Norovirus

Synonyms: Norwalk virus, Norwalk-like virus

Non-bacterial gastroenteritis has been recognised for many years but the causative organisms eluded identification.

In 1972, virus-like particles coated with antibodies were identified as causative agents for an outbreak in a school in Norwalk, Ohio and were named the Norwalk virus. They are members of the Caliciviridae group, which also contains many similar but antigenically distinct viruses, such as Mexico virus or Grimsby virus.¹

The group is one of the small round structured viruses (SRSV), 35 nm in size and is found in 'used' water. They are concentrated in shellfish, oysters and plankton.² They were renamed as Norwalk-like viruses and recently granted the official genus name Norovirus. Noroviruses (NVs) genetically can be classified into 5 different genogroups (GI, GII, GIII, GIV and GV) which can be divided further 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. 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.³

Susceptibility to several NVs is linked to human histo-blood type and its determinant histo-blood group antigens (HBGAs) are regarded as receptors for these viruses. NV for example specifically recognises A- and H-type HBGA. It is thought that the mechanism by which NVs infect broader human populations is by evolving different sites with altered HBGA specificities.⁴ It would appear that the NV capsid (outer coat) evolves to evade the memory immune response while retaining its ability to bind any of several HBGAs.⁵

NV is the most common cause of infectious gastroenteritis in England and Wales.⁶ It is relatively mild but it can cause illness at any age because immunity does not last long.

The illness is often called winter vomiting disease, as this is typically when symptoms occur, but not invariably. The number of cases varies from year to year and in some years it persists into the summer.⁷

Outbreaks of NV gastroenteritis are common in restricted environments such as hospitals, nursing homes, schools, military establishments and cruise ships. It is in these environments that the seasonal distribution is most marked. In the general community the seasonal variation is much less.There are approximately 267,000,000 annual infections worldwide.⁵

In England and Wales in 2003 there were 220 reported outbreaks (not cases) of which 171 were from hospitals or residential homes. In 2004 there were only 148 outbreaks of which 110 were from hospitals or residential homes. Nearly 90% of cases are spread by person to person contact.The numbers seem to have risen since about 1993 and this may in part be spurious due to the introduction of a commercially available enzyme-linked immunosorbent assay (ELISA) test that made diagnosis much easier. However, it may also be due to the emergence of a new strain of NV which is even more virulent than the original strain.^8,9

The Health Protection Agency (HPA) estimates that about 600,000 to 1,000,000 people are affected in the UK each year. The total number of laboratory reports confirming NV infection during the first four weeks of the 2009/2010 season (calendar weeks 27 to 30) was 137, which is a 14% decrease compared with the same period of the 2008/2009 season (159). The total number of reports for whole of the last season (week 27/2008 to week 26/2009) was 7971, which was a 19% increase in the total for the previous season.¹⁰ Worldwide, viral infections are much more numerous than bacterial ones as a cause of gastroenteritis.¹¹

Global pandemics of NV occurred in 1995-1996 and in 2002, caused by a unique clone of the GII.4 cluster.¹² Outbreaks tend to affect no more than about 50% within a community. Outbreaks tend to be within November to April when pressures on hospitals are at their greatest - rotavirus (a double-stranded DNA virus which is the commonest cause of gastroenteritis in children) tends to present a little later.¹³

Symptoms

• The incubation period is usually 24 to 48 hours but, less often, it may be down to 12 hours.
• There is fever, nausea and vomiting that may be projectile along with watery diarrhoea without blood.
• Abdominal cramps are common.
• Symptoms last between 12 and 60 hours.
• Most people make a full recovery in 1 to 2 days but the diarrhoea may last a little longer.
• Seizures occasionally occur.¹⁴ Long-term neurological sequelae are uncommon.¹⁵

Signs

There are no specific signs unique to this infection and the clinical picture is very much as one would expect with gastroenteritis, viz:

• Along with a mild pyrexia, features of dehydration may appear.
• Examination of the abdomen shows no local abdominal tenderness and no guarding.
• In the very young and the very old dehydration may be severe enough to require admission to hospital.
• Severe dehydration may lead to hypotension, electrolyte imbalances and collapse.

• Gastroenteritis, such as salmonella or typhoid and paratyphoid fever
• Diarrhoea, such as amoebiasis and giardiasis
• Gastrointestinal disorders, such as irritable bowel syndrome, Crohn's disease, ulcerative colitis or hepatitis
• Mechanical problems, such as ischaemic colitis from torsion or thrombosis

• Stool samples in outbreaks help to identify bacterial or viral pathogens and sometimes locate the source of infection. This is particularly important when food poisoning is suspected, or the person is a food handler to rule out salmonella.
• In domestic cases there is little point in investigating a trivial and self-limiting condition where management is purely symptomatic.
• Antibody testing is not useful. Most people develop antibody from subclinical infection in developing countries and possibly developed countries too.¹⁶
• In dehydration other tests will be required, such as urea and electrolytes.

• Treatment other than oral fluids is usually unnecessary.
• Fluid and electrolyte replacement is important especially in the very young, elderly and infirm.
• The use of anti-emetics is rarely necessary. Anti-diarrhoeals may occasionally be used in adults but are not recommended for children.¹⁷
• Hygiene (especially in kitchens and bathrooms) and hand washing is important and anyone who is infected should not prepare food for others until at least 3 days after symptoms have gone. A hand rub with high ethanol content is helpful, and careful environmental cleaning with bleach is important to prevent spread.^18,19

• The condition is usually self-limiting and, apart from seroconversion, leaves no lasting effects.
• There is a risk of mortality especially in the frail, immunocompromised and at the extremes of age.^20,21 One study of deaths associated with gastrointestinal pathogens in England and Wales in persons of 65 or over estimated that 80 deaths annually were caused by NV infection between the years 2001-2006.²²
• Although immunity is short-lived (up to 14 weeks), multiple exposure and infection do confer some protection from future attacks.²³

• Person to person spread is by the faecal oral route.
• Education about length of infectivity, modes of spread and hygiene help to reduce inter-personal spread of infection.
• Drinking purified water and avoiding raw unwashed produce and shellfish, especially in times of outbreaks, is important to avoid infection or re-infection.⁶
• There is risk of infection from aerosols of projectile vomit.
• Environmental contamination, especially of toilets, can occur and gloves should be used by cleaners.
• Anywhere that large numbers of people congregate for periods of several days provides an ideal environment for the spread of the disease. Healthcare settings tend to be particularly affected by outbreaks of NV and a study done by the Health Protection Agency showed that outbreaks are shortened when control measures at healthcare settings are implemented quickly, such as closing wards to new admissions within 4 days of the beginning of the outbreak and implementing strict hygiene measures.²⁵
• Infectivity lasts for 48 hours after resolution of symptoms.
• A murine model has been used for research.²⁶. Natural immunity, as well as short-lived, is likely genogroup-specific.²⁷
• Sharing of information via a global network may lead to improved prevention and intervention strategies.²⁸
• A norovirus vaccine has been developed and is currently undergoing trials in humans.

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