Human noroviruses

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Norwalk virus
Norwalk Caspid.jpg

X-ray crystal structure of the Norwalk virus capsid

Systematics
Classification : Viruses
Area : Riboviria
Empire : Orthornavirae
Phylum : Pisuviricota
Class : Pisoniviricetes
Order : Picornavirales
Family : Caliciviridae
Genre : Norovirus
Type : Norwalk virus
Taxonomic characteristics
Baltimore : Group 4
Symmetry : icosahedral
Cover : no
Scientific name
Norwalk virus
Short name
NwV
Left
NCBI  Taxonomy: 142786
ICTV Taxon History: 201852806
ICTVdB Virus Code : 00.012.0.03
Human noroviruses in TEM after negative contrasting (marking corresponds to 50 nm)

The species Norwalk virus ( human norovirus , en. Norwalk virus , abbreviated NwV , also NWV or NV) of the human pathogenic noroviruses comprises non-enveloped , single-stranded RNA viruses with positive polarity from the family Caliciviridae , genus Norovirus . Noro - is an artificially formed prefix from Nor walk, which became the official taxonomic name in 2004 . In addition to numerous other viruses, the highly contagious (highly contagious) noroviruses cause viral gastroenteritis (viral diarrhea, also known colloquially as gastrointestinal flu) in humans . They are in addition to the rotavirus from the family of Reoviridae for the majority of non- bacterial induced diarrhea responsible in humans. Proof of human noroviruses must be reported by name in accordance with Section 7 of the Infection Protection Act in Germany .

Initial description

The Norwalk virus was the first human norovirus to be characterized morphologically in stool samples from a viral gastroenteritis outbreak from 1968 in Norwalk , Ohio , by immunoelectron microscopy in 1972 . In order to be able to prove the connection between the virus found and a gastroenteritis disease, purified stool ultrafiltrate (obtained from human feces of sick patients) was administered orally to volunteers who then also got sick. As of November 2018, this is the only species of the genus Norovirus confirmed by the International Committee on Taxonomy of Viruses (ICTV) .

virology

morphology

Noroviruses are 35 to 39 nm in diameter  . In the electron microscope image, they have a very blurred, round structure. You have an icosahedral (twenty-area) capsid ( T = 3 symmetry ), and about 7.3 to 7.7  kB large genome . Like most single-stranded RNA viruses, noroviruses are very variable in their genome sequence, which is why numerous different subtypes and isolates are known. They show antigen drift and also a seasonal antigen shift due to genetic recombination between different norovirus strains.

classification

For the time being, three human pathogenic norovirus species, namely the species Norwalk virus and the rarer species human norovirus Alphatron and human norovirus Saitama , are distinguished within the genus norovirus . The species Norwalk virus - the only species of the genus confirmed by ICTV as of November 2018 - is currently divided into 7 subtypes, four of these subtypes, based on the amino acid sequence of the VP1 capsid protein, in turn to very extensive genogroups 1–4 (GGI to GGIV) can be summarized. Currently, genotype GII (in particular GII.4) is primarily responsible for infections, followed by GI and GIV. The isolates and subtypes are named and classified according to an international scheme:

  • Species Norwalk virus ( Humanes Norovirus , en. Norwalk virus )
  • Subtype Norwalk virus (Hu / NV / NV / 1968 / US)
  • Subtype Desert Shield Virus (Hu / NV / DSV395 / 1990 / SR)
  • Hawaiian virus subtype (Hu / NV / HV / 1971 / US)
  • Subtype Lordsdale virus (Hu / NV / LD / 1993 / UK)
  • Mexico virus subtype (Hu / NV / MX / 1989 / MX)
  • Subtype Snow Mountain Virus (Hu / NV / SMV / 1976 / US)
  • Subtype Southampton virus (Hu / NV / SHV / 1991 / UK)

Other norovirus subtypes have been discovered in other mammals, such as pigs, cattle, sheep, cats, and rodents. Most of the molecular biological studies on norovirus are carried out on the murine norovirus.

Epidemiology

Noroviruses are common worldwide. Every year there are around 685 million norovirus cases, which make up 18% of the world's acute gastroenteritis cases.

Endemic norovirus infections have been v. a. detected in hospitals (often in geriatric wards ) and old people's or nursing homes . In Switzerland, it is estimated that 400,000 to 600,000 infections from these viruses are expected each year. In Germany, 89,322 cases confirmed by laboratory diagnostics (reference definition since 2011) were transmitted to the Robert Koch Institute for the reporting year 2013 . 19% of these were registered as part of outbreaks, of which around 2/3 were in hospitals or old people's and nursing homes, 1/7 in kindergartens and day-care centers. Up until the 1990s, norovirus diagnostics were reserved for a few specialized laboratories. Since commercial immuno tests have become available, a specific infection with noroviruses can be detected more frequently.

In autumn 2012, almost eleven thousand people in eastern Germany were infected with the norovirus through strawberries imported from China. The 2012 norovirus outbreak attracted a lot of media attention.

Norovirus infections occur seasonally in Central Europe from November to March, the activity in the summer months is only about a tenth as high as in winter. The immunity against a virus strain acquired through an infection lasts longer than until the next season, so that the pathogen is exposed to high selection pressure from herd immunity . He avoids this through gene drift and shift.

Epidemiological studies have shown that people were infected by specific NoV genotypes depending on the histo blood group antigens they formed. Genotype GII.4, which causes the most infections (currently the most widespread genotype, epidemic), binds more different HBGAs than any other genotype. People who have a non-functional fucosyltransferase due to a homozygotic mutation, so-called non-secretors , do not produce any ABH antigen and are significantly less susceptible to a norovirus infection (but do not have absolute protection). About 20% of all Europids are non-secretors.

transmission

With a minimal infectious dose of only 10 to 100 virus particles, the noroviruses are extremely contagious . The transmission takes place from person to person via a smear or droplet infection . The viruses are chair excreted or vomit and go to fecal - oral route, by inhalation of the resulting in vomiting aerosol or via contaminated hands to the mucous membranes of the contact person. Viruses can also be infected via contaminated objects. It is also possible to absorb the pathogens through contaminated water; this can be done through food and drinks prepared with contaminated water, but also through drinking contaminated tap water. Human noroviruses have the resistance to environmental influences that is typical for non-enveloped viruses . They can survive in water for several days to weeks at 25 ° C, they survive temperature fluctuations from −20 to +60  ° C and showed their "ability to survive" on a contaminated carpet even after twelve days.

As a rule, the viruses are excreted by sick people during the acute illness, but also after the clinical symptoms have subsided. The peak of excretion is usually 4 days after infection, i.e. usually after the symptoms have subsided. Asymptomatic infected people can also shed viruses. In a study with intentional infection, the virus was detected in the stool a median of 4 weeks after infection. Therefore, it is very important to carefully observe the usual hygiene rules even after the illness.

The residents and the staff of all types of communal facilities are particularly at risk, as z. B. shared toilets a local outbreak is encouraged. Cruise ships have also been affected in recent years .

Viral RNA of human norovirus subtypes could be detected in stool samples from livestock, and antibodies against animal norovirus subtypes were found in asymptomatic humans. This may mean that noroviruses are zoonotic .

Course of the disease and symptoms

Acute illness

The incubation time of the disease caused by the human noroviruses in humans is approx. 10-50 hours. Symptoms of the disease develop within a few hours or days and consist primarily of gastroenteritis with sudden diarrhea and vomiting , which can lead to considerable loss of fluid (see desiccosis ). Therefore, children and the elderly are particularly at risk. Usually there is a pronounced feeling of illness with abdominal pain, nausea , headache and muscle pain .

The disease is usually short and intense and subsides after one to three days. Vomiting occurs in more than 50% of patients, with adolescents suffering more from vomiting and adults more from diarrhea.

chronic disease

In patients with a weakened immune system, e.g. B. by the variable immunodeficiency syndrome or immunosuppression after a transplant , it can lead to a chronic infection with norovirus. Norovirus can be detected in stool for several years. Patients can suffer from long-lasting diarrhea, but the infection can also be asymptomatic in phases. In severe cases, norovirus-associated enteropathy occurs , which can lead to villus atrophy and malassimilation .

Consequences and complications

Depending on the severity of the disease, the loss of water from the norovirus infection can also lead to death without treatment. Norovirus is responsible for approximately 220,000 deaths, mostly in low and middle income countries. The death rate here is 0.037% compared to a death rate of 0.005% in high-income countries. Older people aged 80 and over and children under 4 years of age are particularly affected, at 70 to 80%. Since 2001 there has been an obligation to report the disease in Germany. According to the Robert Koch Institute (RKI), the number of people who died from noroviruses in Germany was as follows:

  • 2005: 12
  • 2006: 16
  • 2007: 76
  • 2008: 67
  • 2009: 30
  • 2010: 56
  • 2011: 43
  • 2012: 47
  • 2013: 38
  • 2014: -
  • 2015: 21
  • 2016: 22
  • 2017: 36

proof

medicine

In the context of medical diagnostics , it is possible, but not always useful, to detect noroviruses in stool samples. The most frequently used, but also the most expensive method is RT-PCR (detection via reverse transcription with subsequent polymerase chain reaction ). It has a high sensitivity and specificity . Other available detection methods are ELISA (lower specificity) and electron microscopy . A virus isolation in cell culture can be obtained by addition of certain intestinal bacteria be achieved.

The detection of pathogens in the context of outbreaks is of particular importance, as these require special hygienic measures. However, not every disease is examined for the pathogen, so the number of reports does not reflect the true extent of the disease. Also due to the lack of specific therapy, the need for expensive stool diagnostics is doubted by experts if gastroenteritis due to noroviruses has already been detected in the environment. An examination for noroviruses in each individual patient is therefore medically unnecessary and not very economical if cases of disease are known in the area and the classic clinical symptoms are present.

Food

A problem for food analysis is the fact that noroviruses of genogroups I and II are host-specific in humans and a cell culture that enables reproduction has not yet been available. Therefore, extraction and concentration must always be carried out for the analysis of food. According to the official collection of methods § 64 LFGB L 00.00-147 / 2 (adoption of the identical standard DIN CEN ISO / TS 15216-2), recovery rates of 1% based on soft foods with a rough surface (such as strawberries ) are already to be assessed as acceptable. The infectivity of the virus particles is very high. In this regard, the analytical detection limit in food is very low for methodological reasons. Due to limitations in the laboratory, there are always sub-findings to be expected, which lead to a not inconsiderable number of unreported cases in the clarification of norovirus-associated food infections. In particular TK , from rain-deficient areas and -Fruits hygienic underdeveloped countries be introduced are therefore always subject to a considerable risk that can not be completely ruled out by laboratory analysis.

treatment

No causal antiviral therapy is known; the treatment is purely symptomatic and consists only of compensating for the loss of fluids and electrolytes (e.g. sodium, magnesium, potassium, calcium, ...). In the case of severe vomiting, the use of nausea-reducing drugs (anti- emetics ) can be considered. A short hospital stay may be necessary, especially for older patients or small children.

prevention

A preventive vaccination is not yet available. The first experimental vaccines are in development. Therefore, the main focus of prevention is on breaking the chain of infection .

Hygienic measures

The transmission of pathogens can be limited by observing hygiene measures and isolating individual or cohorts . This includes, above all, careful hand disinfection with a virucidal hand disinfectant, the spectrum of which also includes non-enveloped viruses, and, if necessary, the use of respiratory masks with a high protective effect ( category FFP-3 ), as well as the disinfection of contaminated surfaces or materials.

Soaps and towels should not be used by several people together, as the noroviruses are resistant to common soaps and common household disinfectants. Frequent hand washing, however, significantly reduces transmission by mechanically removing viruses.

In medical facilities such as hospitals, materials contaminated with norovirus must be labeled as hazardous waste and disposed of in order to avoid re-infection of other patients and staff. Because of the high risk of infection, gowns, gloves and mouth-nose protection should be disposed of with the infectious waste after a single use. This is immediately at the point of occurrence, z. B. in the patient's room, collected in closed containers and must be disinfected externally with virucidal agents prior to removal. Contaminated and stool-soiled laundry (body clothing, bed linen) must be disposed of as infectious laundry according to the double-bag principle .

Disinfectants and inactivation procedures

Hand disinfectants effective against noroviruses contain, in addition to ethanol - from 80 percent by volume (vol%) - other effective ingredients. Here come z. B. orthophosphoric acid , citric acid , lactic acid , urea, etc. in question. Studies have shown that the effectiveness of alcohol can be increased significantly by adding urea and citric acid . Citric acid in particular is able to modify surface proteins of the norovirus in such a way that the infectivity is probably reduced as a result.

According to Kingsley et al. disinfectants containing chlorine are the most effective for surface disinfection. With regard to other substances, z. B. found that peracetic acid was effective within 10 minutes and glutaraldehyde (1%) within 1 minute at room temperature on work surfaces contaminated with noroviruses and surfaces of vegetables, tomatoes, lettuce, strawberries. Quaternary ammonium compounds , which are bactericidal, on the other hand, showed contradicting results in norovirus inactivation. F. v. Rheinbaben reports on the virus-inactivating effect of acidified potassium permanganate solution (pH 3, at 0.1% to 0.5% potassium permanganate) within 5 to 60 minutes. The virus-inactivating oxidation reaction is complete when the color changes from purple to colorless, but this also kills bacteria.

After the norovirus outbreak in eastern Germany in 2012 , in which strawberries eaten raw led to increased infections, it was discussed whether heating through heating can safely inactivate noroviruses. Since cell culture systems are not yet available, the remaining infectivity after heating and the effects of the pH value cannot be measured. The Federal Institute for Risk Assessment (BfR) is due to the scientific data on the assumption that only a short boiling in the manufacture of stewed dishes is insufficient to noroviruses in contaminated frozen fruit to make sure harmless. A substantial reduction can only be achieved by prolonged heating (200 ° C for 12 minutes) or boiling (100 ° C for 30 minutes). The freezing (-18 ° C) of contaminated food also has no significant effect.

literature

Web links

 Wikinews: Norovirus  - in the news

Individual evidence

  1. ↑ ICTV Master Species List 2018b v1 MSL # 34, Feb. 2019
  2. ↑ a b c d e ICTV: ICTV Taxonomy history: Rabbit hemorrhagic disease virus , EC 51, Berlin, Germany, July 2019; Email ratification March 2020 (MSL # 35)
  3. ^ R. Dolin, NR Blacklow et al. a .: Biological properties of Norwalk agent of acute infectious nonbacterial gastroenteritis. In: Proceedings of the Society for Experimental Biology and Medicine. Volume 140, Number 2, June 1972, pp. 578-583. PMID 4624851 .
  4. ↑ Master Species List 2018a v1 . ICTV , MSL including all taxa updates since the 2017 release. Fall 2018 (MSL # 33)
  5. ↑ Labor Lexicon: Noroviruses. In: laborlexikon.de. January 25, 2011, accessed January 21, 2015 . ISSN 1860-966X  
  6. ↑ Ramirez S, Giammanco GM, De Grazia S, Colomba C, Martella V, Arista S: Genotyping of GII.4 and GIIb norovirus RT-PCR amplicons by RFLP analysis . In: J. Virol. Methods . 147, No. 2, 2008, pp. 250-6. doi : 10.1016 / j.jviromet.2007.09.005 . PMID 17953996 .
  7. ↑ Kroneman, A., Vega, E., Vennema, H. et al .: Proposal for a unified norovirus nomenclature and genotyping . In: Archives of Virology . 158, No. 10, 2013, pp. 2059-2068. doi : 10.1007 / s00705-013-1708-5 .
  8. ↑ a b c Lopman BA, Steele D, Kirkwood CD, Parashar UD: The Vast and Varied Global Burden of Norovirus: Prospects for Prevention and Control . In: PLOS Medicine . 13, No. 4, 2016. doi : 10.1371 / journal.pmed.1001999 .
  9. ^ A b Claude M. Fauquet, MA Mayo (ed.): Virus Taxonomy: Eighth Report of the International Committee on Taxonomy of Viruses. Academic Press, 2005, ISBN 0-08-057548-X , p. 847 ( limited preview in Google Book Search).
  10. ↑ Infection epidemiological yearbook of reportable diseases. Robert Koch Institute, 2013.
  11. ↑ Vomiting diarrhea in East Germany: Chinese strawberries were contaminated with noroviruses. In: Spiegel Online . October 8, 2012, accessed January 21, 2015 .
  12. ↑ B. Lopman, M. Zambon, DW Brown: The evolution of norovirus, the "gastric flu". In: PLoS medicine. Volume 5, number 2, February 2008, p. E42, doi: 10.1371 / journal.pmed.0050042 . PMID 18271623 , PMC 2235896 (free full text) (review).
  13. ↑ L. Lindesmith, C. Moe, S. Marionneau u. a .: Human susceptibility and resistance to Norwalk virus infection. In: Nature Medicine. 9 (5), May 2003, pp. 548-553. Epub 2003 Apr 14. PMID 12692541 .
  14. ↑ Reto Krapf: Frequent illnesses - modern treatment: Norovirus infection. In: nzz.ch. March 27, 2013, accessed January 21, 2015 .
  15. ↑ Leena Maunula, Ilkka T. Miettinen, Carl-Henrik von Bonsdorff: Norovirus epidemics emanating from drinking water. In: Environment, Medicine, Society. Volume 19, 2006, pp. 140-145. ( PDF ( Memento of February 27, 2012 in the Internet Archive ), translation by L. Maunula, I. T. Miettinen, C.-H. von Bonsdorff: Norovirus Outbreaks from Drinking Water. In: Emerging Infectious Diseases . Volume 11, Issue 11, 2005 , Pp. 1716-1721, PMID 16318723 , PMC 3367355 (free full text)).
  16. ↑ J. Bae, KJ Schwab: Evaluation of murine norovirus, feline calicivirus, poliovirus, and MS2 as surrogates for human norovirus in a model of viral persistence in surface water and groundwater. In: Applied Environmental Microbiology. Volume 74, Issue 2, 2008, pp. 477-484. PMID 18065626 , PMC 2223264 (free full text).
  17. ↑ Robert L. Atmar, Antone R. Opekun, Mark A. Gilger u. a .: Norwalk Virus Shedding after Experimental Human Infection. In: Emerging Infectious Diseases. 14 (10), Oct 2008, pp. 1553-1557. PMID 18826818 (online)
  18. ↑ "Freedom of the Seas": Virus rages again on the largest cruise ship in the world. In: Spiegel Online . December 12, 2006, accessed January 21, 2015 .
  19. ↑ K. Mattison, A. Shukla et al. a: Human noroviruses in swine and cattle. . In: Emerging infectious diseases . 13, No. 8, 2007, pp. 1184-1188. doi : 10.3201 / eid1308.070005 . PMID 17953089 .
  20. ↑ Widdowson MA, Rockx B, Schepp R et al .: Detection of serum antibodies to bovine norovirus in veterinarians and the general population in the Netherlands. . In: Journal of Medical Virology . 76, 2005, pp. 119-128. doi : 10.1002 / jmv.20333 .
  21. ↑ a b Bok, K. and Green, K. Y: Norovirus Gastroenteritis in Immunocompromised Patients . In: New England Journal of Medicine . 368, No. 10, March 16, 2013, p. 971. doi : 10.1056 / NEJMc1301022 . PMID 23465122 . PMC 4793940 (free full text).
  22. ^ Infection epidemiological yearbook. In: rki.de. 2011, accessed January 21, 2015 .
  23. ↑ MK Jones, M. Watanabe et al. a .: Enteric bacteria promote human and mouse norovirus infection of B cells. In: Science. Volume 346, Number 6210, November 2014, pp. 755–759, doi: 10.1126 / science.1257147 . PMID 25378626 .
  24. ↑ B. Schütze: Food-associated risks from EHEC and noroviruses , Food Science Meets Industry 2013, Hamburg School of Food Science, University of Hamburg February 18, 2013
  25. ↑ Noroviruses in foods: False-negative analysis results possible with fruits , LABO Online, February 11, 2014
  26. ↑ LADR informs: Noroviruses on food ( Memento from March 19, 2013 in the Internet Archive ) (PDF) November 2012.
  27. ↑ Lars Fischer: Diarrhea: Duel with the perfect virus. In: Spektrum.de. August 15, 2012, accessed January 21, 2015 .
  28. ↑ Christina Berndt: The best way to keep noroviruses at bay. In: Süddeutsche Zeitung . February 21, 2012, accessed January 27, 2013 .
  29. ↑ Dispose of waste contaminated with noroviruses properly. Waste manager medicine, October 1, 2017, accessed on August 9, 2018 .
  30. ^ Friedrich von Rheinbaben, Handbook of virus-effective disinfectants, 2002, p. 113ff.
  31. ^ R. Nims, M. Plavsic: Inactivation of Caliciviruses . In: Pharmaceuticals (Basel), 2013 Mar, 6 (3), pp. 358-392. Review, doi: 10.3390 / ph6030358 , PMC 3816691 (free full text). With 123 references about chemical-physical inactivation of calicivirus noroviruses.
  32. ↑ European patent application from B Braun EP 1 685 854 A1: A virucidal disinfectant with broad spectrum action, which is based on alcohol, acidic phosphorus compounds and polyalkylene glycols
  33. ↑ German patent publication DE-C1-4424325 "Phosphoric acid up to 3% and butanone in virucidal disinfectants"
  34. ↑ G. Ionidis et al .: Development and virucidal activity of a novel alcohol-based hand disinfectant supplemented with urea and citric acid. In: BMC Infectious Diseases 16, 2007, p. 77. doi.org/10.1186/s12879-016-1410-9 , PMID 26864562 .
  35. ↑ AD Koromyslova, PA White, GS Hansman: Treatment of norovirus particles with citrate . In: Virology. 485, Nov 2015, pp. 199-204, doi: 10.1016 / j.virol.2015.07.009 , PMID 26295280
  36. ↑ David H. Kingsley, Emily M. Vincent, Gloria K. Meadea, Clytrice L. Watsonb, Xuetong Fanc: Inactivation of human norovirus using chemical sanitizers . In: International Journal of Food Microbiology. Volume 171, February 3, 2014, pp. 94-99, PMID 24334094 .
  37. ^ BR Gulati, PB Allwood et al .: Efficacy of commonly used disinfectants for the inactivation of calicivirus on strawberry, lettuce, and food-contact surface . In: J Food Prot. 64, 2001, pp. 1430-1434, PMID 11563523 .
  38. ↑ Handbook of Virus Effective Disinfectants. ISBN 978-3-642-63179-5 , p. 69.
  39. ↑ BfR : Tenacity (resistance) of noroviruses in strawberry compote (PDF) Opinion No. 038/2012 of October 6, 2012.
  40. ^ Nicola Siegmund-Schultze: Outbreak of gastroenteritis: Noroviruses in frozen food . In: Dtsch Arztebl . tape 109 , no. 41 , 2012 ( aerzteblatt.de [accessed April 2, 2017]).