View source for Medicine:Norovirus

{{short description|Type of viruses that cause gastroenteritis}}
{{Infobox medical condition (new)
| name          = Norovirus
| synonyms      = Winter vomiting bug,<ref name=NHS2018/> stomach bug
| image         = Norwalk.jpg
| width         = 
| alt           = 
| caption       = Transmission electron micrograph of Norwalk virus. The white bar = 50 nm.
| pronounce     = 
| field         = [[Medicine:Emergency medicine|Emergency medicine]], [[Medicine:Pediatrics|pediatrics]]
| symptoms      = [[Medicine:Diarrhea|Diarrhea]], vomiting, stomach pain, headache<ref name=CDC2016Sym/>
| complications = [[Medicine:Dehydration|Dehydration]]<ref name=CDC2016Sym/>
| onset         = 12 to 48 hours after exposure<ref name=CDC2016Sym/>
| duration      = 1 to 3 days<ref name=CDC2016Sym/>
| types         = 
| causes        = ''Norovirus''<ref name=Yel2017/>
| risks         = 
| diagnosis     = Based on symptoms<ref name=Yel2017/>
| differential  = 
| prevention    = Hand washing, disinfection of contaminated surfaces<ref name=CDC2017Pre/>
| treatment     = Supportive care (drinking sufficient fluids or intravenous fluids)<ref name=CDC2017Tx/>
| medication    = 
| prognosis     = 
| frequency     = 685 million cases per year<ref name=CDC2017Glob/>
| deaths        = 200,000 per year<ref name=CDC2017Glob/><ref name=GBD2017/>
}}

'''Norovirus''', also known as '''Norwalk Virus''' and sometimes referred to as the '''winter vomiting disease''', is the most common cause of [[Medicine:Gastroenteritis|gastroenteritis]].<ref name=NHS2018>{{cite web |title=Norovirus (vomiting bug) |url=https://www.nhs.uk/conditions/norovirus/ |website=nhs.uk |access-date=8 June 2018 |date=2017-10-19 |archive-date=2018-06-12 |archive-url=https://web.archive.org/web/20180612143424/https://www.nhs.uk/conditions/norovirus/ |url-status=live }}</ref><ref name=CDC2017Glob>{{cite web|title=Norovirus Worldwide|url=https://www.cdc.gov/norovirus/worldwide.html|website=CDC|access-date =29 December 2017|language=en-us|date=15 December 2017|archive-url= https://web.archive.org/web/20181207142756/https://www.cdc.gov/norovirus/worldwide.html|archive-date=7 December 2018|url-status=dead}}</ref> Infection is characterized by non-bloody [[Medicine:Diarrhea|diarrhea]], [[Medicine:Vomiting|vomiting]], and stomach pain.<ref name=CDC2016Sym>{{cite web|title=Norovirus Symptoms|url=https://www.cdc.gov/norovirus/about/symptoms.html|website=CDC|access-date=29 December 2017|language=en-us|date=24 June 2016|archive-url=https://web.archive.org/web/20181206210732/https://www.cdc.gov/norovirus/about/symptoms.html|archive-date=6 December 2018|url-status=dead}}</ref><ref name=Yel2017/> Fever or headaches may also occur.<ref name=CDC2016Sym/> Symptoms usually develop 12 to 48 hours after being exposed, and recovery typically occurs within one to three days.<ref name=CDC2016Sym/> Complications are uncommon, but may include [[Medicine:Dehydration|dehydration]], especially in the young, the old, and those with other health problems.<ref name=CDC2016Sym/>

The [[Biology:Virus|virus]] is usually spread by the [[Biology:Fecal–oral route|fecal–oral route]].<ref name=Yel2017/> This may be through contaminated food or water or person-to-person contact.<ref name=Yel2017/> It may also spread via contaminated surfaces or through air from the vomit of an infected person.<ref name=Yel2017/> Risk factors include unsanitary food preparation and sharing close quarters.<ref name=Yel2017/> Diagnosis is generally based on symptoms.<ref name=Yel2017>{{cite book |last1=Brunette |first1=Gary W. |name-list-style=vanc |title=CDC Yellow Book 2018: Health Information for International Travel |date=2017 |publisher=Oxford University Press |isbn=9780190628611 |page=269 |url=https://books.google.com/books?id=np6PDgAAQBAJ&pg=PA269 |access-date=2020-09-05 |archive-date=2022-10-07 |archive-url=https://web.archive.org/web/20221007190854/https://books.google.com/books?id=np6PDgAAQBAJ&pg=PA269 |url-status=live }}</ref> Confirmatory testing is not usually available but may be performed by public health agencies during outbreaks.<ref name=Yel2017/>

Prevention involves proper hand washing and disinfection of contaminated surfaces.<ref name=CDC2017Pre>{{cite web|title=Preventing Norovirus Infection|url=https://www.cdc.gov/norovirus/preventing-infection.html|website=CDC|access-date=29 December 2017|language=en-us|date=5 May 2017|archive-date=9 December 2017|archive-url=https://web.archive.org/web/20171209085135/https://www.cdc.gov/norovirus/preventing-infection.html|url-status=live}}</ref> There is no [[Biology:Vaccine|vaccine]] or specific treatment for norovirus.<ref name=CDC2017Pre/><ref name=CDC2017Tx>{{cite web|url=https://www.cdc.gov/norovirus/about/treatment.html|title=Norovirus – Treatment|publisher=CDC|access-date=29 December 2017|archive-date=22 December 2017|archive-url=https://web.archive.org/web/20171222151627/https://www.cdc.gov/norovirus/about/treatment.html|url-status=live}}</ref> Management involves supportive care such as drinking sufficient fluids or intravenous fluids.<ref name=CDC2017Tx/> Oral rehydration solutions are the preferred fluids to drink, although other drinks without [[Biology:Caffeine|caffeine]] or [[Chemistry:Alcohol (drug)|alcohol]] can help.<ref name=CDC2017Tx/> Alcohol-based hand sanitizers are not effective against the norovirus, according to the NHS information page on the subject;<ref>{{Cite web|date=2017-10-19|title=Norovirus (vomiting bug)|url=https://www.nhs.uk/conditions/norovirus/|access-date=2021-05-29|website=nhs.uk|language=en|archive-date=2018-06-12|archive-url=https://web.archive.org/web/20180612143424/https://www.nhs.uk/conditions/norovirus/|url-status=live}}</ref> this is due to norovirus being a [[Biology:Viral envelope|non-enveloped virus]].

Norovirus results in about 685&nbsp;million cases of disease and 200,000 deaths globally a year.<ref name=CDC2017Glob/><ref name=GBD2017>{{cite web|title=Global Burden of Norovirus and Prospects for Vaccine Development|url=https://www.cdc.gov/norovirus/downloads/global-burden-report.pdf|website=CDC|access-date=29 December 2017|page=3|date=August 2015|archive-date=29 December 2017|archive-url=https://web.archive.org/web/20171229231709/https://www.cdc.gov/norovirus/downloads/global-burden-report.pdf|url-status=live}}</ref> It is common both in the developed and developing world.<ref name=Yel2017/><ref>{{cite journal | vauthors = Nguyen GT, Phan K, Teng I, Pu J, Watanabe T | title = A systematic review and meta-analysis of the prevalence of norovirus in cases of gastroenteritis in developing countries | journal = Medicine | volume = 96 | issue = 40 | pages = e8139 | date = October 2017 | pmid = 28984764 | pmc = 5738000 | doi = 10.1097/MD.0000000000008139 }}</ref> Those under the age of five are most often affected, and in this group it results in about 50,000 deaths in the developing world.<ref name=CDC2017Glob/> Norovirus infections occur more commonly during winter months.<ref name=CDC2017Glob/> It often occurs in outbreaks, especially among those living in close quarters.<ref name=Yel2017/> In the United States, it is the cause of about half of all foodborne disease outbreaks.<ref name=Yel2017/> The virus is named after the city of Norwalk, Ohio, US, where an outbreak occurred in 1968.<ref name=Vesikari2021>{{cite book |last=Vesikari|first=Timo |editor1-last=Vesikari |editor1-first=Timo |editor2-last=Damme |editor2-first=Pierre Van |title=Pediatric Vaccines and Vaccinations: A European Textbook |date=2021 |publisher=Springer |edition=Second|location=Switzerland |isbn=978-3-030-77172-0 |pages=289–292 |chapter=25. Norovirus vaccines in pipeline development|chapter-url=https://books.google.com/books?id=LLg-EAAAQBAJ&pg=PA289|language=en}}</ref>

==Signs and symptoms==
Norovirus infection is characterized by nausea, [[Medicine:Vomiting|vomiting]], watery [[Medicine:Diarrhea|diarrhea]], abdominal pain, and in some cases, loss of taste. A person usually develops symptoms of [[Medicine:Gastroenteritis|gastroenteritis]] 12 to 48 hours after being exposed to norovirus.<ref name=CDC2016>{{Cite web|url=https://www.cdc.gov/norovirus/hcp/clinical-overview.html|title=Norovirus {{!}} Clinical Overview {{!}} CDC|website=www.cdc.gov|access-date=2016-03-28|archive-date=2016-03-17|archive-url=https://web.archive.org/web/20160317184010/http://www.cdc.gov/norovirus/hcp/clinical-overview.html|url-status=live}}</ref> General lethargy, weakness, muscle aches, headaches, and low-grade fevers may occur. The disease is usually [[Biology:Self-limiting|self-limiting]], and severe illness is rare. Although having norovirus can be unpleasant, it is not usually dangerous, and most who contract it make a full recovery within two to three days.<ref name=NHS2018/>

Norovirus can establish a long-term infection in people who are immunocompromised, such as those with [[Medicine:Common variable immunodeficiency|common variable immunodeficiency]] or with a suppressed immune system after [[Medicine:Organ transplantation|organ transplantation]].<ref name=chronic_noro/> These infections can be with or without symptoms.<ref name=chronic_noro/> In severe cases, persistent infections can lead to norovirus‐associated enteropathy, intestinal villous atrophy, and malabsorption.<ref name=chronic_noro>{{cite journal |last1=Bok |first1=K |last2=Green |first2=K. Y. |title=Norovirus Gastroenteritis in Immunocompromised Patients |journal=New England Journal of Medicine |volume=368 |issue=10 |pages=971 |date=2013-03-16 | pmid = 23465122 | pmc = 4793940 | doi = 10.1056/NEJMc1301022}}</ref>

== Virology ==
{{Virusbox
| name = ''Norovirus''
| image = Norovirus 4.jpg
| image_alt = Transmission electron micrograph of Norovirus particles in feces
| image_caption = Transmission electron micrograph of ''Norovirus'' particles in feces
| parent = Norovirus
| species = Norwalk virus
| synonyms =
| synonyms_ref =
| subdivision_ranks =
| subdivision =
}}

=== Transmission ===
Noroviruses are transmitted directly from person to person (62–84% of all reported outbreaks)<ref>{{cite journal |vauthors=Moore MD, Goulter RM, Jaykus L | title = Human Norovirus as a Foodborne Pathogen: Challenges and Developments | journal = Annual Review of Food Science and Technology  | volume = 6 | issue = 1 | pages = 411–33 | date = April 2015 | doi = 10.1146/annurev-food-022814-015643 |pmid= 25884284| doi-access = free }}</ref> and indirectly via contaminated water and food. They are extremely contagious, and fewer than twenty virus particles can cause an infection<ref name="pmid21876931">{{cite journal |vauthors=Morillo SG, Timenetsky Mdo C | title = Norovirus: an overview | journal = Revista da Associação Médica Brasileira | volume = 57 | issue = 4 | pages = 453–8 | year = 2011 | pmid = 21876931 | doi = 10.1016/s0104-4230(11)70094-x | doi-access =  }}</ref> (some research suggests as few as five).<ref name=juan>{{Cite book|title=Immunity Against Mucosal Pathogens|last=Leon|first=Juan|editor1-last=Vajdy|editor1-first=Michael|year=2008|chapter=Chapter 9|page=232|publisher=Springer|chapter-url=https://books.google.com/books?id=0ZYFRep6EykC&pg=PA219|isbn=978-1-4020-8412-6|access-date=2022-10-07|archive-date=2022-10-07|archive-url=https://web.archive.org/web/20221007190855/https://books.google.com/books?id=0ZYFRep6EykC&pg=PA219|url-status=live}}</ref> Transmission can be aerosolized when those stricken with the illness vomit, and can be aerosolized by a toilet flush when vomit or diarrhea is present; infection can follow eating food or breathing air near an episode of vomiting, even if cleaned up.<ref>{{cite web|url=https://www.newscientist.com/article/mg16722551.000-ive-lost-my-appetite.html|title=I've lost my appetite...|author=Robert Matthews|work=New Scientist|access-date=21 February 2016|archive-date=3 May 2015|archive-url=https://web.archive.org/web/20150503052554/http://www.newscientist.com/article/mg16722551.000-ive-lost-my-appetite.html|url-status=live}}</ref> The viruses continue to be [[Biology:Viral shedding|shed]] after symptoms have subsided and shedding can still be detected many weeks after infection.<ref>{{cite journal |vauthors= Atmar RL, Opekun AR, Gilger MA, Estes MK, Crawford SE, Neill FH, Graham DY | title = Norwalk Virus Shedding after Experimental Human Infection | journal = Emerg. Infect. Dis. | volume = 14 | issue = 10 | pages = 1553–7 | date = October 2008 | pmid = 18826818 | pmc = 2609865 | doi = 10.3201/eid1410.080117 |name-list-style=vanc  }}</ref>

Vomiting, in particular, transmits infection effectively and appears to allow airborne transmission. In one incident, a person who vomited spread the infection across a restaurant, suggesting that many unexplained cases of food poisoning may have their source in vomit.<ref>{{cite journal |vauthors=Marks PJ, Vipond IB, Carlisle D, Deakin D, Fey RE, Caul EO | title = Evidence for airborne transmission of Norwalk-like virus (NLV) in a hotel restaurant | journal = Epidemiol. Infect. | volume = 124 | issue = 3 | pages = 481–487 | date = June 2000 | pmid = 10982072 | pmc = 2810934 | doi = 10.1017/s0950268899003805 | citeseerx = 10.1.1.404.2721 }}</ref> In December 1998, 126 people were dining at six tables; one person vomited onto the floor. Staff quickly cleaned up, and people continued eating. Three days later others started falling ill; 52 people reported a range of symptoms, from fever and nausea to vomiting and diarrhea. The cause was not immediately identified. Researchers plotted the seating arrangement: more than 90% of the people at the same table as the sick person later reported becoming ill. There was a direct correlation between the risk of infection of people at other tables and how close they were to the sick person. More than 70% of the diners at an adjacent table fell ill; at a table on the other side of the restaurant, the infection rate was still 25%. The outbreak was attributed to a Norwalk-like virus (norovirus). Other cases of transmission by vomit were later identified.<ref>{{cite journal |vauthors=Marks PJ, Vipond IB, Regan FM, Wedgwood K, Fey RE, Caul EO | title = A school outbreak of Norwalk-like virus: evidence for airborne transmission | journal = Epidemiol. Infect. | volume = 131 | issue = 1 | pages = 727–736 | date = August 2003 | pmid = 12948373 | pmc = 2870014 | doi = 10.1017/s0950268803008689 }}</ref>

In one outbreak at an international scout jamboree in the Netherlands, each person with gastroenteritis infected an average of 14 people before increased hygiene measures were put in place. Even after these new measures were enacted, an ill person still infected an average of 2.1 other people.<ref>{{cite journal |vauthors= Heijne JC, Teunis P, Morroy G, Wijkmans C, Oostveen S, Duizer E, Kretzschmar M, Wallinga J | title = Enhanced Hygiene Measures and Norovirus Transmission during an Outbreak | journal = Emerg. Infect. Dis. | volume = 15 | issue = 1 | pages = 24–30 | year = 2009 | pmid = 19116045 | pmc = 2660689 | doi = 10.3201/eid1501.080299 }}</ref> A US Centers for Disease Control and Prevention (CDC) study of 11 outbreaks in New York State lists the suspected [[Medicine:Transmission|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.<ref name="pmid8395330">{{cite journal |vauthors= Hedberg CW, Osterholm MT | title = Outbreaks of food-borne and waterborne viral gastroenteritis | journal = Clin. Microbiol. Rev. | volume = 6 | issue = 3 | pages = 199–210 | year = 1993 | pmid = 8395330 | pmc = 358282 | doi = 10.1128/CMR.6.3.199 }}</ref>

Shellfish and salad ingredients are the foods most often implicated in norovirus outbreaks. Ingestion of shellfish that has not been sufficiently heated{{spnd}}under {{convert|75|C}}{{spnd}}poses a high risk for norovirus infection.<ref>{{cite web |url=https://www.canada.ca/en/health-canada/services/general-food-safety-tips/safe-internal-cooking-temperatures-chart.html |title=Safe Internal Cooking Temperatures Chart |date=7 May 2015 |publisher=Government of Canada |access-date=27 December 2017 |archive-date=27 December 2017 |archive-url=https://web.archive.org/web/20171227122625/https://www.canada.ca/en/health-canada/services/general-food-safety-tips/safe-internal-cooking-temperatures-chart.html |url-status=live }}</ref><ref>{{cite web|url=http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/Norovirus/oysterconsumptionnorovirus/|archive-url=http://webarchive.nationalarchives.gov.uk/20140714084352/http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/Norovirus/oysterconsumptionnorovirus/|url-status=dead|archive-date=14 July 2014|title= HPA: Shellfish consumption and the risk of norovirus infection|access-date=21 February 2016}}</ref> Foods other than shellfish may be contaminated by infected food handlers.<ref name="pmid11479930">{{cite journal | vauthors = Parashar UD, Monroe SS | title = 'Norwalk-like viruses' as a cause of foodborne disease outbreaks | journal = Rev. Med. Virol. | volume = 11 | issue = 4 | pages = 243–52 | year = 2001 | pmid = 11479930 | doi = 10.1002/rmv.321 | s2cid = 9922865 | url = https://zenodo.org/record/1229350 | access-date = 2020-09-05 | archive-date = 2020-10-31 | archive-url = https://web.archive.org/web/20201031083507/https://zenodo.org/record/1229350 | url-status = live }}</ref> Many norovirus outbreaks have been traced to food that was handled by only one infected person.<ref name="pmid14672828">{{cite journal |vauthors= Koopmans M, Duizer E | title = Foodborne viruses: an emerging problem | journal = Int. J. Food Microbiol. | volume = 90 | issue = 1 | pages = 23–41 | year = 2004 | pmid = 14672828 | doi = 10.1016/S0168-1605(03)00169-7 | pmc = 7127053 }}</ref>

Between March and August 2017, in Quebec, Canada, there was an outbreak of norovirus that sickened more than 700 people. According to an investigation by Canada's CFIA Food Control Agency, the culprit was frozen raspberries imported from Harbin Gaotai Food Co Ltd, a Chinese supplier, and then Canadian authorities issued a recall on raspberries products from Harbin Gaotai.<ref>{{cite web |last1= Sherwood |first1= Dave |title= How a Chilean raspberry scam dodged food safety controls from China to Canada |url= https://www.reuters.com/article/chile-crime-raspberries-insight/how-a-chilean-raspberry-scam-dodged-food-safety-controls-from-china-to-canada-idUSKBN26R1M1 |website= Reuters |access-date= 10 October 2020 |archive-url= https://web.archive.org/web/20201010080047/https://www.reuters.com/article/chile-crime-raspberries-insight/how-a-chilean-raspberry-scam-dodged-food-safety-controls-from-china-to-canada-idUSKBN26R1M1 |archive-date= 10 October 2020 |url-status= dead }}</ref>

According to the CDC, there has been a surge in norovirus cases on thirteen cruise ships in 2023, which marks the highest number of outbreaks since 2012.<ref>{{cite web |title=Cruise ships are seeing the highest number of norovirus outbreaks in a decade |url=https://www.deseret.com/2023/7/13/23793778/highest-number-of-norovirus-outbreaks-on-cruise-ships |access-date=15 July 2023 |website=Deseret News|date=13 July 2023 }}</ref>

=== Classification ===
Noroviruses (NoV) are a genetically diverse group of single-stranded positive-sense RNA, non-enveloped viruses belonging to the family ''[[Biology:Caliciviridae|Caliciviridae]]''.<ref name=ICTV>{{Cite web|url=http://www.ictv.global/report/caliciviridae|title=Family: Caliciviridae &#124; ICTV|website=www.ictv.global|access-date=2019-10-02|archive-date=2021-08-29|archive-url=https://web.archive.org/web/20210829153617/https://talk.ictvonline.org/ictv-reports/ictv_online_report/positive-sense-rna-viruses/w/caliciviridae|url-status=live}}</ref><ref name=health>{{cite web |last1=Public Health Laboratory Network |title=Norovirus Laboratory Case Definition (LCD) |url=http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-phlncd-norwalk.htm |publisher=Australian Government Department of Health and Ageing |language=en |date=25 September 2006 |access-date=15 September 2020 |archive-date=1 May 2008 |archive-url=https://web.archive.org/web/20080501230732/http://www.health.gov.au/internet/main/publishing.nsf/Content/cda-phlncd-norwalk.htm |url-status=live }}</ref> According to the [[Organization:International Committee on Taxonomy of Viruses|International Committee on Taxonomy of Viruses]], the genus ''Norovirus'' has one species, which is called ''Norwalk virus''.<ref name=ICTV/>

Noroviruses can genetically be classified into at least seven different genogroups (GI, GII, GIII, GIV, GV, GVI, and GVII), which can be further divided into other genetic clusters or [[Biology:Genotype|genotype]]s.<ref>{{cite journal |last1=Atmar |first1=Robert L |last2=Baehner |first2=Frank |last3=Cramer |first3=Jakob P |last4=Lloyd |first4=Eric |last5=Sherwood |first5=James |last6=Borkowski |first6=Astrid |last7=Mendelman |first7=Paul M |last8=Al-Ibrahim |first8=Mohamed S |last9=Bernstein |first9=David L |last10=Brandon |first10=Donald M |last11=Chu |first11=Laurence |last12=Davis |first12=Matthew G |last13=Epstein |first13=Robert J |last14=Frey |first14=Sharon E |last15=Rosen |first15=Jeffrey B |last16=Treanor |first16=John J |title=Persistence of Antibodies to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: 1-Year Follow-up With Memory Probe Vaccination |journal=The Journal of Infectious Diseases |date=15 August 2019 |volume=220 |issue=4 |pages=603–614 |doi=10.1093/infdis/jiz170|pmid=31001633 }}</ref>

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.<ref name=health/>

Most noroviruses that infect humans belong to genogroups GI and GII.<ref name="pmid10752550">{{cite journal | vauthors = Vinjé J, Green J, Lewis DC, Gallimore CI, Brown DW, Koopmans MP | title = Genetic polymorphism across regions of the three open reading frames of "Norwalk-like viruses" | journal = Arch. Virol. | volume = 145 | issue = 2 | pages = 223–41 | year = 2000 | pmid = 10752550 | doi = 10.1007/s007050050020 | s2cid = 20525287 }}</ref>
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.<ref>{{cite journal |vauthors=Noel JS, Fankhauser RL, Ando T, Monroe SS, Glass RI | title = Identification of a distinct common strain of "Norwalk-like viruses" having a global distribution | journal = J. Infect. Dis. | volume = 179 | issue = 6 | pages = 1334–44 | year = 2000 | pmid = 10228052 | doi = 10.1086/314783 | doi-access = free }}</ref>

Recent examples include US95/96-US strain, associated with global outbreaks in the mid- to late-1990s; Farmington Hills virus associated with outbreaks in Europe and the United States in 2002 and in 2004; and Hunter virus which was associated with outbreaks in Europe, Japan, and Australasia. In 2006, there was another large increase in NoV infection around the globe.<ref name="pmid18177226">{{cite journal |vauthors=Tu ET, Bull RA, Greening GE, Hewitt J, Lyon MJ, Marshall JA, McIver CJ, Rawlinson WD, White PA | title = Epidemics of gastroenteritis during 2006 were associated with the spread of norovirus GII.4 variants 2006a and 2006b | journal = Clin. Infect. Dis. | volume = 46 | issue = 3 | pages = 413–20 | year = 2008 | pmid = 18177226 | doi = 10.1086/525259 | s2cid = 27972379 | doi-access =  }}</ref> Reports have shown a link between the expression of human histo-blood group antigens (HBGAs) and the susceptibility to norovirus infection. Studies have suggested the [[Biology:Capsid|capsid]] of noroviruses may have evolved from selective pressure of human HBGAs.<ref name="pmid21519121">{{cite journal | author = Shirato H | title = Norovirus and histo-blood group antigens | journal = Japanese Journal of Infectious Diseases | volume = 64 | issue = 2 | pages = 95–103 | year = 2011 | doi = 10.7883/yoken.64.95 | pmid = 21519121 | doi-access = free }}</ref> HBGAs are not, however, the receptor or facilitator of norovirus infection. In fact, co-factors such as bile salts may facilitate the infection, making it more intense when introduced during or after the initial infection of the host tissue.<ref name=":0">{{Cite journal|last1=Graziano|first1=Vincent R.|last2=Wei|first2=Jin|last3=Wilen|first3=Craig B.|date=30 May 2019|title=Norovirus Attachment and Entry|journal=Viruses|language=en|volume=11|issue=6|pages=495|doi=10.3390/v11060495|pmid=31151248|pmc=6630345|doi-access=free}}</ref> Bile salts are produced by the liver in response to eating fatty foods, and they help with the absorption of consumed [[Chemistry:Lipid|lipid]]s. It is not yet clear as to at what specific point in the Norovirus replication cycle bile salts facilitate infection: penetration, uncoating, or maintaining capsid stability.<ref name=":0" />

The protein MDA-5 may be the primary immune sensor that detects the presence of noroviruses in the body.<ref>{{cite journal | vauthors = McCartney SA, Thackray LB, Gitlin L, Gilfillan S, Virgin HW, Virgin Iv HW, Colonna M | title = MDA-5 Recognition of a Murine Norovirus | journal = PLOS Pathog | volume = 4 | issue = 7 | page = e1000108 | date = July 18, 2008 | pmid = 18636103 | pmc = 2443291 | doi = 10.1371/journal.ppat.1000108 | veditors = Baric RS | doi-access = free }}</ref>  Some people have common variations of the MDA-5 gene that could make them more susceptible to norovirus infection.<ref>[http://newswise.com/articles/view/542714/ Researchers Discover Primary Sensor That Detects Stomach Viruses] {{Webarchive|url=https://web.archive.org/web/20090202094714/http://newswise.com/articles/view/542714/ |date=2009-02-02 }} Newswise, Retrieved on July 20, 2008.</ref>

=== Structure ===
[[File:Norwalk Caspid.jpg|thumb|X-ray crystallographic structure of the Norwalk virus capsid]]

{| class="wikitable" style="text-align:center"
|-
! Genus !! Structure || Symmetry !! Capsid !! Genomic arrangement !! Genomic segmentation
|-
|Norovirus||Icosahedral||T=1, T=3||Non-enveloped||Linear||Monopartite
|}

Viruses in Norovirus are non-enveloped, with icosahedral geometries. [[Biology:Capsid|Capsid]] diameters vary widely, from 23 to 40&nbsp;nm in diameter. The larger capsids (38–40&nbsp;nm) exhibit [[Biology:Capsid#Triangulation number|T=3 symmetry]] and are composed of 180 [[Biology:Major capsid protein VP1|VP1 proteins]]. Small capsids (23&nbsp;nm) show T=1 symmetry, and are composed of 60 VP1 proteins.<ref name=ViralZone>{{cite web|title=Viral Zone|url=http://viralzone.expasy.org/all_by_species/194.html|publisher=ExPASy|access-date=15 June 2015|archive-date=9 January 2017|archive-url=https://web.archive.org/web/20170109200451/http://viralzone.expasy.org/all_by_species/194.html|url-status=live}}</ref> The virus particles demonstrate an amorphous surface structure when visualized using [[Physics:Electron microscopy|electron microscopy]].<ref name="pmid11444031">{{cite book |vauthors=Prasad BV, Crawford S, Lawton JA, Pesavento J, Hardy M, Estes MK | title = Gastroenteritis Viruses | chapter = Structural Studies on Gastroenteritis Viruses | volume = 238 | pages = 26–37; discussion 37–46 | year = 2001 | pmid = 11444031 | doi = 10.1002/0470846534.ch3 | isbn = 978-0-470-84653-7 | series = Novartis Foundation Symposia }}</ref>

===Genome===

Noroviruses contain a linear, non-segmented,<ref name=ViralZone /> [[Biology:Sense (molecular biology)|positive-sense]] [[Biology:RNA|RNA]] [[Biology:Genome|genome]] of approximately 7.5 kilobases, encoding a large polyprotein which is cleaved into six smaller non-structural proteins (NS1/2 to NS7)<ref>{{cite journal | vauthors = Thorne LG, Goodfellow IG | title = Norovirus gene expression and replication | journal = The Journal of General Virology | volume = 95 | issue = Pt 2 | pages = 278–91 | date = February 2014 | pmid = 24243731 | doi = 10.1099/vir.0.059634-0 | doi-access = free }}</ref> by the viral [[Biology:3C-like protease|3C-like protease]] (NS6), a major structural protein ([[Biology:Major capsid protein VP1|VP1]]) of about 58~60 kDa and a minor capsid protein (VP2).<ref name="pmid10804143">{{cite journal | vauthors = Clarke IN, Lambden PR | title = Organization and expression of calicivirus genes | journal = The Journal of Infectious Diseases | volume = 181 | pages = S309-16 | date = May 2000 | issue = Suppl 2 | pmid = 10804143 | doi = 10.1086/315575 | doi-access = free }}</ref>

The most variable region of the viral capsid is the P2 domain, which contains [[Biology:Antigen presentation|antigen-presenting]] sites and carbohydrate-receptor binding regions.<ref>{{cite journal |vauthors=Tan M, Hegde RS, Jiang X | title = The P Domain of Norovirus Capsid Protein Forms Dimer and Binds to Histo-Blood Group Antigen Receptors | journal = J. Virol. | volume = 78 | issue = 12 | pages = 6233–42 | year = 2004 | pmid = 15163716 | pmc = 416535 | doi = 10.1128/JVI.78.12.6233-6242.2004 }}</ref><ref>{{cite journal |vauthors=Tan M, Huang P, Meller J, Zhong W, Farkas T, Jiang X |title=Mutations within the P2 domain of norovirus capsid affect binding to human histo-blood group antigens: evidence for a binding pocket |journal=J. Virol. |volume=77 |issue=23 |pages=12562–71 |year=2003 |pmid=14610179 |pmc=262557 |doi=10.1128/jvi.77.23.12562-12571.2003}} {{cite journal|title=Erratum |journal=J. Virol.  |volume=78 |issue=6 |page=3200 |year=2004|doi=10.1128/JVI.78.6.3201.2004 |author=Tan M|citeseerx=10.1.1.212.5257|s2cid=220476008 }}</ref><ref>{{cite journal |vauthors=Cao S, Lou Z, Tan M, Chen Y, Liu Y, Zhang Z, Zhang XC, Jiang X, Li X, Rao Z | title = Structural Basis for the Recognition of Blood Group Trisaccharides by Norovirus | journal = J. Virol. | volume = 81 | issue = 11 | pages = 5949–57 | year = 2007 | pmid = 17392366 | pmc = 1900264 | doi = 10.1128/JVI.00219-07 }}</ref><ref>{{cite journal | vauthors = Lundborg M, Ali E, Widmalm G | title = An ''in silico'' virtual screening study for the design of norovirus inhibitors: fragment-based molecular docking and binding free energy calculations | journal = Carbohydr. Res. | volume = 378 | pages = 133–8 | year = 2013 | pmid = 23582100 | doi = 10.1016/j.carres.2013.03.012 | s2cid = 9941188 | url = https://su.diva-portal.org/smash/get/diva2:656620/FULLTEXT01.pdf | archive-url = https://web.archive.org/web/20210829153644/https://su.diva-portal.org/smash/get/diva2:656620/FULLTEXT01.pdf |access-date = 2019-06-24 | archive-date = 2021-08-29 |url-status=live }}</ref><ref>{{cite journal |vauthors=Ali ES, Rajapaksha H, Jillian MC, Petrovsky N | title = Norovirus drug candidates that inhibit viral capsid attachment to human histo-blood group antigens | journal = Antiviral Res. | volume = 133 | pages = 14–22 | year = 2016 | pmid = 27421712 | doi = 10.1016/j.antiviral.2016.07.006 | pmc=5026924}}</ref>

===Evolution===

Groups 1, 2, 3, and 4 last shared a common ancestor in AD 867.<ref name=Kobayashi2016>{{cite journal |doi=10.1038/srep29400 |title=Molecular evolution of the capsid gene in human norovirus genogroup II |year=2016 |last1=Kobayashi |first1=Miho |last2=Matsushima |first2=Yuki |last3=Motoya |first3=Takumi |last4=Sakon |first4=Naomi |last5=Shigemoto |first5=Naoki |last6=Okamoto-Nakagawa |first6=Reiko |last7=Nishimura |first7=Koichi |last8=Yamashita |first8=Yasutaka |last9=Kuroda |first9=Makoto |last10=Saruki |first10=Nobuhiro |last11=Ryo |first11=Akihide |last12=Saraya |first12=Takeshi |last13=Morita |first13=Yukio |last14=Shirabe |first14=Komei |last15=Ishikawa |first15=Mariko |last16=Takahashi |first16=Tomoko |last17=Shinomiya |first17=Hiroto |last18=Okabe |first18=Nobuhiko |last19=Nagasawa |first19=Koo |last20=Suzuki |first20=Yoshiyuki |last21=Katayama |first21=Kazuhiko |last22=Kimura |first22=Hirokazu |journal=Scientific Reports |volume=6 |page=29400 |pmid=27384324 |pmc=4935990 |bibcode=2016NatSR...629400K }}</ref> The group 2 and group 4 viruses last shared a common ancestor in approximately AD 1443 (95% highest posterior density AD 1336–1542).<ref name=Ozaki2018>{{cite journal | doi=10.3389/fmicb.2018.03070 | doi-access=free | title=Molecular Evolutionary Analyses of the RNA-Dependent RNA Polymerase Region in Norovirus Genogroup II | year=2018 | last1=Ozaki | first1=Keita | last2=Matsushima | first2=Yuki | last3=Nagasawa | first3=Koo | last4=Motoya | first4=Takumi | last5=Ryo | first5=Akihide | last6=Kuroda | first6=Makoto | last7=Katayama | first7=Kazuhiko | last8=Kimura | first8=Hirokazu | journal=Frontiers in Microbiology | volume=9 | page=3070 | pmid=30619155 | pmc=6305289 }}</ref> Several estimates of the evolution rate have been made varying from 8.98 × 10<sup>−3</sup> to 2.03 × 10<sup>−3</sup> substitutions per site per year.{{cn|date=August 2022}}

The estimated [[Biology:Mutation rate|mutation rate]] (1.21{{e|−2}} to 1.41 {{e|−2}} substitutions per site per year) in this virus is high even compared with other RNA viruses.<ref name=Victoria2009>{{cite journal |vauthors=Victoria M, Miagostovich MP, Ferreira MS, Vieira CB, Fioretti JM, Leite JP, Colina R, Cristina J | title = Bayesian coalescent inference reveals high evolutionary rates and expansion of Norovirus populations | journal = Infect Genet Evol | volume = 9 | issue = 5 | pages = 927–932 | year = 2009 | pmid = 19559104 | doi = 10.1016/j.meegid.2009.06.014 | doi-access = free }}</ref>

In addition, a [[Biology:Recombination hotspot|recombination hotspot]] exists at the ORF1-ORF2 (VP1) junction.<ref>{{cite journal | vauthors = Tsimpidis M, Bachoumis G, Mimouli K, Kyriakopoulou Z, Robertson DL, Markoulatos P, Amoutzias GD | title = T-RECs: rapid and large-scale detection of recombination events among different evolutionary lineages of viral genomes | journal = BMC Bioinformatics | volume = 18 | issue = 1 | pages = 13 | date = January 2017 | pmid = 28056784 | pmc = 5216575 | doi = 10.1186/s12859-016-1420-z | doi-access = free }}</ref>

===Replication cycle===
[[Biology:Viral replication|Viral replication]] is cytoplasmic. Entry into the host cell is achieved by attachment to host receptors, which mediates [[Biology:Endocytosis|endocytosis]]. Positive-stranded RNA virus transcription is the method of replication. Translation takes place by [[Biology:Leaky scanning|leaky scanning]] and RNA termination-reinitiation. Humans and other mammals serve as the natural host. Transmission routes are fecal-oral and contamination.<ref name=ViralZone />

{| class="wikitable sortable" style="text-align:center"
|-
! Genus !! Host details !! Tissue tropism !! Entry details !! Release details !! Replication site !! Assembly site !! Transmission
|-
|Norovirus||Humans; mammals||Intestinal epithelium||Cell receptor endocytosis||Lysis||Cytoplasm||Cytoplasm||Oral-fecal
|}

== Pathophysiology ==
When a person becomes infected with norovirus, the virus replicates within the [[Biology:Small intestine|small intestine]]. The principal symptom is acute [[Medicine:Gastroenteritis|gastroenteritis]], characterized by nausea, forceful vomiting, watery [[Medicine:Diarrhea|diarrhea]], and abdominal pain, that develops between 12 and 48 hours after exposure, and lasts for 24–72 hours.<ref name="cdcfactsheet">{{cite web |url=https://www.cdc.gov/ncidod/dvrd/revb/gastro/norovirus-factsheet.htm |title=Norovirus: Technical Fact Sheet |publisher=National Center for Infectious Diseases, CDC |url-status=dead |archive-url=https://web.archive.org/web/20120308152422/http://www.cdc.gov/ncidod/dvrd/revb/gastro/norovirus-factsheet.htm |archive-date=2012-03-08 }}</ref> Sometimes there is loss of taste, general lethargy, weakness, muscle aches, [[Medicine:Headache|headache]], cough, and/or low-grade [[Medicine:Fever|fever]]. The disease is usually self-limiting.{{cn|date=August 2022}}

Severe illness is rare; although people are frequently treated at the emergency ward, they are rarely admitted to the hospital. The number of deaths from norovirus in the United States is estimated to be around 570–800<ref>{{cite journal | vauthors = Hall AJ, Lopman BA, Payne DC, Patel MM, Gastañaduy PA, Vinjé J, Parashar UD | title = Norovirus disease in the United States | journal = Emerging Infectious Diseases | volume = 19 | issue = 8 | pages = 1198–205 | date = August 2013 | pmid = 23876403 | pmc = 3739528 | doi = 10.3201/eid1908.130465 }}</ref> each year, with most of these occurring in the very young, the elderly, and persons with weakened immune systems. Symptoms may become life-threatening in these groups if [[Medicine:Dehydration|dehydration]] or [[Medicine:Electrolyte imbalance|electrolyte imbalance]] is ignored or left untreated.<ref name="pmid16968608">{{cite journal | vauthors = Goodgame R | title = Norovirus gastroenteritis | journal = Current Gastroenterology Reports | volume = 8 | issue = 5 | pages = 401–8 | date = October 2006 | pmid = 16968608 | doi = 10.1007/s11894-006-0026-4 | s2cid = 54521495 }}</ref>

== Diagnosis ==
Specific diagnosis of norovirus is routinely made by [[Biology:Polymerase chain reaction|polymerase chain reaction]] (PCR) assays or quantitative PCR assays, which give results within a few hours. These assays are very [[Sensitivity and specificity|sensitive]] and can detect as few as 10 virus particles.<ref name="pmid17175887">{{cite journal |vauthors=Marshall JA, Bruggink LD | title = Laboratory diagnosis of norovirus | journal = Clin. Lab. | volume = 52 | issue = 11–12 | pages = 571–81 | year = 2006 | pmid = 17175887 }}</ref>
Tests such as ELISA that use [[Biology:Antibody|antibodies]] against a mixture of norovirus strains are available commercially, but lack specificity and sensitivity.<ref name="pmid17391396">{{cite journal | vauthors = Wilhelmi de Cal I, Revilla A, del Alamo JM, Román E, Moreno S, Sánchez-Fauquier A | title = Evaluation of two commercial enzyme immunoassays for the detection of norovirus in faecal samples from hospitalised children with sporadic acute gastroenteritis | journal = Clin. Microbiol. Infect. | volume = 13 | issue = 3 | pages = 341–3 | year = 2007 | pmid = 17391396 | doi = 10.1111/j.1469-0691.2006.01594.x | doi-access = free }}</ref>

== Prevention ==
After [[Medicine:Infection|infection]], [[Medicine:Immunity (medical)|immunity]] to the ''same'' strain of the virus&nbsp;– the genotype&nbsp;– protects against reinfection for between six months to two years.<ref name="pmid25490691">{{cite journal | vauthors = Payne DC, Parashar UD, Lopman BA | title = Developments in understanding acquired immunity and innate susceptibility to norovirus and rotavirus gastroenteritis in children | journal = Current Opinion in Pediatrics | volume = 27 | issue = 1 | pages = 105–9 | date = February 2015 | pmid = 25490691 | pmc = 4618547 | doi = 10.1097/MOP.0000000000000166 }}</ref> This immunity does not fully protect against infection with the other diverse genotypes of the virus.<ref name="pmid25490691"/>

In {{wipe|Canada}}, norovirus is a [[Medicine:Notifiable disease|notifiable disease]].<ref>{{cite web | title=Diseases Under National Surveillance (as of January 2009) | publisher=Public Health Agency of Canada | url=http://www.phac-aspc.gc.ca/bid-bmi/dsd-dsm/duns-eng.php | access-date=21 November 2017 | date=2003-09-17 | archive-date=2017-09-23 | archive-url=https://web.archive.org/web/20170923142027/http://www.phac-aspc.gc.ca/bid-bmi/dsd-dsm/duns-eng.php | url-status=live }}</ref> In both the US and the UK it is not notifiable.<ref>{{cite web|last1=Anonymous|title=Notifiable diseases and causative organisms: how to report – GOV.UK|url=https://www.gov.uk/guidance/notifiable-diseases-and-causative-organisms-how-to-report|website=www.gov.uk|publisher=[[Organization:Public Health England|Public Health England]]|access-date=26 November 2017|language=en|date=1 May 2010|archive-date=17 July 2018|archive-url=https://web.archive.org/web/20180717024817/https://www.gov.uk/guidance/notifiable-diseases-and-causative-organisms-how-to-report|url-status=live}}</ref><ref>{{cite web|last1=Anonymous|title=Norovirus {{!}} Reporting and Surveillance {{!}} CDC|url=https://www.cdc.gov/norovirus/reporting/index.html|website=www.cdc.gov|publisher=Centers for Disease Control and Prevention|access-date=26 November 2017|language=en-us|date=28 December 2016|archive-date=9 December 2017|archive-url=https://web.archive.org/web/20171209145710/https://www.cdc.gov/norovirus/reporting/index.html|url-status=live}}</ref>

===Hand washing and disinfectants===
Hand washing with soap and water is an effective method for reducing the transmission of norovirus pathogens. Alcohol rubs (≥62% [[Chemistry:Isopropyl alcohol|isopropyl alcohol]]) may be used as an adjunct, but are less effective than hand-washing, as norovirus lacks a [[Chemistry:Lipid|lipid]] [[Biology:Viral envelope|viral envelope]].<ref name="pmid16765204">{{cite journal |vauthors=Jimenez L, Chiang M | title = Virucidal activity of a quaternary ammonium compound disinfectant against feline calicivirus: a surrogate for norovirus | journal = Am J Infect Control | volume = 34 | issue = 5 | pages = 269–73 | year = 2006 | pmid = 16765204 | doi = 10.1016/j.ajic.2005.11.009 }}</ref> Surfaces where norovirus particles may be present can be sanitised with a solution of 1.5% to 7.5% of household bleach in water, or other disinfectants effective against norovirus.<ref name="cdcfactsheet"/><ref>{{cite web|url=https://www.epa.gov/pesticide-registration/list-g-epa-registered-hospital-disinfectants-effective-against-norovirus|title=List G: EPA Registered Hospital Disinfectants Effective Against Norovirus (Norwalk-like virus)|publisher=US Environmental Protection Agency|access-date=9 May 2016|date=2015-09-28|archive-date=2016-04-15|archive-url=https://web.archive.org/web/20160415170327/https://www.epa.gov/pesticide-registration/list-g-epa-registered-hospital-disinfectants-effective-against-norovirus|url-status=live}}</ref><ref>{{cite web |url=http://www.thenakedscientists.com/HTML/content/interviews/interview/838/ |title=Gastroenteritis and Noroviruses—Dr Jim Grey, Health Protection Agency |publisher=The Naked Scientists |date=2007-12-09 |access-date=2014-02-09 |archive-date=2014-03-31 |archive-url=https://web.archive.org/web/20140331051859/http://www.thenakedscientists.com/HTML/content/interviews/interview/838/ |url-status=live }}</ref>

===Health care facilities===
In healthcare environments, the prevention of nosocomial infections involves routine and [[Chemistry:Terminal cleaning|terminal cleaning]]. Nonflammable alcohol vapor in CO<sub>2</sub> systems is used in health care environments where medical electronics would be adversely affected by aerosolized chlorine or other caustic compounds.<ref name="pmid10833336">{{cite journal |vauthors=Chadwick PR, Beards G, Brown D, Caul EO, Cheesbrough J, Clarke I, Curry A, O'Brien S, Quigley K, Sellwood J, Westmoreland D | title = Management of hospital outbreaks of gastroenteritis due to small round structured viruses | journal = J. Hosp. Infect. | volume = 45 | issue = 1 | pages = 1–10 | year = 2000 | pmid = 10833336 | doi = 10.1053/jhin.2000.0662 }}</ref>

In 2011, the CDC published a clinical practice guideline addressing strategies for the prevention and control of norovirus gastroenteritis outbreaks in healthcare settings.<ref>{{cite web|last1=HICPAC|title=Guideline for the Prevention and Control of Norovirus Gastroenteritis Outbreaks in Healthcare Settings, 2011|url=https://www.cdc.gov/hicpac/norovirus/002_norovirus-toc.html|website=Healthcare Infection Control Practices Advisory Committee (HICPAC)|publisher=Centers for Disease Control and Prevention (CDC)|access-date=19 March 2015|archive-date=27 March 2015|archive-url=https://web.archive.org/web/20150327010357/http://www.cdc.gov/hicpac/norovirus/002_norovirus-toc.html|url-status=live}}</ref><ref>{{cite journal | vauthors = MacCannell T, Umscheid CA, Agarwal RK, Lee I, Kuntz G, Stevenson KB | title = Guideline for the prevention and control of norovirus gastroenteritis outbreaks in healthcare settings | journal = Infection Control and Hospital Epidemiology | volume = 32 | issue = 10 | pages = 939–69 | date = October 2011 | pmid = 21931246 | doi = 10.1086/662025 | s2cid = 27996748 }}</ref> Based on a systematic review of published scientific studies, the guideline presents 51 specific [[Medicine:Evidence-based medicine|evidence-based]] recommendations, which were organized into 12 categories: 1) patient cohorting and isolation precautions, 2) hand hygiene, 3) patient transfer and ward closure, 4) food handlers in healthcare, 5) diagnostics, 6) personal protective equipment, 7) environmental cleaning, 8) staff leave and policy, 9) visitors, 10) education, 11) active case-finding, and 12) communication and notification. The guideline also identifies eight high-priority recommendations and suggests several areas in need of future research.{{cn|date=August 2022}}

===Vaccine trials===
LigoCyte announced in 2007 that it was working on a vaccine and had started phase 1 trials.<ref name="Norovac">{{cite web| title=Norovirus Vaccine| url=http://www.ligocyte.com/downloads/Noro.pdf| access-date=2008-08-26| archive-date=2008-10-02| archive-url=https://web.archive.org/web/20081002175650/http://www.ligocyte.com/downloads/Noro.pdf| url-status=live}}</ref> The company has since been taken over by [[Company:Takeda Pharmaceutical Company|Takeda Pharmaceutical Company]].<ref>{{cite web| title=Takeda to Acquire LigoCyte Pharmaceuticals, Inc.| url=http://www.takeda.com/news/2012/20121005_4001.html| access-date=2013-06-22| archive-date=2013-06-29| archive-url=https://web.archive.org/web/20130629235039/http://www.takeda.com/news/2012/20121005_4001.html| url-status=live}}</ref> {{As of|2019||df=}}, a bivalent (NoV GI.1/GII.4) intramuscular vaccine had completed phase 1 trials.<ref>{{Cite journal|last1=Baehner|first1=F.|last2=Bogaerts|first2=H.|last3=Goodwin|first3=R.|date=2016-12-01|title=Vaccines against norovirus: state of the art trials in children and adults|journal=Clinical Microbiology and Infection|series=Vaccines for Mutual Protection: Selected Proceedings from the 3rd ESCMID Conference on Vaccines|volume=22|pages=S136–S139|doi=10.1016/j.cmi.2015.12.023|pmid=27130672|issn=1198-743X|doi-access=free}}</ref><ref>{{Cite web|url=https://www.takeda.com/siteassets/system/what-we-do/research-and-development-rd-in-takeda/our-pipeline/pipeline_en_2019_q2.pdf|title=Key Products and Pipeline (FY2019 Q2 Pipeline Table)|date=2019|website=[[Company:Takeda Pharmaceutical Company|Takeda Pharmaceutical Company]]|access-date=9 December 2019|archive-date=6 November 2019|archive-url=https://web.archive.org/web/20191106132837/https://www.takeda.com/siteassets/system/what-we-do/research-and-development-rd-in-takeda/our-pipeline/pipeline_en_2019_q2.pdf|url-status=live}}</ref> In 2020 the phase 2b trials were finished.<ref>{{cite web |title=HilleVax Pipeline |url=https://www.hillevax.com/pipeline.html |website=Hillevax Pipeline |access-date=1 October 2021 |archive-date=1 October 2021 |archive-url=https://web.archive.org/web/20211001201039/https://www.hillevax.com/pipeline.html |url-status=live }}</ref><ref>{{cite journal |last1=Sherwood |first1=J |last2=Mendelman |first2=PM |last3=Lloyd |first3=E |last4=Liu |first4=M |last5=Boslego |first5=J |last6=Borkowski |first6=A |last7=Jackson |first7=A |last8=Faix |first8=D |last9=US Navy study |first9=team. |title=Efficacy of an intramuscular bivalent norovirus GI.1/GII.4 virus-like particle vaccine candidate in healthy US adults. |journal=Vaccine |date=22 September 2020 |volume=38 |issue=41 |pages=6442–6449 |doi=10.1016/j.vaccine.2020.07.069 |pmid=32878708 |doi-access=free }}</ref> The vaccine relies on using a [[Biology:Virus-like particle|virus-like particle]] that is made of the norovirus capsid proteins in order to mimic the external structure of the virus. Since there is no RNA in this particle, it is incapable of reproducing and cannot cause an infection.<ref name="Norovac"/>

=== Persistence ===
The norovirus can survive for long periods outside a human host depending on the surface and temperature conditions:  it can survive for weeks on hard and soft surfaces,<ref>{{cite web |url=http://www.webmd.com/cold-and-flu/features/how-to-stay-well-when-everyone-else-is-sick |title=How To Stay Well (When Everyone Else Is Sick) |publisher=Webmd.com |access-date=2017-01-28 |url-status=dead |archive-url=https://web.archive.org/web/20140103204322/http://www.webmd.com/cold-and-flu/features/how-to-stay-well-when-everyone-else-is-sick |archive-date=2014-01-03 }}</ref> and it can survive for months, maybe even years in contaminated still water.<ref>{{cite web| url=http://blogs.scientificamerican.com/artful-amoeba/2012/01/17/misery-inducing-norovirus-can-survive-for-months-perhaps-years-in-drinking-water/| title=Misery-inducing Norovirus Can Survive for Months—Perhaps Years—in Drinking Water| vauthors=Frazer J| date=January 17, 2012| website=Scientific American| access-date=February 27, 2012| archive-date=March 7, 2012| archive-url=https://web.archive.org/web/20120307190724/http://blogs.scientificamerican.com/artful-amoeba/2012/01/17/misery-inducing-norovirus-can-survive-for-months-perhaps-years-in-drinking-water/| url-status=live}}</ref> A 2006 study found the virus remained on surfaces used for food preparation seven days after contamination.<ref>{{cite journal |vauthors=D'Souza DH, Sair A, Williams K, Papafragkou E, Jean J, Moore C, Jaykus L | title = Persistence of caliciviruses on environmental surfaces and their transfer to food | journal = International Journal of Food Microbiology | volume = 108 | issue = 1 | pages = 84–91 | year = 2006 | pmid = 16473426 | doi = 10.1016/j.ijfoodmicro.2005.10.024 }}</ref>

=== Detection in food ===
Routine protocols to detect norovirus in clams and oysters by [[Biology:Reverse transcription polymerase chain reaction|reverse transcription polymerase chain reaction]] are being employed by governmental laboratories such as the [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) in the US.<ref name="pmid10804149">{{cite journal |vauthors=Shieh Y, Monroe SS, Fankhauser RL, Langlois GW, Burkhardt W, Baric RS | title = Detection of Norwalk-like virus in shellfish implicated in illness | journal = J. Infect. Dis. | volume = 181 | issue = Suppl 2 | pages = S360–6 | year = 2000 | pmid = 10804149 | doi = 10.1086/315578 | doi-access = free }}</ref>

== Treatment ==
There is no specific medicine to treat people with norovirus illness. Norovirus infection cannot be treated with antibiotics because it is a virus. Treatments aim to avoid complications by measures such as the management of dehydration caused by fluid loss in vomiting and diarrhea,<ref name=CDC2017Tx/> and to mitigate symptoms using antiemetics and antidiarrheals.<ref>{{cite web|url=http://www.merckmanuals.com/home/digestive_disorders/gastroenteritis/travelers_diarrhea.html|title=Traveler's Diarrhea|work=Merck Manuals Consumer Version|access-date=21 February 2016|archive-date=28 February 2015|archive-url=https://web.archive.org/web/20150228230806/http://www.merckmanuals.com/home/digestive_disorders/gastroenteritis/travelers_diarrhea.html|url-status=live}}</ref>

== Epidemiology ==
[[File:Reports by Month of Norovirus.svg|thumb|300px|Annual Trend in Reports of Norovirus Infection in England and Wales (2000–2011). Source: HPA]]
[[File:Norovirus Cases per Year.png|thumb|300px|Laboratory reports of norovirus infections in England and Wales 2000–2012. Source: HPA, NB Testing methods changed in 2007.<ref>{{cite news|url=https://www.telegraph.co.uk/health/healthnews/9698039/Winter-vomiting-bug-cases-up-40-per-cent-Health-Protection-Agency.html|archive-url=https://web.archive.org/web/20121124173337/http://www.telegraph.co.uk/health/healthnews/9698039/Winter-vomiting-bug-cases-up-40-per-cent-Health-Protection-Agency.html|url-status=dead|archive-date=November 24, 2012|title=Winter vomiting bug cases up 40 percent: Health Protection Agency|date=24 November 2012|work=Telegraph.co.uk|access-date=21 February 2016|last1=Smith|first1=Rebecca | name-list-style = vanc }}</ref>]]

Norovirus causes about 18% of all cases of acute gastroenteritis worldwide. It is relatively common in developed countries and in low-mortality developing countries (20% and 19% respectively) compared to high-mortality developing countries (14%). Proportionately it causes more illness in people in the community or in hospital outpatients (24% and 20% respectively) as compared with hospital inpatients (17%) in whom other causes are more common.<ref name=FERG>{{cite journal |vauthors=Ahmed SM, Hall AJ, Robinson AE, etal |title=Global prevalence of norovirus in cases of gastroenteritis: a systematic review and meta-analysis |journal=Lancet Infect Dis |volume=14 |issue=8 |pages=725–30 |date=August 2014 |pmid=24981041 |doi=10.1016/S1473-3099(14)70767-4 |pmc=8006533 |url=https://zenodo.org/record/1260252 |access-date=2019-06-24 |archive-date=2020-04-03 |archive-url=https://web.archive.org/web/20200403224838/https://zenodo.org/record/1260252 |url-status=live }}</ref>

Age and emergence of new norovirus strains do not appear to affect the proportion of gastroenteritis attributable to norovirus.<ref name=FERG/>

Norovirus is a common cause of epidemics of gastroenteritis on [[Engineering:Cruise ship|cruise ship]]s. The CDC has put through its Vessel Sanitation Program records and investigates outbreaks of gastrointestinal illness&nbsp;– mostly caused by norovirus&nbsp;– on cruise ships with both a US and foreign itinerary;<ref name=CDC>{{cite web | author=CDC VSP | url=https://www.cdc.gov/nceh/vsp/surv/gilist.htm | title=Vessel Sanitation Program – Outbreak Updates for International Cruise Ships | publisher=Centers for Disease Control and Prevention | access-date=9 May 2016 | archive-date=10 May 2016 | archive-url=https://web.archive.org/web/20160510060625/http://www.cdc.gov/nceh/vsp/surv/gilist.htm | url-status=live }}</ref> there were 12 in 2015, and 10 from 1&nbsp; January to 9&nbsp; May 2016. An outbreak may affect over 25% of passengers, and a smaller proportion of crew members.<ref>{{cite web |url=https://www.cdc.gov/nceh/vsp/surv/outbreak/2016/april16_balmoral.htm |title=CDC – Vessel Sanitation Program – Balmoral, April 16, 2016 |website=Cdc.gov |access-date=9 May 2016 |archive-date=14 May 2016 |archive-url=https://web.archive.org/web/20160514100616/http://www.cdc.gov/nceh/vsp/surv/outbreak/2016/april16_balmoral.htm |url-status=live }}</ref>

== Human genetics ==
Epidemiological studies have shown that individuals with different ABO(H) (histo-blood group) phenotypes are infected with NoV strains in a [[Biology:Genotype|genotype]]-specific manner.<ref name="Infect"/><ref name="pmid20053852">{{cite journal |vauthors=Le Guyader FS, Krol J, Ambert-Balay K, Ruvoen-Clouet N, Desaubliaux B, Parnaudeau S, Le Saux JC, Ponge A, Pothier P, Atmar RL, Le Pendu J |title=Comprehensive analysis of a norovirus-associated gastroenteritis outbreak, from the environment to the consumer |journal=Journal of Clinical Microbiology |volume=48 |issue=3 |pages=915–920 |date=March 2010 |pmid=20053852 |pmc=2832421 |doi=10.1128/JCM.01664-09}}</ref> GII.4 includes global epidemic strains and binds to more histo-blood group antigens than other genogroups.<ref name="Infect" /> [[Biology:FUT2|FUT2]] [[Biology:Fucosyltransferase|fucosyltransferase]] transfers a [[Chemistry:Fucose|fucose]] sugar to the end of the ABO(H) precursor in gastrointestinal cells and saliva glands. The ABH-antigen produced is thought to act as a receptor for human norovirus: A non-functional [[Biology:Fucosyltransferase|fucosyltransferase]] FUT2 provides high protection from the most common norovirus strain, GII.4.<ref>{{cite journal |vauthors=Carlsson B, Kindberg E, Buesa J, Rydell GE, Lidón MF, Montava R, Abu Mallouh R, Grahn A, Rodríguez-Díaz J, Bellido J, Arnedo A, Larson G, Svensson L |title=The G428A nonsense mutation in FUT2 provides strong but not absolute protection against symptomatic GII.4 norovirus infection |journal=PLOS ONE |volume=4 |issue=5 |page=e5593 |date=May 2009 |pmid=19440360 |pmc=2680586 |doi=10.1371/journal.pone.0005593 |bibcode=2009PLoSO...4.5593C|doi-access=free }}</ref>

Homozygous carriers of any nonsense mutation in the FUT2 gene are called ''non-secretors'', as no ABH-antigen is produced. Approximately 20% of [[Biology:Caucasian race|Caucasians]] are non-secretors due to G428A and C571T nonsense mutations in FUT2 and therefore have strong&nbsp;– although not absolute&nbsp;– protection from the norovirus GII.4.<ref name=Rydell2011>{{cite journal |vauthors=Rydell GE, Kindberg E, Larson G, Svensson L |title=Susceptibility to winter vomiting disease: A sweet matter |journal=Rev. Med. Virol. |volume=21 |issue=6 |pages=370–382 |date=November 2011 |pmid=22025362 |doi=10.1002/rmv.704|s2cid=6679013 }}</ref> Non-secretors can still produce ABH antigens in erythrocytes, as the precursor is formed by FUT1.<ref name="Infect">{{cite journal |author=Shirato H |title=Norovirus and histo-blood group antigens |journal=Jpn. J. Infect. Dis. |volume=64 |issue=2 |pages=95–103 |year=2011 |doi=10.7883/yoken.64.95 |pmid=21519121|doi-access=free }}</ref> Some norovirus genotypes (GI.3) can infect non-secretors.<ref name=Nordgren2010>{{cite journal |vauthors=Nordgren J, Kindberg E, Lindgren PE, Matussek A, Svensson L |title=Norovirus gastroenteritis outbreak with a secretor-independent susceptibility pattern, Sweden |journal=Emerg. Infect. Dis. |volume=16 |issue=1 |pages=81–87 |date=January 2010 |pmid=20031047 |doi=10.3201/eid1601.090633 |pmc=2874438}}</ref>

== History ==
The norovirus was originally named the "Norwalk agent" after Norwalk, Ohio, in the United States, where an outbreak of acute gastroenteritis occurred among children at Bronson Elementary School in November 1968 (although an outbreak had already been discovered in 1936 in Roskilde, Denmark, where it is commonly known as "Roskilde syge" or "Roskilde illness"). In 1972, electron microscopy on stored human stool samples identified a virus, which was given the name "Norwalk virus". Numerous outbreaks with similar symptoms have been reported since. The [[Biology:Cloning|cloning]] and sequencing of the Norwalk virus genome showed that these viruses have a genomic organization consistent with viruses belonging to the family [[Biology:Caliciviridae|Caliciviridae]].<ref name="pmid9015097">{{cite book | author = Kapikian AZ  | title = Viral Gastroenteritis | chapter = Overview of viral gastroenteritis | series = Archives of Virology | volume = 12 | pages = 7–19 | year = 1996 | pmid = 9015097 | doi =  10.1007/978-3-7091-6553-9_2| isbn = 978-3-211-82875-5 | doi-access = free }}</ref> The name "norovirus" (''Norovirus'' for the genus) was approved by the [[Organization:International Committee on Taxonomy of Viruses|International Committee on Taxonomy of Viruses]] (ICTV) in 2002.<ref>ICTVdB Management (2006). 00.012.0.03. Norovirus. In: ICTVdB—The Universal Virus Database, version 4. Büchen-Osmond, C. (Ed), Columbia University, New York, USA</ref> In 2011, however, a press release and a newsletter<ref>{{cite web|title=2011 ICTV Newsletter #9, November 2011|url=http://talk.ictvonline.org/files/ictv_documents/m/newsletters/4069.aspx|publisher=ICTV|date=November 14, 2011|access-date=December 23, 2012|archive-date=July 30, 2012|archive-url=https://web.archive.org/web/20120730225245/http://talk.ictvonline.org/files/ictv_documents/m/newsletters/4069.aspx|url-status=dead}}</ref> were published by ICTV, which strongly encouraged the media, national health authorities, and the scientific community to use the virus name Norwalk virus, rather than the genus name Norovirus when referring to outbreaks of the disease. This was also a public response by ICTV to the request from an individual in Japan to rename the Norovirus genus because of the possibility of negative associations for people in Japan and elsewhere who have the family name "Noro". Before this position of ICTV was made public, ICTV consulted widely with members of the Caliciviridae Study Group and carefully discussed the case.{{cn|date=August 2022}}

In addition to "Norwalk agent" and "Norwalk virus", the virus has also been called "Norwalk-like virus", "small, round-structured viruses" (SRSVs), Spencer flu, and "Snow Mountain virus".<ref name="pmid3036438">{{cite book | author = Appleton H | title = Ciba Foundation Symposium 128 – Novel Diarrhoea Viruses | chapter = Small Round Viruses: Classification and Role in Food-Borne Infections | series = Novartis Foundation Symposia | volume = 128 | pages = 108–25 | year = 1987 | pmid = 3036438 | doi =  10.1002/9780470513460.ch7 | isbn = 9780470513460 }}</ref> Common names of the illness caused by noroviruses still in use include "Roskilde illness", "winter vomiting disease",<ref>{{cite journal |vauthors=Parashar U, Quiroz ES, Mounts AW, Monroe SS, Fankhauser RL, Ando T, Noel JS, Bulens SN, Beard SR, Li JF, Bresee JS, Glass RI |year=2001 |title="Norwalk-Like Viruses". Public Health Consequences and Outbreak Management |journal= MMWR. Recommendations and Reports |volume=50 |issue=RR-9 |pages=1–18 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5009a1.htm |pmid=15580799 |access-date=2017-09-10 |archive-date=2017-06-06 |archive-url=https://web.archive.org/web/20170606134739/https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5009a1.htm |url-status=live }}</ref> "winter vomiting bug",<ref name="bbc sussex">{{cite news | url=https://www.bbc.co.uk/news/uk-england-kent-16509830 | title=Norovirus shuts wards and unit at three Sussex hospitals | work=BBC News | date=January 11, 2012 | access-date=January 20, 2012 | archive-date=January 15, 2012 | archive-url=https://web.archive.org/web/20120115055919/http://www.bbc.co.uk/news/uk-england-kent-16509830 | url-status=live }}</ref><ref name="bbc norfolk">{{cite news | url=https://www.bbc.co.uk/news/uk-england-norfolk-16531668 | title=Norovirus at Norfolk hospitals: Disruption continues | work=BBC News | date=January 12, 2012 | access-date=January 20, 2012 | archive-date=January 20, 2012 | archive-url=https://web.archive.org/web/20120120172326/http://www.bbc.co.uk/news/uk-england-norfolk-16531668 | url-status=live }}</ref> "viral gastroenteritis", and "acute nonbacterial gastroenteritis".<ref name="pmid16968608"/>

== See also ==
* [[Biology:Norovirus cis-acting replication element|Norovirus cis-acting replication element]]
* [[Biology:Norovirus GII.4 Sydney|Norovirus GII.4 Sydney]]
{{spaces}}

== References ==
{{Reflist}}

== External links ==
* [https://www.nhs.uk/conditions/norovirus/ Norovirus (vomiting bug) NHS] Norovirus infections
* [https://www.rivm.nl/en/noronet Global network and database noroviruses]
* [https://web.archive.org/web/20170511101027/https://www.cdc.gov/nceh/vsp/pub/FAQ/faq.pdf CDC Viral Gastroenteritis FAQs]: Center for Disease Control and Prevention of Food Illness Fact Sheet
* [https://www.cdc.gov/hai/pdfs/norovirus/229110-ANoroCaseFactSheet508.pdf "Norovirus in Healthcare Facilities Fact Sheet"], CDC, released December 21, 2006
* [https://web.archive.org/web/20171122001545/https://www.cdc.gov/nceh/vsp/pub/CruisingTips/healthycruising.pdf tips from CDC for cruise vacationers]
* [http://www.viprbrc.org/brc/home.do?decorator=calici Virus Pathogen Database and Analysis Resource (ViPR): Caliciviridae] {{Webarchive|url=https://web.archive.org/web/20190913003110/https://www.viprbrc.org/brc/home.spg?decorator=calici |date=2019-09-13 }}
* [http://www.pdbe.org/emsearch/noro*%20AND%20comp_type:virus 3D macromolecular structures of Noroviruses from the EM Data Bank (EMDB)]
* [http://viralzone.expasy.org/all_by_species/194.html Viralzone: Norovirus]
* [https://ictv.global/report/chapter/caliciviridae/caliciviridae ICTV Report: ''Caliciviridae'']

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{{Baltimore classification}}

[[Category:Norovirus| ]]
[[Category:Virus genera]]
[[Category:Wikipedia medicine articles ready to translate]]

{{Sourceattribution|Norovirus}}