Noroviruses in humans: genotypes, tests, complications

Norovirus infection, also known as "stomach flu" or "viral gastroenteritis," is a viral disease that affects the gastrointestinal tract. Noroviruses are the most common cause of viral gastrointestinal infections in humans.

According to taxonomic classification, norovirus, first identified in the late 1960s among schoolchildren in the small town of Norwalk (Ohio, USA), belongs to the Caliciviridae family, Norovirus genus, Norwalk virus type. Virologists introduced its short designation – NоV and recognized it as highly contagious, causing outbreaks of acute viral gastroenteritis.

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Structure

The norovirus capsid is icosahedral (23-37 nm in diameter) and amorphous in structure, with no outer shell. Norovirus has linear non-segmented RNA+; the main structural proteins of the virus (VP1 and VP2) are monomeric and bind to the surface of host cells (infected person). The pathogenesis of acute viral gastroenteritis is associated with the fact that the norovirus capsid penetrates the cytoplasm of serous cells and retrogradely into the endoplasmic reticulum of the mucous membrane of the proximal small intestine, quickly affecting the large intestine.

The virus then begins to replicate by RNA replication, destroying the villi of mature epithelial cells and causing a decrease in the absorption of sodium and water from the intestinal lumen.

Pathogenesis

The results of several studies show that there is a connection between the intensity of norovirus infection and a person's blood group: people with blood group III and IV (B and AB according to the classification accepted abroad) have a reduced risk of infection, while those with blood group I (0) have an increased risk. It is assumed that the salivary glands of people with blood group I have receptors to which the virus can easily attach without getting into the stomach and intestines.

Noting the risk factors for norovirus infection, experts name: weakened immunity, unsanitary living or cooking conditions, lack of clean water sources, prolonged stay in crowded places (hospitals, nursing homes, penitentiary institutions, schools, kindergartens, etc.).

How is norovirus transmitted?

The question of how norovirus is transmitted is very important, since it has been established that NoV is capable of surviving for a long time outside the human body, depending on the environment and temperature conditions: on contaminated tissues it can remain viable for up to twelve days, on hard surfaces for several weeks, and in stagnant water it lives for several months.

The main routes of transmission of norovirus are: feco-oral, airborne, through water (from water pipes, wells, lakes, swimming pools, etc.), and contact, that is, from person to person.

In this case, the carriage of norovirus as such is not considered, but virologists answer the question of how contagious a person is with norovirus as follows: Norwalk virus can be in human feces for several weeks after all symptoms of infection have disappeared. Other researchers argue that people infected with norovirus should not prepare food during the illness and for three days after recovery. And so far, no one has established exactly how contagious a person is after norovirus, and there is no evidence that an infected person can become a long-term carrier of this virus. Although the version of possible carriage is indirectly confirmed by the fact that food workers infected with norovirus are often the source of outbreaks of infection.

A study by the National Center for Infectious Diseases found that of 11 outbreaks of acute viral gastroenteritis in New York State, norovirus was transmitted from person to person in seven cases.

In early April 2016, an unusually large number of isolated outbreaks of norovirus genotype GI were reported, which were found to have entered the bodies of cafe and restaurant customers who ordered a dish with fresh green salad of the Lollo Bionda variety.

In the spring of the same year, The Guardian reported on an outbreak of norovirus infection in Spain (in Barcelona and Tarragona), where 4,146 people fell ill due to drinking water from office coolers.

Shellfish, vegetable salad ingredients, and sandwiches are the most common food sources of infection. There is a very high risk of contracting the virus when eating shellfish and crustaceans that have not been cooked properly. For example, in the fall of 2016, the Associated Press reported that 75 people who ate raw oysters were infected with norovirus after an oyster festival on Cape Cod in Massachusetts.

Norovirus genotypes

It may seem that norovirus genotypes are counted differently by everyone. Some experts distinguish NoV into five genogroups or strains – GI-GV, others – six (GI-GVI).

Experts from the International Committee on Taxonomy of Viruses distinguish the following serotypes of norovirus: Hawaii virus, Snow Mountain virus, Mexico virus, Desert Shield virus, Southampton virus, Lordsdale virus, Wilkinson virus.

According to the latest data, norovirus genotypes are divided into at least 38 genetic clusters, although in 2002 there were half as many. Moreover, each genotype has additional subtypes. For example, genogroups I, II and IV infect humans, and norovirus GI is divided into 7 genotypes, genogroup II contains 19 genotypes (according to other data, 12). Genogroup III infects cows, and NoV GV was isolated from mice.

The most common virus that infects humans is norovirus genotype 2: the NoV strain of genogroup II genotype 4 or GII.4.

After the widespread infection of Sydney residents with this genotype of norovirus in 2012, Australian epidemiologists unofficially named it the Hunter virus and, according to an analysis of all outbreaks of infection with this virus, in almost 40% of cases it “hunted” in combination with other NoV genotypes.

According to experts, new strains of this virus appear approximately every two years. And the reason is that, like many RNA viruses, norovirus has a very high mutation rate - due to low replication fidelity and frequent recombination of RNA to protect against host antigens. Incidentally, this is what makes it difficult to create vaccines to prevent the disease.

Norovirus Infection Statistics

Noroviruses are endemic in the human population. According to Viral Gastroenteritis: Global Status, almost one in five cases of acute gastroenteritis worldwide is caused by norovirus, with 685 million cases occurring each year. And up to 200 million of those cases are in children under five. This results in an estimated 50,000 child deaths each year, almost all of which occur in developing countries.

According to other data, norovirus infection causes about 18% of all cases of acute gastroenteritis worldwide.

In Australia, norovirus accounts for 20% of gastroenteritis outbreaks in young children, and in Italy for up to 18.6%.

There have been three studies of sporadic cases of infectious gastroenteritis in the UK, and NHS statistics suggest that between 500,000 and a million Britons of all ages are infected with the virus each year.

Sporadic outbreaks of norovirus are more common in colder months. About half of all cases occur between December and February in countries above the equator, and between June and August in the Southern Hemisphere.

The new genotype of norovirus GII.P17-GII.17 was the cause of the gastroenteritis epidemic in China and Japan in early spring 2015, and the first cases of norovirus infection of this strain in Europe were registered in October of the same year – in a hospital in the Romanian city of Arad. Experts suggest that this genotype may soon become the dominant strain of NoV on the European continent.

Symptoms of norovirus infection

Norovirus causes acute intestinal inflammation in the form of infectious gastroenteritis. The incubation period ranges from 12 hours to two days. Usually the first signs appear as general malaise and persistent nausea.

Other symptoms of the disease join in very quickly:

• debilitating vomiting, sometimes sudden;
• pain in the stomach and abdomen:
• intestinal spasms;
• repeated watery diarrhea;
• fever or chills, the temperature with norovirus increases slightly;
• headache;
• muscle pain and leg cramps;
• loss of taste (rarely).

A small percentage of people who are infected with norovirus do not have any symptoms, and it is believed that in these cases, an as yet unknown factor in the body's natural defense against the virus is at work.

In most cases, norovirus in adults is active for two to three days.

Consequences and complications

Consequences and complications most often occur in children and the elderly, since vomiting and diarrhea exhaust the body and lead to dehydration - intestinal exsiccosis, accompanied by obvious signs of dehydration and electrolyte imbalance: lethargy, dry mucous membranes, decreased diuresis, dizziness, increased heart rate, decreased blood pressure, cyanosis; in children under one year - sunken fontanelle. It is dehydration in norovirus in children and the elderly that can lead to the development of shock and cause fatal consequences.

It is easy to catch norovirus during pregnancy (given the physiologically conditioned decrease in immunity that accompanies this condition). Doctors say that this virus is not dangerous for a child in the womb. But there is a risk of dehydration and premature birth - due to intestinal spasms and tension in the abdominal wall during vomiting attacks, which increase the tone of the uterus.

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Diagnosis of norovirus

In the vast majority of cases, diagnosis of norovirus is based on symptoms, but the infection can be identified by testing stool for norovirus.

As for other laboratory tests, blood tests to detect

Antibodies in serum using electron microscopic or immunological methods, then these complex diagnostic techniques can only be used in large laboratories that have the necessary reagents.

A rapid norovirus test, the polymerase chain reaction (PCR) test or RT-PCR, can detect Norwalk virus within a few hours.

The ELISA test is available in commercial laboratories, but it is not sensitive enough and is not specific. And rapid diagnostic methods of nucleic acids (NAD technologies) are not available in our clinical laboratories.

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Differential diagnostics

Differential diagnosis of norovirus infection is difficult: it is often called food poisoning (because food can be contaminated with norovirus) or stomach flu, although the flu virus is not involved, and there are no respiratory symptoms.

In terms of the manifestation of infectious gastrointestinal tract damage, it is easy to confuse rotavirus and norovirus, although they belong to different families: rotavirus - to the Reoviridae family (Sedoreovirina subfamily). But rotavirus infection begins with vomiting, and then severe diarrhea begins (for almost a week).

Without special tests, which are not available in all medical institutions, it is difficult to differentiate norovirus and enterovirus. Despite the fact that they are single-stranded RNA viruses, they also belong to different families: enterovirus and all its serotypes belong to the picornavirus family (Picornaviridae).

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Treatment of norovirus

To date, treatment of norovirus consists of symptomatic therapy, since there are no specific drugs for norovirus gastroenteritis.

Like other viruses, noroviruses do not respond to antibiotics, which are designed to kill bacteria. And no antiviral drug will help here. Doctors say that in healthy people, the disease should go away on its own within a few days: it is necessary to drink more water and unsweetened juices (to replenish lost fluid and electrolytes), observe rest and hygiene rules.

Treatment is necessary to avoid complications such as dehydration from fluid loss caused by vomiting and diarrhea. Antiemetic and antidiarrheal medications can be used to relieve symptoms. However, these medications are not recommended for young children.

After each vomiting and diarrhea, children should be given a solution of Regidron to drink (it contains potassium and sodium chloride, sodium citrate and glucose): for a child weighing up to 10 kg - 60-120 ml (in several doses, not all at once); for a child weighing more than 10 kg - 120-240 ml.

In a hospital setting, isotonic Ringer-Locke solution (with approximately the same composition) is administered intravenously (drip).

For diarrhea associated with norovirus in adults, you can take Smecta (Diosmectin): one packet (3 g), which should be dissolved in 100 ml of water – three times a day.

Preparations containing loperamide hydrochloride (Loperamide, Imodium, Stoperan) are not used in cases of a combination of diarrhea and fever.

But Desmol for viral diarrhea is recommended to be taken two tablets up to five times a day. And Desmol in the form of a suspension - two tablespoons every 4 hours. Dosage for children under 6 years old - a teaspoon no more than five times a day, over 6 years old - a dessert spoon.

Motilium can be taken as an antiemetic for norovirus, as it contains domperidone (other trade names: Motilak, Motinorm, Peridon, Domrid). The standard dose is 10-20 mg three times a day. But it should be borne in mind that this drug can cause side effects in the form of sleep disorders, convulsions, dry mouth, headache, heartburn, cardiac arrhythmia, urticaria; it is also possible to increase abdominal pain and diarrhea. Motilium is contraindicated for pregnant women and children under five years of age.

It is recommended to take the antiemetic Cerucal (Metoclopramide, Gastrosil) - one tablet two to three times a day (30 minutes before meals). The drug is contraindicated in bronchial asthma, prolactinoma, epilepsy, during pregnancy and breastfeeding, as well as in children under 14 years of age. Side effects of this drug can be expressed by headache, tinnitus, depression, skin allergies, tachycardia, etc.

Folk remedies

Folk treatment of diarrhea with norovivirus enterogastritis is allowed in the form of green tea (without sugar) or tea with ginger root (two cups a day). Herbal treatment includes drinking a decoction of chamomile or oak bark (a tablespoon of dry raw materials per glass of water) - five tablespoons several times during the day (children two tablespoons three times a day).

You can also use plantain (leaves), calamus (root), fireweed (leaves and flowers), and calendula (flowers) to prepare a decoction against diarrhea. The decoctions are prepared in the same proportions as chamomile; several sips are taken throughout the day.

To improve immunity, it is recommended to take vitamins A, C, B6, B9, E, PP, and also eat foods containing potassium and iron.

A norovirus diet should be followed, including easily digestible foods - see Diet for diarrhea

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Prevention

Prevention of infection with norovirus of any strain is personal hygiene: washing hands with soap in running water, especially after using the toilet, changing a baby's diapers, before preparing food and eating it.

Norovirus is quickly inactivated either by boiling for 10 minutes or by using chlorine-containing disinfectants, such as a solution of chlorine bleach (15 tablespoons per liter of water), which should be periodically used to treat plumbing, door handles, waste containers, etc. Ethyl alcohol is not very effective for disinfecting norovirus.

It is important to thoroughly wash raw fruits and vegetables, and to cook shellfish rather than eat them raw.

Norovirus prognosis

The prognosis for acute viral gastroenteritis caused by norovirus is positive in the vast majority of cases. However, given the statistics, this viral pathology does not tolerate a frivolous attitude, although immunity is developed against norovirus. However, the duration of its protective action rarely exceeds six months or a year.