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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 and concentrated in shellfish.2 They were renamed as Norwalk-like viruses, recently granted the official genus name Norovirus. 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.3

Epidemiology1

Norovirus is the commonest cause of infectious gastroenteritis in England and Wales.4
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.5

Outbreaks of Norovirus 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.

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.
Since about 1994 the total number in England and Wales has varied between about 1700 a year and 2700 a year with the exception of 2002 that saw 4263 cases with persistence into the summer.6 The numbers seem to have risen since about 1993 and this may in part be spurious due to the introduction of a commercially available ELISA test that made diagnosis much easier. However, it may also be due to the emergence of a new strain of Norovirus which is even more virulent than the original strain.7,8

The Health Protection Agency estimates that about 600,000 to 1,000,000 people are affected in the UK each year. Worldwide, viral infections are much more numerous than bacterial ones as a cause of gastroenteritis.9

Global pandemics of Norovirus occurred in 1995-6 and 2002, caused by a unique clone of the G-II/4 cluster.10 Outbreaks tend to affect no more than about 50% within a community. Outbreaks tend to be with November to April when pressures on hospitals are at their greatest - Rotavirus tends to present a little later.11

Presentation1

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.12

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.
Differential diagnosis1
Investigations1
  • 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.13
  • In dehydration other tests will be required such as urea and electrolytes.
Management
  • 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 antiemetics is rarely necessary. Anti-diarrhoeals may occasionally be used in adults but are not recommended for children.14
  • Hygiene 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.15
Prognosis
  • 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.16,17
  • Although immunity is short-lived (up to 14 weeks), multiple exposure and infection do confer some protection from future attacks.18
Prevention1,19
  • 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.4
  • There is evidence of worldwide infection of oysters with Norovirus.20
  • 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 provide an ideal environment for the spread of the disease. Healthcare settings tend to be particularly affected by outbreaks of Norovirus and a recent 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.21
  • Infectivity lasts for 48 hours after resolution of symptoms.
  • Work is being done to invent a vaccine, but Norovirus is pathogenic only to humans and resistant to cell culture. Natural immunity as well as short-lived, is likely genogroup-specific.22
  • New oral vaccines based on transgenic plants will soon be evaluated in humans.23


Document references
  1. Wills T, Jaworski M, Sutton S; Norwalk Virus eMedicine.com 2006
  2. Wang J, Jiang X, Madore HP, et al; Sequence diversity of small, round-structured viruses in the Norwalk virus group. J Virol. 1994 Sep;68(9):5982-90. [abstract]
  3. Trujillo AA, McCaustland KA, Zheng DP, et al; Use of TaqMan real-time reverse transcription-PCR for rapid detection, quantification, and typing of norovirus. J Clin Microbiol. 2006 Apr;44(4):1405-12. [abstract]
  4. UK Publicly Funded Research Relating to Food-borne Viruses; Report to the Microbiological Safety of Food Funders Group 2005
  5. Lopman BA, Reacher M, Gallimore C, et al; A summertime peak of "winter vomiting disease": surveillance of noroviruses in England and Wales, 1995 to 2002. BMC Public Health. 2003 Mar 24;3:13. Epub 2003 Mar 24. [abstract]
  6. Norovirus outbreaks in England and Wales : 2003 and 2004; CDR Weekly 2004;14 (47):4
  7. Lopman B, Vennema H, Kohli E, et al; Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of new norovirus variant. Lancet. 2004 Feb 28;363(9410):682-8. [abstract]
  8. Leuenberger S, Widdowson MA, Feilchenfeldt J, et al; Norovirus outbreak in a district general hospital--new strain identified. Swiss Med Wkly. 2007 Jan 27;137(3-4):57-81. [abstract]
  9. Clark B, McKendrick M; A review of viral gastroenteritis. Curr Opin Infect Dis. 2004 Oct;17(5):461-9. [abstract]
  10. Bull RA, Tu ET, McIver CJ, et al; Emergence of a new norovirus genotype II.4 variant associated with global outbreaks of gastroenteritis. J Clin Microbiol. 2006 Feb;44(2):327-33. [abstract]
  11. Meakins SM, Adak GK, Lopman BA, et al; General outbreaks of infectious intestinal disease (IID) in hospitals, England and Wales, 1992-2000. J Hosp Infect. 2003 Jan;53(1):1-5. [abstract]
  12. Kawano G, Oshige K, Syutou S, et al; Benign infantile convulsions associated with mild gastroenteritis: A retrospective study of 39 cases including virological tests and efficacy of anticonvulsants. Brain Dev. 2007 Jun 1;. [abstract]
  13. Black RE, Greenberg HB, Kapikian AZ, et al; Acquisition of serum antibody to Norwalk Virus and rotavirus and relation to diarrhea in a longitudinal study of young children in rural Bangladesh. J Infect Dis. 1982 Apr;145(4):483-9. [abstract]
  14. Gastroenteritis, Clinical Knowledge Summaries (January 2007)
  15. Kampf G, Grotheer D, Steinmann J; Efficacy of three ethanol-based hand rubs against feline calicivirus, a surrogate virus for norovirus. J Hosp Infect. 2005 Jun;60(2):144-9. [abstract]
  16. No authors listed; The norovirus on the march: triggers of acute diseases of the stomach and intestine. Clin Lab. 2003;49(5-6):267-8. [abstract]
  17. Okada M, Tanaka T, Oseto M, et al; Genetic analysis of noroviruses associated with fatalities in healthcare facilities. Arch Virol. 2006 Aug;151(8):1635-41. Epub 2006 Mar 9. [abstract]
  18. Ryder RW, Singh N, Reeves WC, et al; Evidence of immunity induced by naturally acquired rotavirus and Norwalk virus infection on two remote Panamanian islands. J Infect Dis. 1985 Jan;151(1):99-105. [abstract]
  19. HPA - Norovirus (Norwalk-like Virus, Small Round Structured Virus (SRSV)) Guidelines. Health Protection Agency, 2008.
  20. Cheng PK, Wong DK, Chung TW, et al; Norovirus contamination found in oysters worldwide. J Med Virol. 2005 Aug;76(4):593-7. [abstract]
  21. Chadwick P, Beards G, Brown D et al; Management of hospital outbreaks of gastroenteritis due to small round structured viruses; Journal of Hospital Infection(2000) 45:1-10
  22. Lindesmith L, Moe C, Lependu J, et al; Cellular and humoral immunity following Snow Mountain virus challenge. J Virol. 2005 Mar;79(5):2900-9. [abstract]
  23. Tacket CO; Plant-derived vaccines against diarrheal diseases. Vaccine. 2005 Mar 7;23(15):1866-9. [abstract]

Internet and further reading Acknowledgements EMIS is grateful to Dr Laurence Knott for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2008.
DocID: 2521
Document Version: 21
DocRef: bgp24697
Last Updated: 17 Aug 2007
Review Date: 16 Aug 2009
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