History of identification

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 was approved by the International Committee on Taxonomy of Viruses in 2002. 

Synonyms of disease

Common names of the illness caused by Noroviruses are winter vomiting disease, viral gastroenteritis and acute non-bacterial gastroenteritis.

 Nature of disease

The disease is usually self-limiting, and characterized 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 of human illness

Specific diagnosis of Norovirus is routinely made by broadly reactive conventional polymerase chain reaction (PCR) assays which more recently were replaced by real-time PCR assays, which give results within a few hours. Furthermore, these assays are very sensitive and can detect concentrations as low as 10 virus particles per assay.

Less technically demanding assays such as ELISA assays based on antibodies against a cocktail of different virus-like particles are commercially available but have been reported to lack both 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.

Associated foods

Norwalk gastroenteritis is transmitted by the fecal-oral route 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 Norwalk viruses 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. There is some evidence that blood types B and AB confer

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, with most of these occurring in the very young, elderly and persons with weakened immune systems.

Susceptible populations

All individuals who ingest the virus and who have not (within 24 months) had an infection with the same or related strain, are susceptible to infection and can develop the symptoms of gastroenteritis. Disease is more frequent in adults and older children than in the very young.

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.

Classification

Transmission electron micrograph of Norovirus particles in faeces

Noroviruses can genetically be classified into 5 different genogroups (GI, GII, GIII, GIV, and GV) which can be further divided into different genetic groups 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.^[

Norwalk viruses 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 got sick. Two new GII.4 variants caused around 80% of those Norovirus associated outbreaks and they have been termed 2006a and 2006b.

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.

Notable outbreaks