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==Natural History, Complications and Prognosis==
*Incubation 24-48 hours
*Onset can be gradual or abrupt
*[[Diarrhea]] is moderate volume, noninflammatory, mechanism is unknown (no detectable [[enterotoxin]])
*Lasts 48-72 hours with full and rapid recovery
== Signs and symptoms ==
The disease is usually [[self-limiting]], and characterised by [[nausea]], vomiting, [[diarrhea]], and abdominal pain. General lethargy, weakness, muscle aches, headache, and low-grade fever may occur. Symptoms may persist for several days and may become life-threatening in the young, the elderly, and the immune-compromised if [[dehydration]] is ignored or not treated.<ref name="pmid16968608">{{cite journal
|author=Goodgame R
|title=Norovirus gastroenteritis
|journal=Curr Gastroenterol Rep
|volume=8
|issue=5
|pages=401–8
|year=2006
|pmid=16968608
|doi=10.1007/s11894-006-0026-4
|issn=
}}</ref>
==Diagnosis ==
Specific diagnosis of norovirus is routinely made by [[polymerase chain reaction]] (PCR) [[assay]]s or [[Real-time polymerase chain reaction|real-time PCR]] assays, which give results within a few hours. These assays are very sensitive and can detect concentrations as low as 10 virus particles.<ref name="pmid17175887">{{cite journal
|author=Marshall JA, Bruggink LD
|title=Laboratory diagnosis of norovirus
|journal=Clin. Lab.
|volume=52
|issue=11-12
|pages=571–81
|year=2006
|pmid=17175887
|doi=
|issn=
}}</ref>
Tests such as [[EIA]] that use [[antibody|antibodies]] against a mixture of norovirus strains are  available commercially but lack [[Specificity (tests)|specificity]] and [[Sensitivity (tests)|sensitivity]].<ref name="pmid17391396">{{cite journal
|author=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
|url=http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=1198-743X&date=2007&volume=13&issue=3&spage=341
|issn=
}}</ref>
===Physical Examination===
Noroviruses present as:
*Mild febrile illnesss with watery [[diarrhea]] or
*Severe febrile illness with [[vomiting]], [[headache]], etc.
*First symptoms are usually [[cramps]] and/or [[nausea]]
**Most have both vomiting and diarrhea but can have either
*Headache
*[[Myalgia]]s
*[[Malaise]] in about 50%
====Vital Signs====
*Temperature of 101-102
== Prevention and infection control ==
[[Hand washing]] remains an effective method to reduce the spread of norovirus [[pathogen]]s. Norovirus can be [[aerosolized]] when those stricken with the illness vomit. Surface sanitizing is recommended in areas where the Norovirus may be present on surfaces.
In health care environments, the prevention of [[nosocomial infection]]s involves routine and [[terminal cleaning]]. [[Nonflammable alcohol vapor in CO2]] systems are used in health care environments where medical electronics would be adversely affected by aerosolized chlorine or other caustic compounds.<ref name="pmid10833336">{{cite journal
|author=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 gastro-enteritis due to small roundstructured viruses
|journal=J. Hosp. Infect.
|volume=45
|issue=1
|pages=1–10
|year=2000
|pmid=10833336
|doi=10.1053/jhin.2000.0662
|url=http://linkinghub.elsevier.com/retrieve/pii/jhin.2000.0662
|issn=
}}</ref>
Ligocyte is working on a vaccine and has already started phase 1 trials.  http://www.ligocyte.com/pdf/norovirus.pdf
== Associated foods ==
Noroviruses are transmitted directly via person to person or indirectly via contaminated water and foods. A [[Centers for Disease Control and Prevention|CDC]] study of eleven outbreaks in [[New York|New York State]] lists  the suspected [[Transmission (medicine)|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
|author=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
|doi=
|url=http://cmr.asm.org/cgi/pmidlookup?view=long&pmid=8395330
|issn=
}}</ref>
[[Shellfish]] and [[salad]] ingredients are the foods most often implicated in Norwalk outbreaks. Ingestion of raw or insufficiently steamed [[clam]]s and [[oyster]]s poses a high risk for infection with the Norwalk virus. Foods other than shellfish are contaminated by ill food handlers.<ref name="pmid11479930">{{cite journal
|author=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
|issn=
}}</ref>
}}</ref>


Revision as of 16:50, 17 December 2012

style="background:#Template:Taxobox colour;"|Norovirus
Transmission electron micrograph of noroviruses. The bar = 50 nm
Transmission electron micrograph of noroviruses. The bar = 50 nm
style="background:#Template:Taxobox colour;" | Virus classification
Group: Group IV ((+)ssRNA)
Family: Caliciviridae
Genus: Norovirus

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Overview

Norovirus (was "Norwalk-like viruses")[1], an RNA virus of the Caliciviridae taxonomic family, causes approximately 90% of epidemic non-bacterial outbreaks of gastroenteritis around the world,[2][3] and is responsible for 50% of all foodborne outbreaks of gastroenteritis in the US.[4] Norovirus affects people of all ages. The viruses are transmitted by faecally contaminated food or water and by person-to-person contact.[5]

After infection, immunity to norovirus is not complete nor long-lasting.[6] There is an inherited predisposition to infection and people whose blood type can be detected in their saliva are more often infected.[2]

Outbreaks of norovirus disease often occur in closed or semi-closed communities, such as long-term care facilities, hospitals, prisons, dormitories, and cruise ships where once the virus has been introduced, the infection spreads very rapidly by either person-to-person transmission or through contaminated food.[7] Many norovirus outbreaks have been traced to food that was handled by one infected person.[8]

Norovirus is rapidly killed by chlorine-based disinfectants, but because the virus particle does not have a lipid envelope, it is less susceptible to alcohols and detergents.[9]

There are different genogroups of norovirus and the majority of noroviruses that infect humans are classified into genogroup G1 and G2.[10]

Historical Perspective

Originally, norovirus was named after Norwalk, Ohio, where an outbreak of acute gastroenteritis occurred among children at an elementary school in November 1968. In 1972, immune electron microscopy on stored stool samples identified a virus, which was given the name Norwalk virus. Numerous outbreaks with similar symptoms have been reported since. The cloning and sequencing of the Norwalk virus genome showed that these viruses have a genomic organization consistent with viruses belonging to the family Caliciviridae.[11] The name norovirus (Norovirus for the genus) was approved by the International Committee on Taxonomy of Viruses in 2002. [12]

Common names of the illness caused by noroviruses are winter vomiting disease, viral gastroenteritis and acute non-bacterial gastroenteritis[5], also colloquially known as "stomach flu" (a broad name which can also refer to gastric inflammation caused by other viruses and bacteria).

Some previously used names which can be used for PubMed and other internet searches are Norwalk virus, Norwalk-like virus, SRSVs (Small Round Structured Viruses), Sapporo virus and Snow Mountain.[13]

Relative frequency of disease

Only the common cold is reported more frequently than viral gastroenteritis as a cause of illness in the U.S. Although viral gastroenteritis is caused by a number of viruses, it is estimated that noroviruses are responsible for about 1/3 of the cases over the 6-to-24-month age group. In developing countries the percentage of individuals who have developed immunity at an early age is very high. In the U.S. the percentage increases gradually with age, reaching 50% in the population over 18 years of age. Immunity, however, is not permanent and reinfection can occur. Recent studies demonstrate that blood types B and AB confer partial protection against symptomatic infection.[14][15]

Course of disease and complications

Norovirus causes acute gastroenteritis that develops between 24 and 48 hours after exposure with a median of 33-36 hours, and lasts for 24-60 hours.[3] Severe illness is rare: although people are frequently treated in emergency rooms/A&E, they are rarely admitted to the hospital. The number of deaths from norovirus in the US is estimated to be around 300 each year, with most of these occurring in the very young, elderly and persons with weakened immune systems.

Detection of norovirus in foods

Routine protocols to detect norovirus (norovirus RNA) in clams and oysters by RT-PCR (reverse transcription polymerase chain reaction) are being employed by governmental laboratories such as the FDA in the USA. However, routine methods to detect the virus on other food items are not readily available due to the variable nature of different food items affecting concentration and extraction of the virus and presence of factors that make PCR (Polymerase chain reaction) analysis techniques ineffective.[16]

Outbreaks

Microbiology

Classification

Transmission electron micrograph of Norovirus particles in faeces

Noroviruses (NoV) are a genetically diverse group of single stranded RNA, nonenveloped viruses belonging to the Caliciviridae family.[18] According to the International Committee on Taxonomy of Virus, the genus Norovirus has one species which is called "Norwalk virus" and assigned the abbreviation "NV". Serotypes, strains and isolates include:[1]

  • Desert Shield virus [U04469] (Hu/NLV/DSV395/1990/SR)
  • Lordsdale virus [X86557] (Hu/NLV/LD/1993/UK)
  • Mexico virus [U22498] (Hu/NLV/MX/1989/MX)
  • Norwalk virus [M87661] (Hu/NLV/NV/1968/US)
  • Hawaii virus [U07611] (Hu/NLV/HV/1971/US)
  • Snow Mountain virus [L23831] (Hu/NLV/SMV/1976/US)
  • Southampton virus [L07418] (Hu/NLV/SHV/1991/UK)

"Noroviruses are a major cause of acute gastroenteritis worldwide, often causing explosive outbreaks in institutions. They are highly contagious, with an inoculum of as few as ten particles being able to cause infection. Transmission occurs through ingesting contaminated food and water and by person-to-person spread. Transmission is predominantly faecal-oral but may be airborne due to aerosolisation of vomitus [...] 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."[18]

Noroviruses can genetically be classified into 5 different genogroups (GI, GII, GIII, GIV, and GV) which can be further divided into different genetic clusters 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.[19]

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. Recent examples include US95/96-US strain, associated with global outbreaks in the mid- to late-90s, Farmington Hills virus associated with outbreaks in Europe and the United States in 2002 and in 2004 Hunter virus was associated with outbreaks in Europe, Japan and Australasia. In 2006 there was another large increase in NoV infection around the globe.[20] In December, 2007 there was an outbreak at a country club in northern California where around 80-100 people were infected. Two new GII.4 variants caused around 80% of those Norovirus associated outbreaks and they have been termed 2006a and 2006b. Recent reports have shown a link between blood group and susceptibility to infection by norovirus.[21][22][23]

Virus structure

Noroviruses contain a positive-sense RNA genome of approximately 7.5 kbp, encoding a major structural protein (VP1) of about 58~60 kDa and a minor capsid protein (VP2).[24] The virus particles demonstrate an amorphous surface structure when visualized using electron microscopy and are between 27-38 nm in size.[25]

References

  1. ↑ 1.0 1.1 ICTVdB Family 00.012. Caliciviridae
  2. ↑ 2.0 2.1 Lindesmith L, Moe C, Marionneau S; et al. (2003). "Human susceptibility and resistance to Norwalk virus infection". Nat. Med. 9 (5): 548–53. doi:10.1038/nm860. PMID 12692541.
  3. ↑ 3.0 3.1 "Norovirus: Technical Fact Sheet". National Center for Infectious Diseases, CDC.
  4. ↑ Widdowson MA, Sulka A, Bulens SN; et al. (2005). "Norovirus and foodborne disease, United States, 1991-2000". Emerging Infect. Dis. 11 (1): 95–102. PMID 15705329.
  5. ↑ 5.0 5.1 Goodgame R (2006). "Norovirus gastroenteritis". Curr Gastroenterol Rep. 8 (5): 401–8. doi:10.1007/s11894-006-0026-4. PMID 16968608.
  6. ↑ Lindesmith L, Moe C, Lependu J, Frelinger JA, Treanor J, Baric RS (2005). "Cellular and humoral immunity following Snow Mountain virus challenge". J. Virol. 79 (5): 2900–9. doi:10.1128/JVI.79.5.2900-2909.2005. PMID 15709009.
  7. ↑ Noda M, Fukuda S, Nishio O (2007). "Statistical analysis of attack rate in norovirus foodborne outbreaks". Int J Food Microbiol: 216. doi:10.1016/j.ijfoodmicro.2007.11.073. PMID 18177970.
  8. ↑ Koopmans M, Duizer E (2004). "Foodborne viruses: an emerging problem". Int. J. Food Microbiol. 90 (1): 23–41. doi:10.1016/S0168-1605(03)00169-7. PMID 14672828.
  9. ↑ Jimenez L, Chiang M (2006). "Virucidal activity of a quaternary ammonium compound disinfectant against feline calicivirus: a surrogate for norovirus". Am J Infect Control. 34 (5): 269–73. doi:10.1016/j.ajic.2005.11.009. PMID 16765204.
  10. ↑ Vinjé J, Green J, Lewis DC, Gallimore CI, Brown DW, Koopmans MP (2000). "Genetic polymorphism across regions of the three open reading frames of "Norwalk-like viruses"". Arch. Virol. 145 (2): 223–41. PMID 10752550.
  11. ↑ Kapikian AZ (1996). "Overview of viral gastroenteritis". Arch. Virol. Suppl. 12: 7–19. PMID 9015097.
  12. ↑ 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
  13. ↑ Appleton H (1987). "Small round viruses: classification and role in food-borne infections". Ciba Found. Symp. 128: 108–25. PMID 3036438.
  14. ↑ "Norwalk Virus Infection and Disease Is Associated with ABO Histo-Blood Group Type". The Journal of Infectious Diseases. 2002. Retrieved 2007-02-05.
  15. ↑ "Binding of Norwalk Virus-Like Particles to ABH Histo-Blood Group Antigens Is Blocked by Antisera from Infected Human Volunteers or Experimentally Vaccinated Mice". Journal of Virology. 2002. Retrieved 2007-02-05.
  16. ↑ Shieh Y, Monroe SS, Fankhauser RL, Langlois GW, Burkhardt W, Baric RS (2000). "Detection of norwalk-like virus in shellfish implicated in illness". J. Infect. Dis. 181 Suppl 2: S360–6. PMID 10804149.
  17. ↑ "Investigation Update on the Carnival Liberty". Centers for Disease Control and Prevention (CDC). United States Department of Health and Human Services. 25 November 2006. Check date values in: |date= (help)
  18. ↑ 18.0 18.1 Department of Health and Ageing Norovirus laboratory case definition
  19. ↑ Ramirez S, Giammanco GM, De Grazia S, Colomba C, Martella V, Arista S (2008). "Genotyping of GII.4 and GIIb norovirus RT-PCR amplicons by RFLP analysis". J. Virol. Methods. 147 (2): 250–6. doi:10.1016/j.jviromet.2007.09.005. PMID 17953996.
  20. ↑ Tu ET, Bull RA, Greening GE, Hewitt J, Lyon MJ, Marshall JA, McIver CJ, Rawlinson WD, White PA (2008). "Epidemics of gastroenteritis during 2006 were associated with the spread of norovirus GII.4 variants 2006a and 2006b". Clin. Infect. Dis. 46 (3): 413–20. doi:10.1086/525259. PMID 18177226.
  21. ↑ Huang P, Farkas T, Marionneau S, Zhong W, Ruvoën-Clouet N, Morrow AL, Altaye M, Pickering LK, Newburg DS, LePendu J, Jiang X (2003). "Noroviruses bind to human ABO, Lewis, and secretor histo-blood group antigens: identification of 4 distinct strain-specific patterns". J. Infect. Dis. 188 (1): 19–31. doi:10.1086/375742. PMID 12825167.
  22. ↑ Huang P, Farkas T, Zhong W, Tan M, Thornton S, Morrow AL, Jiang X (2005). "Norovirus and histo-blood group antigens: demonstration of a wide spectrum of strain specificities and classification of two major binding groups among multiple binding patterns". J. Virol. 79 (11): 6714–22. doi:10.1128/JVI.79.11.6714-6722.2005. PMID 15890909.
  23. ↑ Rockx BH, Vennema H, Hoebe CJ, Duizer E, Koopmans MP (2005). "Association of histo-blood group antigens and susceptibility to norovirus infections". J. Infect. Dis. 191 (5): 749–54. doi:10.1086/427779. PMID 15688291.
  24. ↑ Clarke IN, Lambden PR (2000). "Organization and expression of calicivirus genes". J. Infect. Dis. 181 Suppl 2: S309–16. PMID 10804143.
  25. ↑ Prasad BV, Crawford S, Lawton JA, Pesavento J, Hardy M, Estes MK (2001). "Structural studies on gastroenteritis viruses". Novartis Found. Symp. 238: 26–37, discussion 37–46. PMID 11444031.

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