Acute intestinal infections (AII) in adults: clinical guidelines

List of Abbreviations

IBD – inflammatory bowel disease

WHO – World Health Organization

Dr. Med. Sci. – Doctor of Medical Sciences

DNA – deoxyribonucleic acid

GI – gastrointestinal tract

Essential Drugs - List of Vital and Essential Drugs

Cand. Med. Sci. – Candidate of Medical Sciences

CHD – coronary heart disease

BMI – body mass index

EIA – enzyme immunoassay

CT – computed tomography

Ministry of Health of the Russian Federation – Ministry of Health of the Russian Federation

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

INN – International Nonproprietary Name

NVI – norovirus infection

CHI – Compulsory Health Insurance

AII – Acute intestinal infections

ICU – intensive care unit

BV – blood volume

FTI – food-borne toxicoinfection

PCR – polymerase chain reaction

RRS – rectosigmoidoscopy

RF – Russian Federation

US – ultrasound examination

FL – Federal Law

LCS – lower gastrointestinal series / fibrocolonoscopy

EFGDS – esophagogastroduodenoscopy

Terms and Definitions

Evidence-based medicine is an approach to medical practice that aims to optimize decision-making by emphasizing the use of evidence from well-designed and well-conducted research regarding the effectiveness and safety of prophylactic, diagnostic, and therapeutic interventions, while such evidence is searched, compared, summarized, and widely disseminated for patient care

Disease – a disorder of bodily function, working capacity, and the ability to adapt to changing environmental and internal conditions arising from the impact of pathogenic factors, accompanied by alterations in the body's protective-compensatory and protective-adaptive reactions and mechanisms.

Primary disease – a disease that, by itself or through complications, necessitates primary medical care due to the greatest threat to working capacity, 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, 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 impairment of their functions caused by the disease or condition or their complication;

Outcomes of diseases – medical and biological consequences of a disease;

Consequences (results) – disease outcomes, social and economic results of the application of medical technologies;

Complication of a disease:

• addition of a physiological process impairment syndrome to the disease;

• violation of the integrity of an organ or its wall;

• bleeding;

• developed acute or chronic failure of the function of an organ or organ system;

Instrumental diagnostics – diagnostics using various devices, apparatuses, and instruments to examine a patient.

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

Clinical guidelines – a document based on proven clinical experience that describes the physician's actions regarding the diagnosis, treatment, rehabilitation, and prevention of diseases, helping them make correct clinical decisions.

Laboratory diagnostics – a set of methods aimed at analyzing test material using various specialized equipment.

Patient model – a set of clinical, laboratory, and instrumental diagnostic features allowing to identify a disease (poisoning, trauma, physiological state) and classify it into a group of conditions with common etiology and pathogenesis, clinical manifestations, and general approaches to treatment and condition correction;

Medical worker– an individual who has medical or other education, works in a medical organization and whose labor (job) duties include the implementation of medical activities, or an individual who is an individual entrepreneur directly.

Nosological form – a set of clinical, laboratory, and instrumental diagnostic features allowing to identify a disease (poisoning, trauma, physiological state) and classify it into a group of conditions with a common etiology and pathogenesis, clinical manifestations, and general features.

Syndrome - a condition developing as a consequence of a disease and defined by a set of clinical, laboratory, and instrumental diagnostic features allowing to identify it and classify it into a group of conditions with different etiology, but common pathogenesis and clinical features.

Diarrhea – frequent (three times or more) loose stools (loose enough to take the shape of the vessel it falls into) within 24 hours.

Level of certainty of evidence – reflects the degree of confidence that the found effect of a medical intervention is true.

Level of recommendation certainty – reflects not only the degree of confidence in the validity of the intervention's effect, but also the degree of confidence that following the recommendations will bring more benefit than harm in a specific situation.

Drug formularies – a section of patient treatment protocols containing information on medications, regimens, and specific features of their prescription used for a particular disease (syndrome).

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

In clinical practice, there is a collective concept of "acute intestinal infections" (AII), which includes a number of diseases of the gastrointestinal tract of predominantly bacterial, viral, or unspecified etiology, manifested by the symptom complex of acute infectious diarrhea, which are discussed in this document.

Clinical guidelines for some specific pathogens of AII (e.g., cholera, salmonellosis, dysentery (shigellosis), yersiniosis (pseudotuberculosis), botulism, protozoal and helminthic infestations, typhoid fever, and paratyphoid fevers) are set out in separate documents and are not discussed in these guidelines.

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

• Pathogens of AII discussed in these guidelines are mainly viruses and bacteria of the family Enterobacteriaceae. In the etiological structure of infectious diarrhea globally at the present stage, enteropathogenic viruses dominate: rotaviruses (more often gr A), noroviruses (more often type II), astroviruses, adenoviruses (gr F), enteroviruses, etc. [1, 2]. With age, the etiological role of viruses decreases, but remains significant. Pathogenic representatives of the family Enterobacteriaceae are bacteria of the genera: Salmonella, Shigella, Yersinia, diarrheagenic Escherichia. Opportunistic enterobacteria (genera Citrobacter, Klebsiella, Enterobacter, Serratia, Proteus, Morganella) can cause acute intestinal diarrheal diseases in the presence of additional conditions: a massive infecting dose of bacteria (e.g., in food poisoning), the acquisition of additional pathogenicity factors by the bacterial strain (adhesiveness plasmids, enterotoxigenicity, etc.). Under certain conditions (massive infecting dose of bacteria, decreased body resistance), diarrheal diseases can be caused by bacteria from other families: Aeromonas hydrophila, Pseudomonas aeruginosae, Staphylococcus aureus, Streptococcus feacalis, Clostridium perfringens, Clostridium difficile, Bacillus cereus [2, 3].

• There are 3 pathogenetic types of diarrhea based on different mechanisms. Moreover, each intestinal disease is characterized by a specific type of diarrhea, or sometimes a combination of them [2, 3, 4].

• Secretory diarrhea. It is based on increased secretion of sodium and water into the intestinal lumen. Less commonly, it is caused by decreased absorptive capacity of the intestine. Bacterial exotoxin penetrates through receptor zones into enterocytes and activates adenylyl cyclase, which promotes increased synthesis of cyclic 3’–5’–adenosine monophosphate (cAMP). This leads to increased secretion of electrolytes and water into the intestine by enterocytes in a fairly constant ratio: 5 g of sodium chloride, 4 g of sodium bicarbonate, and 1 g of potassium chloride per 1 liter of excrement. A certain role is assigned to prostaglandins, which stimulate cAMP synthesis. Pathogens that produce enterotoxin are V. cholerae, enterotoxigenic Escherichia, and many opportunistic bacteria. The diseases manifest as a loss of intestinal fluid with feces, leading to dehydration. In secretory diarrhea, the osmotic pressure of feces is lower than the osmotic pressure of blood plasma. Stool in patients is watery and copious.

• Hyperexudative (inflammatory, invasive) diarrhea. Its development is based on the exuding of plasma, blood, mucus, and serum proteins into the intestinal lumen. In invasive acute intestinal diarrheal infections, bacteria attach to the intestinal mucosa and then penetrate into it, where they multiply and produce toxins. As a result of the death of a large number of shigellae, salmonellae, escherichiae, etc., endotoxin is formed, which penetrates through protective barriers into the blood. Intoxication caused by the endotoxins of shigellae, salmonellae, certain escherichiae, intestinal yersiniae, and campylobacters is of decisive importance in the pathogenesis of invasive acute intestinal diarrheal infections. Intoxication, fever, damage to the intestinal mucosa, and diarrhea develop. The osmotic pressure of fecal masses is higher than the osmotic pressure of blood plasma. The stool in patients is loose, with an admixture of mucus, blood, and pus.

• Hyperosmolar diarrhea. It is observed in malabsorption syndrome—a disorder of the absorption of one or more nutrients in the small intestine and impaired metabolic processes. In acute intestinal diarrheal infections of viral etiology, pathogens attach to the receptors of epithelial cells covering the tips of the villi of the small intestinal mucosa and then penetrate into these cells. The replication of viruses within the cell leads to its destruction (lysis). The free surface of the upper part of the villi becomes exposed, and cells that absorb fluid from the intestine and synthesize disaccharidases are lost. Only immature epithelial cells of the crypts, which secrete fluid and electrolytes, remain. Undigested disaccharides accumulate in the intestinal contents, increasing osmotic pressure, which draws fluid into the intestinal lumen and leads to diarrhea. Increased osmotic pressure enhances putrefactive decomposition in the large intestine down to low-molecular-weight acids (lactic, acetic, etc.). Fluid is not absorbed in the large intestine due to high osmotic pressure (malabsorption). The osmotic pressure of fecal masses is higher than the osmotic pressure of blood plasma. The stool in patients is profuse, loose, with an admixture of semi-digested food.

1.3 Epidemiology of the Disease or Condition

Acute intestinal infections occupy a significant share in the overall structure of human infectious disease morbidity, second only to acute respiratory viral infections in terms of economic damage.

In the Russian Federation (RF), the incidence of acute intestinal infections of established and unspecified etiology reaches 400 per 100,000 population, and the annual total economic damage is estimated at 40 billion rubles. Among acute intestinal infections of established etiology in the RF, almost half of the cases are accounted for by rotavirus infection (characteristic of children). The proportion of acute intestinal infections and foodborne toxicoinfections of unspecified etiology is about 70% [5].

In the structure of group morbidity outbreaks with a fecal-oral transmission mechanism, norovirus infection prevails both in the number of outbreaks and in the number of affected individuals. In 2023, 269 outbreaks of group morbidity caused by norovirus infection were registered in the Russian Federation with a total number of affected individuals of 3,957 (in 2021—210 and 2,882, respectively). The highest number of affected individuals was registered in preschool, general education, and summer health-improving organizations.

The peak incidence of acute intestinal infections occurs in the period from June to September, which is associated with the activation of infection transmission routes.

Acute intestinal infections are predominantly anthroponotic diseases. The source of infection is patients with clinically pronounced and mild (subclinical) forms of the disease, as well as healthy bacterial and viral carriers. The main transmission mechanism is fecal-oral, realized through waterborne, foodborne, and contact-household routes. The foodborne route is the leading one. Establishing the transmission factor has a definite differential diagnostic value (Table 1). For certain diseases (viral infections), the realization of an aerosol transmission mechanism is possible [2]. The epidemic process of acute intestinal infections manifests as outbreak and sporadic incidence. Depending on the type of pathogen, seasonal and epidemic increases in morbidity are observed in individual territories or climatic zones.

Table 1. Relationship between the transmission factor and the type of pathogen [1].

Official statistics figures do not fully reflect the real picture of acute intestinal morbidity: a significant number of cases are not registered because patients do not seek medical care at healthcare facilities.

1.4 Features of Coding the Disease or Condition

I. International Classification of Diseases, 10th Revision (ICD-10):

• A04 Other bacterial intestinal infections

A04.0 – Enteropathogenic Escherichia coli infection

A04.1 – Enterotoxigenic Escherichia coli infection

A04.2 – Enteroinvasive Escherichia coli infection

A04.3 – Enterohemorrhagic Escherichia coli infection

A04.4 – Other intestinal Escherichia coli infections

A04.5 – Campylobacter enteritis

A04.6 – Yersinia enterocolitica enteritis

A04.7 – Clostridium difficile enterocolitis

A04.8 – Other specified bacterial intestinal infections

A04.9 – Bacterial intestinal infection, unspecified

• A05 Other bacterial foodborne intoxications, not elsewhere classified

A05.0 – Staphylococcal food poisoning

A05.3 – Food poisoning caused by Vibrio parahaemolyticus

A05.4 – Food poisoning caused by Bacillus cereus

A05.8 – Other specified bacterial foodborne intoxications

A05.9 – Bacterial foodborne intoxication, unspecified

• A08 Viral and other specified intestinal infections

A08.0 – Rotoviral enteritis

A08.1 – Acute gastroenteropathy caused by Norovirus

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

• B34.1 – Enteroviral infection, unspecified

1.5 Classification of the disease or condition

A. By clinical course:

1. Typical (manifest);

2. Atypical (asymptomatic, mild/subclinical);

3. Carriage (acute, chronic, transient);

B. By severity:

1. Mild course;

2. Moderate course;

3. Severe course;

C. By nature of the course:

1. Uncomplicated;

2. Complicated;

D. By duration of the course:

1. acute (up to 13 days);

2. protracted (persistent) (14–29 days);

3. chronic (30 days or more) [1];

D. By localization of the gastrointestinal tract lesion:

1. Acute gastritis;

2. Acute enteritis;

3. Acute colitis;

4. Acute gastroenteritis;

5. Acute enterocolitis;

6. Acute gastroenterocolitis.

E. By the degree of dehydration [10].:

• grade I dehydration — body weight loss does not exceed 3%;

• grade II dehydration — body weight loss of 4–6%;

• grade III dehydration — body weight loss of 7–9%;

• grade IV dehydration — body weight loss of 10% or more.

1.6 Clinical presentation of the disease or condition

The incubation period for acute intestinal infections caused by the most common pathogens ranges from 1 to 7 days, most frequently 1–2 days. In foodborne toxicoinfections, the incubation period is shorter, typically ranging from 30 minutes to 6 hours.

The typical clinical presentation of acute intestinal infections is represented by two main acutely developed syndromes: the intoxication syndrome and the gastrointestinal dysfunction syndrome.

In infectology, intoxication syndrome is understood primarily as fever (an increase in body temperature above 37°C).

Dysfunction of various parts of the gastrointestinal tract (gastritis, enteritis, colitis) is explained by the mechanism and routes of infection, the dose of the infectious agent, the tropism of pathogens (toxins) for specific segments of the digestive tract, the premorbid state of the gastrointestinal tract, the anatomical and physiological characteristics of the body in different age periods, and the state of the immune status in general and local immunity in particular.

Clinical forms of acute intestinal infections

Acute gastritis syndrome is characterized by sudden onset of pain and a feeling of heaviness in the epigastric region. The pain syndrome is accompanied, and sometimes preceded, by nausea and vomiting. Vomiting brings relief; in severe cases, it becomes indomitable and occurs after every intake of fluid. Palpation of the abdomen reveals tenderness of varying severity in the epigastric region.

Acute enteritis syndrome manifests as gurgling and sloshing sounds in the abdomen, often audible at a distance; periodic pain throughout the abdomen or in the umbilical region; an persistent urge to defecate; and profuse, loose stools. The stools are watery, and may contain lumps of undigested food due to impaired enzymatic processes and absorption in the small intestine. The color of the stool is light, golden-yellow, or greenish (found not only in salmonellosis) due to the presence of unchanged bile pigments, increased peristalsis, and rapid transit of intestinal contents. In severe acute enteritis, the stools may resemble a translucent, whitish, turbid liquid with flaked or bran-like suspended particles that settle to form a sediment. Abdominal palpation reveals gurgling and a "squishing sound" along the course of the small and large intestines. For diseases in which enteritis is the main syndrome, the development of dehydration is characteristic in the majority of cases.

Acute colitis syndrome is characterized by periodic cramping pains in the lower abdomen, more frequently in the left iliac region, false urges to defecate, tenesmus (painful urges), and a feeling of incomplete bowel emptying after defecation. Colitic syndrome is typified by a homogeneous character of the stools, a mushy or semi-fluid consistency, and the presence of pathological impurities: mucus, blood, and pus. In severe colitis accompanied by frequent bowel movements, the stools become increasingly scant with each defecation and lose their fecal character. When a hemorrhagic process develops in the terminal sections of the large intestine, the stool consists of mucus, blood, and pus ("rectal spit"). When hemorrhages and necrosis are localized predominantly in the right half of the large intestine, the mucus is evenly colored red or brownish-red ("raspberry jelly"). Pus in its pure form (without mucus) is practically never observed in the acute period of the disease. It can be detected during the convalescence period in the final portions of the stool or on the surface of formed fecal masses, which almost always indicates a persisting focal inflammatory or ulcerative process in the rectum and sigmoid colon. On palpation, the large intestine has the character of a dense, rigid tube, undergoes tonic contraction, and becomes less mobile. The diameter and consistency of the intestine are approximately uniform, unlike what is observed in chronic colitis.

Gastroenteritis, enterocolitis, and gastroenterocolitis syndromes are represented by a combination of the corresponding symptoms.

Specific complications

Dehydration shock [7, 18] is a type of non-hemorrhagic hypovolemic shock that develops as a result of a primary decrease in circulating blood volume due to isotonic dehydration. The hemodynamic profile of hypovolemic shock is characterized by a decrease in preload and cardiac index, and an increase in the systemic vascular resistance index. The clinical picture consists of signs of inadequate perfusion of multiple organs and systems—the "shock windows." The first window is the condition of the skin (coldness, mottling, delayed capillary refill time of the nail bed, etc.); the second is varying depths of impaired consciousness or qualitative changes in consciousness; and the third is a decreased urine output rate. One of the most important criteria for shock is hemodynamic disturbances (arterial hypotension, tachycardia). The clinical and laboratory characteristics of the degrees of dehydration are presented in Appendix G1. Treatment involves rapid intravenous administration of balanced isotonic saline solutions in volumes depending on the degree of dehydration.

Septic shock is the most common type of distributive shock, characterized by marked vasodilation and primary microcirculatory-mitochondrial distress. The hemodynamic profile of septic shock is characterized by a decrease in preload and systemic vascular resistance index, and an increase in cardiac index. The clinical presentation is a combination of tissue hypoperfusion signs: "windows of shock" (see description above). The most important characteristics of septic shock are: 1) the need for vasopressors to maintain MAP ≥65 mmHg despite adequate fluid resuscitation, and 2) an elevated blood lactate concentration > 2 mmol/L [11].

Mixed shock (dehydration + septic) should be suspected if, after 2–3 hours of adequate volume rehydration, the patient requires a vasopressor drug to maintain blood pressure.

Acute kidney injury (AKI). Based on KDIGO criteria and national guidelines of the Russian Nephrologists Association, AKI is currently defined as an increase in plasma creatinine by ≥ 26.4 µmol/L within 48 hours; or an increase in creatinine by ≥ 1.5 times from baseline (known or presumed to have occurred within the prior 7 days); or a urine output < 0.5 mL/kg/h for 6 hours [8]. By pathophysiological mechanism, AKI in acute intestinal infections is prerenal. Phenomena of hypovolemia, hypotension, and shock lead to changes in intrarenal hemodynamics with the development of cortical ischemia and the progression of ischemic damage to the tubuloglomerular regulatory mechanism [7].

Acute liver dysfunction syndrome is a component of systemic organ dysfunction in sepsis, characterized by an increase in bilirubin levels above 20 µmol/L for two days or an increase in transaminase levels by two or more times the upper limit of the reference interval [7]. Acute liver dysfunction syndrome must be differentiated from drug-induced (and other toxic) liver injury.

Acute pancreatitis: characterized by persistent severe pain, vomiting, abdominal distension; elevated blood amylase and lipase / urine amylase levels; pancreatic enlargement, blurred contours, effusion in the lesser sac, and dilation of the main pancreatic duct on ultrasound/CT.

The course of acute intestinal infections can also be complicated by acute cerebral insufficiency, appendicitis, interintestinal abscess, pneumonia, venous and arterial thrombosis, sepsis, etc.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnostics of acute intestinal infections in adults is carried out by taking a medical and epidemiological history, clinical examination, laboratory and special diagnostic methods, and is aimed at determining the nosology and clinical form, the severity of the condition, and identifying complications and indications for treatment.

2.1 Complaints and Anamnesis

Comments: Such factors may include drug intolerance; an inadequate psycho-emotional state of the patient before treatment; a life-threatening acute condition/disease or exacerbation of a chronic disease requiring the involvement of a specialist physician in the relevant field; refusal of treatment

Comments:

The decree-bound group includes: officials and employees of organizations whose activities are related to the production, storage, transportation, and sale of food products and drinking water, the upbringing and education of children, communal and consumer services for the population [2, 4, 6].

Comments: in Order of the Russian Ministry of Health No. 203n dated May 10, 2017, a mandatory quality criterion is the assessment of dehydration using the Clinical Dehydration Scale, however, this scale is not used to assess fluid losses in adults. Instead of the CDS scale, adult dehydration is assessed using V.I. Pokrovsky's classification (Appendix A3).

2.2 Physical Examination

• superficial and deep palpation of the abdomen;

• determination of peritoneal irritation signs;

• percussion determination of the borders of the liver and spleen;

• auscultation of bowel sounds

GSI CGrade of Recommendations – C (Level of Evidence – 5).

2.3 Laboratory Diagnostics

2.3.1. Nonspecific laboratory diagnostics

Comments: the leukocyte and band neutrophil count is important in differential diagnosis; an increase in leukocytosis over time is an unfavorable sign that requires ruling out a number of surgical complications (appendicitis, abscess, peritonitis, etc.). Hematocrit is an important complete blood count parameter for assessing dehydration in acute intestinal infections. Thrombocytopenia is possible in severe septic variants.

Comments: in uncomplicated acute intestinal infections, there are no pathological changes. In the presence of leukocyturia (leukocytes ≥ 7 in the field of view), urine analysis according to Nechyporenko is recommended (urine collection via catheter is preferred). With leukocyturia >2000 leukocytes per 1 ml of urine, it is advisable to perform a microbiological (culture) urine test for aerobic and facultatively anaerobic opportunistic pathogens and/or a microbiological (culture) urine test for bacterial pathogens using automated plating.

Comments: the coprogram allows for detecting an inflammatory process in the colon (colitis), assessing pancreatic function, and suspecting the development of dysbiosis [11, 20, 21].

A26.19.010 Microscopic examination of feces for helminth eggs and larvae

A26.19.011 Microscopic examination of feces for protozoa

GSI CGrade of Recommendations – C (Level of Evidence – 5).

Comments: this test allows for differential diagnosis with parasitic infection and/or detection of concomitant parasitosis (ascariasis, giardiasis, opisthorchiasis, etc.). For the differential diagnosis of acute intestinal infections in immunocompromised populations, cryptosporidiosis, isosporiasis, and microsporidiosis are relevant.

• For patients with dehydration ≥ grade II and/or severe acute intestinal infection and/eor signs of any shock, in order to diagnose organ damage, it is recommended to perform a therapeutic biochemical blood test within the first 12 hours with determination of [2, 4, 6, 11]:

A09.05.020 Determination of blood creatinine level

A09.05.031 Determination of blood potassium level

A09.05.030 Determination of blood sodium level

A09.05.041 Determination of blood aspartate aminotransferase activity

A09.05.042 Determination of blood alanine aminotransferase activity

A09.05.023 Determination of blood glucose level

A09.05.021 Determination of blood total bilirubin level

A09.05.022.001 Determination of blood conjugated (direct) bilirubin level

GSI CGrade of Recommendations – C (Level of Evidence – 5).

• For severe patients admitted to the ICU due to the development of complications, it is recommended to perform:

B03.016.011 Determination of acid-base balance and blood gases [7].

GSI CGrade of Recommendations – C (Level of Evidence – 5).

• For differential diagnosis with mesenteric (or other) thrombosis; as well as in generalized (septic) forms of acute intestinal infections; in patients in the ICU for the timely diagnosis of hemostatic disorders, it is recommended to perform B03.005.006 Coagulogram (screening hemostasis test) with determination of [7]: A12.05.039 Activated partial thromboplastin time; A12.05.027 Prothrombin time in blood or plasma; A12.05.028 Thrombin time in blood; A09.05.050 Blood fibrinogen level; A09.05.051.001 Blood D-dimer concentration.

GSI CGrade of Recommendations – C (Level of Evidence – 5).

• For the purpose of timely diagnosis of HIV infection, patients with a generalized (septic) course of acute intestinal infection (AII) or with diarrhea lasting ≥30 days are recommended [2, 6]:

A26.06.048 Determination of antibodies of classes M, G (IgM, IgG) to human immunodeficiency virus HIV-1 (Human immunodeficiency virus HIV 1) in blood

A26.06.049 Determination of antibodies of classes M, G (IgM, IgG) to human immunodeficiency virus HIV-2 (Human immunodeficiency virus HIV 2) in blood

GCR CLOC 5Grade of Recommendation – C (Level of Evidence - 5)

2.3.2. Specific laboratory diagnostics

Comments: Molecular biological studies of feces for the presence of RNA/DNA of the leading spectrum of AII pathogens are characterized by high sensitivity (over 90%) and specificity (over 95%), which significantly reduces the time required to establish the etiological diagnosis, determine treatment tactics, and carry out anti-epidemic measures in the focus (in case of registered focal incidence).

A26.19.001 Microbiological (culture) examination of feces/rectal swab for the causative agent of dysentery (Shigella spp.);

A26.19.002 Microbiological (culture) examination of feces for the causative agents of typhoid fever and paratyphoid fevers (Salmonella typhi);

A26.19.003 Microbiological (culture) examination of feces/rectal swab for microorganisms of the genus Salmonella (Salmonella spp.);

A26.19.078 Microbiological (culture) examination of feces/rectal swab for diarrheagenic Escherichia (EHEC, EPEC, ETEC, EAgEC, EIEC);

A26.19.008 Microbiological (culture) examination of feces for aerobic and facultatively anaerobic microorganisms.

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comment: the frequency of the initial bacteriological examination of feces is not specified (with the exception of screening for cholera). The main material for studies in AII is stool samples, and seeding of vomit, gastric and intestinal lavage water is performed only when necessary. Blood and urine are subject to bacteriological examination in AII with fever ≥5 days; with organ dysfunction and elevated blood lactate (i.e., suspected sepsis). Urine culture is required in the presence of reliable leukocyturia. Cerebrospinal fluid culture is indicated only in the presence of meningeal syndrome. Blood, urine, and bile must be examined when determining the carrier state in regulated occupational groups only for typhoid fever and salmonellosis [2, 6].

In fatal cases of diseases, samples of both ante-mortem and autopsy (native or fixed) material obtained during pathological examination are studied [6].

• Follow-up bacteriological examination of stool samples after clinical recovery is performed once, 1–2 days after the end of treatment, and only for patients of the regulated occupational group with an established etiology of AII [6].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• For the purpose of timely diagnosis of cholera in all patients with AII during the season (the duration of the season depends on the type of region), as well as in patients with AII that developed within five calendar days after arrival from cholera-endemic countries, and in patients with diarrhea and vomiting presenting with a severe course of the disease and pronounced dehydration, it is recommended to perform A26.19.006 Microbiological (culture) examination of feces for cholera vibrios (Vibrio cholerae) three times at 3-hour intervals [2, 6].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

A26.19.039 Determination of rotavirus antigens (Rotavirus gr.A) in feces samples;

A26.19.040 Determination of norovirus antigens (Norovirus) in feces samples

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: detection of viruses in stool is mandatory for all cases of AII [25, 27, 39]. However, the list of viruses to be screened for in sporadic cases of AII is not specified.

• Serological testing to determine the level of antibodies to AII pathogen antigens is not recommended for all patients [1, 6, 11].

GSI CGrade of Recommendations – C (Level of Evidence – 5).

Comments: serological test results should be treated with utmost caution, interpreted only dynamically, and the possibility of late antibody appearance (by the end of the 2nd to the beginning of the 3rd week) should be kept in mind. It is advisable to use this method for the differential diagnosis of subclinical forms of AII and carrier states, as well as for the differential diagnosis of AII with non-infectious diarrheas.

• When Clostridium difficile infection is suspected, it is recommended: A26.19.095 Rapid immunochromatographic stool test for Clostridium difficile toxins A and B, or A26.19.071 Molecular biological examination of feces for the causative agent of Clostridium difficile infection [6, 11, 36].

GSI CGrade of Recommendations – C (Level of Evidence – 5).

2.4 Instrumental Diagnostics

Comments: ECG is performed primarily for differential diagnosis with the abdominal form of myocardial infarction and to identify comorbid conditions that affect the decision on patient hospitalization and the treatment plan.

• For differential diagnostic purposes when gastrointestinal bleeding is suspected; in persistent diarrhea (more than 14 days) and/or suspected IBD, amebiasis, balantidiasis, pseudomembranous colitis, it is recommended [2, 6, 10]:

A03.16.001 Esophagogastroduodenoscopy and/or

A03.18.001 Colonoscopy and/or

A03.19.002 Rectosigmoidoscopy

GSI CGrade of Recommendations – C (Level of Evidence – 5).

2.5 Other Procedures

• Appointment (examination, consultation) with a cardiologist in acute cardiovascular failure, decompensation of chronic cardiac pathology;

• Appointment (examination, consultation) with an obstetrician-gynecologist if AII develops during pregnancy,

• Appointment (examination, consultation) with a neurologist when botulism is suspected to determine further management tactics [3, 4, 10].

GCR CLOE 5Grade of recommendation C (level of evidence – 5).

2.5.1 Differential diagnosis [2, 3, 4, 6, 10, 12, 15, 20, 28, 36, 39]

The variety of clinical manifestations of AII makes differential diagnosis with a number of infectious and non-infectious diseases practically important.

It is necessary to differentiate AII caused by rotaviruses, noroviruses, astroviruses, adenoviruses, enteroviruses; salmonellosis, dysentery, escherichiosis, yersiniosis, cholera, foodborne toxicoinfections, botulism, campylobacteriosis, amebiasis, balantidiasis, giardiasis, and certain helminthiases.

Often, acute intestinal infections must be differentiated from poisonings with various toxic substances, surgical conditions (appendicitis, acute and chronic pancreatitis, acute intestinal obstruction, mesenteric vessel thrombosis, GI tumors, ectopic pregnancy); myocardial infarction, IBD, drug-induced, hormonal, and allergic diarrheas [6, 12, 20].

At all stages of identifying acute intestinal infection cases, differential diagnosis must be performed to rule out pathologies associated with high prognostic risks for patients (pneumonia, acute surgical and gynecological conditions, coronary artery disease, fulminant forms of infectious diseases, non-microbial enteral intoxications, and others). Reasonable doubts during differential diagnosis should be interpreted in favor of nosologies associated with higher prognostic risks for the patient [6].

Differential diagnosis of acute intestinal infections is presented in Appendix A3.4.

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

The principles of treatment for patients with acute intestinal infections involve achieving the following objectives:

• preventing the further progression of the pathological process caused by the disease, achieving a complete and stable recovery;

• preventing the development of potential complications of the disease.

The choice of treatment tactics is influenced by the following factors [2, 3, 4, 6, 10, 12, 13]:

period of the disease; severity of the disease; clinical form of the disease; leading clinical manifestations and course features of the disease taking into account signs of immunodeficiency (chronic alcoholism, cachexia, severe concomitant pathology, advanced age); patient's age; presence and nature of complications; availability and feasibility of treatment in accordance with the required type of medical care [2, 4, 13].

Comments: to obtain complete information (regarding dosages, indications for use, and routes of administration) on a particular medicinal product, consult the instructions for medical use (IMU).

3.1. Conservative management

3.1.1. Etiotropic therapy

• Antimicrobial therapy is recommended for patients with severe and moderate courses of acute intestinal infections: with signs of colitis (invasive diarrhea) and/or generalization of infection and/or presence of serious underlying and concomitant diseases (diabetes mellitus, tuberculosis, HIV infection, and others); as well as in case of prolonged bacterial excretion during the reconvalescence period in occupational risk groups [2, 4, 6, 12, 19].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments: an individual belonging to an occupational risk group independently determines the choice of active (with repeated adjusted courses of antibiotic therapy) or passive (waiting for the natural cessation of bacterial excretion) tactics during the reconvalescence period to obtain work clearance [6].

• Furazolidone 0.1 g 4 times a day;

• Nifuroxazide 0.2 g 4 times a day;

• #Nifuratel 0.4 g 3 times a day [53];

• Rifaximin 0.4 g 2 times a day;

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments: intestinal antiseptics are antimicrobial agents that, after oral administration, provide an antimicrobial effect almost exclusively within the intestinal contents and do not exert a systemic resorptive effect. Therefore, for the treatment of acute intestinal infections prone to a septic course, the use of intestinal antiseptics is irrational. The duration of etiotropic therapy is determined by the normalization of temperature and, as a rule, is limited to 3-5 days. The persistence of liquid stools, asthenovegetative syndrome, abdominal pain, and flatulence are not in themselves grounds for continuing antibiotic therapy [4, 6].

• When bacterial acute intestinal infections are suspected, systemic antibacterial drugs are recommended for moderate infection and/or the presence of signs of generalization: ciprofloxacin**, Co-trimoxazole [Sulfamethoxazole+Trimethoprim]** [2, 4, 6, 19]

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments:

• Ciprofloxacin** 0.5 g 2 times a day;

• Co-trimoxazole [Sulfamethoxazole + Trimethoprim]** 0.48 g twice daily.

When choosing antimicrobial agents, it is necessary to be guided by the drug resistance of AIF pathogens circulating in the region.

Comments: Intesti-bacteriophage has the ability to specifically lyse staphylococcal bacteria and pathogens of infections: S. flexneri types I, II, III, IV, and VI, and S. sonnei, S. paratyphi A, S. paratyphi B, S. typhimurium, S. infantis, S. choleraesuis, S. oranienburg, S. enteritidis; Escherichia coli, Proteus vulgaris and mirabilis, Enterococcus, Staphylococcus, Pseudomonas aeruginosa.

• Intesti-bacteriophage is administered at 30-40 ml 4 times a day, 0.5-1 hour before meals.

Comments: recommended parenteral fluoroquinolones, aminoglycosides, 3rd generation cephalosporins (ceftriaxone**, cefotaxime**, ceftazidime**, cefoperazone+sulbactam**), carbapenems (meropenem**).

Ceftriaxone** and ceftazidime** may be used during pregnancy. Combinations of 2 or more antibiotics should be strictly limited to severe generalized cases of the disease.

The use of aminoglycosides is not recommended upon the development of AKI.

3.1.2. Pathogenetic and symptomatic therapy

Comments: Baseline therapy includes bed rest, diet, and gastric lavage.

Comments: it is advisable to perform gastric lavage regardless of the time elapsed since the onset of the disease. For gastric lavage, 5-10 L of boiled water at a temperature of 20-30 °C is used. An exception is a suspected case of botulism. In this case, gastric lavage using the "stomach tube" method is not recommended.

Comments: at the peak of AIF, the following are permitted: mucilaginous soups, fruit jelly, rice porridge; potatoes, crackling bread rings, white rusks, pasta; homemade cottage cheese, meatballs, lean fish; sweet pomegranates, blueberries, cornelian cherries. The organization of therapeutic dietary nutrition for patients with AIF during inpatient treatment in medical organizations is carried out in accordance with the orders of the Russian Ministry of Health dated August 5, 2003, No. 330 "On measures to improve therapeutic nutrition in healthcare institutions of the Russian Federation", dated June 12, 2013, No. 395n "On approval of therapeutic nutrition standards", and dated September 23, 2020, No. 1008n "On approval of the procedure for providing patients with therapeutic nutrition".

Comments: rehydration is the main component of pathogenetic therapy for AIF, especially those occurring with secretory and hyperosmolar diarrhea. Often, adequate rehydration therapy leads to the recovery of patients even without any additional treatments. Rehydration is carried out in two stages:

• Rehydration to eliminate existing fluid losses (initial) – 1.5-3 hours.

• Rehydration to correct ongoing fluid losses (secondary or compensatory).

Oral rehydration solutions are warmed to 37-40°C. The volume of the solution is determined by the degree of dehydration and the patient's body weight. For stage I, this is 30-40 mL/kg; for stages II-III, it is 40-70 mL/kg. Fractional administration of the solution is recommended—1 glass every 8-12 minutes. Rehydration is carried out using oral rehydration salts (ORS) [32, 33, 34]. According to the pharmacological index, oral rehydration salts belong to the group "Combinations of electrolytes and water balance regulators and acid-base regulators".

• dextrose + potassium chloride + sodium chloride + sodium citrate**;

• dextrose + potassium chloride + sodium chloride + sodium citrate + silicon dioxide + amino acid zinc chelate (specialized dietary therapeutic food for children from the first days of life and adults);

• dextrose + sodium citrate dihydrate + potassium chloride + sodium chloride (specialized dietary therapeutic food for children from the first days of life and adults)

Dehydration correction should be carried out using salt-free solutions as well, among which drinking water should be preferred.

Comments: decoction of alder catkins, bilberry fruits, pomegranate peel, and infusion of bird cherry fruits have astringent properties, which makes them suitable for use in secretory diarrhea. Decoction of badan, bistort rhizome, eucalyptus leaves, and tormentil rhizome have anti-inflammatory, bactericidal, hemostatic, and antidiarrheal effects and can therefore be successfully used in inflammatory (invasive) diarrhea [31].

Comments: solutions of the following composition are recommended for intravenous rehydration:

• Potassium chloride + Calcium chloride + Magnesium chloride + Sodium acetate + Sodium chloride**;

• Potassium chloride + Sodium hydrogen carbonate + Sodium chloride**;

• Sodium lactate compound solution [Potassium chloride + Calcium chloride + Sodium chloride + Sodium lactate]**;

• Potassium chloride + Magnesium chloride + Sodium chloride + Sodium fumarate**;

• Potassium chloride + Calcium chloride + Magnesium chloride + Sodium acetate + Sodium chloride + Malic acid**;

• Potassium chloride + Sodium acetate + Sodium chloride**;

In clinical practice, the volume of initial rehydration is most often calculated based on the clinical signs of dehydration. For example, a patient of average weight (75 kg) with signs of grade III dehydration needs to receive 4.5 - 6.5 L of fluid over 2 hours. The first stage is considered complete provided that hemodynamics are restored, vomiting ceases, and diuresis is restored. A complete transition to oral rehydration is possible under the following conditions: the appearance of formed stool; absence of vomiting for 12 hours; urine output exceeding stool volume for 12 hours.

Comments: the volume depends on the severity of the patient's condition

Mild and moderate severity – oral detoxification in a volume of 2–3 liters of fluid per day (black tea with lemon, cornelian cherry jam, blueberry jam; pomegranate juice, fruit jelly; as well as drinking water).

• Moderate and severe cases in inpatient treatment – infusion therapy: 800–1200 ml of glucose-saline solutions , In patients with elevated blood glucose levels, it is recommended to administer compound sodium chloride solution [Potassium chloride + Calcium chloride + Sodium chloride]**, potassium chloride + sodium acetate + sodium chloride solution**, sodium acetate + sodium chloride solution, potassium chloride + sodium bicarbonate + sodium chloride solution, 0.9% sodium chloride solution** at a daily dose of 5 – 20 ml/kg, meglumine sodium succinate** at a rate of up to 90 drops/min (1–4.5 ml/min) - average daily dose - 10 ml/kg. [52-55]. Duration is determined by the severity and duration of the intoxication syndrome.

Comment:

• paracetamol** orally 1–2 tabl. (500–1000 mg) up to 4 times a day (maximum daily dose – 4000 mg),

• metamizole sodium intramuscularly or intravenously (in severe hyperthermia) 1–2 mL of a 500 mg/mL solution 2–3 times a day, but not more than 2 g per day.

Comment: all sorbents used in the treatment of acute intestinal infections can be divided into groups by composition:

• Silicon dioxide-based preparations:

  colloidal silicon dioxide is prescribed at an average daily dose of 100-200 mg/kg of body weight (6-12 g). Frequency of administration is 3-4 times. The maximum daily dose in adults is 330 mg/kg of body weight (20 g);

• Lignin-based preparations:

  hydrolyzed lignin is prescribed at 0.5–1.0 g/kg of body weight per day in 3–4 doses;

• Preparations based on naturally occurring diosmectite, possessing adsorbing and antidiarrheal action:

  diosmectite** is prescribed at 1 sachet 3 times a day

• Polyvinylpyrrolidone preparations:

  Povidone is prescribed as 100 mL of solution 3 times a day

Comments:

• Racecadotril is an enkephalinase inhibitor and has a direct suppressive effect on the processes of intestinal hypersecretion of water and electrolytes induced by the pathogenic action of viruses and bacterial toxins; it is prescribed at 100 mg 3 times a day before meals only as an adjunct to rehydration and etiotropic therapy (if possible)

• Octreotide** is a synthetic somatostatin analog that increases the absorption rate of water and electrolytes in the small intestine and reduces the number of bowel movements. It is indicated in cases of refractory AIDS-associated diarrhea. It is administered subcutaneously at an initial dose of 0.1 mg (100 mcg) 3 times a day. After a week, the dose is increased to 0.25 mg 3 times a day.

Comments: Saccharomyces boulardii CNCM I-745 possesses genetically determined resistance to almost all groups of antibiotics, sulfonamides, and other antimicrobial agents. It is used as an antidiarrheal and antiseptic agent in acute intestinal infections of any etiology; antibiotic-associated diarrhea and gastrointestinal infections caused by C. difficile; parasitic diarrhea and intestinal dysbiosis, including microbial contamination of the small intestine by opportunistic pathogens [42, 43, 44, 45]. It is prescribed at 1-2 capsules 2 times a day.

Comment: used

• papaverine**: the single adult dose is 0.02–0.04 g (1–2 ml of a 20 mg/ml solution); the interval between administrations is at least 4 hours. Intravenous administration is performed by pre-diluting 20 mg/ml of the drug solution in 10–20 ml of isotonic sodium chloride solution;

• drotaverine** — 40 mg up to 6 times a day, maximum daily dose corresponding to 240 mg;

• platiphylline** — the drug is administered subcutaneously, 1–2 ml of a 0.2% solution 1–2 times a day;

• mebeverine** one tablet (200 mg) 2 times a day, approximately 20 minutes before meals;

• trimebutine — 100–200 mg 3 times a day

Comment: the following are used for antiemetic purposes

• Metoclopramide** is a specific blocker of dopamine ($D_2$) and serotonin ($5 ext{-HT}_3$₃) receptors, inhibits brainstem trigger zone chemoreceptors, and weakens the sensitivity of visceral nerves transmitting impulses from the pylorus and duodenum to the vomiting center. It is administered at 10 mg (2 ml) 1–3 times a day parenterally. In case of overdose, extrapyramidal symptoms rapidly appear, in some cases requiring differential diagnosis with botulism.

• #Ondansetron** — inhibits the onset of the vomiting reflex by blocking $5 ext{-HT}_3$₃ receptors at the level of neurons in both the central and peripheral nervous systems. Slows down intestinal motility with repeated use. It has an anxiolytic effect, does not impair motor coordination, and does not reduce performance. For vomiting, it is administered at 4 mg 2–3 times a day. According to meta-analysis results, oral ondansetron increased the proportion of patients who stopped vomiting and reduced the number of patients requiring intravenous rehydration and immediate hospitalization [1, 6, 38].

3.2. Surgical treatment

Not performed.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Comments: Gradual increase in dosed physical and mental stress, as well as the differentiated application of various impact methods, are important.

Comments: the rate and degree of recovery of the functional state and professionally significant functions of convalescents are taken into account (using indirect and direct methods).

5. Prevention and Dispensary Observation

5.1. Specific prophylaxis

Specific vaccine prophylaxis of acute intestinal infections (described in this document) is not carried out for adults [2, 4, 6, 10].

5.2 Non-specific prevention

Comments: the number of examined persons and the scope of studies performed are determined by the specialist responsible for organizing the epidemiological investigation.

Comments: the duration of medical supervision is 7 days and includes questioning, examination, monitoring of stool characteristics, and thermometry.

Comments: concurrent disinfection is carried out by family members after briefing by medical workers. Terminal disinfection is performed by specialists of organizations authorized to engage in disinfection activities.

Quarantine and isolation measures regarding contact persons are not organized.

5.3 Clinical follow-up (dispensary observation)

• When the etiology of acute intestinal infection is undetermined, it is recommended to allow decreed categories of workers back to work no earlier than 3 calendar days from the date of cessation of clinical manifestations of the acute phase of the disease (absence of fever, normalization of stool, cessation of vomiting) [6].

GCR CLEL 5Grade of Recommendation C (Level of Evidence - 5)

Comment: clearance for work is carried out on the basis of the attending physician's conclusion (certificate) of clinical recovery and a negative result of follow-up laboratory testing for acute intestinal infection pathogens (except for opportunistic pathogens), unless other requirements regarding specific pathogens are provided by sanitary and epidemiological requirements.

6. Organization of Medical Care

The choice of treatment tactics is influenced by the following factors [2, 4, 6, 10, 12, 13]: patient's age; nature of comorbidities; clinical form of the disease; pattern of the disease course (rate of symptom progression); disease severity; presence and nature of complications.

• with severe forms of the disease,

• with moderate acute intestinal infections (AII) in the presence of a burdened premorbid background,

• with disease complications,

• pregnant women,

• according to epidemiological indications (living in dormitories or adverse residential environment conditions, belonging to decreed occupational categories), including those with a mild course of the disease [3, 6, 10, 12, 13].

Level of Recommendations C Level of Evidence 5Level of recommendations C (level of evidence – 5).

Indications for patient discharge from a medical organization:

• normalization of body temperature;

• cessation of vomiting

Conditions for the provision of medical services

Medical care is provided in the following forms:

• emergency medical care;

• urgent medical care;

Medical care is provided in the form of:

• primary health care;

• emergency medical care, including specialized emergency medical care;

• specialized medical care, including high-tech medical care.

Medical care for adult patients with ARVI can be provided under the following conditions:

• outpatient (in settings not providing round-the-clock medical observation and treatment);

• inpatient (in settings providing round-the-clock medical observation and treatment).

Primary health care is provided to patients on an outpatient basis and in a day hospital setting.

Primary paramedic-led health-care in outpatient settings is provided at feldsher-midwifery stations.

Primary physician-delivered health care is provided by a district general practitioner or general practitioner (family doctor) on an outpatient basis.

Primary specialized primary health care is provided by an infectious disease specialist of a medical organization providing medical care to outpatients.

Specialized, including high-tech, medical care is provided in an inpatient setting by infectious disease specialists and other medical specialists and includes the prevention, diagnosis, and treatment of diseases and conditions requiring the use of special methods and complex medical technologies, as well as medical rehabilitation.

Patient treatment is carried out in an inpatient setting upon referral by a general practitioner (district physician); general practitioner (family physician); infectious disease specialist; medical workers who identified the AII; as well as in cases of self-referral for medical care.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Gorodin V.N. — MD, PhD, Professor, Head of the Department of Infectious Diseases and Epidemiology of the Faculty of Advanced Training and Professional Retraining of Specialists, Kuban State Medical University of the Ministry of Health of Russia, Chief Physician of Infectious Diseases Hospital No. 2 of the Ministry of Health of Krasnodar Krai, Chief Freelance Specialist in Infectious Diseases of the Ministry of Health of the Russian Federation in the Southern Federal District

2. Moisova D.L. — MD, PhD, Associate Professor, Professor of the Department of Infectious Diseases and Epidemiology of the Faculty of Advanced Training and Professional Retraining of Specialists, Kuban State Medical University of the Ministry of Health of Russia

3. Chulanov V.P. — MD, PhD, Deputy Director for Research and Innovative Development, National Medical Research Center for Phthisiopulmonology and Infectious Diseases of the Ministry of Health of the Russian Federation, Chief Freelance Specialist in Infectious Diseases of the Ministry of Health of the Russian Federation

4. Maleev V.V. — Academician of the Russian Academy of Sciences, MD, PhD, Professor, Advisor to the Director for Scientific Work, Central Research Institute of Epidemiology of Rospotrebnadzor

5. Gorelov A.V. — Academician of the Russian Academy of Sciences, Professor, Deputy Director for Scientific Work, Central Research Institute of Epidemiology of Rospotrebnadzor, Head of the Department of Infectious Diseases and Epidemiology, A.I. Evdokimov Moscow State University of Medicine and Dentistry of the Ministry of Health of Russia.

6. Ploskireva A.A. — MD, PhD, Professor of the Russian Academy of Sciences, Deputy Director for Clinical Work, Central Research Institute of Epidemiology of Rospotrebnadzor

7. Usenko D.V. — MD, PhD, Leading Researcher of the Clinical Department of Infectious Pathology, Professor of the Educational Center, Central Research Institute of Epidemiology of Rospotrebnadzor

8. Ponezheva Zh.B. — MD, PhD, Professor of the Department of Infectious Diseases of the Faculty of Medicine, Head of the Clinical Department of Infectious Pathology, Central Research Institute of Epidemiology of Rospotrebnadzor

9. Tagirova Z.G. — MD, PhD, Leading Researcher, Professor of the Educational Center, Central Research Institute of Epidemiology of Rospotrebnadzor

10. Ivanova M.R. — MD, PhD, Chief Physician of the State Budgetary Healthcare Institution "Center for Prevention and Control of AIDS and Infectious Diseases" of the Ministry of Health of the Kabardino-Balkarian Republic, Chief Freelance Specialist in Infectious Diseases of the Ministry of Health of the Russian Federation in the North Caucasian Federal District

11. Esaulenko E.V. - MD, PhD, Professor, Head of the Department of Infectious Diseases in Adults and Epidemiology, Saint Petersburg State Pediatric Medical University of the Ministry of Health of Russia

12. Novak K.E. - Candidate of Medical Sciences, Associate Professor, Associate Professor of the Department of Infectious Diseases in Adults and Epidemiology, Saint Petersburg State Pediatric Medical University of the Ministry of Health of Russia

13. Antonova T.V. — MD, PhD, Professor, Professor of the Department of Infectious Diseases and Epidemiology, Academician I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Health of Russia.

14. Gorchakova O.V. — Candidate of Medical Sciences, Researcher at the Laboratory of Chronic Viral Infections of the Research Center, Assistant of the Department of Infectious Diseases and Epidemiology, Academician I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Health of Russia.

15. Ermolenko K.D. — Candidate of Medical Sciences, Researcher at the Department of Intestinal Infections, Children's Research and Clinical Center for Infectious Diseases of the Federal Medical-Biological Agency.

16. Karnaukhova E.Yu. — Candidate of Medical Sciences, Associate Professor of the Department of Infectious Diseases and Epidemiology, Academician I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Health of Russia.

17. Lioznov D.A. — MD, PhD, Professor, Director of the Smorodintsev Research Institute of Influenza of the Ministry of Health of Russia, Head of the Department of Infectious Diseases and Epidemiology, Academician I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Health of Russia.

18. Pobegalova O.E. — Candidate of Medical Sciences, Assistant of the Department of Infectious Diseases and Epidemiology, Academician I.P. Pavlov First Saint Petersburg State Medical University of the Ministry of Health of Russia.

All members of the working group are members of the Academician V.I. Pokrovsky National Association of Infectious Disease Specialists (NAIDS)

There is no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience of the clinical guidelines:

1. Infectious disease specialist;

2. General practitioner (internist);

3. General practitioner;

4. Medical students, residents, postgraduate students.

In these clinical guidelines, all data are ranked by level of reliability (evidence) depending on the quantity and quality of studies on the issue.

Determination of levels of evidence and grades of recommendation for diagnostic interventions

Table A1 — Levels of evidentiary validity for diagnostic interventions

¹The generally accepted standard for clinical trials of diagnostic interventions is a cross-sectional study design, in which each included patient undergoes both the investigational diagnostic method and the reference method (the diagnostic "gold standard" for the disease or condition under study) in parallel and under identical conditions. The investigational and reference methods must be applied independently of each other (i.e., the investigational method cannot be part of the reference method) and must be interpreted by the investigator without knowledge of the results of the other method (blinding is recommended).

Table A2 — Scale for determining the grades of recommendation (GR) for diagnostic interventions

Table A3. Possible combinations of levels of evidentiary validity and grades of recommendation for diagnostic interventions

*If a single clinical trial is evaluated, this condition is not taken into account

Determination of the levels of credibility of evidence and grades of recommendation for therapeutic, rehabilitation, and preventive interventions

Table A4 - Levels of evidentiary validity for therapeutic, rehabilitation, and preventive interventions

Table A5 — Scale for determining the grades of recommendation for therapeutic, rehabilitation, and preventive interventions

Procedure for updating clinical guidelines

Clinical guidelines are updated every 3 years.

Appendix A3. Reference Materials

These clinical guidelines were developed taking into account the following regulatory legal documents:

1. Federal Law of the Russian Federation No. 326-FZ of November 29, 2010, "On Compulsory Medical Insurance in the Russian Federation".

2. Federal Law No. 323-FZ of November 21, 2011, "On the Fundamentals of Protecting the Health of Citizens in the Russian Federation".

3. Order of the Ministry of Health and Social Development of Russia No. 494 of August 9, 2005, "On the Procedure for the Use of Medicinal Products in Patients for Vital Indications".

4. Order of the Ministry of Health of Russia No. 804n dated October 13, 2017, "On Approval of the Nomenclature of Medical Services" (as amended by Orders of the Ministry of Health of the Russian Federation No. 217n dated April 16, 2019, No. 148n dated March 5, 2020, No. 1010n dated September 24, 2020, October 26, 2022).

5. Order of the Ministry of Health and Social Development of Russia No. 69n dated January 31, 2012, "On Approval of the Procedure for Providing Medical Care to Adult Patients with Infectious Diseases"

6. Order of the Ministry of Health of Russia No. 203n dated May 10, 2017, "On Approval of Criteria for Assessing the Quality of Medical Care."

7. SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases" (Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 2 dated January 28, 2021

8. Order of the Ministry of Health of the Russian Federation No. 330 dated August 5, 2003, "On measures to improve therapeutic nutrition in medical and preventive institutions of the Russian Federation"

9. Order of the Ministry of Health and Medical Industry of the Russian Federation No. 295 dated October 30, 1995, "On the introduction of rules for mandatory medical examination for HIV and the list of professions, industries, enterprises, institutions and organizations whose workers undergo mandatory medical examination for HIV"

10. Order of the Ministry of Health of the Russian Federation No. 330 dated August 5, 2003, "On measures to improve therapeutic nutrition in medical and preventive institutions of the Russian Federation."

11. Order of the Ministry of Health of the Russian Federation No. 395n dated June 21, 2013, "On approval of therapeutic nutrition standards".

12. Order of the Ministry of Health of the Russian Federation No. 1008 dated September 23, 2020, "On approval of the procedure for providing patients with therapeutic nutrition."

13. Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 4 dated January 28, 2021, "On approval of Sanitary Rules and Norms SANPIN 3.3686-21 Sanitary and epidemiological requirements for the prevention of infectious diseases" (registered by the Ministry of Justice of Russia on February 15, 2021, registration No. 62500)

Appendix A3.1.

Assessment of dehydration severity according to V.I. Pokrovsky [2]

Appendix A3.2

GLASGOW COMA SCALE

Russian name: Glasgow Coma Scale

Original name (if any): Glasgow Coma Scale

Type: rating scale

Purpose: assessment of surgical risk depending on the timing of intervention in intracranial aneurysm repair

Content (template):

Key (interpretation):

Appendix A3.3

RICHMOND AGITATION-SEDATION SCALE (RASS SCALE)

RASS Assessment Procedure

1. Patient observation

   • Is the patient alert, calm, and attentive? — 0 points.

   • Does the patient exhibit behavioral signs of anxiety or agitation — score from +1 to +4 points using the criteria listed above in the description.

2. If the patient is drowsy, ask them in a loud voice, calling them by name, to open their eyes and look at you. Repeat this several times if necessary. Ask the patient to maintain eye contact.

   • Can eye contact be established with the patient, lasting more than 10 seconds — score -1 point.

   • Can eye contact be established with the patient, but is not maintained for 10 seconds — score -2 points.

   • If the patient makes any movement in response to voice, other than eye contact, score 3 points.

3. The patient does not respond to voice. Perform physical stimulation by shaking the shoulder and rubbing the sternum.

   • If the patient responds with any movement to physical stimulation, score 4 points.

   • If the patient does not respond to voice or physical stimulation, score 5 points.

Appendix A3.4

DIFFERENTIAL DIAGNOSIS OF FREQUENTLY ENCOUNTERED ACUTE INTESTINAL INFECTIONS