Noroviruses in humans: genotypes, tests, complications

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

[1], [2], [3], [4], [5], [6]

Structure

Norovirus capsid of the icosahedral shape (diameter 23-37 nm) and amorphous structure, the outer shell is absent. Norovirus has linear non-segmented RNA +; the main structural proteins of the virus (VP1 and VP2) are monomeric and bind to the surface of the host cells (the infected person). The pathogenesis of acute viral gastroenteritis is associated with the fact that the norovirus capsid penetrates into the cytoplasm of serous cells and retrograde into the endoplasmic reticulum of the mucous membrane of the proximal small intestine, hitting the large intestine fairly quickly.

After this, the virus begins to multiply by replication of RNA, 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 correlation between the intensity of development of norovirus infection and the blood group of a person: in people with blood groups III and IV (B and AB according to the classification accepted abroad), the risk of infection is reduced, and in group I (0) - increased. It is suggested that in the salivary glands of people with the I blood group there are receptors to which the virus can easily attach without getting into the stomach and intestines.

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

How is the norovirus transmitted?

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

The main ways of transferring norovirus: fecal-oral, airborne, through the water (from the aqueduct, wells, lakes, pools, etc.), as well as contact, that is, from person to person.

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

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

At the beginning of April 2016, an unusually large number of point-like outbreaks of norovirus genotype GI was recorded, which, as it turned out, entered the body of visitors to cafes and restaurants ordering a dish with fresh green salad of Lollo Bionda.

In the spring of the same year, The Guardian reported an outbreak of norovirus infection in Spain (in Barcelona and Tarragona), where 4146 people became ill due to drinking water from office coolers.

More often than other products, mollusks, vegetable salad ingredients and sandwiches become the culprits. There is a very high risk of catching this virus when using shellfish and crustaceans that have not undergone sufficient heat treatment. For example, in the fall of 2016, the Associated Press reported that after an oyster festival at Cape Cod in Massachusetts, norovirus infected 75 people who tasted raw oysters.

Norovirus genotypes

It may seem that the genotypes of norovirus are all considered in different ways. Some specialists distinguish between NoV five genogroups or strains - GI-GV, others - six (GI-GVI).

Experts of the International Committee on the Systematics of Viruses distinguish such serotypes of norovirus as Hawaii virus, Snow Mountain virus, Mexico virus, Desert Shield virus, Southampton virus, Lordsdale virus, Wilkinson virus.

According to recent data, the genotypes of norovirus are divided into at least 38 genetic clusters, although in 2002 they were half as many. Moreover, each genotype has additional subtypes. For example, the geneticogroups I, II and IV infect humans, and norivirus GI is divided into 7 genotypes, genotype II contains 19 genotypes (according to other sources, 12). Geno group III infects cows, and NOV GV has been isolated from mice.

The most common virus that affects people is norovirus of the second genotype: strain NoV of genotype II of genotype 4 or GII.4.

After the general infection of this genotype of norovirus in Sydney in 2012, Australian epidemiologists unofficially named it virus Hunter (hunter) and, according to the analysis of all outbreaks of infection with this virus, in almost 40% of cases it was "hunted" in combination with other NoV genotypes.

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

Statistics of defeat by norovirus

Noroviruses are endemic in the human population. According to information from Viral Gastroenteritis: Global Status, almost every fifth case of acute gastroenteritis is caused by norovirus, and there are 685 million such cases each year. Up to 200 million children are up to five years old. This leads, according to some estimates, to 50,000 deaths of children every year, and almost all of them are noted in developing countries.

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

In Australia, norovirus in young children causes 20% of gastroenteritis outbreaks, in Italy - up to 18.6%.

In the UK, three studies of sporadic cases of infectious gastroenteritis have been conducted, and the National Health Service (NHS) statistics show that 500,000 to 1 million Britons of different ages are infected each year.

Sporadic outbreaks of norovirus often occur in colder months. About half of all cases occur between December and February in countries above the equator, and from June to August - in the countries of the Southern Hemisphere.

The new genotype of norovirus GII.P17-GII.17 was the cause of the epidemic of gastroenteritis in China and Japan in early spring of 2015, and the first cases of norovirus failure of this strain in Europe were registered in October of the same year - in the hospital of the Romanian city of Arad. Experts suggest that in the near future this genotype may 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 manifest as a general malaise and persistent nausea.

Very quickly, other symptoms of the disease join:

• vomiting, sometimes sudden;
• pain in the stomach and in the abdomen:
• spasms of the intestine;
• multiple watery diarrhea;
• fever or chills, the temperature of norovirus rises slightly;
• headache;
• pain in the muscles and leg cramps;
• loss of taste (occasionally).

A small percentage of people who are infected with norovirus do not have any symptoms, and there is an assumption that in such cases an unknown factor of natural protection against the virus works so far.

In most cases, norovirus in adults actively manifests itself within two to three days.

Consequences and complications

Consequences and complications are most often in children and elderly people, as vomiting and diarrhea deplete the body and lead to its dehydration - intestinal exciks, accompanied by obvious signs of dehydration and electrolyte imbalance: lethargy, dry mucous membranes, decreased diuresis, dizziness, palpitations , the fall of blood pressure, cyanosis; in children up to one year - with the fontanel. It is dehydration in norovirus in children and in elderly people that can lead to shock and cause fatal consequences.

It is easy to pick up norovirus during pregnancy (given the physiologically determined decrease in immunity that accompanies this condition). Doctors say that the virus in the womb of the mother is not dangerous. But there is a threat of dehydration and the risk of premature birth - due to spasms of the intestine and tension of the abdominal wall during vomiting, which increase the tone of the uterus.

[7], [8], [9], [10], [11], [12], [13], [14], [15]

Diagnostics of norovirus

In the overwhelming majority of cases, the diagnosis of norovirus is based on symptoms, but the infection can be identified by passing the feces to norovirus.

As for other laboratory tests, blood tests to detect

Antibodies in the serum with the help of electron microscopy or immunological methods, then these complex diagnostic techniques can be applied only in large laboratories that have the necessary reagents.

Such an express test for norovirus, like polymerase chain reaction (PCR analysis or RT-PCR), can reveal Norwalk virus within a few hours.

The ELISA test is available in commercial laboratories, but it is not sensitive enough or specific. And the methods of express diagnostics of nucleic acids (NAD-technologies) in our clinical laboratories are unavailable.

[16], [17], [18], [19], [20], [21], [22]

Differential diagnostics

Differential diagnosis of norovirus infection is difficult: it is often called food poisoning (because food can be infected with norovirus) or intestinal flu, although the influenza virus has nothing to do with it and there are no respiratory symptoms.

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

Without special analyzes, available not 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: the enterovirus and all its seropathies are included in the family of picornaviruses (Picornaviridae).

[23], [24], [25], [26], [27], [28]

Treatment of norovirus

To date, the treatment of norovirus is symptomatic therapy, since there are no specific agents for norovirus gastroenteritis.

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

Treatment is necessary to avoid complications such as dehydration from fluid loss caused by vomiting and diarrhea. Anti-emetic and antidiarrheal drugs can be used to alleviate symptoms. But these tools are not recommended for young children.

Children after each vomiting and diarrhea should be given a solution of Regidron (in its composition there are potassium and sodium chloride, sodium citrate and glucose): with a child weighing up to 10 kg - 60-120 ml (in several receptions, not a volley); with a weight of more than 10 kg - 120-240 ml.

In hospital conditions, intravenously (dropwise) is introduced isotonic solution of Ringer-Lock (approximately with the same composition).

Diarrhea in norovirus in adults can take Smect (Diosmectin): one packet (3 g), which should be dissolved in 100 ml of water - three times during the day.

Drugs with loperamide hydrochloride (Loperamide, Imodium, Stoperan) are not used for a combination of diarrhea and fever.

But Desmol from diarrhea of a viral origin is recommended to take two tablets up to five times during the day. A Desmol in the form of a suspension - two tablespoons every 4 hours. Dosage for children under 6 years - a teaspoon no more than five times a day, over 6 years - according to a dessert spoon.

Motilium in norovirus can be taken as an antiemetic, as it contains domperidone (other trade names are 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, seizures, dry mouth, headache, heartburn, cardiac arrhythmia, urticaria; it is also possible to increase abdominal pain and diarrhea. Motilium is contraindicated in pregnant women and children under five years of age.

It is recommended to take Tserukal antiemetic (Metoclopramide, Gastrosil) - one tablet two or three times a day (30 minutes before meals). The drug is contraindicated in bronchial asthma, prolactinoma, epilepsy, during pregnancy and lactation, as well as children under 14 years. Side effects of this drug can be expressed by headache, noise in the ears, depressive condition, skin allergy, tachycardia, etc.

Alternative treatment

Alternative treatment of diarrhea in noroviviral enterogastreet is allowed in the form of green tea (without sugar) or tea with the root of ginger (two cups a day). Herbal treatment includes the use of decoction of chamomile or oak bark (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 for planting decoction against plant diarrhea plantain (leaves), ayr (root), kaprej narrow-leaved (leaves and flowers), calendula (flowers). Decoctions are prepared in the same proportion as chamomile; are used for several sips throughout the day.

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

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

[29], [30], [31], [32], [33], [34], [35], [36]

Prevention

Prophylaxis of norovirus infection of any strain - observance of personal hygiene: washing hands with soap in running water, especially after visiting the toilet, changing diapers to the baby, before cooking and eating.

Norovirus quickly inactivated either by boiling for 10 minutes, or with chlorine-containing disinfectants, for example, a solution of chlorine bleach (15 tablespoons of water liter), which should be periodically treated with plumbing, door handles, a container for household waste, etc. Ethyl alcohol for disinfection with norovirus is ineffective.

It is necessary to thoroughly wash raw fruits and vegetables, and cook shellfish, and not to eat raw.

Prognosis of norovirus

The prognosis of acute viral gastroenteritis due to 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 in norovirus. True, the duration of his protective effect rarely exceeds six months or a year.