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Norovirus infection

Category: Illness or disabilities

Type

Involuntary

Introduction and description

Norovirus is the most common cause of gastroenteritis.  The disease is named after Norwalk, Ohio, where an outbreak occurred in 1968.

Common names of the illness caused by noroviruses still in use include "winter vomiting disease", "winter vomiting bug", "viral gastroenteritis", and "acute nonbacterial gastroenteritis". The term "Roskilde illness", refers to an outbreak in 1936 in Roskilde, Denmark, where it is commonly known as "Roskilde syge".

Noroviruses can genetically be classified into five different genogroups (GI, GII, GIII, GIV, and GV), which can be further divided into different genetic clusters or genotypes.  Noroviruses attack many species besides humans.   For example, genogroups I, II and IV infect humans, whereas genogroup III infects bovine species, and genogroup V has recently been isolated in mice.

Norovirus results in about 685 million cases of illness and 200,000 deaths globally a year. It is common both in the developed and developing world. 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.  In the United States it is the cause of about half of food-borne disease outbreaks.

Disease more commonly occurs in winter months. It often occurs in outbreaks, especially among those living in close quarters.

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.

Norovirus is a common cause of epidemics of gastroenteritis on cruise ships. The US Centers for Disease Control and Prevention through its Vessel Sanitation Program record and investigate outbreaks of gastrointestinal illness—mostly caused by norovirus—on cruise ships with both a U.S. and foreign itinerary; there were 12 in 2015, and 10 from 1 January to 9 May 2016. An outbreak may affect over 25% of passengers, and a smaller proportion of crew members.

Symptoms


Acute

When a person becomes infected with norovirus, the virus is replicated within the small intestine. After approximately one to two days, norovirus infection symptoms can appear. The principal symptom is acute gastroenteritis that develops between 12 and 48 hours after exposure, and lasts for 24–72 hours.

The disease is characterized by nausea, forceful vomiting, watery diarrhoea, and abdominal pain, and in some cases, loss of taste. General lethargy, weakness, muscle aches, headache, coughs, and low-grade fever may occur.

The disease is usually self-limiting. 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.

After infection, immunity to the same strain of the virus – the genotype – protects against reinfection for between 6 months to 2 years. This immunity does not fully protect against infection with the other diverse genotypes of the virus.

Chronic

Norovirus infections can become extremely severe in the elderly and in patients with several underlying diseases.

Severe clinical features include diarrhoea lasting well over the normal 1-3 days, acute renal failure, arrhythmia and signs of acute graft organ rejection in renal transplant patients.  Cardiovascular disease and renal transplant are risk-factors.  Immunosuppressants and so called immunosuppressive ‘therapy’ greatly increase the risk of severe disease and have led to ‘severe consequences typified by decreased potassium levels, increased levels of C-reactive protein and creatine phosphokinase’.

Norovirus is able to cause chronic infections in immunocompromised patients with considerable associated morbidity.  In one study, super-infections occurred in 17% of chronically infected patients who were continuously PCR positive; including two with mixed norovirus infections.  The median duration of infection was 107 days longer in those with super-infections.

A third of patients with interrupted norovirus shedding continued to be infected with the same virus despite up to 2 months of PCR negative stools, classified as a relapse. The majority (67%) of patients with interrupted shedding were re-infected with a different genotype.

In essence, chronically infected patients who are continuously PCR positive are most likely to remain infected with the same virus; however super-infections do occur leading to mixed infection. Patients with interrupted shedding are likely to represent re-infection with a different genotype, however relapsing infections also occur.

Norovirus in more detail

Noroviruses (NoV) are a genetically diverse group of single-stranded positive-sense RNA, non-enveloped viruses belonging to the family Caliciviridae. According to the International Committee on Taxonomy of Viruses, the genus Norovirus has one species, which is called Norwalk virus. Serotypes, strains and isolates include:

  • Norwalk virus
  • Hawaii virus
  • Snow Mountain virus
  • Mexico virus
  • Desert Shield virus
  • Southampton virus
  • Lordsdale virus
  • Wilkinson virus
  • Grimsby virus


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.

Epidemiological studies have shown that individuals with different ABH phenotypes are infected with NoV strains in a genotype-specific manner. GII.4 includes global epidemic strains and binds to more Histo-blood group antigens than other genogroups.

Not only has genetics a part to play in epidemics but it appears that some people can be asymptomatic carriers and the weather also has a part to play!

Norovirus outbreaks frequently occur as epidemics which appear to be related to both genetic and environmental factors. … The norovirus genome undergoes continuous change and this appears to be important in the persistence of the virus in the community. Studies on the common GII.4 genotype have shown that some norovirus outbreak epidemics involving this genotype are correlated with specific changes in the genome. … the role of environmental factors is less well understood. Topics reviewed here include long term excretion of norovirus in some individuals, long term survivability of norovirus in the environment, the role of meteorological factors in the control of norovirus outbreaks and the possible zoonotic transmission of the virus.  PMID:  21695033

A very complex interaction appears to take place in the intestine mediated by Vitamin A, in some cases appearing to show that Norovirus helps to adjust the intestinal flora and even kick-start its protective role – especially in the young.  Oral administration of Vitamin A and MNV [the mouse virus], significantly altered intestinal microbiome profiles, in one study, particularly, bacterial species belonging to the Lactobacillaceae families, which were remarkably increased.  Although this was a study using mice, the implication seems to be that norovirus is not all ‘bad’.   [PMID: 27180604].

Asymptomatic carriers have a major influence on the spreading of norovirus infections and recent research has shown that asymptomatic carriers have a different intestinal biome to those with symptomatic infection, particularly regarding the genera Pseudomonas, Bacteroides, and Erwinia, as well as the Ruminococcaceae family.

Furthermore, viral replication is cytoplasmic and entry into the host cell is achieved by attachment to host receptors, which mediates endocytosis. Positive stranded RNA virus transcription is the method of replication.  It is almost as if the body and virus were designed to co-exist.

Cause

Noroviruses are transmitted directly from person to person (62–84% of all reported outbreaks) and indirectly via contaminated water and food.

The source of waterborne outbreaks may include water from municipal supplies, wells, recreational lakes, swimming pools and ice machines. 

Many norovirus outbreaks have been traced to food that was handled by one infected person.  It may also spread via contaminated surfaces or through the air.


norovirus outbreaks reported in London and South East England in a 2-year period were reviewed. One hundred eighty-six outbreaks were associated with a food outlet or registered caterer in this period. These occurred throughout the year with peaks in quarter 1 of study years. A case series of 17 outbreaks investigated by the local field epidemiological service were evaluated further, representing more than 606 cases. In five outbreaks, symptomatic food handlers were tested and found positive for norovirus.  PMID:  28221985

Noroviruses are extremely contagious, and fewer than twenty virus particles can cause an infection (some research suggests as few as five). Transmission can be aerosolized when those stricken with the illness vomit, and can be aerosolized by a toilet flush when vomit or diarrhoea is present; infection can follow eating food or breathing air near an episode of vomiting, even if cleaned up. The viruses continue to be shed after symptoms have subsided and shedding can still be detected many weeks after infection.

The norovirus can survive for long periods outside a human host depending on the surface and temperature conditions: it can stay for weeks on hard surfaces, and up to twelve days on contaminated fabrics, and it can survive for months, maybe even years in contaminated still water. A 2006 study found the virus remained on surfaces used for food preparation seven days after contamination.

Prevention

Norovirus infection is, as one can see, very difficult to prevent.  One way of avoiding the virus is not to drink from sources of still water unless the water has been boiled.  Prevention involves proper hand washing and disinfection of contaminated surfaces.   However in a world in which we are almost constantly in contact with other human beings, often many of them, avoiding the virus becomes impossible.  Some may argue that given its role of booster to and adjuster of the intestinal immune system, it should not be avoided. 

There are however two courses of action that would seem to be essential related to the use of immunosuppressants and antibiotics

Immunosuppression as cause

Immunosuppressants and so called immunosuppressive ‘therapy’ greatly increase the risk of severe disease.  Furthermore in hospital settings, care homes and other places where the sick are given this treatment, the chances of long term infection of patients increases considerably with the added risk of the virus spreading to everyone else.  In one study, for example, of five outbreak wards, 84 patients and 60 nurses were infected (an overall attack rate of 32% in patients, and 76% in nurses).

In 2011, the Centers for Disease Control and Prevention (CDC) published a clinical practice guideline addressing strategies for the prevention and control of norovirus gastroenteritis outbreaks in health-care settings.  One can only assume that the need for such a document has been fuelled by the increasing use of immunosuppression – the suppression of the immune system.

Antibiotics as cause

Epidemiologic studies that have evaluated the relationship between previous antibiotic use and acute gastroenteritis (AGE) in the paediatric population, have shown that children are far more susceptible to norovirus and rotavirus, with both recent and previous antibiotic use.  Antibiotics disrupt the intestinal flora. 

Treatment

The diarrhoea and vomiting are the body’s attempts to rid itself of the virus, as such the best treatment is to let nature take its course. 

The use of antiemetics and antidiarrhoeals is extremely unwise and will serve only to prolong the symptoms and may lead to complications.  Whilst the virus is in the gastrointestinal tract it can be fought by the immunological reaction of this system – the intestinal flora, stomach acid etc.  Pharmaceuticals can disrupt the natural intestinal flora and even damage the intestinal lining, if the virus breaches the intestine wall it will get into the bloodstream.

Norovirus infection MUST NOT be treated with antibiotics because it is not a bacterial infection.

The best treatment is warmth, sleep and the provision of fluids to prevent dehydration caused by fluid loss in vomiting and diarrhoea.  Symptoms may become life-threatening in vulnerable groups if dehydration or electrolyte imbalance is ignored or not treated.

References and further reading

  • Clin Microbiol Infect. 2006 Jan;12(1):69-74.  Risk groups for clinical complications of norovirus infections: an outbreak investigation.  Mattner F1, Sohr D, Heim A, Gastmeier P, Vennema H, Koopmans M.  PMID:  16460549 
  • J Clin Virol. 2017 Nov;96:44-48. doi: 10.1016/j.jcv.2017.09.009. Epub 2017 Sep 20.  Super-infections and relapses occur in chronic norovirus infections.  Brown JR1, Roy S2, Tutill H2, Williams R2, Breuer J3. PMID: 28950185
  • J Pediatric Infect Dis Soc. 2018 Aug 17;7(3):e86-e91. doi: 10.1093/jpids/piy044.  Evaluating Previous Antibiotic Use as a Risk Factor for Acute Gastroenteritis Among Children in Davidson County, Tennessee, 2014-2015.  Kolsin JM1,2, Lopman BA1, Payne DC2, Wikswo ME2, Dunn JR3, Halasa NB4, Hall AJ1,2.  PMID: 29788403
  • BMC Infect Dis. 2017 Jan 23;17(1):92. doi: 10.1186/s12879-017-2206-2.  Norovirus infections in young children in Lusaka Province, Zambia: clinical characteristics and molecular epidemiology.  Howard LM1, Mwape I2, Siwingwa M2, Simuyandi M2, Guffey MB2, Stringer JS3, Chi BH3, Edwards KM4, Chilengi R5,6. [Noroviruses were detected in approximately 10% of young children with diarrhoea in the Lusaka Province of Zambia, with GII representing the majority of infections.]  PMID: 28114885
  • J Food Prot. 2017 Feb;80(2):257-264. doi: 10.4315/0362-028X.JFP-16-083.  Role of Food Handlers in Norovirus Outbreaks in London and South East England, 2013 to 2015.  Rumble C1, Addiman S2, Balasegaram S1, Chima K2, Ready D3, Heard J4, Alexander E3.
  • Int J Environ Res Public Health. 2011 Apr;8(4):1141-9. doi: 10.3390/ijerph8041141. Epub 2011 Apr 15.  The dynamics of norovirus outbreak epidemics: recent insights.  Marshall JA1, Bruggink LD.
  • J Med Virol. 2018 Dec;90(12):1882-1887. doi: 10.1002/jmv.25079. Epub 2018 Sep 24.  Comparison between patients with norovirus-related gastroenteritis and asymptomatic carriers with respect to distribution of antibody-complexed viral particles and intestinal flora.  Mori K1, Konishi N1, Suzuki Y1, Harada S1, Maeda M1, Akase S1, Obata H1, Monma C1, Nagano M1, Kimoto K1, Oda M1, Somura Y1, Hirai A1, Shinkai T1, Noda M2, Sadamasu K1.  PMID:  29603260

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