX)
 * Norwalk virus [M87661] 	(Hu/NLV/NV/1968/US)
 * Hawaii virus [U07611] 	(Hu/NLV/HV/1971/US)
 * Snow Mountain virus [L23831] 	(Hu/NLV/SMV/1976/US)
 * Southampton virus [L07418] 	(Hu/NLV/SHV/1991/UK)

"Noroviruses are a major cause of acute gastroenteritis worldwide, often causing explosive outbreaks in institutions. They are highly contagious, with an inoculum of as few as ten particles being able to cause infection. Transmission occurs through ingesting contaminated food and water and by person-to-person spread. Transmission is predominantly faecal-oral but may be airborne due to aerosolisation of vomitus [...] Noroviruses commonly isolated in cases of acute gastroenteritis belong to two genogroups: genogroup I (GI) includes Norwalk virus, Desert Shield virus and Southampton virus and II (GII) which includes Bristol virus, Lordsdale virus, Toronto virus, Mexico virus, Hawaii virus and Snow Mountain virus."

Noroviruses can genetically be classified into 5 different genogroups (GI, GII, GIII, GIV, and GV) which can be further divided into different genetic clusters or genotypes. For example genogroup II, the most prevalent human genogroup, presently contains 19 genotypes. Genogroups I, II and IV infect humans, whereas genogroup III infects bovine species and genogroup V has recently been isolated in mice.

Noroviruses from Genogroup II, genotype 4 (abbreviated as GII.4) account for the majority of adult outbreaks of gastroenteritis and often sweep across the globe. Recent examples include US95/96-US strain, associated with global outbreaks in the mid- to late-90s, Farmington Hills virus associated with outbreaks in Europe and the United States in 2002 and in 2004 Hunter virus was associated with outbreaks in Europe, Japan and Australasia. In 2006 there was another large increase in NoV infection around the globe. In December, 2007 there was an outbreak at a country club in northern California where around 80-100 people were infected. Two new GII.4 variants caused around 80% of those Norovirus associated outbreaks and they have been termed 2006a and 2006b. Recent reports have shown a link between blood group and susceptibility to infection by norovirus.

Virus structure
Noroviruses contain a positive-sense RNA genome of approximately 7.5 kbp, encoding a major structural protein (VP1) of about 58~60 kDa and a minor capsid protein (VP2). The virus particles demonstrate an amorphous surface structure when visualized using electron microscopy and are between 27-38 nm in size.