List of Abbreviations
WHO – World Health Organization
CHI – Compulsory Health Insurance
ICD-10 – International Statistical Classification of Diseases and Related Health Problems 10th Revision
MPS – Simple Medical Procedure
Ministry of Health of the Russian Federation – Ministry of Health of the Russian Federation
OKONH – All-Union Classifier of the National Economy Branches
FL – Federal Law
** – included in the list of vital and essential drugs for medical use
ARF – acute renal failure
TIS – toxic-infectious shock
DIC – disseminated intravascular coagulation
IIFA – indirect immunofluorescence assay
ELISA – enzyme-linked immunosorbent assay method
PCR – polymerase chain reaction
IHA – indirect hemagglutination assay
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.
Quality of medical care – a set of characteristics reflecting the timeliness of medical care, 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.
Clinical guidelines – a document based on proven clinical experience, describing the physician's actions regarding the diagnosis, treatment, rehabilitation and prevention of diseases, and helping them make correct clinical decisions.
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.
Instrumental diagnostics – diagnostics utilizing various devices, apparatuses, and instruments to examine a patient.
Laboratory diagnostics – a set of methods aimed at analyzing test material using various specialized equipment.
Medical intervention – diagnostic and/or therapeutic medical examinations and/or procedures, as well as artificial termination of pregnancy, performed by a medical professional or other employee authorized to carry out medical activities, affecting the physical or mental state of a person and having a preventive, diagnostic, therapeutic, rehabilitative, or research focus.
1. Brief information on the disease or condition
1.1 Definition of the disease or condition
Salmonellosis is an acute infectious zooanthroponotic disease with a fecal-oral transmission mechanism, caused by Salmonella spp., characterized by diverse clinical manifestations ranging from asymptomatic carriage to the development in rare cases of generalized forms (typhoid-like, septicemic, and septicopyemic). In most cases, it occurs with predominant involvement of the digestive tract organs (gastroenteritis, colitis) [1, 2, 3, 4, 12]
1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)
The causative agents of salmonellosis belong to the family Enterobacteriaceae, genus Salmonella, which includes 2 species (based on DNA structure): Salmonella enterica with five subspecies (each containing numerous serotypes depending on the presence of O- and H-antigens) and Salmonella bongori (including fewer than 10 very rare serovars), the latter being non-pathogenic to humans. Each subspecies is divided into serovars in accordance with the O- and H-antigenic specificity of the strains. Currently, there are more than 2,500 Salmonella serotypes, but 10-15 serotypes are of practical importance, accounting for up to 90% of morbidity worldwide; these include: S. enteritidis (S. enterica), S. typhimurium, S. derby, S. newport, S. heidelberg, S. panama, S. london, S. infantis, S. anatum. Clinical manifestations caused by various Salmonella serovars do not significantly differ from each other; therefore, the diagnosis currently indicates only the clinical form of the disease and the serovar of the isolated Salmonella, which is important for identifying the source of infection. [1, 2, 3, 4, 12]
Salmonellae are gram-negative rods measuring 0.7-1.5 × 2-5 µm, possessing 8 to 20 flagella, motile, non-spore-forming, facultative anaerobes, growing well on nutrient media at temperatures from +6 to +46 °C (optimum growth +37 °C, at pH 7.2-7.4). Salmonellae have three main antigens: O-somatic (thermostable), H-flagellar (thermolabile), and K-surface (capsular). In addition, other antigens have been described in some Salmonella serovars: Vi-antigen, or "virulence" antigen (one of the components of the O-antigen), and M-antigen (mucous). Salmonellae persist in the environment for a long time, tolerating low temperatures for several months. At 60 °C, salmonellae die within 20-30 minutes; at 100 °C, instantly. On linen, bacteria can persist for 14-80 days, in excrement up to 30 days, and in dried feces up to 4 years. In running water they survive up to 10 days, in tap water up to 4-5 months, and in dust up to 6 months. In food products, salmonellae not only survive well—in frozen meat for up to 3-6 months, in frozen poultry carcasses for up to 1 year, in sausages and frankfurters for up to 2-3 months, in butter, cheese, and egg powder for 9-12 months—but also multiply. Salmonellae are characterized by the ability to rapidly develop resistance to many antimicrobial drugs. [1, 2, 3, 4, 12, 29]
The primary site of the pathological process in salmonellosis is the gastrointestinal tract, most commonly the small intestine, less frequently involving the large intestine; the generalized form is characterized by involvement of other organs and systems (liver, spleen, lungs, lymph nodes, bones). In chronic forms of salmonellosis against the background of primary immunodeficiency, histological examination of parenchymal organs reveals lymphoid tissue hyperplasia, focal sclerosis, and signs of chronic inflammation without specific features. In the mucosa of the gastrointestinal tract (both in the small and large intestines), changes ranging from catarrhal and erosive to ulcerous and ulcerative-necrotic are detected, with characteristic hyperplasia of the lymphoid follicles of the small intestine. Hyperemia, edema, and macrophage infiltration are noted in the lamina propria. In generalized forms, dystrophic changes develop in the kidneys, adrenal glands, and myocardium. [1, 2, 3, 4]
There are 5 main pathogenicity islands (Salmonella Pathogenicity Islands, SPI: SPI-1, SPI-2, SPI-3, SPI-4, SPI-5) that determine the pathogenicity of salmonellae. Among the pathogenicity factors of salmonellae are: the ability to adhere, invade, persist in the cytoplasm of cells, and the ability to cause bacteremia and toxin production.
Due to their flagella, salmonellae overcome the mucus layer and rapidly attach to enterocytes. They ensure the rapid overcoming of the mucosal barrier, resistance to the bactericidal action of cationic proteins, and mucosal colonization. Invasion factors (SPI-1, SPI-2, SPI-4) determine the ability of the pathogen to invade. Salmonellae penetrate the intestinal mucosa through mucosal M cells; as a result of invasion, M cells die, and the bacteria invade the lamina propria and lymphoid formations of the intestine, after which salmonellae penetrate the mesenteric lymph nodes, the thoracic lymphatic duct, and enter the bloodstream. Pathogenicity factors SPI-2 and SPI-4 cause penetration and survival in the cytoplasm of phagocytes and the ability to initiate their apoptosis. As a result, phagocytosis becomes incomplete, which may be a factor in the generalization of the infection. In most cases, the penetration of salmonellae into the bloodstream does not cause clinical manifestations of bacteremia, as they rapidly die under the influence of serum bactericidal factors. Some salmonellae that escape death are fixed in the macrophage-histiocytic system, where, in the presence of an immunodeficiency state, foci of proliferative or purulent inflammation can form. When salmonellae die, a significant amount of endotoxin is released, which causes nonspecific reactions of the macroorganism: fever, vomiting, abdominal pain, nonspecific activation of immune system cells in the form of their synthesis of a wide range of cytokines, and intravascular blood coagulation, etc. Products of the genes of the fifth "pathogenicity island" – SPI-5 – play an important role in the development of diarrheal syndrome. Under their action, cytotoxins are secreted that inhibit chloride ion secretion, leading to excessive fluid efflux from cells and the development of diarrhea. Lipopolysaccharide (LPS), released after bacterial death, is of significant importance in the development of the inflammatory reaction; the ability to produce a thermostable enterotoxin is of lesser importance in the development of diarrheal syndrome, its damaging capacity being realized through an increase in cAMP levels with impaired sodium and chloride ion secretion. [1, 2, 3, 4, 12, 20]
Immunity after a past infection is unstable (3-6 months), serospecific.
1.3 Epidemiology of the Disease or Condition
The incidence of salmonellosis is sporadic in nature, but large food-borne outbreaks, less frequently water-borne outbreaks, foci of nosocomial infection (maternity hospitals, intensive care units, departments for early-age children), and outbreaks in closed institutions (nursing homes, psycho-neurological boarding schools) are also recorded [1, 2, 3, 11, 15, 22, 30]. The highest incidence of salmonellosis is characteristic of early and preschool age children. The source of infection in salmonellosis is animals and humans (sick individuals and bacterial carriers), with animal bacterial excretors posing a major danger. The infecting dose is 105-108 microbial cells. The incidence of salmonellosis is recorded throughout the year with a peak in the summer-autumn period. The main route of transmission of the infection is food-borne, with the leading transmission factor being infected poultry products: chicken meat, turkey, waterfowl, and eggs; pork and beef are of lesser epidemiological significance. It has been proven that certain animals serve as reservoirs for specific Salmonella serotypes. Infection via water and contact-household routes is significantly less common. The contact-household transmission route (staff hands, instruments, linen, toys, care items, etc.) is characteristic of hospital strains of salmonellosis carrying multiple antibiotic resistance plasmids, with S. typhimurium in first place. [1, 2, 3, 4, 11, 12, 29, 31].
Salmonella bacteria are one of the primary causes of acute intestinal infections of bacterial etiology in residents of both developing and developed countries; the global incidence has increased 6-10 times over a short period. In most countries, Salmonella ranks first or second in the structure of invasive diarrheas. The long-term incidence trend for salmonellosis is characterized by an overall decline. In 2021, the incidence rate of salmonellosis was 13.61 per 100,000 population; in 2022, it was 17.1 per 100,000 population, which is lower than the multi-year average for the 2019-2019 period (29.10); and in 2023, it rose to 21.45 per 100,000 population, approaching pre-pandemic levels. The etiological structure is dominated by salmonellosis caused by group D Salmonella (72.5%). Salmonellosis remains significant in outbreak incidence and ranks third (after viral acute intestinal infections) in the structure of group infection foci with a fecal-oral transmission mechanism. The disease occurs in all age groups, but preschool and school-age children are most susceptible to salmonellosis [1, 2, 3, 4, 30, 33].
1.4 Features of Coding the Disease or Condition
A02 – Other salmonella infections:
A02.0 – Salmonella enteritis
A02.1 – Salmonella sepsis
A02.2 – Localized salmonella infections
A02.8 – Other specified salmonella infections
A02.9 – Salmonella infection, unspecified
1.5 Classification of the disease or condition
Clinical classification of salmonellosis [1, 2, 3, 4, 12, 13]
Gastrointestinal form
- gastritis variant
- gastroenteritis variant
- gastroenterocolitis variant
Generalized form
- typhoid-like variant
- septicopyemic variant
Bacterial shedding
- acute
- chronic
- transient
1.6 Clinical presentation of the disease or condition
The incubation period lasts from 6 hours to 3 days (most commonly 12-24 hours).
The gastritic variant is characterized by an acute onset, recurrent vomiting, and epigastric pain. The intoxication syndrome is mild. The disease typically lasts 2-3 days. The gastroenteritis variant of the disease is the most common. It begins acutely with symptoms of intoxication: a high body temperature reaching 38.5–39.5 °C from the first hours of the disease, headache, chills, and cramping abdominal pain. Nausea and vomiting develop, usually preceding diarrhea. Stools are initially fecal in character but rapidly become copious, watery, foamy, foul-smelling, sometimes with a greenish hue resembling "swamp mud," and occasionally containing mucus. Tenesmus and false urges are absent. Skin pallor is noted. The tongue is dry and coated. The abdomen is distended, tender upon palpation in all regions—more so in the epigastrium and right iliac fossa—and gurgles upon palpation. Heart sounds are muffled, tachycardia is present, blood pressure is decreased, and urine output is reduced. Muscle cramps are possible.
In the gastroenterocolitis variant, the clinical picture is similar, but by days 2-3, the volume of stool decreases, with admixed mucus and sometimes blood. Palpation reveals spasm and tenderness of the sigmoid colon. Tenesmus may occur.
In the typhoid-like variant, the temperature curve becomes continuous or remittent. Pronounced headache, insomnia, and dizziness are observed. The skin is pale; a roseolous rash may appear on days 5-7. Scattered dry rales may be auscultated over the lungs. Examination of the cardiovascular system reveals muffled heart sounds, tachycardia, and rarely bradycardia. The abdomen is distended. Hepatomegaly and splenomegaly are observed by days 5-7. Renal involvement presents as oliguria.
In the generalized septicopyemic variant of salmonellosis, initial manifestations resemble the typhoid-like variant, but the patient's condition subsequently worsens. Temperature fluctuations become irregular with wide daily swings, repeated chills, profuse sweating, tachycardia, and myalgia. Purulent foci develop in the lungs, heart, kidneys, liver, and other organs. The disease has a protracted course and can be fatal [1, 2, 3, 4, 11, 13].
Following recovery from salmonellosis, some patients become bacterial carriers. In acute bacterial shedding, salmonella excretion ceases within 3 months; if it persists for more than 3 months, it is classified as chronic. In transient bacterial shedding, a single or double isolation of salmonellae from stool is not accompanied by clinical manifestations or antibody production.
Criteria for assessing disease severity based on clinical signs – Appendix A3:
- presence and severity of dehydration syndrome;
- severity of gastrointestinal tract involvement;
- severity of general infection symptoms;
- internal organ involvement with functional failure;
- development of a septic process or infectious-toxic shock
Complications
Dehydration shock, toxic-infectious shock, circulatory disorders in the coronary, mesenteric, and cerebral vessels, acute renal failure, and septic complications [1, 2, 3, 4, 7, 8, 16].
Complications of salmonellosis:
1. Specific
Toxic-infectious shock
Dehydration shock
Acute renal failure
2. Nonspecific
Vascular circulatory disorders (coronary, mesenteric, cerebral)
Abscess
Infectious psychosis
Infectiously toxic encephalopathy
Anemia
Pancreatitis
Meningitis
Myocarditis
Pneumonia
Thrombophlebitis
Cholecystitis
Osteomyelitis, etc.
2. Diagnostics, medical indications and contraindications for diagnostic methods
Diagnostic criteria
The diagnosis of salmonellosis is based on pathognomonic data [1, 2, 3, 4]:
1) Anamnestic data: consumption of food products or water infected (or potentially infected) with salmonellae (poultry products, meat products) 8–72 hours before the onset of the disease, or contact with individuals suffering from infectious diarrhea.
2) Complaints and physical examination findings: acute onset, high fever, pronounced intoxication symptoms, abdominal pain (most often spasmodic, localized in the epigastric and umbilical regions), nausea, repeated vomiting, and diarrhea. Stools are initially fecal, then become copious, watery, foul-smelling, and greenish in tint. Defecation is generally not accompanied by tenesmus.
3) Laboratory tests: isolation of a specific Salmonella serovar from clinical material.
4) instrumental examination data are not used for routine diagnostics.
2.1 Complaints and Anamnesis
It is recommended to clarify with all patients whether they consumed food products infected (or potentially infected) with salmonellae (poultry, meat, and dairy products) 8–72 hours before the onset of the disease to establish the infection transmission factor [1, 2, 3, 4].
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
It is recommended to clarify with all patients whether they consumed water infected (or potentially infected) with salmonellae 8–72 hours before the onset of the disease to establish the infection transmission factor [1, 2, 3, 4].
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
It is recommended to verify in all patients any contact (household or in a hospital setting) with a patient suffering from infectious diarrhea to establish the infection transmission factor [1, 2, 3, 4].
GCR CLEL 5Grading of Recommendations Assessment, Development and Evaluation — Recommendation Grade C (Level of Evidence – 5).
Comments: Infection may occur as a result of consuming contaminated water; consuming contaminated meat and dairy products; via contaminated hands and household items; or in round-the-clock patient care facilities (hospitals, psychoneurological boarding facilities).
2.2 Physical Examination
It is recommended to assess all patients for the presence of fever to determine the severity of the disease course [2].
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
It is recommended in all patients to determine the percentage of acute body weight loss, decreased tissue turgor, dry skin and mucous membranes, condition of the eyeballs, and diuresis in order to detect signs of dehydration shock [1, 2, 3, 4, 11, 12].
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
It is recommended in all patients to measure peripheral blood pressure, assess the pulse and their ratio (Allgower index), measure respiratory rate, evaluate the skin condition (pallor, cold to the touch, acrocyanosis), and determine urine output (oliguria, oligoanuria) to detect signs of toxic-infectious shock [1, 2, 3, 4, 11, 12].
GCR CLEL 5Grading of Recommendations Assessment, Development and Evaluation — Recommendation Grade C (Level of Evidence – 5).
It is recommended in all patients to determine the size of the liver and spleen to establish the form of the disease and identify concomitant pathology [1, 2, 3, 4, 11, 12].
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
It is recommended in all patients to determine the nature and frequency of diarrhea to assess the severity of the disease [1, 2, 3, 4, 11, 12].
GCR CLEL 5Grading of Recommendations Assessment, Development and Evaluation — Recommendation Grade C (Level of Evidence – 5).
2.3 Laboratory Diagnostics
At the diagnostic stage:
It is recommended that all patients with suspected salmonellosis undergo a complete blood count (CBC) with differential leukocyte count and a urinalysis for a general patient assessment, determination of the disease stage, and exclusion of complications and comorbidities [1, 2, 3, 4, 6, 9, 11, 14].
GCR CLEL 5Grading of Recommendations Assessment, Development and Evaluation — Recommendation Grade C (Level of Evidence – 5).
Comments: clinical and biochemical blood parameters depend on the clinical form and severity of the disease. A complete blood count in the first 2–3 days of the illness is characterized by moderate leukocytosis. Hemoglobin levels and platelet counts may be elevated, along with an accelerated ESR. At the peak of the disease, urinalysis reveals an increase in urine relative density, microproteinuria, microhematuria, and cylindruria. In cases of generalized forms of the disease, the complete blood count reveals more pronounced leukocytosis, neutrophilia, and an accelerated ESR. Urine changes in generalized forms are characterized by the development of proteinuria, microhematuria, cylindruria, and bacteriuria.
It is recommended to perform a general clinical biochemical blood test in patients with suspected moderate and severe forms of salmonellosis: determination of blood urea nitrogen, blood creatinine, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood electrolytes (potassium, sodium, chlorides, total calcium) to detect the presence and severity of internal organ dysfunction, complications, and comorbid conditions [1, 2, 3, 4, 6, 9, 11, 14].
GCR CLEL 5Grading of Recommendations Assessment, Development and Evaluation — Recommendation Grade C (Level of Evidence – 5).
Comments: Clinical and biochemical blood parameters change depending on the period of the disease. Laboratory shifts are characterized by a slight increase in serum creatinine and urea levels, moderate hyperenzymemia (ALT, AST), and altered electrolyte levels – potassium, sodium, chlorine, and calcium.
It is recommended to perform an acid-base balance and blood gas analysis (blood hydrogen ion (pH) level, pCO2, standard plasma bicarbonate, and blood buffer substances) in patients with moderate and severe forms to determine pathogenetic therapy tactics [1, 2, 3, 4, 6, 9, 11, 14].
GCR CLEL 5Grading of Recommendations Assessment, Development and Evaluation — Recommendation Grade C (Level of Evidence – 5).
Comments: acid-base balance changes depending on the form and severity of the disease, typically characterized by the development of acidosis. Laboratory shifts are characterized by a decrease in blood pH, an increase in pCO2, and a decrease in standard blood bicarbonate.
It is recommended that all patients undergo microbiological (culture) examination of feces/rectal swab and, in the presence of vomiting, vomitus and gastric lavage fluid for Salmonella spp., microbiological (culture) examination of feces for typhoid and paratyphoid pathogens (Salmonella typhi, Salmonella Paratyphi A, Salmonella Paratyphi B), and rapid immunochromatographic stool testing for Salmonella spp. to confirm the etiology of the disease and select etiotropic therapy [1, 2, 3, 4, 6, 9, 11, 14].
GPP CLevel of Evidence 5Strength of Recommendation C (Level of Evidence – 5).
Comments: Isolation of a pure culture of the pathogen is the primary method of laboratory diagnosis; testing is preferably performed in the early stages of the disease before initiating antibacterial therapy. Ordinary media are suitable for isolating salmonellae from normally sterile environments, whereas fecal cultures require – selective media to suppress the growth of concomitant flora. Low-selectivity media include Ploskirev agar, MacConkey agar, deoxycholate agar, Levine's agar; moderately selective media include Salmonella-Shigella agar, xylose lysine deoxycholate agar; and bismuth sulfite agar is a highly selective medium for salmonellae.
It is recommended to use molecular biological testing of feces for Salmonella spp., determining Salmonella spp. DNA in stool samples by PCR, if laboratory capacity permits, for early confirmation of the disease etiology [1, 2, 3, 4, 6, 9, 11, 14]
GCR CLEL 5Grading of Recommendations Assessment, Development and Evaluation — Recommendation Grade C (Level of Evidence – 5).
Comments: detection of Salmonella spp. DNA is an auxiliary method used when rapid diagnosis is necessary.
It is recommended that patients with a severe clinical course and suspected generalized infection undergo microbiological (culture) blood testing for the typhoid-paratyphoid group of microorganisms and microbiological (culture) urine testing for bacterial pathogens using automated plating to confirm the etiology of the disease, rule out typhoid fever, and select etiotropic therapy [1, 2, 3, 4, 6, 9, 11, 14]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
It is recommended that patients with suspected salmonellosis and negative bacteriological test results for salmonellae undergo antibody testing and dynamic titer monitoring for Salmonella enterica in the blood, Salmonella paratyphi A antibodies in the blood, Salmonella paratyphi B antibodies in the blood, Salmonella paratyphi C antibodies in the blood, Salmonella typhi antibodies in the blood, and salmonella antigens in feces [1, 2, 3, 4, 6, 9, 11, 14]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Comments: serological testing: determination of antibody levels (IgM, IgG) by ELISA or anti-salmonella antibodies by indirect hemagglutination assay (IHA). This is an auxiliary method. Serological diagnostics (IHA, ELISA, IFA) are important only for epidemiological studies and determining the association of complications with a past infection.
2.4 Instrumental Diagnostics
It is recommended to perform a comprehensive ultrasound examination of the abdominal cavity, lymph nodes (one anatomical region), and kidneys in patients with suspected organ and system involvement or development of generalized forms to detect possible changes in internal organs and for differential diagnosis [1, 2, 3, 4, 6, 9, 11, 14]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
It is recommended to perform computed tomography of the abdominal cavity and magnetic resonance imaging of the abdominal cavity in patients with unclear focal changes in the abdominal cavity or ambiguous, contradictory data obtained from abdominal ultrasound, in order to clarify the detected pathology [1, 2, 3, 4, 6, 9, 11, 14]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
It is recommended to perform imaging studies: chest radiography in patients with auscultatory changes in the lungs to detect infiltrative lung changes and differentiate from pneumonia, and plain abdominal radiography in patients with suspected surgical pathology to detect free gas in the abdominal cavity and ensure timely consultation with a surgeon [1, 2, 3, 4, 6, 9, 11, 14]
Level of Evidence 5Strength of Recommendation C (Level of Evidence – 5).
2.5 Other Procedures
It is recommended to perform rigid sigmoidoscopy or colonoscopy in patients with clinical symptoms of salmonellosis and prolonged invasive diarrhea to objectively assess the nature of intestinal mucosal damage and for differential diagnosis [1, 2, 3, 4, 6, 9, 11, 14]
GPP CLevel of Evidence 5Strength of Recommendation C (Level of Evidence – 5).
It is recommended to record an electrocardiogram in patients with suspected cardiac involvement and auscultatory changes to detect cardiac alterations associated with microcirculatory disorders, hypoxia, and dystrophic changes [1, 2, 3, 4, 6, 9, 11, 14]
GCR CLEL 5Grading of Recommendations Assessment, Development and Evaluation — Recommendation Grade C (Level of Evidence – 5).
It is recommended to perform colonoscopy or video colonoscopy in patients with abdominal pain and signs of lower gastrointestinal bleeding in order to provide timely specialized care and conduct differential diagnosis [1, 2, 3, 4, 6, 9, 11, 14]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
It is recommended that patients presenting with emergency conditions receive an evaluation (examination, consultation) by an anesthesiologist-resuscitologist within 30 minutes of hospital admission to determine indications for transfer to the intensive care unit (ICU) [1, 2, 3, 4, 6, 9, 11, 14]
Level of Evidence 5Strength of Recommendation C (Level of Evidence – 5).
Recommended appointment (examination, consultation) by a surgeon for patients presenting with severe abdominal pain and hypotension within up to 30 minutes of hospital admission to rule out acute surgical pathology and determine indications for transfer to the surgical department [1, 2, 3, 4, 6, 9, 11, 14]
Level of Evidence 5Strength of Recommendation C (Level of Evidence – 5).
Recommended coagulogram (exploratory hemostasis study): unactivated clotting time of non-stabilized blood or plasma recalcification time, bleeding time, prothrombin (thromboplastin) time in blood or plasma, thrombin time in blood, and international normalized ratio (INR) determination in severe and complicated forms of the disease in case of generalized forms and complicated course for timely assessment of hemostatic parameter changes associated with DIC syndrome development requiring correction [27]
GCR CLEL 5Grading of Recommendations Assessment, Development and Evaluation — Recommendation Grade C (Level of Evidence – 5).
Recommended for patients with severe salmonellosis to undergo lumbar puncture to rule out CNS involvement [32]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Recommended for patients with severe salmonellosis to perform microscopic examination of cerebrospinal fluid and cell counting in a counting chamber (cytosis determination) to rule out CNS involvement [32]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Recommended for patients with severe salmonellosis to determine protein level in cerebrospinal fluid to rule out CNS involvement [32]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Recommended for patients with severe salmonellosis to perform microbiological (culture) blood test for sterility, microbiological (culture) urine and cerebrospinal fluid tests for aerobic and facultatively anaerobic opportunistic microorganisms to rule out generalization [32]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Recommended for patients with severe salmonellosis to study immunological status to rule out primary/secondary immunodeficiency [1, 2, 3, 4, 6, 9, 11, 14]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Recommended for patients with an atypical disease course to undergo a complex of studies to assess systemic inflammatory responses to rule out ulcerative colitis and Crohn's disease [32]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
3. Treatment, including drug and non-drug therapies, diet therapy, and pain management
Recommended is comprehensive and multifaceted treatment of patients with salmonellosis: protective regimen; meticulous hygienic care by medical staff for severely ill patients; therapeutic nutrition; targeted action against the pathogen; detoxification and restoration of homeostasis; resolution of structural and functional gastrointestinal changes [1, 2, 3, 4, 5, 9, 11, 12]
Level of confidence in recommendations C (level of evidence 5).
Recommended for patients in the acute period of salmonellosis with pronounced general infectious and local symptoms to keep a water balance record (fluid volume including oral and/or parenteral rehydration, food, losses with vomit, diarrhea, urination) and follow a sparing diet (2-4 days) [1, 2, 3, 4, 11, 12].
Level of confidence in recommendations C (level of evidence 5).
Comments: permitted: puréed vegetarian or lean meat broth cereal soups or first courses with finely chopped or puréed vegetables, various dishes made from lean meats; boiled dishes from lean fish, hard cheese; dried white bread, crackers, rusks, plain cookies. Baked, puréed apples are permitted.
3.1 Conservative Treatment
3.1.1 Etiotropic therapy
Not recommended is antimicrobial therapy for patients with mild gastrointestinal salmonellosis [1, 2, 3, 4, 11, 12]
LoE CGoE 5Level of confidence in recommendations C (level of evidence – 5).
Recommended is the administration of antibacterial therapy to patients who develop generalized forms and severe course of gastrointestinal salmonellosis, as well as moderate forms of gastrointestinal salmonellosis in individuals with a burdened premorbid background to reduce the severity of the disease and decrease the risk of specific complications [1, 2, 3, 4, 11, 12, 28].
LoE CGoE 5Level of confidence in recommendations C (level of evidence – 5).
Comments: when choosing systemic antibacterial drugs, it is necessary to be guided by the drug resistance of Salmonella strains circulating in the region.
Recommended for the above patient groups is the prescription of nifuroxazide, rifaximin, third-generation cephalosporins (cefotaxime**, ceftriaxone**, ceftazidime**, etc.), fluoroquinolones (ciprofloxacin**, etc.) with a treatment course duration of 7-14 days for etiotropic purposes [1, 2, 3, 4, 11, 12].
LoE CGoE 5Level of confidence in recommendations C (level of evidence – 5).
Comments: etiotropic treatment is prescribed after establishing the clinical and epidemiological diagnosis. Antibacterial therapy is carried out taking into account the sensitivity of Salmonella spp. to systemic antibacterial drugs; before receiving resistance assays, it is based on the drug resistance of Salmonella strains circulating in the region, and after receiving bacteriological test results and systemic antibacterial drug resistance data, drugs are replaced if necessary. Combination antibacterial therapy is used to treat patients with severe, complicated courses (fluoroquinolones and aminoglycosides; 3rd generation cephalosporins and aminoglycosides). The duration of the antibacterial therapy course is determined by the form and severity of the disease.
3.1.2 Pathogenetic therapy
Recommended is rehydration for patients with signs of dehydration, including oral rehydration and infusion therapy, in order to restore circulating blood volume; reduce intoxication; prevent specific complications (toxic-infectious shock, acute renal failure, pulmonary edema, cerebral edema, DIC syndrome); and correct water-electrolyte balance disorders [1, 2, 3, 4, 11, 12]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Comments: The volume and intensity of therapy are determined by the form, severity of the disease, and presence of complications. The principles of oral rehydration include fractional fluid administration and the use of solutions with an optimal composition (rehydration solutions with reduced osmolarity of 200-240 mOsm/l). Oral rehydration is carried out in two stages:
Stage I – within the first 6 hours after patient admission, the water-salt deficit that arose before the start of treatment is eliminated. Stage II – maintenance oral rehydration, which is carried out throughout the entire subsequent period of the disease in the presence of ongoing fluid and electrolyte losses. The effectiveness of oral rehydration is assessed by the following signs: a decrease in fluid loss volume; a decrease in the rate of body weight loss; disappearance of clinical signs of dehydration; normalization of diuresis; improvement in general condition.
Parenteral rehydration is resorted to in the absence of an effect from oral rehydration, in the development of grade II and II-III dehydration, in grade I-II dehydration combined with intoxication symptoms, and in the development of emergency conditions (toxic-infectious shock, dehydration shock, acute renal failure, etc.).
To correct dehydration, hypokalemia, and hyponatremia, the administration of saline solutions is recommended (potassium chloride + sodium acetate + sodium chloride**, potassium chloride + sodium acetate + sodium chloride, potassium chloride + calcium chloride + magnesium chloride + sodium acetate + sodium chloride**, potassium chloride + sodium bicarbonate + sodium chloride).
Recommended is the timely diagnosis of toxic-infectious shock and dehydration shock in all patients (within 10 min) for prompt condition stabilization within 6-8 hours [1, 2, 3, 4, 11, 12]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Recommended for patients with moderate and severe salmonellosis for detoxification purposes is the use of solutions affecting the water-electrolyte balance (800-1200 ml of 5% dextrose solution** intravenously drip, meglumine sodium succinate** at a rate of up to 90 drops/min (1-4.5 ml/min) – 400-800 ml/day. (Average daily dose is 10 ml/kg.) Volume and duration depend on the patient's severity and are carried out until intoxication symptoms are completely resolved [34-39].
GCR BLEL 2Grading of Recommendations Assessment, Development and Evaluation — Recommendation Grade B (Level of Evidence – 2).
Recommended for all patients is the oral administration of adsorbent intestinal preparations to bind and remove toxins from the gastrointestinal tract (activated charcoal 1-2 g – 3 or 4 times/day, diosmectite** (1 sachet 3 times a day, dissolving its contents in 1/2 cup of water), colloidal silicon dioxide (average daily dose in adults 0.1-0.2 g per 1 kg of body weight (6-12 g), taken 3-4 times/day, dissolved in 1/4-1/2 cup of water), hydrolysis lignin (orally, in the form of granules, powder, tablets (before meals) 3-4 times a day. Before use, the preparation is stirred/dissolved in a glass of water for 2 min, then slowly drunk. The dose is set individually, the average dose for adults is 5-7 g/day) [1, 2, 3, 4, 11, 12]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Comments: The direct action of intestinal adsorbent drugs is aimed at binding and eliminating metabolic toxins and inflammatory products from the gastrointestinal tract; their indirect action is due to the prevention or mitigation of the clinical manifestations of endotoxoxicosis, toxic-allergic reactions, and diarrheal syndrome. The average duration of use is 3–5 days for mild and moderate forms of the disease, and up to 10–14 days for severe forms.
It is recommended to prescribe medications for functional gastrointestinal disorders and antispasmodics to patients with pain syndrome to relieve smooth muscle spasms of the gastrointestinal tract [1, 2, 3, 4, 11, 12]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Comments: as adjunctive therapy.
It is recommended for patients during the convalescent period, once the acute inflammatory reaction has been controlled, to use antidiarrheal microorganisms (Bifidobacterium bifidum**, Lactobacillus, Saccharomyces boulardii, etc.) for 3–4 weeks to correct intestinal microbiocenosis [1, 2, 3, 4, 11, 12]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: Antidiarrheal microorganisms exert an antimicrobial effect through an antagonistic action against pathogenic and opportunistic microorganisms, exhibit cyto- and enterotoxin-neutralizing activity, and enhance the enzymatic function of the gut.
It is recommended to prescribe prebiotics (fructooligosaccharides, galactooligosaccharides, lactulose**) for 10–14 days after stool normalization in the convalescent period to stimulate the growth of normal intestinal microflora [1, 2, 3, 4, 11, 12]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
It is recommended to prescribe digestion-promoting medications, including enzyme preparations, for insufficient secretory function of the gastric, intestinal, and pancreatic glands as replacement therapy [1, 2, 3, 4, 11, 12]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
It is recommended to prescribe antiemetic drugs to patients with severe vomiting in the first days of the disease to regulate the motor activity of the upper gastrointestinal tract. [1,2,3,4,11,12]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Comments: antiemetic drugs reduce the sensitivity of visceral nerves transmitting impulses from the stomach and duodenum to the vomiting center. Through the hypothalamus and the parasympathetic nervous system, they exert a regulatory and coordinating effect on the tone and motor activity of the upper gastrointestinal tract.
3.2 Surgical Treatment
Not performed [1, 2, 3, 4, 11, 12].
4. Medical Rehabilitation and Sanatorium-Resort Treatment
4.1 Rehabilitation
It is recommended to initiate rehabilitation measures as early as the acute phase or the early convalescence period in all patients with salmonellosis [1, 2, 3, 4, 11, 12]
GCR CLEL 5 Grade of Recommendation C (Level of Evidence – 5)
It is recommended to implement a comprehensive approach to rehabilitation involving various specialists and utilizing diverse methods for all patients with salmonellosis [1, 2, 3, 4, 11, 12]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended to maintain consistency and continuity of implemented measures, ensuring seamlessness across various stages of rehabilitation and clinical follow-up (dispensary observation) for all patients with salmonellosis [1, 2, 3, 4, 11, 12].
LeRR CLOE 5Level of Recommendation Readiness C (Level of Evidence – 5)
It is recommended that rehabilitation and recovery measures be adequate to the adaptive and reserve capacities of the patient with salmonellosis [1, 2, 3, 4, 11, 12].
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: it is important to gradually increase dosed physical and mental stress, as well as to apply various intervention methods in a differentiated manner
It is recommended to continuously monitor the effectiveness of the implemented measures [1, 2, 3, 4, 11, 12].
Level of Evidence CGrade of Recommendation 5Level of Clinical Effectiveness C (level of evidence – 5)
Comments: the rate and degree of recovery of the functional state and occupationally significant functions of convalescents are taken into account (using indirect and direct methods).
5. Prevention and Dispensary Observation
5.1 Prevention
It is recommended that all healthcare facilities, regardless of ownership, that identify a patient or a carrier of salmonellosis submit a mandatory emergency notification to the territorial body exercising state sanitary and epidemiological surveillance [1, 2, 3, 4, 11, 12]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended that an epidemiological investigation of the salmonellosis outbreak be conducted by state sanitary and epidemiological surveillance authorities to determine the boundaries of the outbreak, identify the source of the pathogen, contact persons, and individuals at risk of infection, as well as to determine the routes and factors of pathogen transmission and the conditions that contributed to the outbreak [1, 2, 3, 4, 11, 12]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended to isolate patients suspected of having salmonellosis from organized groups and collectives [1, 2, 3, 4, 11, 12]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended to hospitalize identified patients (or patients with suspected salmonellosis) and bacterial carriers based on clinical and epidemiological indications [1, 2, 3, 4, 11, 12]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended to perform mandatory laboratory testing for salmonellosis using any methods available to the laboratory in the epidemic focus for identified patients with symptoms, individuals in contact with patients, and workers in specific occupations related to the production, storage, and transportation of food products and certain goods [1, 2, 3, 4, 11, 12]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: recommendations for laboratory testing for salmonellosis are provided in section 2.3 Laboratory Diagnostic Studies.
The number of examined individuals and the scope of tests performed are determined by the specialist responsible for organizing the epidemiological investigation.
It is recommended to test remnants of food products or dishes suspected of acting as a transmission factor, food raw materials, swabs from eggs, equipment, hands, utensils, and other environmental objects in the epidemic focus to identify the routes and factors of pathogen transmission [1, 2, 3, 4, 11, 12]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended that individuals at risk of infection in epidemic foci be monitored by medical staff of the institutions where the focus is registered or by territorial healthcare facilities [1, 2, 3, 4, 11, 12]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: the duration of medical observation is 7 days and includes questioning, physical examination, stool monitoring, and thermometry.
It is recommended to carry out disinfection in the household focus [1, 2, 3, 4, 11, 12]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: concurrent disinfection is carried out by family members after briefing by medical personnel. Terminal disinfection is performed by specialists from organizations authorized to engage in disinfection activities.
It is recommended to administer emergency prophylaxis using an immunobiological agent – a bacteriophage (ATC code: A07AX Other intestinal anti-infectives) – namely, Salmonella bacteriophage, to individuals at risk of infection [1, 2, 3, 4, 11, 12]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended that healthcare facilities comply with sanitary and hygienic standards and rules, as well as the anti-epidemic regime, in accordance with current regulatory legal acts on the prevention of nosocomial Salmonella infections [1, 2, 3, 4, 11, 12]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: monitoring and evaluation of compliance with sanitary and hygienic standards and rules, as well as the state of the anti-epidemic regime in healthcare facilities, are carried out by bodies exercising state sanitary and epidemiological surveillance, as well as by the healthcare facility's epidemiologist. To conduct pre-epidemic diagnostics in hospitals, monitoring of the circulation of "hospital" Salmonella strains is carried out, taking into account their antibiotic resistance and certain pathogenicity factors (persistent characteristics of strains – antilysozyme, anti-interferon, and other activities).
It is recommended to implement anti-epidemic measures to prevent nosocomial salmonellosis infection among patients and staff in healthcare facilities [1, 2, 3, 4, 11, 12]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: establishment of diagnostic wards (boxes) in non-infectious departments (admission units) for the hospitalization of patients with loose stools; examination of certain categories of patients upon admission to the hospital: children under 2 years of age, mothers and other persons hospitalized to care for patients, individuals admitted to psychoneurological inpatient facilities. Also, examination of individuals upon admission to specialized social service institutions for the elderly and disabled, and children under 2 years of age upon admission to orphanages; suspension from work of personnel with detected Salmonella carriage, treatment and follow-up dispensary observation; transfer of healthcare facility personnel with chronic Salmonella carriage to work not related to food handling, childcare, or the care of patients requiring continuous nursing care; monitoring the completeness of examination, timeliness of return to work, and dynamic follow-up observation of employees who have had salmonellosis; compliance with established requirements for preventive disinfection, hygienic treatment of patients' skin and body, hygienic and antiseptic treatment of personnel hands, disinsection, and deratization; monitoring of catering organization and food quality in accordance with regulatory and methodological documents, including enteral nutrition, nutrition of newborns and infants; monitoring the operation of supply and exhaust ventilation, the condition of basements and attics; monitoring compliance with the assortment, storage rules, and expiration dates of foods permitted to be passed to patients by visitors.
5.2 Dispensary monitoring
It is recommended that if positive results of control laboratory tests are obtained for workers in certain occupations, industries, and organizations after a repeated course of treatment, they shall be placed under dispensary observation with temporary transfer for 15 days to another job not related to the production, preparation, storage, transportation, and sale of food products, nor to work at water supply facilities, or direct care of children, the elderly, and disabled individuals in inpatient and round-the-clock residential facilities [1, 2, 3, 4, 11, 12]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
It is recommended to perform a single microbiological (culture) examination of feces/rectal swab for microorganisms of the genus Salmonella (Salmonella spp.) during these 15 days [1, 2, 3, 4, 11, 12]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
Comments: in case of a negative result – individuals are allowed to return to their main duties; in case of a positive result – testing is continued at 15-day intervals. If Salmonella is isolated for 3 months, such individuals are suspended from their main duties for a period of at least 1 year. Upon expiration of this period, a 3-fold microbiological (culture) examination of feces/rectal swab and a single examination of bile for microorganisms of the genus Salmonella (Salmonella spp.) are performed at 1-2 day intervals. If negative results are obtained, these individuals are cleared to return to their main duties. If at least one positive result is obtained, they are considered chronic bacterial carriers and are suspended from work where they may pose an epidemiological hazard.
It is recommended that workers in certain occupations, industries, and organizations, as well as adults and children staying in closed round-the-clock residential facilities who have recovered from acute forms of salmonellosis, be allowed to return to work and visit these institutions after discharge from the hospital or completion of outpatient treatment, based on a physician's certificate of recovery and provided they have a negative laboratory test result for salmonellosis [1, 2, 3, 4, 11, 12]
GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)
6. Organization of Medical Care
It is recommended to hospitalize patients with moderate, severe, and complicated forms of the disease, grade III-IV dehydration, generalized complications, or according to epidemiological indications, and to provide outpatient treatment for patients with mild forms of the disease in the absence of epidemiological or social indications for hospitalization [1].
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
It is recommended that an infectious disease specialist examine the patient no later than 20 minutes from the moment of admission to the hospital [1]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
It is recommended that discharge from the infectious disease department be based on clinical and laboratory indicators: achieved positive dynamics—absence of complaints, clinical symptoms, normalization of stool consistency, and negative bacteriological stool tests [1]
GR CLEL 5Grade of Recommendation C (Level of Evidence – 5).
Medical care for patients with salmonellosis is provided in the following forms:
primary health care;
emergency medical care, including specialized emergency medical care;
specialized medical care, including high-tech medical care.
Medical care for patients with salmonellosis may 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 includes:
primary pre-medical health care;
primary medical (physician-led) health care;
primary specialized health care.
Primary health care is provided in outpatient settings.
Primary health-care pre-medical services in outpatient settings are provided by mid-level medical personnel at feldsher-midwife stations, maternity hospitals, and primary and secondary vocational education institutions (hereinafter referred to as educational institutions).
Primary health-care medical services are provided by a district general practitioner or a general practitioner (family physician) in an outpatient setting. Upon suspicion or detection of an infectious disease in a patient that does not require inpatient treatment based on their health status, the district general practitioner (general practitioner / family physician, or mid-level medical staff of medical organizations or educational institutions) refers the patient, upon medical indications, for a consultation at the infectious diseases office of a medical organization to receive primary specialized health-care services.
Primary specialized health care is provided by an infectious disease specialist.
Specialized, including high-tech, medical care is provided by infectious disease specialists and includes prevention, diagnosis, treatment of diseases and conditions requiring the use of special methods and complex medical technologies, as well as medical rehabilitation.
Treatment is carried out in an inpatient setting upon referral by a district general practitioner, general practitioner (family physician), infectious disease specialist, or medical personnel who identified the infectious disease.
7. Additional Information
Factors negatively affecting the outcome of the disease include:
Late seeking of medical care and late admission to the hospital;
Presence of specific complications: toxic-infectious shock (TIS), disseminated intravascular coagulation (DIC) syndrome, dehydrational shock;
Presence of comorbid conditions aggravating the course of salmonellosis (HIV infection, oncopathology, etc.).
Criteria for Evaluating the Quality of Medical Care
№ | Quality criteria | Level of Evidence | Level of recommendation certainty |
|---|---|---|---|
1. Diagnosis stage | |||
1 | Examination by an infectious disease specialist was performed no later than 20 minutes from the moment of admission to the hospital | 5 | C |
2 | Examination by an anesthesiologist-resuscitologist was performed within 30 minutes from the moment of admission for patients with emergency conditions to determine indications for transfer to the intensive care unit (ICU) | 5 | C |
3 | Examination by a surgeon was performed for patients with intense abdominal pain and hypotension within 30 minutes from the moment of admission to rule out acute surgical pathology and determine indications for transfer to the surgical department | 5 | C |
4 | A general (clinical) blood count with differential leukocyte count was performed | 5 | C |
5 | A general (clinical) urinalysis was performed | 5 | C |
6 | A general biochemical blood test (investigation of blood urea, creatinine, total bilirubin levels, determination of alanine aminotransferase [ALT] and aspartate aminotransferase [AST] activity in the blood, and blood electrolyte testing [potassium, sodium, chlorides, total calcium levels]) was performed for patients with moderate and severe forms | 5 | C |
7 | An assessment of acid-base balance and blood gases (blood pH, pCO2, standard plasma bicarbonate, capillary blood buffer bases) was performed for patients with moderate and severe forms. | 5 | C |
8 | A coagulogram (exploratory study of the hemostatic system) was performed in severe and complicated forms of the disease | 5 | C |
9 | A microbiological (culture) examination of feces/rectal swab and, in the presence of vomiting, vomitus and gastric lavage fluid for microorganisms of the genus Salmonella (Salmonella spp.), as well as microbiological (culture) examination of feces for the causative agents of typhoid fever and paratyphoid fevers (Salmonella typhi, Salmonella Paratyphi A, Salmonella Paratyphi B), and a rapid immunochromatographic stool test for Salmonella (Salmonella spp.) were performed | 5 | C |
10 | For patients with severe illness and suspected systemic infection, a microbiological (culture) examination of blood for the typhoid-paratyphoid group of microorganisms and a microbiological (culture) examination of urine for bacterial pathogens using automated seeding were performed | 5 | C |
11 | If laboratory capabilities permit, a molecular biological examination of feces for microorganisms of the genus Salmonella (Salmonella spp.) and detection of Salmonella spp. DNA in stool samples by PCR were performed | 5 | C |
12 | Rectosigmoidoscopy and/or colonoscopy was performed in patients with clinical symptoms of salmonellosis and prolonged invasive-type diarrhea | 5 | C |
2. Treatment stage | |||
13 | Treatment with systemic antibacterial drugs (nitrofuran derivatives, fluoroquinolones, third-generation cephalosporins) was performed | C | 5 |
14 | Rehydration therapy was administered to patients with signs of dehydration | 5 | C |
15 | Timely diagnosis (within 10 min) and stabilization of condition (within 6-8 hours) were achieved in cases of toxic-infectious shock (TIS) and dehydrational shock | 5 | C |
16 | Positive dynamics—absence of complaints, clinical symptoms, normalization of stool consistency, and negative bacteriological stool tests—were achieved by the time of discharge from the hospital | 5 | C |
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Appendix A1. Working Group Composition
Alena N. Burganova – Associate Professor, Department of Infectious Diseases with the Course of Advanced Professional Education, Bashkir State Medical University, Ministry of Health of Russia, Candidate of Medical Sciences
Damir A. Valishin – Head of the Department of Infectious Diseases with the Course of Postgraduate Education, Bashkir State Medical University, Ministry of Health of Russia, Doctor of Medical Sciences, Professor
Aleksandr V. Gorelov – Academician of the RAS, Professor, Deputy Director for Research, 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, Ministry of Health of Russia
Gulnara R. Latypova – Assistant, Department of Infectious Diseases with the Course of Advanced Professional Education, Bashkir State Medical University, Ministry of Health of Russia, Candidate of Medical Sciences
Ksenia E. Novak – Associate Professor, Department of Adult Infectious Diseases and Epidemiology, St. Petersburg State Pediatric Medical University, Ministry of Health of Russia, Candidate of Medical Sciences, Associate Professor
Denis V. Usenko – Doctor of Medical Sciences, Head of the Educational Center, Leading Researcher, Clinical Department of Infectious Pathology, Central Research Institute of Epidemiology of Rospotrebnadzor
Vladimir P. Chulanov – Deputy Director for Research and Innovative Development, National Medical Research Center of Phthisiopulmonology and Infectious Diseases, Ministry of Health of the Russian Federation, Doctor of Medical Sciences, Professor
Liana R. Shaykhullina – Associate Professor, Department of Infectious Diseases with the Course of Advanced Professional Education, Bashkir State Medical University, Ministry of Health of Russia, Candidate of Medical Sciences
Elena V. Esaulenko – Head of the Department of Adult Infectious Diseases and Epidemiology, St. Petersburg State Pediatric Medical University, Ministry of Health of Russia, Doctor of Medical Sciences, Professor
All members of the working group are members of the Non-Profit Partnership "National Association of Infectiousists" (NAI).
There is no conflict of interest.
Appendix A2. Methodology for Developing Clinical Guidelines
Target audience of the clinical guidelines:
Infectious disease specialist;
General practitioner (internist);
Gastroenterologist;
General practitioner;
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 evidence certainty for diagnostic interventions
LoE | Hierarchy of clinical research designs in descending order of levels of evidence certainty from 1 to 5 |
|---|---|
1 | Systematic reviews of studies controlled with a reference method1 |
2 | Individual studies with reference standard control |
3 | Studies without consecutive reference standard control or studies with a reference standard that is not independent of the evaluated method |
4 | Non-comparative studies, case report |
5 | Only justification of mechanism of action or expert opinion is available |
1The generally accepted standard for diagnostic intervention clinical trials is a cross-sectional study design, in which the investigational diagnostic method and the reference method—acting as the "gold standard" for diagnosing the disease or condition under study—are applied in parallel and under identical conditions to each included patient. 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 А2 – Scale for determining the level of reliability of evidence (LRE) for diagnostic interventions
GoR | Hierarchy of clinical research designs in descending order of levels of evidence certainty from 1 to 5 |
|---|---|
A | Unambiguous (strong) recommendation (all studies are of high or moderate methodological quality, and their conclusions on the outcomes of interest are consistent) |
C | Ambiguous (conditional) recommendation (not all studies are of high or moderate methodological quality and/or their conclusions on the outcomes of interest are inconsistent) |
C | Low (weak) recommendation – lack of adequate quality evidence (all studies are of low methodological quality, and their conclusions on the outcomes of interest are inconsistent) |
Table P3 – Possible combinations of LCE and LCR for diagnostic interventions
LoE | Criteria for determining GGR | Final GoR |
|---|---|---|
1 = Most reliable evidence: systematic reviews of studies with control by a reference method | Both of the following conditions are met: 1. All studies are of high or fair methodological quality; 2. Study findings for the outcomes outcomes are consistent* | A |
Fulfilling at least one of the following conditions: 1. Not all studies are of high or fair methodological quality; 2. Study conclusions regarding outcomes of interest are not consistent* | C | |
Fulfilling at least one of the following conditions: 1. All studies have low methodological quality; 2. Study findings for the outcomes of interest are inconsistent* | C | |
2 = Individual studies with control by a reference method | Both of the following conditions are met: 1. All studies are of high or satisfactory methodological quality; 2. Study conclusions regarding outcomes of interest are consistent* | A |
Fulfilling at least one of the following conditions: 1. Not all studies are of high or fair methodological quality; 2. Study conclusions regarding outcomes of interest are not consistent* | C | |
Fulfilling at least one of the following conditions: 1. All studies are of low methodological quality; 2. Study conclusions regarding outcomes of interest are not consistent* | C | |
3 = Studies without sequential control by a reference method or studies with a reference method that is not independent of the evaluated method | Fulfilling at least one of the following conditions: 1. Not all studies are of high or fair methodological quality; 2. Study conclusions regarding outcomes of interest are not consistent* | C |
Fulfilling at least one of the following conditions: 1. All studies are of low methodological quality; 2. Study conclusions regarding outcomes of interest are not consistent* | C | |
4 = Non-comparative studies, case series/case report | C | |
5 = Least reliable evidence: only a rationale for the mechanism of action or expert opinion is available | C | |
*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 S4 – Levels of evidence (LoE) for therapeutic, rehabilitative, and preventive interventions
LoE | Hierarchy of clinical research designs in descending order of levels of evidence certainty from 1 to 5 |
|---|---|
1 | Systematic review of randomized controlled trials with meta-analysis |
2 | Individual randomized clinical trials and systematic reviews of studies of any design except randomized clinical trials with meta-analysis |
3 | Non-randomized comparative studies, including cohort studies |
4 | Non-comparative studies, case reports or case series, case-control studies |
5 | There is only justification for the mechanism of action of the intervention (preclinical studies) or expert opinion. |
Table P5 – Scale for determining the grades of recommendation for therapeutic, rehabilitation, and preventive interventions
GoR | Definition |
|---|---|
A | Unambiguous (strong) recommendation (all evaluated efficacy criteria (outcomes) are important, all studies are of high or moderate methodological quality, and their conclusions on the outcomes of interest are consistent) |
C | Ambiguous (conditional) recommendation (not all efficacy criteria (outcomes) are important, not all studies are of high or satisfactory methodological quality and/or their results regarding the outcomes of interest are inconsistent) |
C | Low (weak) recommendation – lack of adequate quality evidence (all evaluated efficacy criteria (outcomes) are unimportant, all studies are of low methodological quality, and their conclusions on the outcomes of interest are inconsistent) |
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:
Federal Law No. 323-FZ of November 21, 2011, "On the Fundamentals of Protecting the Health of Citizens in the Russian Federation" (Collected Legislation of the Russian Federation, 2011, No. 48, Art. 6724);
Federal Law of the Russian Federation No. 326-FZ of November 29, 2010, "On Compulsory Medical Insurance in the Russian Federation";
Order of the Ministry of Health and Social Development of Russia No. 69n of January 31, 2012, "On Approval of the Procedure for Providing Medical Care to Adult Patients with Infectious Diseases", registered with the Ministry of Justice of the Russian Federation on April 4, 2012, registration No. 23726;
Order of the Ministry of Health and Social Development of Russia No. 1664n of December 27, 2011, "On Approval of the Nomenclature of Medical Services", registered with the Ministry of Justice on January 24, 2012, registration No. 23010;
Order of the Ministry of Health and Social Development of Russia No. 541n of July 23, 2010, "On Approval of the Unified Qualification Reference Book of Positions of Managers, Specialists, and Employees, Section 'Qualification Characteristics of Employee Positions in Healthcare'", registered with the Ministry of Justice of the Russian Federation on August 25, 2010, registration No. 18247.
SanPiN 3.3686-21 "Sanitary and Epidemiological Requirements for the Prevention of Infectious Diseases" XXXI. Prevention of Viral Hepatitis A and E (Registered with the Ministry of Justice of Russia on February 15, 2021, No. 62500).
Differential diagnosis
Carried out taking into account clinical polymorphism and the features of the disease course.
Gastrointestinal forms of salmonellosis must be differentiated from acute intestinal infections caused by other pathogens (Campylobacter, Shigella, pathogenic Escherichia, rotaviruses, adenoviruses, caliciviruses, etc.), and bacterial food poisoning (staphylococcal toxin, C. perfringens toxin, B. cereus toxin).
Generalized forms of salmonellosis are differentiated from sepsis of various etiologies. In case of severe abdominal pain, acute appendicitis, pseudotuberculosis and yersiniosis, intestinal intussusception, etc., are ruled out. In case of prolonged damage to the colon, Crohn's disease and ulcerative colitis must be ruled out (via colonoscopy with endoscopic biopsy of the colon). A comprehensive assessment of the severity of dehydration, hemorrhagic, and renal syndromes reflects the severity and prognosis of the infection [1, 2, 3, 4, 5, 10, 14, 17].
Differential diagnosis of salmonellosis and shigellosis
Clinical features | Salmonellosis | Shigellosis |
|---|---|---|
Incubation period | 2-72 hours | 1-7 days |
Onset of the disease | Hyperacute or acute | Acute, sometimes with a short prodrome |
Type of disease progression | Rapid | Slower |
Patient appearance | Paleness, cyanosis of the extremities | Average |
Body temperature | Often high | Often normal |
Duration of fever | Often 5-7 days | Often 3-5 days |
Cardiovascular system | Tachycardia, arterial hypotension, muffled heart sounds | Arterial hypotension, muffled heart sounds less frequently |
Nervous system involvement | Weakness, headache, insomnia | Weakness, headache |
Tenderness upon palpation of the anterior abdominal wall | Predominantly in the epigastrium and around the umbilicus | Along the colon, predominantly in the sigmoid region |
Liver | Hepatomegaly often | Normal |
Rectosigmoidoscopy and colonoscopy | Predominantly mild catarrhal proctosigmoiditis or normal mucous membrane | Pronounced catarrhal proctosigmoiditis; at the height of the disease, destructive changes in the mucous membrane (hemorrhages, erosions, ulcers) are characteristic |
Stool | Abundant, watery, greenish or dark brown in color, with a foul odor, often with an admixture of greenery and mucus, sometimes resembling "swamp slime." Frequency of defecation up to 10 times, less frequently more than 10 times per day. | Scanty, with streaks of mucus and blood, often more than 10 times a day |
False urges (tenesmus) | Not characteristic | Characteristic |
Peripheral blood | Leukocytosis. With hemoconcentration, an increase in hematocrit, hemoglobin, and erythrocyte count | Minor leukocytosis |
Bacteriological examination | Isolation of salmonella from gastric lavage fluid, feces. In generalized forms, from blood and urine | Isolation of shigella from feces |
Serological testing | Presence of antibodies and their dynamic increase to Salmonella enterica starting from the 2nd week of the disease | Presence of antibodies and their dynamic increase to Shigella spp starting from the 2nd week of the disease |
Criteria for assessing severity based on clinical and laboratory diagnostics
Clinical features | Severity grade | ||
|---|---|---|---|
mild | moderate | severe | |
Maximum body temperature elevation, 0C | Up to 37.9 | 38-39,5 | 39.6 and higher |
Duration of body temperature above 390C, days | 1-2 days | 2-4 days | 5 or more, hypothermia possible |
Severity and duration of intoxication | Absent or mild, 1-3 days | Moderate severity, 3-4 days | Pronounced, more than 6-8 days |
Loss of appetite, days | Up to 4 | Up to 5-6 | 7 or more |
Maximum blood pressure, mm Hg | Above 110 | 90-110 | Below 90 |
Duration of arterial hypotension below 100 mm Hg, days | - | - | More than 5 |
Nausea. Vomiting | Absent or single episode | Nausea, recurrent vomiting | Repeated vomiting |
Stool character and frequency | Semi-formed or loose greenish stool, 2-5 times a day. Duration 1-3 days | Watery stool with mucus admixture, 6-15 times a day. Duration 4-7 days | Diarrhea more than 15 times a day with admixture of mucus and blood. Duration 7 days or more. |
Tongue | Moist, moderately coated | Slightly dry, heavily coated | Dry, densely coated |
Pain syndrome | Epigastric pain, sometimes mild and diffuse | Abdominal pain, mostly diffuse, moderately pronounced | Intense abdominal pain lasting more than 7 days |
Hepatomegaly | - | ± | +++ |
Splenomegaly | - | ± | +++ |
Jaundice | - | - | ± |
Severity of dehydration symptoms | - | Grade 1, 1-2 | Grade 2-3 |
Complications: | |||
Toxic-infectious shock | - | - | + |
Dehydration shock | - | - | + |
Acute renal failure | - | - | + |
Myocarditis, etc. | - | - | + |
Hematocrit level | Normal | Normal or elevated | Sharply elevated |
Leukocyte count | Leukocytes normal or elevated up to 10×109/L | Leukocytes elevated up to 20×109/L | Leukocytes elevated above 20×109/L |
Creatinine and urea levels | Normal | Normal | Elevated |
Potassium level | Normal or decreased | Normal or decreased | Elevated |
Albumin concentration | Normal | Normal or decreased | Decreased |
Acid-base balance parameters | Normal | Normal or altered | Severely altered |
Appendix B. Physician Action Algorithms
Appendix C. Patient Information
Salmonellosis is an infectious disease caused by various species of bacteria of the genus Salmonella. Salmonellosis is characterized by a variety of clinical manifestations and can present in both asymptomatic and severe septic forms. In most cases, salmonellosis in children and adults leads to lesions of the digestive tract, which are frequently complicated by toxic and dehydrating shock.
Currently, researchers know more than 2,000 Salmonella serotypes. Domestic birds and animals are the main sources of salmonellosis, although humans can also act as carriers. Most often, salmonellosis symptoms appear after consuming contaminated food and develop due to improper food preparation. Special risk groups include: mammalian meat and poultry, fish, eggs, milk, cottage cheese, and sour cream. Salmonellosis can also be contracted by consuming substandard water from open bodies of water or municipal water supplies.
Upon entering the body, salmonellae rapidly overcome the protective barriers of the stomach and invade the mucosa of the small intestine. Their activity is accompanied by the intensive release of toxins, which cause the main clinical signs of salmonellosis. This includes the development of nosocomial outbreaks, where the disease is transmitted through household contact; in such cases, salmonellosis symptoms usually appear within 3-8 days.
The most common form of salmonellosis is gastrointestinal, diagnosed in 96-98% of patients seeking medical attention with suspected salmonellosis. The initial clinical signs of the infection depend on the severity of the disease and the prominence of clinical symptoms, which include: general weakness, headache, body temperature rise up to 40 °C and above, nausea, vomiting, periumbilical pain, and stool disorders.
Symptoms of salmonellosis indicating gastrointestinal involvement appear 2-3 days after the onset of the disease. In the first days, the patient feels only mild intoxication and fever. In mild salmonellosis, symptoms are rather mild, and the patient practically experiences no unpleasant consequences of the infection. A completely different picture is observed when severe gastrointestinal salmonellosis develops, requiring inpatient treatment. In this form of salmonellosis, patients suffer from: high fever lasting more than 5 days; pronounced intoxication; foul-smelling, watery stool (10 times a day or more), sometimes mixed with mucus; skin pallor; a significant drop in blood pressure; tachycardia; hepatosplenomegaly; renal involvement, oliguria, and acute renal failure.
If left untreated, salmonellosis in children and adults leads to significant water-electrolyte metabolism disorders and grade II-III dehydration. In this state, patients exhibit cramps, dry skin, cyanosis, and aphonia. Fluid loss frequently reaches 10-12% of body weight, causing multiple dysfunctions in major body systems. The most frequent clinical variant of the gastrointestinal form is gastroenteritic salmonellosis, the consequences of which manifest as destructive changes in the large intestine and colitis.
The typhoid-like form of salmonellosis begins acutely, manifesting with intestinal disorders in the very first days after disease onset, but intestinal dysfunction resolves after a few days. Nevertheless, the patient's temperature remains steadily high. Patients also exhibit: apathy, lethargy, skin pallor, and herpetic or roseolous rash. In some cases, typhoid-like salmonellosis leads to bradycardia, decreased blood pressure, and muffled heart sounds. Signs of liver and spleen involvement appear by the end of the 1st week.
Septic salmonellosis: symptoms of this form are very severe and life-threatening. The disease begins with high fever, and the patients' condition progressively deteriorates. Patients exhibit the following signs of salmonellosis: profuse sweating, significant daily fluctuations in body temperature, severe chills, formation of purulent foci in the musculoskeletal system, endocarditis and aortitis with subsequent aneurysm development, tonsillitis, and cholecystocholangitis.
The septic form also leads to other serious consequences: meningitis (most commonly seen in children with salmonellosis), liver abscess, ovarian infection, and gluteal abscess. The disease is characterized by a protracted course and can be fatal; therefore, upon any suspicion of salmonellosis, treatment should be initiated as early as possible following mandatory consultation with medical specialists.
It is necessary to consult a doctor in a timely manner (within the first 2-3 days of illness). If the doctor identifies symptoms suggestive of salmonellosis, the following tests are prescribed on the same day: complete (clinical) blood count, urinalysis, stool culture, and gastric lavage fluid analysis, the results of which help clarify the diagnosis. If the diagnosis is confirmed or suspicion of severe salmonellosis persists, the patient is referred to an infectious diseases hospital on the same day. Timely hospitalization allows for necessary therapy to be initiated, prevents complications, and promotes faster recovery.
Rational nutrition of patients plays an important role in the ward. Food should be easily digestible, contain a sufficient amount of vitamins, with no restriction on table salt. In the first days of illness, abundant fluid intake is indicated (tea, non-carbonated mineral waters).
Patients are discharged from the hospital upon normalization of their condition, absence of fever and clinical symptoms, normal stool, and negative stool culture results for Salmonella. After discharge, convalescents are advised to follow a balanced diet rich in macro- and micronutrients and vitamins, excluding spicy, pungent foods and alcohol.
If asthenic syndrome persists (weakness, fatigue, decreased appetite), a sparing regimen, fractional meals, multivitamins, B-group vitamins, herbal medicine (rosehip and lingual berry decoction), and anti-diarrheal micro-organisms (Bifidobacterium bifidum**, Lactobacillus), anti-diarrheal micro-organisms (lactulose**, etc.) are recommended. In the absence of complaints and with a negative stool culture, patients who have suffered from salmonellosis are removed from follow-up monitoring.
Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools
Appendix G1. Allgower Shock Index
Russian title: Allgower shock index
Original title (if applicable): -
Source (official developer website, validation publication): [34, 35]:
Type: index
Purpose: Determination of blood loss volume
Content (template):
Circulating blood volume (CBV) deficit, % of expected CBV | Shock index |
|---|---|
0 | 0,54 |
10-20 | 0,78 |
20-30 | 0,99 |
30-40 | 1,11 |
40-50 | 1,38 |
Key (interpretation): Allgower Index
(ratio of pulse rate to systolic blood pressure):
0.8 – blood loss volume 10%
0.9-1.2 – blood loss volume 20%
1.3-1.4 – blood loss volume 30%
1.5 – blood loss volume 40%
(blood volume in men 5200 ml, in women 3900 ml)
Notes: ___________________________________________________________