Viral Intestinal Infections (Gastroenteritis) in Children: Clinical Guidelines

List of Abbreviations

BP – blood pressure

WHO – World Health Organization

GI – gastrointestinal tract

EIA – enzyme immunoassay

ICD-10 – International Statistical Classification of Diseases and Related Health Problems 10th Revision

VGE – viral gastroenteritis

OKI – acute intestinal infections

HPeV – human parechoviruses

PCR – polymerase chain reaction

FTA – fluorescent treponemal antibody test

FZ – federal law

CNS – central nervous system

HR – heart rate

EV – enteroviruses

CDS (Clinical Dehydration Scale) – Clinical Dehydration Scale

Ig M, G – class M, G immunoglobulins

pH – hydrogen ion exponent

HRV – rotaviruses

HuNoV – noroviruses

HAstV – astroviruses

Terms and Definitions

Clinical guidelines (treatment protocol) are a regulatory document of the healthcare standardization system that define the requirements for providing medical care to a patient with a specific disease, syndrome, or clinical situation.

Nosological form— is a combination of clinical, laboratory, and instrumental diagnostic signs that allow identifying a disease (poisoning, trauma, physiological state) and classifying it into a group of conditions with a common etiology and pathogenesis, clinical manifestations, and general approaches to treatment and condition correction.

Disease — an event arising in connection with the impact of pathogenic factors disrupting the body's activity, performance, and ability to adapt to changing conditions of the external and internal environment while simultaneously altering the protective-compensatory and protective-adaptive reactions and mechanisms of the body.

Primary disease — a disease that, by itself or in connection with complications, creates the primary need for medical care due to the greatest threat to performance, life, and health, or leads to disability, or causes death.

Concomitant disease – a disease that has no causal relationship with the primary disease, is secondary to it in terms of the need for medical care, impact on working capacity, and danger to life and health, and is not the cause of death.

Severity of a disease or condition – a criterion determining the degree of damage to human organs and/or body systems or the impairment of their functions caused by the disease, condition, or their complications.

Disease outcomes – the medical and biological consequences of a disease.

Consequences (results) – disease outcomes, as well as the social and economic results of applying medical technologies.

Disease complication – the addition to a disease of a syndrome of physiological process impairment: disruption of the integrity of an organ or its wall; hemorrhage; developing acute or chronic dysfunction of an organ or organ system.

Condition – bodily changes arising from the impact of pathogenic and/or physiological factors that require medical care.

Clinical situation – a case requiring the regulation of medical care regardless of the disease or syndrome.

Syndrome – a condition developing as a consequence of a disease and defined by a set of clinical, laboratory, and instrumental diagnostic features that allow its identification and classification into a group of conditions with different etiologies, but a common pathogenesis, clinical manifestations, and general approaches to treatment, which nevertheless depend on the underlying diseases forming the basis of the syndrome.

Symptom – any sign of a disease that can be determined regardless of the method used for this purpose.

Patient – an individual receiving medical care or applying for medical care, regardless of the presence of a disease and their condition.

Medical intervention – a, performed by a medical worker in relation to a patient, affecting the physical or mental state of a person and having a preventive, exploratory, diagnostic, therapeutic, or rehabilitative orientation, types of medical examinations and/or medical manipulations, as well as artificial termination of pregnancy.

Medical service – a medical intervention or a complex of medical interventions aimed at the prevention, diagnosis, and treatment of diseases, and medical rehabilitation, and having an independent completed significance.

Quality of medical care – a set of characteristics reflecting the timeliness of medical care provision, the correctness of the choice of prevention, diagnostic, treatment, and rehabilitation methods during the provision of medical care, and the degree of achievement of the planned result.

Physiological process – an interrelated aggregate activity of various cells, tissues, organs, or organ systems (an aggregate of functions) aimed at satisfying a vital need of the entire organism.

Function of an organ, tissue, cell, or group of cells – a property constituting a physiological process that implements an action specific to the corresponding structural unit of the organism.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Viral diarrhea (gastroenteritis) refers to acute, highly contagious anthroponotic infectious diseases transmitted via the fecal-oral route, caused by viruses with tropism for the small intestinal epithelium and characterized by the development of gastritis, gastroenteritis, and dehydration syndrome [1-6].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

The etiology of many cases of viral gastroenteritis (VGE) remains unexplained, partly because these illnesses are characterized by a short and benign course. After rotavirus and norovirus, astroviruses and sapoviruses are the leading viral causes of sporadic gastroenteritis in children [1-5]. Other viruses associated with gastroenteritis in humans include coronaviruses, toroviruses, picornaviruses, picobirnaviruses, and enteroviruses [1-6].

According to international statistics, more than 70% of gastroenteritis cases are caused by viruses, with the highest incidence occurring during the cold season. The opinion that viruses cause acute gastroenteritis was proposed in the 1940s, but their etiological role remained unproven for a long time. It was not until 1972 that Kapikian A.Z. first identified noroviruses in feces as the causative agent of gastroenteritis during an outbreak of diarrhea. A year later, Bishop R.F. et al. isolated rotavirus from the duodenal mucosa of children with gastroenteritis, and in 1975, astroviruses [Madeley C.R., 1975] and adenoviruses [Flewett T.H., 1975] were identified in the feces of children with acute diarrhea. Subsequently, the number of viruses capable of causing acute gastroenteritis steadily increased: coronaviruses [Caul E.O.K., 1975], pestiviruses [Yolken R.H., 1989], picobirnaviruses [Chandra R., 1997], and toroviruses [Beards G.M., 1986, Jamieson F., 1998]. In addition, diarrhea is caused by enteroviruses (Coxsackievirus A 2, 4, 7, 9, 16; Coxsackievirus B 1-5; ECHO 11-14, 16-22) and parechoviruses.

Adenovirus infection ranks third in frequency following rotavirus and norovirus etiologies. Acute infectious diarrhea is caused by adenovirus serotypes 40 and 41, the so-called "enteric adenoviruses," which belong to species F; recently, there have also been reports on the role of adenovirus serotype 31 in the development of gastroenteritis [1-6].

Adenoviruses are more resistant in the environment than other human viruses. They are stable within a pH range of 5.0–9.0, retain activity at 36–37°C for 7 days, at 22–23°C for 14 days, and at 4°C for 70 days; they can be stored frozen and lyophilized without loss of activity. They are inactivated by heating at 56°C for 30 minutes, and by exposure to a 5% phenol solution, a 1% chloramine solution, or a 3% hydrogen peroxide solution for 15–30 minutes. Because the viral capsid does not contain lipids, they are resistant to ether and detergents [8-10].

The replication site of enteric adenoviruses is the duodenal mucosa and mesenteric lymph nodes [Wadell G., 1994; Allard A., 1992]. Adenoviruses have been proven to cause villous atrophy and compensatory crypt hyperplasia, leading to impaired absorption and fluid loss [Farthing M.J.G., 1997; Wadell G., 1999] [5, 10].

Astroviruses are small (virion diameter ~30 nm), RNA-containing viruses belonging to the family Astroviridae; 8 serotypes of astroviruses have been identified, with serotypes 1–5 being of particular clinical significance, and most cases of disease associated with HAstV-1. Along with caliciviruses and several others, these viruses belong to the group of so-called small round structured viruses (SRSVs), which are distinguished by their distinctly structured surface from the group of small round viruses (SRVs) that possess a smooth, unstructured surface. The SRV group also includes, among others, parvoviruses and picornaviruses [1-6].

Human volunteer studies demonstrated that astroviruses have low pathogenicity because, despite infection, clinical signs of disease were recorded in only a small number of individuals, whereas an antibody response was detected in the majority of subjects [1, 3, 5, 6, 9]. Overall, HAstV causes a diarrheal illness that is milder than HRV or HuNoV and is associated with abdominal pain, vomiting, and fever lasting 2–3 days. Although infections are typically self-limiting, immunocompromised individuals may develop disseminated infection. Asymptomatic infections have been reported in both children and adults [1, 3, 5]. The genus Enterovirus includes 15 species. Among the existing species, the first 4 species (A, B, C, D) cause enteroviral diseases in humans. The three poliovirus serotypes now belong to the species Enterovirus C, and the species Poliovirus no longer exists. Currently, more than 100 EV serotypes isolated from both animals and humans are known.

Originally, EVs were classified based on their antigenic properties and pathogenicity for humans and laboratory animals into polioviruses (PV), Coxsackie A viruses (CA), Coxsackie B viruses (CB), and echoviruses (ECHO). However, it soon became evident that this classification was inadequate. To avoid confusion, it was proposed that new EV serotypes should not be assigned to any group, but instead given sequential numbers. Enteroviruses 68–71, ECHO viruses 5, 6, 7, 9, 11, 17, 18, 19, 30, and Coxsackieviruses A8, B1, 2, 5 are of significance in the etiology of gastroenteritis, but other enterovirus serotypes can also cause VGE.

EVs are highly stable: in feces at room temperature, they survive for several weeks, and at low temperatures and in the frozen state, for several months or even years. At 37°C, enteroviruses can persist for 50–65 days. The viruses survive for extended periods in water: 18 days in tap water, 33 days in river water, and 65 days in wastewater. Because EVs lack lipids, they are relatively resistant to ether and lipid solvents. They are also relatively resistant to 70% alcohol, 5% Lysol solution, 3% phenol solution, and low and high pH (from 3 to 10).

Human parechoviruses (HPeVs)—RNA-containing viruses of the family Picornaviridae—are widespread worldwide [1]. To date, 19 HPeV types have been identified, the most common of which is HPeV type 1 (HPeV-1) [1, 2, 3]. Parechovirus infection (HPeVI) can manifest with diverse clinical features ranging from enteric and respiratory symptoms to severe neuroinfections (encephalitis, meningitis, acute flaccid paralysis) and fatal sepsis-like illnesses in neonates. According to recent data, HPeVI may also be associated with several other conditions, including acute liver failure, hepatitis, hemolytic uremic syndrome, myocarditis, myalgia, myositis, herpangina, apnea, hand-foot-and-mouth disease, sudden infant death syndrome, and Reye syndrome.

Bocavirus (HBoV) is a DNA virus belonging to the genus Bocavirus in the family Parvoviridae. Bocavirus infection is part of the spectrum of acute respiratory viral infections in children. Possessing tropism for the respiratory tract epithelium, bocavirus infects the small bronchi and bronchioles, causing bronchiolitis accompanied by acute respiratory failure, lower airway obstruction, and a persistent pertussis-like cough. In addition to the typical course involving the respiratory tract, there are confirmed cases of bocavirus gastroenteritis in children [5].

The nature of diarrhea is identical for all diarrheagenic viruses—watery diarrhea accompanied by flatulence and bloating. Because the primary site of viral replication is the small intestine, the diarrhea is watery. Diarrhea develops due to impaired mucosal digestion and transient enzyme deficiency (decreased disaccharidase activity, particularly lactase). This leads to the accumulation of large amounts of undigested intermediate- and low-molecular-weight substances (primarily disaccharides) that cannot be absorbed by the intestinal wall, resulting in impaired water and electrolyte reabsorption. Upon entering the large intestine, carbohydrates serve as substrates for fermentation by the gut microbiota, generating large amounts of organic acids, hydrogen, carbon dioxide, and water. This results in increased intestinal gas production and lower luminal pH. Severe villous damage in adeno-, astro-, and enterovirus infections can lead to secondary disaccharidase (most commonly lactase) deficiency [5, 9, 12].

1.3 Epidemiology of the Disease or Condition

The past decade has shown an increase in acute enteric infections (AEIs) of viral etiology, driven both by the overall predominance of viral infections in the structure of AEIs and by the widespread adoption of molecular diagnostic methods in the detection of intestinal pathogens [76].

Astroviruses are among the causative agents of viral gastroenteritis. Investigation of the role of astroviruses in acute non-bacterial gastroenteritis began in 1975, when electron microscopy was first used to detect them in the stool of children with diarrhea [3].

Astrovirus-induced gastroenteritis occurs in all age groups, but is most common in children under 7 years of age (with the highest incidence registered in children under 1 year) and the elderly. It has been established that up to 71% of children have blood antibodies against astroviruses by the age of 3–4 years, indicating a wide distribution of this infection.

The etiological role of astroviruses in the structure of acute intestinal infections ranges from 1.3–2.2% in Russia [Podkolzin A.T., 2004] to 10% in Japan [Méndez-Toss M, Romero-Guido P 2000, Shigemoto N, Fukuda S, 2013], while in developing countries the detection rate is up to 20% in Chile and 26% in Mexico. The fecal-oral transmission mechanism is realized through water, food, and contact-household pathways. Some sources consider the contact-household pathway to be the leading infection route. Outbreaks of this disease are particularly common in kindergartens, schools, hospitals, and nursing homes.

A study conducted in Egypt showed that, according to their epidemiological significance (in descending order), astroviruses can be ranked as follows: HAstV-1; HAstV-5; HAstV-8; HAstV-3; HAstV-6; HAstV-4; HAstV-2. Seasonality is not characteristic of astroviral gastroenteritis [2, 4].

Diarrhea as a manifestation of enteritis in patients with bokavirus infection occurs in 10–29% of cases. Its duration is most often 1 to 4 days, stool frequency ranges from 3 to 20 times per day, and in some cases, blood and mucus impurities in the stool are registered. Vomiting is noted in a third of cases. In the age group from 1 month to 1 year, symptoms of acute intestinal infection occur more frequently compared to children aged 3 to 7 years [4].

1.4 Features of Coding the Disease or Condition

A08.2 – Adenoviral enteritis

A08.3 – Other viral enteritis

A08.4 – Viral intestinal infection, unspecified

A08.5 – Other specified intestinal infections

A09 – Other gastroenteritis and colitis of infectious and unspecified origin

A09.0 – Other and unspecified gastroenteritis and colitis of infectious origin

A09.9 – Gastroenteritis and colitis of unspecified origin

1.5 Classification of the disease or condition

There is no universally accepted classification of viral gastroenteritis. A classification indicating the type, severity, and course of the disease is used.

By type: typical (manifest form); atypical (latent form, or carrier state)

By form: monoinfection; combined form (with other infectious diseases)

By severity: mild form, moderate form, severe form.

By the presence of complications: uncomplicated, complicated.

By clinical course: acute (up to 14 days); chronic [1].

1.6 Clinical presentation of the disease or condition

Clinical manifestations of viral gastroenteritis are characterized by gastroenteritis or enteritis. Depending on which part of the gastrointestinal tract is affected, the topical diagnosis may be:

1. Gastritis – lesion of the gastric mucosa, accompanied by pain and a feeling of heaviness in the epigastric region, nausea, and repeated vomiting against the background of moderate fever and intoxication. Short-term loosening of the stool with a foul odor is possible.

2. Enteritis – lesion of the small intestine, manifested by non-localized (or periumbilical) constant or intermittently recurring abdominal pain, spontaneous or upon palpation, flatulence, loose, abundant, watery, often foamy stool with undigested food particles, yellow or yellow-green in color with a sharp sour odor and a small amount of transparent mucus (in the form of lumps or flakes).

3. Gastroenteritis – a combination of gastritis with enteritis, most commonly seen in acute intestinal infections of viral etiology. The appearance of general symptoms is characteristic: fever, chills, cramps and abdominal pain, nausea, vomiting, general weakness, malaise, and decreased appetite. The tongue is moderately coated and somewhat dry. In some children with viral gastroenteritis, respiratory symptoms may be noted in the first days of the disease (hyperemia of the mucous membrane of the hard and soft palate, palatine arches, tonsils, rhinitis, slight dry cough).

The most characteristic sign of viral gastroenteritis is enteritic stool. Defecation frequency is up to 10–15 times a day; stools are abundant, watery, yellow or yellow-green, foamy, with a sharp unpleasant (often sour) odor. There are no mucus or blood impurities in the stool.

Abdominal palpation is characterized by borborygmus. Due to rapid water and electrolyte loss in children, especially during the first year of life, dehydration (isotonic or hypertonic) frequently develops, which determines the severity of the patient's condition. The disease proceeds cyclically. The incubation period for viral gastroenteritis usually lasts from 12 hours to 3 days, and sometimes may be prolonged up to 5–7 days. Elevated body temperature and intoxication symptoms are observed during the first 2–3 days. The duration of diarrhea usually does not exceed 3–6 days. The total duration of the illness is 5–17 days. In severe cases, a more prolonged course is possible. Convalescent virus shedding can be prolonged – up to many months [12].

Adenoviral intestinal infection is characterized by a long incubation period (8–10 days) and a significant duration of the disease (up to 2 weeks). A fundamental difference between intestinal adenoviruses and respiratory ones is that patients do not develop typical clinical signs such as nasopharyngitis and keratoconjunctivitis, although viremia is also registered in these patients.

The disease is characterized by moderately pronounced intoxication and a low-grade fever that persists for several days. In cases where the disease lasts up to 2 weeks, patients are more likely to exhibit an irregular type of fever, which sometimes takes a undulating character [13].

Dyspeptic manifestations in the form of vomiting and diarrhea are moderately expressed and persist for 1–3 days or more. Patients significantly more often than with other viral gastroenteritis note abdominal pain, which may be caused by enlargement of the mesenteric lymph nodes. Cases have been described where fever and abdominal pain were the only manifestations of adenoviral gastroenteritis. The diarrheal syndrome usually lasts up to 8–9 days, and in individual cases can persist for up to 1 month (mainly associated with adenovirus serotype 41). In some cases, patients may simultaneously exhibit respiratory tract changes along with signs of gastroenteritis, but the mechanisms and nature of the developing pathology have been insufficiently studied [15].

The incubation period for astroviral gastroenteritis is 1–2 days. Quite often, even with established infection and the detection of astroviruses in the stool, children lack clinical signs of the disease, which indicates the prevalence of asymptomatic forms of infection. Clinically, the development of the disease resembles rotavirus infection, although it proceeds more mildly with a predominance of watery diarrhea. In recent years, increasing attention has been paid to the growing importance of astroviruses in the development of diarrhea in immunocompromised individuals, including HIV infection, as well as in nosocomial infections. Reports have appeared linking astrovirus infection with the development of necrotizing enterocolitis in newborns [1].

Diarrhea as a manifestation of enteritis in patients with bokavirus infection occurs in 10–29% of cases. Its duration is most often 1 to 4 days, stool frequency ranges from 3 to 20 times per day, and in some cases, blood and mucus impurities in the stool are registered. Vomiting is noted in a third of cases. In the age group from 1 month to 1 year, symptoms of acute intestinal infection occur more frequently compared to children aged 3 to 7 years [4].

Enteroviral gastroenteritis (enteroviral diarrhea) can be observed in both children and adults, but as an independent disease form, it is most common in young children. This form of disease is more frequently associated with ECHO viruses (5, 17, 18), and less commonly with Coxsackie B (1, 2, 5). The disease begins acutely with elevated body temperature and intoxication symptoms; mild catarrhal manifestations (slight runny nose, nasal congestion, cough, and oropharyngeal mucosal hyperemia) may occur. Simultaneously with this or 1–3 days later, abdominal pain appears, frequently localized in the ileocecal region (upon involvement of mesenteric lymph nodes), along with loose enteritic-type stool, sometimes containing mucus (without blood). Repeated vomiting and abdominal bloating are common. Intoxication symptoms are mildly pronounced. Severe dehydration does not develop. The duration of the illness does not exceed 1–2 weeks; a biphasic course is possible.

With manifestations of mesadenitis, the onset of acute abdominal pain syndrome in children can lead to hospitalization in a surgical hospital with suspected appendicitis and surgical intervention. During surgery, moderately enlarged lymph nodes of the small intestine mesentery and serous effusion in the abdominal cavity are found, without changes in the appendix. Histological examination of biopsied mesenteric lymph nodes reveals hyperemia of the lymphoreticular tissue with necrosis phenomena in the center of lymphoid follicles and lymphoid elements of the peripheral part of the node [6].

According to the clinical course of viral gastroenteritis, smooth and non-smooth forms are distinguished, including those with exacerbations and relapses. Viral gastroenteritis in young children may have certain features. The onset of the disease is usually gradual, enteritic syndrome prevails compared to older children, and dehydration syndrome develops rapidly. The severity of the child's condition is caused by microcirculation disorders and water-electrolyte metabolism disturbances.

Complications. Complications of viral gastroenteritis are divided into specific and non-specific. Specific ones include: dehydration syndrome and hypovolemic shock, cardiomyopathy, hepatitis, pancreatitis, and central nervous system (CNS) lesions. Non-specific complications are usually caused by the development of intercurrent diseases (urinary tract infection, pneumonia, otitis).

Typically, viral gastroenteritis is characterized by a benign cyclic course and a symptom complex characteristic of this disease (most often a combination of vomiting and watery diarrhea), as well as the detection of diarrhea-causing virus antigens in feces by enzyme-linked immunosorbent assay (ELISA) or the detection of diarrhea-causing virus nucleic acids in feces. Mild and subclinical forms present with mild and rapidly transient symptoms, and are diagnosed predominantly in epidemic foci. The asymptomatic form presents with no clinical symptoms of the disease, but with an increase in specific antibody titers in the blood, and is detected in infection foci. Carriage of diarrhea-causing viruses can be reconvalescent (after past VGE), or transient (detected in healthy individuals in foci of infectious diarrhea) [7-8].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing a VGE diagnosis: the diagnosis is established based on the epidemiological history, analysis of complaints, clinical examination data, and etiological diagnostics.

2.1 Complaints and Anamnesis

Comments: Transmission can occur through contact with VGE patients or carriers of diarrhea-causing viruses, as well as through the consumption of water and food contaminated with diarrhea-causing viruses.

Comments: Repeated vomiting combined with abdominal pain and meteorism is characteristic.

Comments: VGE is characterized by watery stools combined with abdominal pain and meteorism.

Comments: VGE is characterized by the development of dehydration syndrome.

Comments: Moderately severe headaches, decreased appetite, lethargy, and nausea indicate the development of intoxication in patients with VGE.

2.2 Physical Examination

Physical examination findings are described in the section «Clinical Presentation».

Comments: An increase in body temperature in VGE above 40⁰ °C and/or persistence of fever for more than 3 days indicate the possible development of complications.

Comments: Changes in heart rate, respiratory rate, and blood pressure may indicate the development of complications.

Comments: with the development of dehydration syndrome, weight loss may occur.

Comments: VGE is characterized by the development of dehydration syndrome of varying severity.

Comments: VGE is characterized by the development of dehydration syndrome of varying severity, which can be characterized based on the assessment of skin fold turgor (skin recoil time).

2.3 Laboratory Diagnostics

At the diagnostic stage:

Comments: Coprograms reveal an acidic pH and enzymatic disorders—gastritic and enteral coprogram syndromes (muscle fibers, digestible fiber, starch, neutral fat)—as well as transparent mucus.

Comments: The study is informative for the etiological diagnosis of the disease. However, it is known that the etiology of acute gastroenteritis does not affect the tactics of pathogenetic therapy [9-13].

Comments: The test is informative for identifying the etiological nature of the disease. However, it is known that the etiology of acute gastroenteritis does not affect the tactics of pathogenetic therapy. A high incidence of combined infectious gastroenteritis is registered in children.

Comments: The test is informative for the diagnosis of electrolyte disorders in VGE; it must be performed before starting infusion therapy and monitored dynamically in the presence of hyponatremia.

Comments: The test is informative for diagnosing an uncomplicated or complicated course of VGE; however, the detection of leukocytosis and neutrophilia in the clinical blood count without a left shift of the leukocyte formula in the absence of a significant increase in C-reactive protein does not indicate a bacterial infection. Hematocrit is necessarily evaluated as a marker of hemoconcentration in dehydration

Comments: Informative for detecting inflammatory changes in the urinary tract in patients with VGE.

Comments: The test is informative in patients with moderate and severe AGE to detect complications and determine the severity of the disease.

Comments: The test is informative in patients with moderate and severe AGE to detect complications and determine the severity of the disease.

2.4 Instrumental Diagnostics

Comments: The test is informative for diagnosing the disease, identifying complications (pancreatitis, etc.), and differential diagnosis with surgical pathology.

Comments: The test is informative for diagnosing cardiovascular complications of VGE.

2.5 Other Procedures

Not applicable

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

The choice of VGE treatment method depends on the clinical presentation, disease severity, and presence of complications [10-12, 18, 19].

3.1 Conservative Treatment

Comments: The use of reduced-osmolarity solutions (210–260 mOsm/L) is indicated until the dehydration syndrome is completely resolved

Comments: Parenteral fluid administration is carried out based on physiological requirements, ongoing pathological losses, and the existing fluid deficit.

Comments: prescribed to children until diarrhea resolves.

Comments: prescribed to children until diarrhea stops. The use of antidiarrheal drugs that reduce the tone and motility of smooth muscles of the intestine, slow down the passage of intestinal contents, and reduce the excretion of fluid and electrolytes with feces is not indicated.

Comments: Anti-diarrheal microorganisms (probiotics) are prescribed in accordance with the package leaflet, age, and strain composition of the product. Clinical efficacy has been proven for Bifidobacterium animalis subsp. lactis, Lactobacillus acidophilus, S. boulardii CNCM I-745, and Lactobacillus GG. Anti-diarrheal microorganisms should be administered during both the acute phase of the illness and the convalescence phase [55, 56, 76-80].

Comments: Preparations of human recombinant #interferon alfa-2b** in suppositories may be used (one suppository twice daily; for children under seven years old – 150,000 IU, over seven years old – 500,000 IU, prescribed for at least 5 days), as well as other immunostimulants containing affinity-purified antibodies to human gamma-interferon (#Anaferon for Children according to the schedule for children older than 1 month: day 1 – 8 doses (1 tablet every 30 min for 2 hours – 5 doses, then 1 tablet every 3 hours), days 2–5 – 1 tablet 3 times a day. If the child is under 3 years old, dissolve the tablet in 15 ml of drinking water immediately before administration. Give the resulting solution to the child to drink. or preparations containing affinity-purified antibodies to human gamma-interferon, CD4, and histamine (Erogferon, prescribed for children older than 6 months) [89, 92-95].

Comments: Ondansetron**, metoclopramide**, or domperidone** may be used with dosages and age restrictions in accordance with the instructions for use [10-11, 36, 37, 82, 86, 88, 90, 91].

Comments: Used with dosages and age restrictions in accordance with the instructions for use.

Comments: Antipyretics (N02B – other analgesics and antipyretics; M01A – non-steroidal anti-inflammatory and anti-rheumatic drugs) in healthy children ≥3 months of age are justified at temperatures above 39°C. For milder fever (38–38.5°C), temperature-lowering medications are indicated for children under 3 months, patients with chronic conditions, and in cases of temperature-related discomfort. Regular (scheduled) administration of antipyretics is not recommended; a repeat dose should be given only after a new temperature spike. They are used in accordance with the instructions for use and age restrictions.

At the outpatient, primary health care, and emergency medical care stages, a single administration of metamizole sodium** in an age-appropriate dose is acceptable for persistent fever in accordance with the instructions for use and age restrictions.

Comments: pancreatin** is prescribed with dosages according to the instructions for use, course duration 5-7 days.

3.2 Diet therapy

Comments: Dietary therapy helps accelerate reparative processes in the affected digestive organs in patients with gastrointestinal salmonellosis. In infants, breastfeeding should be maintained; in formula-fed infants with moderate disease severity, specialized infant dietary (therapeutic) products may be used, such as specialized dry lactose-free formula or dry low-lactose milk formula; for severe disease and pronounced malabsorption syndrome, a lactose-free formula based on complete protein hydrolysate should be used (in case of lactase deficiency).

In children over 2 years of age, a mechanically and chemically sparing diet is indicated.

3.3 Other Treatment

Comments: medicines for the prevention of pain associated with procedures/medical manipulations may be used : application of topical local anesthetics (cream/patch) 1 hour before the procedure (when placing a peripheral catheter, etc.)

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Currently, no special rehabilitation methods have been developed for patients with VGE.

Acute infectious diseases are a contraindication for sanatorium-resort treatment.

5. Prevention and Dispensary Observation

Preventive measures are aimed at early and active diagnosis and isolation of patients from organized groups. Requirements for the set of organizational, therapeutic, sanitary, and anti-epidemic (preventive) measures carried out to prevent the occurrence and spread of VGE are established by Sanitary Rules SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases".

Detection of patients with VGE is carried out by physicians of all specialties and mid-level medical personnel of medical organizations, health resorts, and other institutions, regardless of departmental affiliation and forms of ownership. Patients with VGE are subject to mandatory recording and registration in the established manner. Information on each detected case of the disease is transmitted from the medical organization by phone within 2 hours, and an emergency notification is sent within 12 hours to the territorial body of the federal executive authority authorized to exercise federal state sanitary and epidemiological supervision at the place where the patient is identified (regardless of their place of residence).

Medical observation of contact persons belonging to privileged occupational groups (decreed populations) and children attending preschool educational institutions and summer health camps is carried out not only at their place of residence but also at their place of work (study, recreation).

The results of medical observation are recorded in outpatient records, child development histories, and in hospitals – in case histories (when an outbreak is registered in a hospital).

The duration of medical observation is 7 days and includes questioning, physical examination, monitoring of stool consistency, and thermometry.

Individuals who have recovered from VGE and do not belong to decreed occupational groups are discharged after clinical recovery. The necessity of their laboratory testing before discharge is determined by the attending physician, taking into account the clinical course of the disease and the recovery process.

Follow-up observation (dispensary monitoring) for children who have had VGE is 1 month.

6. Organization of Medical Care

Treatment of patients diagnosed with mild to moderate VGE in the absence of risk factors is carried out in outpatient settings; treatment for severe VGE, moderate VGE with concomitant diseases or risk factors, or according to epidemiological indications is carried out in an inpatient setting; treatment for life-threatening complications is carried out in an intensive care unit (ICU).

Hospitalization of detected patients (patients with suspected acute intestinal infections) and carriers of acute intestinal infection pathogens is carried out according to clinical and epidemiological indications.

Hospitalization is indicated for patients with severe and moderate forms of acute intestinal infections in children under 2 years of age and in children with burdened premorbid background, patients of all ages with severe comorbidities, patients with prolonged forms of the disease, patients with various forms of acute intestinal infections when it is impossible to comply with the anti-epidemic regime at the place of residence (detection of the patient), patients with acute intestinal infections from among decreed occupational groups, and patients with acute intestinal infections of various ages in closed institutions.

Indications for discharging a patient from a medical organization: relief of dehydration syndrome, normalization of body temperature, and stool consistency.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Lobzin, Yuri Vladimirovich — D.Sc. in Medicine, Professor, Academician of the Russian Academy of Sciences, President of the Pediatric Research and Clinical Center for Infectious Diseases of the Federal Medical-Biological Agency (PRCCID FMBA), President of the Euro-Asian Society for Infectious Diseases, and the Association of Infectious Disease Physicians of Saint Petersburg and Leningrad Region

2. Zhdanov Konstantin Valerievich – D.Sc. in Medicine, Professor, Corresponding Member of the Russian Academy of Sciences, Director of the Scientific Research Institute of Children's Infections of the Federal Medical-Biological Agency (DNKTSIB FMBA), Member of the Euro-Asian Society of Infectious Diseases, and the Association of Infectious Disease Physicians of St. Petersburg and Leningrad Region

3. Uskov Alexander Nikolaevich – D.Sc. in Medicine, Associate Professor, Advisor to the Director of the DNKTSIB FMBA, Member of the Euro-Asian Society of Infectious Diseases, and the Association of Infectious Disease Physicians of St. Petersburg and Leningrad Region

4. Bekhtereva Maria Konstantinovna – Ph.D. in Medicine, Senior Researcher at the Department of Intestinal Infections, Member of the Euro-Asian Society of Infectious Diseases, and the Association of Infectious Disease Physicians of St. Petersburg and Leningrad Region

5. Rychkova Svetlana Vladislavovna – D.Sc. in Medicine, Associate Professor, Head of the Medical Care Organization Department at the DNKTSIB FMBA, Gastroenterologist

6. Komarova Anna Mikhailovna – Infectious Disease Physician at the DNKTSIB FMBA of Russia

7. Zakharenko, Sergei Mikhailovich — Ph.D. in Medicine, Associate Professor, Deputy Director of the PRCCID FMBA, Member of the Euro-Asian Society for Infectious Diseases, and the Association of Infectious Disease Physicians of Saint Petersburg and Leningrad Region

Conflict of interest: none

Appendix A2. Methodology for Developing Clinical Guidelines

Methodology Methods used for collecting/selecting evidence: - search in electronic databases.

Description of methods used for evidence collection/selection: 41 — the evidence base for the recommendations includes publications from the Cochrane Library, EMBASE, MEDLINE, ClinicalKey ELSEVIER, and the electronic library (www.elibrary.ru). The search depth was 10 years.

Methods used to assess the quality and strength of evidence: - expert consensus; - assessment of significance in accordance with the levels of evidence and grades of recommendation.

Target audience for these clinical guidelines:

– disinfectologist;

- infectious disease physician;

- clinical laboratory diagnostics physician;

- clinical pharmacologist;

– general practitioner (family physician);

- pediatrician;

- precinct pediatrician;

– medical prevention physician;

- emergency admission physician;

– epidemiologist

Table 1. Levels of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing levels of evidence (LE) for methods of prevention, treatment, and medical rehabilitation, including those based on natural therapeutic factors (preventive, therapeutic, and rehabilitation interventions)

Table 3. Scale for evaluating the levels of recommendation certainty (LRC) for prevention, diagnostic, treatment, and medical rehabilitation methods, including those based on natural healing factors (preventive, diagnostic, therapeutic, and rehabilitation interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

• Federal Law No. 323-FZ of November 21, 2011, "On the Fundamentals of Protecting the Health of Citizens in the Russian Federation" (as amended on August 8, 2024);

• Federal Law of the Russian Federation No. 326-FZ of November 29, 2010, "On Compulsory Medical Insurance in the Russian Federation" (as amended on October 29, 2024);

• Federal Law of the Russian Federation No. 52-FZ of March 30, 1999, "On the Sanitary and Epidemiological Welfare of the Population" (as amended on August 8, 2024);

• Order of the Ministry of Health and Social Development of Russia No. 521n of May 5, 2012, "On Approval of the Procedure for Providing Medical Care to Children with Infectious Diseases" (as amended on February 21, 2020);

• Order of the Ministry of Health of Russia No. 804n of October 13, 2017, "On Approval of the Nomenclature of Medical Services" (as amended on March 24, 2020);

• Order of the Ministry of Health and Social Development of Russia No. 541n of July 23, 2010, "On Approval of the Unified Qualification Handbook of Positions of Managers, Specialists, and Employees", section "Qualification Characteristics of Healthcare Worker Positions" (as amended on April 9, 2018);

• Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 4 of January 28, 2021 (as amended on May 25, 2022) "On Approval of Sanitary Rules and Norms SanPiN 3.3686-21 'Sanitary and Epidemiological Requirements for the Prevention of Infectious Diseases'" (together with "SanPiN 3.3686-21. Sanitary Rules and Norms...");

• State Report "On the State of Sanitary and Epidemiological Welfare of the Population in the Russian Federation in 2018". Moscow: Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 2019.

• On the state of sanitary and epidemiological welfare of the population in the Russian Federation in 2022: State Report. Moscow: Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 2023. 368 p.

• On the State of Sanitary and Epidemiological Welfare of the Population in the Russian Federation in 2023: State Report. Moscow: Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 2024. – 364 p.

• State Register of Medicines. Available from: https://grls.rosminzdrav.ru/

• Therapeutic nutrition standards. Methodological guide. 2017. Access: http://cr.rosminzdrav.ru/

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Viral gastroenteritis comprises acute, highly contagious, infectious anthroponotic diseases with a fecal-oral transmission mechanism, caused by diarrheagenic viruses, and characterized by the development of gastritis or gastroenteritis and dehydration.

The fecal-oral transmission mechanism is most often realized via the waterborne route (contamination of drinking water by sewage). In such cases, children are most commonly infected while swimming in stagnant water bodies (ponds, small pools, etc.) or when using substandard water for drinking, cooking, and household needs. The foodborne route of transmission is significant for viral gastroenteritides and is most often realized through the consumption of contaminated milk, dairy products, infant formula, and other products. It should be noted that the contact-transmission route is especially significant in families and organized childcare settings.

The primary method for preventing viral gastroenteritides is strict adherence to personal hygiene rules. If a family member has viral gastroenteritis, sanitary and hygienic rules must be observed with particular care: wash hands as frequently as possible, perform daily wet cleaning in the patient's room using disinfectants, thoroughly treat "common areas" or the child's potty with detergent complexes; provide the patient with separate toys, dishware, linens, and towels, and change bed linen more frequently. The patient's laundry must be washed at a water temperature above 60^◦C, and washed clothes and linens should preferably be ironed. These simple measures will help prevent other family members from falling ill.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix D1. Clinical Dehydration Scale (CDS)

Russian name: Clinical Dehydration Scale (CDS)

Original title (if available): Clinical Dehydration Scale

Source (official developer website, validated publication): Goldman R. D., Friedman J. N., Parkin P. C. Validation of the clinical dehydration scale for children with acute gastroenteritis // Pediatrics. – 2008. – Vol. 122. – No. 3. – P. 545-549; Jauregui J. et al. External validation and comparison of three pediatric clinical dehydration scales // PLoS One. – 2014. – Vol. 9. – No. 5. – P. e95739.

Type (underline): - rating scale

Purpose: assessment of dehydration severity in children

Content (template):

Key (interpretation): 0 points — no dehydration; 1 to 4 points — mild dehydration; 5–8 points correspond to moderate and severe dehydration.