Synonyms: Norwalk virus, Norwalk-like virus
Noroviruses (NVs) are a genus of the Caliciviridae family of viruses found in 'used' water. They are concentrated in shellfish, oysters and plankton. They were renamed as Norwalk-like viruses and were granted the official genus name Norovirus. They are very diverse and are divided into at least five genogroups (GI-GV) with 32 distinct genotypes currently recognised.Genogroups I, II and IV infect humans, whereas genogroup III infects bovine species and genogroup V has 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.
- Approximately 3,000 people a year are admitted to hospital with NV in England and the incidence in the community is thought to be about 16.5% of the 17 million cases of infectious intestinal disease in England per year.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 new strains of NV which are even more virulent than the original strain.[4, 5]
- The illness is often called winter vomiting disease, as it typically occurs between November and April. When outbreaks occur in hospitals and residential facilities this can add to the pressure on healthcare systems.However, this seasonality is not invariable. The emergence of a novel GII.4 virus in 2002/03 led to persistence of the condition into the summer.
- 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.
- Global pandemics of NV occurred in 1995-1996, 2002, 2006 and 2007 caused by a unique clone of the GII.4 cluster.Outbreaks tend to affect no more than about 50% within a community. Rotavirus (a double-stranded RNA virus which is the most common cause of gastroenteritis in children) tends to present a little later in the year.
NV is usually relatively mild but it can cause illness at any age because immunity does not last long.
- The incubation period is usually 24 to 48 hours but, less often, it may be down to 12 hours.
- Common symptoms include 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. Long-term neurological sequelae are uncommon.
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.
- Other causes of infective gastroenteritis - eg, salmonella, amoebiasis or 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. The two main types of laboratory tests available are enzyme-linked immunosorbent assays (ELISAs) to detect norovirus antigens and polymerase chain reaction (PCR) tests to detect norovirus nucleic acid. The current gold standard test at present is PCR.
- In community 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 cases with complications, such as dehydration, other tests will be required, such as renal function and electrolytes.
- The mainstay of the clinical treatment of norovirus is the avoidance or correction of dehydration, by oral rehydration regimen in patients who can tolerate oral fluids, or subcutaneous or intravenous administration of appropriate fluids for those unable to tolerate oral fluids.
- Fluid and electrolyte replacement is important, especially in the very young, elderly and infirm.
- The use of anti-emetic agents and antidiarrhoeal agents is discouraged and care must be taken to avoid adverse consequences of their use in other infective gastroenteritides (eg, Clostridium difficile).
- Key control measures include increased frequency of cleaning, environmental disinfection and prompt clearance of soiling caused by vomit or faeces. Hygiene (especially in kitchens and bathrooms) and hand washing are important and anyone who is infected should not prepare food for others until at least 48 hours after symptoms have gone.
- The condition is usually self-limiting and, apart from seroconversion, leaves no lasting effects.
- There is a risk of mortality especially in the frail, the immunocompromised and at the extremes of age.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. Another study in the Netherlands reported that deaths were more likely in outbreaks associated with GII.4 virus strains, independent of other factors.
- Person-to-person spread is by the faecal-oral route.
- Education about length of infectivity, modes of spread and hygiene help to reduce interpersonal 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.[16, 17]
- 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 four days of the beginning of the outbreak and implementing strict hygiene measures.
- Infectivity lasts for 48 hours after resolution of symptoms.
- A murine model has been used for research.Natural immunity, as well as short-lived, is likely genogroup-specific.
- An informal network of scientists working in public health institutes or universities has been set up in Europe (NoroNet) to share virological, epidemiological and molecular data on NV. Similar networks have been set up in other parts of the world.
- NV vaccines are currently undergoing trials in humans.
Further reading and references
Elliott EJ; Acute gastroenteritis in children. BMJ. 2007 Jan 6334(7583):35-40.
Guidelines for the management of norovirus outbreaks in acute and community health and social care settings; Public Health England (March 2012)
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 Apr44(4):1405-12.
Verhoef L, Depoortere E, Boxman I, et al; Emergence of new norovirus variants on spring cruise ships and prediction of winter epidemics. Emerg Infect Dis. 2008 Feb14(2):238-43. doi: 10.3201/eid1402.061567.
Eden JS, Hewitt J, Lim KL, et al; The emergence and evolution of the novel epidemic norovirus GII.4 variant Sydney 2012. Virology. 2014 Feb450-451:106-13. doi: 10.1016/j.virol.2013.12.005. Epub 2013 Dec 25.
Iturriza-Gomara M, Lopman B; Norovirus in healthcare settings. Curr Opin Infect Dis. 2014 Oct27(5):437-43. doi: 10.1097/QCO.0000000000000094.
Ahmed SM, Lopman BA, Levy K; A systematic review and meta-analysis of the global seasonality of norovirus. PLoS One. 2013 Oct 28(10):e75922. doi: 10.1371/journal.pone.0075922. eCollection 2013.
Donaldson EF, Lindesmith LC, Lobue AD, et al; Norovirus pathogenesis: mechanisms of persistence and immune evasion in human populations. Immunol Rev. 2008 Oct225:190-211.
Bull RA, Eden JS, Rawlinson WD, et al; Rapid evolution of pandemic noroviruses of the GII.4 lineage. PLoS Pathog. 2010 Mar 266(3):e1000831. doi: 10.1371/journal.ppat.1000831.
PHE; Monthly National Norovirus and Rotavirus Report Public Health England, 2013
Chen SY, Tsai CN, Lai MW, et al; Norovirus infection as a cause of diarrhea-associated benign infantile seizures. Clin Infect Dis. 2009 Apr 148(7):849-55.
Prevention of norovirus infection in schools and childcare facilities; European Centre for Disease Prevention and Control, 2013
van Asten L, Siebenga J, van den Wijngaard C, et al; Unspecified gastroenteritis illness and deaths in the elderly associated with norovirus epidemics. Epidemiology. 2011 May22(3):336-43. doi: 10.1097/EDE.0b013e31821179af.
Harris JP, Edmunds WJ, Pebody R, et al; Deaths from norovirus among the elderly, England and Wales. Emerg Infect Dis. 2008 Oct14(10):1546-52.
Desai R, Hembree CD, Handel A, et al; Severe outcomes are associated with genogroup 2 genotype 4 norovirus outbreaks: a systematic literature review. Clin Infect Dis. 2012 Jul55(2):189-93. doi: 10.1093/cid/cis372. Epub 2012 Apr 4.
Jack S, Bell D, Hewitt J; Norovirus contamination of a drinking water supply at a hotel resort. N Z Med J. 2013 Dec 13126(1387):98-107.
FSA activity and research on norovirus; Food Standards Agency, 2014
Makison Booth C; Vomiting Larry: a simulated vomiting system for assessing environmental contamination from projectile vomiting related to norovirus infection. J Infect Prev. 2014 Sep15(5):176-180.
Mitchell B; Norovirus Int J Infect Control 2006, 2:1
Hwang S, Alhatlani B, Arias A, et al; Murine norovirus: propagation, quantification, and genetic manipulation. Curr Protoc Microbiol. 2014 May 133:15K.2.1-15K.2.61. doi: 10.1002/9780471729259.mc15k02s33.
Sakon N, Yamazaki K, Nakata K, et al; Impact of Genotype-Specific Herd Immunity on the Circulatory Dynamism of Norovirus: A 10-Year Longitudinal Study of Viral Acute Gastroenteritis. J Infect Dis. 2014 Sep 9. pii: jiu496.
van Beek et al; Indications for worldwide increased norovirus activity associated with emergence of a new variant of genotype II.4, late 2012. Euro Surveill. 201318(1):
Bernstein DI, Atmar RL, Lyon GM, et al; Norovirus Vaccine Against Experimental Human GII.4 Virus Illness: A Challenge Study in Healthy Adults. J Infect Dis. 2014 Sep 9. pii: jiu497.
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