Shigellosis: Clinical Guidelines

List of Abbreviations

CDC – Centers for Disease Control and Prevention

Sd1 – Shigella dysenteriae 1

WHO – World Health Organization

Infectious toxic shock

ELISA – Enzyme-linked immunosorbent assay

IDD – Infectious Diseases Department / Clinic

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

OKONH – All-Union Classifier of the National Economy Branches

CHI – Compulsory Health Insurance

MPS – Simple Medical Procedure

PTI – Food-borne Toxicoinfection

PCR – Polymerase chain reaction

AHA – Agglutinating Hemagglutination Assay

IFA – Immunofluorescence Assay

CoA – Coagglutination Assay

LA – Latex Agglutination Assay

Ultrasound – Ultrasound Investigation

FL – Federal Law

** - included in the list of vital and essential drugs for medical use. CDC - Centers for Disease Control and Prevention

Sd1 – Shigella dysenteriae 1

WHO – World Health Organization

Infectious toxic shock

ELISA – Enzyme-linked immunosorbent assay

IDD – Infectious Diseases Department / Clinic

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

OKONH – All-Union Classifier of the National Economy Branches

CHI – Compulsory Health Insurance

MPS – Simple Medical Procedure

PTI – Food-borne Toxicoinfection

PCR – Polymerase chain reaction

AHA – Agglutinating Hemagglutination Assay

IFA – Immunofluorescence Assay

CoA – Coagglutination Assay

LA – Latex Agglutination Assay

Ultrasound – Ultrasound Investigation

FL – Federal Law

** - included in the list of vital and essential drugs for medical use

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 is 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, 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.

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

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

Medical intervention is any type of medical examination and/or medical manipulation, as well as artificial termination of pregnancy, performed by a medical worker or other healthcare professional with the right to carry out medical activities in relation to a patient, affecting their physical or mental state and having a prophylactic, diagnostic, therapeutic, rehabilitative, or research focus.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Shigellosis (bacterial dysentery, shigellosis, dysenteria) is an acute anthroponotic infectious disease caused by bacteria of the genus Shigella with a fecal-oral transmission mechanism, characterized by symptoms of general intoxication and predominant involvement of the distal large intestine.

The term "dysentery" was used by Hippocrates to describe a clinical syndrome complex characterized by diarrhea and abdominal pain. The term closest to the modern definition of dysentery is sekiri ("red diarrhea"), which was widespread in China and Japan to denote conditions characterized by small-volume stools with mucus, blood, and painful defecation. It was only in 1898 that the Japanese researcher Kiyoshi Shiga isolated a bacillus from patients' stool samples, which was recognized as the causative agent of bacterial dysentery. Due to the establishment of different etiologies for dysentery, the medical literature of the first half of the 20th century used the terms "bacillary" and "amebic" dysentery. Currently, dysentery refers exclusively to diseases caused by shigellae. It belongs to socially significant diarrheal diseases. [1,2,3,12,28].

Amebic dysentery (A06.0) is an acute protozoan anthroponosis characterized by ulceration of the large intestine and general intoxication symptoms, and is therefore included in the differential diagnostic list of diseases when shigellosis is suspected.

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

Despite the diversity of shigella species, S. flexneri and S. sonnei have the greatest epidemiological significance globally. S. flexneri is the main cause of epidemic shigellosis in developing countries. In Russia, which has a long tradition of mass production and consumption of dairy products, and other industrialized countries of the Northern Hemisphere, a high incidence of Sonne shigellosis is observed. Poorly controlled by sanitary and hygienic methods, Sonne shigellosis has earned the definition of a "disease of civilization" due to its ability to cause outbreaks in modern public catering and food industry enterprises, schools and preschool childcare facilities, elite military units, and among compact communities of homosexual individuals.

Shigella species are non-motile, Gram-negative bacteria of the genus Shigella within the family Enterobacteriaceae, classified as facultative anaerobes; they grow well on ordinary nutrient media, forming S- and R-colonies. [1,2,3,4,5,12]

Identification of shigellae is based on their biochemical and antigenic (O-antigen) properties, according to which four serogroups are distinguished (Table 1):

Classification of bacteria of the genus Shigella

Serogroup A: *S. dysenteriae* (15 serotypes, including: *S. dysenteriae* serotype 1 — Grigoriev-Shiga bacillus (produces Shiga toxin); *S. dysenteriae* serotype 2 — Stutzer-Schmitz bacillus; *S. dysenteriae* serotypes 3–7 — Large-Sachs bacillus);

Serogroup B: *S. flexneri* (8 serotypes, including: *S. flexneri* serotypes 1–6 — S. newcastle; and 9 subserotypes)

Serogroup C: S. boydii (19 serotypes)

Serogroup D: S. sonnei (serologically homogeneous)

Groups A-C are physiologically similar; S. sonnei can be differentiated based on biochemical tests of its metabolism.

A common and essential property of all members of the genus Shigella is invasiveness—the ability to intracellularly penetrate, multiply, and parasitize cells of the colonic mucosa (predominantly in the distal segment) and resident macrophages of the lamina propria. In addition to invasiveness, shigellae exhibit colicinogeny—the ability to synthesize colicins, which are substances causing the death of related bacterial species (hence colicin typing and colicin types of shigellae, e.g., S. boydii P-I produces colicin S1, S. sonnei P-9 produces colicin S3+1, etc.), and they also produce hyaluronidase, fibrinolysin, and lecithinase.

Different shigella species differ sharply in their initial biological properties, which ultimately determines the degree of their virulence and pathogenicity for humans. The highest virulence is exhibited by S. dysenteriae 1, which produces not only endotoxin but also one of the most potent exotoxins—Shiga toxin—which irreversibly inhibits protein synthesis by intestinal epithelial ribosomes and exhibits enterotoxin and neurotoxin properties. It is hypothesized that Shiga toxin can destroy capillary endothelium and cause tissue ischemia in the intestine, and systemic absorption of this exotoxin can lead to hemolytic-uremic syndrome and thrombotic microangiopathy.

Certain other shigella species are also capable of producing Shiga-like toxins, but with substantially lower activity. The exceptionally high virulence properties of S. dysenteriae 1 determine the extremely low infectious dose of Sd1: from a few to 200 viable microbial cells. For other shigella species, the infectious dose is one to two orders of magnitude higher.

The virulence of S. flexneri, especially S. flexneri 2a, is quite high. The deficiency in virulence of S. sonnei is compensated by their high biochemical activity and multiplication rate in infected substrates (salads, vinaigrettes, boiled meat, minced meat, boiled fish, milk and dairy products, fruit compotes, and kissels). Accumulation of the infectious dose of S. sonnei in milk at room temperature takes from 8 to 24 hours. In hot weather, these periods are drastically reduced and do not exceed 1–3 hours (for children). During the multiplication of S. sonnei in food products, a heat-stable endotoxin accumulates, capable of causing severe disorders even when bacteriological testing of the infected food yields negative results. S. sonnei is distinguished by high antagonistic activity against saprophytic and lactic acid microflora. An important feature of Sonne shigellae is resistance to antimicrobial drugs [2,5,12,16,31].

Shigellae are relatively resistant to environmental factors and can persist for long periods on household items; in water, they remain viable for up to two to three weeks (specifically S. flexneri and S. sonnei), and in a dried or frozen state, for up to several months. Conversely, high temperatures promote their rapid destruction: above 60°C within 10 minutes, and instantly upon boiling. Shigellae exhibit high sensitivity to disinfectants, ultraviolet radiation, and direct sunlight, especially S. flexneri. In recent years, thermotolerant strains of S. flexneri and S. sonnei (capable of surviving at 59°C) have been isolated [2,5,12].

Amebiasis is caused by Entamoeba histolitica, which is widespread in Southeast Asia, Africa, South and Central America. In the Russian Federation, endemic areas include the southern part of Primorsky Krai and the Republic of Dagestan. Imported cases from Georgia, Armenia, Tajikistan, and Kyrgyzstan are possible. The source of infection is a human excreting cysts of the dysentery amoeba in feces; the transmission mechanism is fecal-oral; transmission factors include soil, sewage, open water bodies, household and work items, fruits, vegetables, food products, and hands contaminated with Entamoeba histolitica cysts.

Pathogenesis

Shigellae possess quite pronounced virulence properties, as a result of which the disease can develop even at a low infectious dose (unlike other enteropathogenic bacteria, e.g., salmonellae and E. coli). Due to relative resistance to gastric juice and bile acids, shigellae pass through the gastric barrier and the proximal small intestine without losing their virulence [1,2,3,4,5].

The pathogenesis of shigellosis involves small- and large-intestinal phases, the severity of which determines the clinical course variant of the disease.

In patients with the typical, colitic variant of acute dysentery, the small-intestinal phase is not clinically manifested at all, and the disease initially presents with lesions of the distal large intestine.

The small-intestinal phase is usually short-lived and limited to two to three days. The initial translocation of shigellae across the epithelial barrier is carried out by specialized M cells capable of transporting both the bacteria themselves and their antigens into the lymphoid formations of the intestine (follicles, Peyer's patches) with their subsequent penetration into epithelial cells and resident macrophages. Toxic substances released during the translocation of shigellae (exo- and endotoxins, enterotoxins, etc.) initiate the development of intoxication syndrome, which in shigellosis always precedes the development of diarrheal syndrome.

The key virulence factor of shigellae is their invasiveness. Via macrocytopinocytosis, shigellae penetrate into the cytoplasm of epithelial cells, where they very quickly lyse the phagosomal membrane, leading to cell damage and death. Subsequent spread of shigellae occurs through the basolateral membranes of epithelial cells. Damage and destruction of epithelial cells are accompanied by inflammatory infiltration of the lamina propria by polymorphonuclear leukocytes, the formation of ulcers and erosions of the colonic mucosa, which clinically manifests as exudative-type diarrhea. The capacity for invasion and intracellular multiplication of shigellae is encoded by genetic mechanisms whose expression occurs only under in vivo conditions. Despite their invasiveness, shigellae are not capable of deep spread, which is why systemic dissemination of the pathogen in shigellosis generally does not occur (except for S. dysenteriae 1, especially in severe and extremely severe courses) [1,2,3,4,11,12,25].

Shigella toxins have a pronounced enterotropic effect and lead primarily to local disorders in the large intestine:

- acting reflexively on the neural apparatus of the intestine, they alter blood and lymph circulation in it;

- acting on Meissner's and Auerbach's plexuses, they lead to intestinal spasm, pain syndrome, and frequent stools.

The general effect of the toxin consists in:

- the development of intoxication syndrome, the extreme degree of which is infectious-toxic shock;

- damage to the central nervous system, leading to the formation of excitation foci in autonomic innervation centers in the abdominal ganglia and spinal cord segments;

- suppression of the sympathoadrenal system, development of vagotonia, which is characterized by hypotension down to collapse, and increased frequency of defecation;

- blocking of cellular respiration and oxidative phosphorylation, and disruption of carbohydrate, protein, and lipid metabolism.

Intestinal motility is an important defense mechanism that limits and prevents the attachment and invasion of shigellae to epithelial cells, as clearly demonstrated by the prolongation and aggravation of the infectious process in individuals receiving motility-suppressing drugs.

Dysbiotic changes in the normal microflora of the large intestine observed in patients with shigellosis have a significant impact on the rate of mucosal repair during the convalescence stage and the restoration of functional intestinal activity.

Pathogenesis of amebic dysentery: infection occurs when mature cysts (tetranucleate) enter the human digestive system, followed by excystation in the small intestine and the formation of lumen amoeba forms, which localize in the proximal large intestine (cecum). Pathogenic forms of amoeba produce trypsin, which destroys the epithelial cells of the mucosa. The tissue form of amoeba produces hyaluronidase, collagenase, and phospholipase A, which dissolve the connective tissue of the mucosal, submucosal, and muscular layers. Multiplying in the intestinal wall, the amoeba causes microabscesses that rupture into the intestinal lumen, forming mucosal ulcers predominantly in the cecum and the ascending colon.

1.3 Epidemiology of the Disease or Condition

Shigellosis is registered everywhere, but it is most common in developing countries (99% of all registered cases) among populations with poor sanitation and hygiene conditions (low quality of drinking water, consumption of contaminated food, unsanitary housing conditions, customs and prejudices contradicting basic sanitary standards, low level of general and sanitary culture and medical care, lack of safe waste disposal, etc.). The spread of shigellosis is facilitated by migration processes, natural disasters, military conflicts, etc. [1,2,3,4,11,12,15,17].

About 200 million cases of shigellosis are registered worldwide annually, of which 1.1 million patients die. However, according to studies using mathematical modeling methods, for every case of dysentery coming to the attention of medical services, there are 4 unrecorded cases. The "iceberg" phenomenon is even more pronounced in shigellosis caused by S. flexneri — 1:10–1:15, and reaches maximum figures in Sonne dysentery — 1:30–1:50.

Over the past two decades, major outbreaks caused by Shigella dysenteriae serotype 1 (Sd1) have occurred in Africa, South Asia, and Central America. In 1993–1995, outbreaks were reported in several central and southern African countries. In 1994, during an "explosive" outbreak among Rwandan refugees in Zaire, about 20,000 patients died within the first month of the epidemic alone. Between 1999 and 2003, outbreaks were reported in Sierra Leone, Liberia, Guinea, Senegal, Angola, the Central African Republic, and the Democratic Republic of the Congo. In 2000, outbreaks of bloody diarrhea caused by fluoroquinolone-resistant Sd1 were recorded in India and Bangladesh. In Central America, the last major dysentery epidemic lasted from 1969 to 1973: more than 500,000 cases and 20,000 deaths [1,2,32,33].

In the Russian Federation in the 1990s, an epidemic of Flexner 2a and 3a shigellosis was registered, which was accompanied by the development of severe forms of the disease and a significant number of fatalities [1,2,3,4,11,12,15,17].

The incidence of shigellosis is recorded throughout the year, but in temperate climates, it peaks in the summer-autumn period. The main role in the seasonal rise in incidence is played by climatic factors, increased consumption of vegetables and fruits, swimming in water bodies contaminated with sewage, and increased population migration. City dwellers fall ill 2–3 times more often than rural residents [1,2, 26].

Susceptibility to shigellosis is universal, but children under five years of age are most frequently infected (~ 70% of cases) and die (~ 60% of cases) from shigellosis. According to WHO data, only about 1% of them receive hospital treatment. A high level of morbidity and mortality among adults is mainly registered in socially disadvantaged and vulnerable population groups [20,23].

After the disease, a short-lived (up to 6 months to 1 year) species- and type-specific immunity develops. To form a longer-lasting solid immunity, repeated reinfection with shigellae of the same species and serotype is necessary. Individuals who have had dysentery as a result of primary infection are much less likely to fall ill upon reinfection with the homologous strain S. flexneri 2a. The protective efficacy of the primary infection (post-infection immunity) is 64%. Reinfection is possible.

Shigellosis is classified as an anthroponotic infection with a fecal-oral mechanism of transmission, which is realized through food, water, and contact-household routes. Vector insects, such as flies and cockroaches, play a certain role in the spread of the infection.

The practical implementation of each specified transmission route depends on many factors and conditions (Shigella species, patient age, premorbid background, etc.). [1,2,3,4,5,11,12,23,24] Since S. dysenteriae 1 has the highest virulence, the contact-household transmission route is most characteristic of it, although this route can also be realized by other Shigella species, especially in children, the elderly, and debilitated patients.

In group outbreaks, specific Shigella species correspond to their most typical transmission route: the contact-household route for group A (S. dysenteriae), the foodborne route for group D (S. sonnei), and the waterborne route for groups B (S. flexneri) and C (S. boydii).

Currently, the spread of S. flexneri occurs predominantly via a secondary foodborne route through various food products: a chronic decentralized foodborne transmission route comes into play, realized without prior accumulation of Shigella species, which are characterized by high virulence and an extremely low infectious dose.

The source of infection is a patient with shigellosis and a bacterial carrier (transient or chronic). The greatest epidemiological risk is posed by patients with mild and subclinical forms of acute shigellosis and convalescents with prolonged Shigella excretion, especially those who, by the nature of their work, belong to designated occupational groups (food preparation, storage, transportation, and retail workers; healthcare facilities; educational institutions of all types; water supply facilities related to water treatment and maintenance of water supply networks, etc.).

The epidemiological role of convalescents and patients shedding S. flexneri is somewhat higher compared to carriers of other Shigella species.

Amebiasis incidence is characterized by a spring-summer seasonality. Human susceptibility is high, immunity is non-sterile, specific antibodies are detected in high titers in the blood for 4–8 months after recovery, and the likelihood of reinfection is high.

1.4 Features of Coding the Disease or Condition

A03 Shigellosis

A03.0 Shigellosis due to Shigella dysenteriae

A03.1 Shigellosis due to Shigella flexneri

A03.2 Shigellosis due to Shigella boydii

A03.3 Shigellosis due to Shigella sonnei

A03.8 Other shigellosis

A03.9 Shigellosis, unspecified

A06.0 Acute amebic dysentery [1]

1.5 Classification of the disease or condition

By type:

1. Typical.

2. Atypical: subclinical; asymptomatic; transient bacterial carriage.

By severity:

1. Mild form.

2. Moderate form.

3. Severe form (with prevailing symptoms of toxicosis; with prevailing local disorders).

By course:

A. By duration:

1. Acute (up to 1 month).

Clinical variants: colitis, gastroenterocolitis, gastroenteritis.

2. Prolonged (up to 3 months).

3. Chronic (over 3 months): continuous; relapsing; prolonged bacterial shedding with normal stool.

B. By character:

1. Smooth.

2. Non-smooth: with complications; with exacerbations and relapses; with secondary infection superimposition; with exacerbation of chronic diseases [1,2,13].

Clinical classification of shigellosis (V.I. Pokrovsky, N.D. Yushchuk, 1994, 1996)

Criteria for assessing the severity of shigellosis

The criterion for the severity of shigellosis is the degree of manifestation of:

intoxication syndrome;

local changes;

dehydration syndrome.

For the assessment of toxicosis severity in shigellosis, see Appendix A3

1.6 Clinical presentation of the disease or condition

It is a typical (classic) manifestation of shigellosis. The incubation period ranges from 1 to 7 days (most often 2–5 days).

The prodromal period is not characteristic or presents with mild chills, abdominal discomfort, and headache.

Acute phase (height of illness): acute onset, chills, sensation of heat, cramping pains in the lower abdomen or on the left, in the iliac region, sometimes generalized pain. Concurrently with pain, there is an urge to defecate, followed by a short-term decrease in pain intensity after defecation.

Stool is initially fecal in character, then its volume decreases to the size of a "rectal spit", mucus appears, followed by blood (in the form of blood spots or streaks). Tenesmus (dragging spasmodic pain in the rectal region) and false urges to defecate (unproductive urges) develop.

In overt forms of shigellosis, stool frequency increases from 3–5 times up to 10 times with a mild course, and up to 20–30 times a day or more in severe shigellosis. Defecation, as a rule, does not bring relief. Despite the multiple bowel movements, the amount of feces excreted by patients per day is small and rarely exceeds 0.5–1 L. In the first hours, the stool is quite abundant, fecal, semi-liquid or liquid, often mucous. As frequency increases, the stool loses its fecal character. The stool consists of thick, transparent mucus, which is subsequently admixed with blood and later pus ("rectal spit"). The stool may acquire the appearance of meat-water slop containing suspended "sago" lumps of mucus. Symptoms of hemocolitis are observed in 70–75% of patients.

Dysentery disrupts the functions of all parts of the digestive tract. Salivation is inhibited, causing dry mouth. Gastric juice secretion changes—in the majority of patients, reduced acidity down to achlorhydria is detected, the proteolytic activity of the gastric contents drops, and gastric motility is distorted. The functions of the small intestine, its motility, and secretion are impaired, and membrane hydrolysis and resorption suffer.

Palpation of the abdominal organs reveals a spastic, tonically tense large intestine; in milder cases, only its distal part—the sigmoid colon. The latter is palpated as a dense, infiltrated, slightly mobile, sharply painful cord. Palpation often enhances intestinal muscle spasm and provokes urges to defecate.

Intoxication – fever, elevation of body temperature from 37⁰C to maximum levels (38–40 C), persisting at this level from several hours to 2–5 days, usually decreasing by accelerated lysis type, headache, weakness, apathy, anorexia, systolic murmur, muffled heart sounds, drop in blood pressure, extrasystole. In the most severe cases, infectious-toxic shock may develop.

The duration of uncomplicated shigellosis does not exceed 5–10 days.

Neurotoxicosis, outpacing intestinal dysfunction, is characterized by encephalitic, meningeal, meningoencephalitic, and hyperthermic (malignant hyperthermia) syndromes.

Colitic variant with mild disease severity: changes in the hemogram are insignificant. Sigmoidoscopy may reveal catarrhal or catarrhal-hemorrhagic proctosigmoiditis and sphinkteritis.

Colitic variant of moderate severity: the hemogram shows accelerated ESR, moderate leukocytosis, a shift of the leukocyte formula to the left, and monocytosis. Sigmoidoscopy reveals catarrhal-erosive proctosigmoiditis.

In the severe course of the colitic variant of dysentery, the blood reveals leukocytosis or leukopenia with a left shift of the leukocyte formula and toxic granulation in leukocytes. Sometimes in severe cases, mild proteinuria, microhematuria, and cylindruria appear. In the severe course of Flexner dysentery, fibrinous-necrotic, fibrinous-ulcerative, and phlegmonous-necrotic lesions of the large intestine mucosa are found.

During the convalescence period, complete restoration of disturbed organ and system functions and elimination of the pathogen from the body occur. However, as intravital morphological studies show, anatomical "recovery" is delayed and lags behind clinical recovery by 2–3 weeks. Late hospitalization, inadequate therapy, and an unfavorable premorbid background can lead to the transition of the disease into a chronic form and more frequently to the development of so-called post-dysenteric states. They manifest as functional disorders of secretion, resorption, and motility of the gastrointestinal tract, and asthenia. Depending on the severity and nature of the dysenteric process, the clinical picture may vary [1, 2, 3, 4, 5, 12, 17, 21, 28].

Gastroenterocolitic, gastroenteritic variants

They share features of acute food-borne toxic infections with a short incubation period and a stormy onset of the disease. The main syndromes at the beginning of the disease are gastroenteritis, signs of dehydration and intoxication. Subsequently, symptoms of enterocolitis begin to dominate. The clinical manifestations of colitis are less pronounced [1, 2, 3, 4, 5, 12, 17, 21, 28].

Mild (abortive/inapparent) course of shigellosis

Registered in approximately 10% of cases and characterized by a mild course without the symptom complex typical of shigellosis. Colitis is short-lived and poorly expressed. It occurs in both typical and atypical variants of the disease; patients feel satisfactory and practically do not seek medical help. Stools are semi-fluid, without mucus and blood, no more than 3–4 times a day. Abdominal pain is insignificant and persists for 1–2 days. Body temperature is normal, less often subfebrile. Palpation of the abdomen reveals tenderness and possibly spasm of the descending colon. The diagnosis is most often made based on the result of bacteriological stool examination [1, 2, 3, 4, 5, 12, 17, 21, 28].

Subclinical course

Occurs relatively rarely. Clinical symptoms of the disease are absent. It is diagnosed, as a rule, during examinations for epidemiological indications. Shigellae are detected in the patient's feces, and coprological examination reveals an increased number of leukocytes and mucus. Serological examination shows the dynamics of the specific antibody titer. Sigmoidoscopy reveals virtually no changes, but examination of colonic mucosal biopsies reveals morphological changes characteristic of shigellosis [1, 2, 3, 4, 5, 12, 17, 21, 28].

Protracted course

Observed in any variant of the shigellosis process and occurs in 0.2–0.5% of patients. The disease is characterized by the persistence of symptoms and the detection of shigellae in the stool for more than 2 weeks in the mild form of the disease, more than 3 weeks in the moderately severe form, and more than 4 weeks but less than 3 months in the severe form of the disease. Periodic remissions are possible. Sometimes a protracted course manifests as prolonged (1.5–3 months) bacterial excretion with persistent protracted damage to the large intestine.

Protracted forms of acute shigellosis caused by S. flexneri 2a are generally accompanied by general wasting with reduced immunobiological reactivity and severe fibrinous-purulent lesions of the colon and distal small intestine. The addition of a secondary infection, including anaerobic infection, is accompanied by hectic fever and deep intestinal ulcers.

A prognostic sign of a protracted course of shigellosis is the absence or weak expression of the immunomorphological reaction in the intestinal mucosa during histological and histochemical examination of its biopsy specimen at the height of the disease [1, 2, 3, 4, 5, 12, 17, 21, 28].

Chronic shigellosis

It proceeds in a continuous or relapsing manner for more than 3 months with periods of exacerbation (relapses) or as a sluggish process without marked intoxication. Sigmoidoscopy reveals mild inflammatory and atrophic changes. It develops rarely—after acute Flexner shigellosis in 2–5% of cases, and Sonne dysentery in 1% of cases. The clinical manifestations of shigellosis depend on a number of factors: the type of pathogen, the patient's age, and concomitant diseases. Usually, chronic shigellosis lasts no more than 1.5–2 years.

In the continuous form of chronic shigellosis, remission is practically absent, the pathological process progresses steadily, and the patient's condition worsens. Symptoms of general intoxication are mild; the neuropsychiatric sphere suffers to a greater extent (irritability, mild excitability, poor sleep, sweating, lability of autonomic reactions, etc.). Patients complain of chills, low-grade fever, intestinal dysfunction, abdominal pain, bloating, and rumbling. Diarrhea is persistent, with stool frequency up to 5–6 times a day, watery or formed, sometimes mixed with mucus, pus, and less commonly blood. Intestinal dysbiosis, anemia, and hypovitaminosis frequently develop. Sigmoidoscopy reveals polymorphic changes in the colonic mucosa, which intensify during exacerbations. Other organs of the gastrointestinal tract (stomach, small intestine, pancreas) are totally involved in the pathological process.

In the relapsing course of chronic shigellosis, exacerbations alternate with periods of remission lasting from several weeks to 2–3 months, sometimes longer. During remission, the phenomena of intoxication and intestinal dysfunction are not as pronounced as in the acute period of shigellosis. The patients' general well-being is not significantly impaired, body temperature is usually normal, rarely subfebrile. Stool frequency usually does not exceed 3–5 times a day, blood in the stool is generally absent, and in the inter-relapse period, the patients' condition is satisfactory. Stools may be unstable, especially after eating heavy meals, milk, vegetables, fruits, and physical exertion.

In the asymptomatic course of chronic shigellosis only sigmoidoscopy reveals signs of a chronic process in the form of mucosal subatrophy, polyps, ulcers, scars, erosions, granulations, and scars, etc. [1, 2, 3, 4, 5, 12, 17, 21, 28].

Bacteriologic carriage

It is a form of an infectious process proceeding subclinically. A characteristic difference between bacteriologic carriage and all forms of acute and chronic dysentery is the detection of Shigella in the feces in the absence of any intestinal dysfunction during the examination period and for the preceding 5–6 weeks, maximum 3 months.

The diagnosis of bacteriologic carriage can be made on the basis of a single isolation of Shigella from the patient's feces in the absence of any clinical manifestations of the disease, pathological changes in the colonic mucosa, negative results of dynamic immunological (IHA) examination, and control bacteriological stool examination. It is registered in 24–25% of cases for Sonne shigellosis and in 6–7% for Flexner shigellosis.

Bacteriologic carriers should be clearly distinguished from:

• convalescents after acute dysentery with subsequent prolonged shedding of Shigella, which may last up to 2–4 weeks, rarely longer (convalescent bacteriologic carriage);

• patients with acute dysentery presenting in a mild or masked form;

• patients with chronic dysentery in remission.

When formulating the diagnosis of bacteriologic carriage, the species of the isolated pathogen is additionally indicated, for example, S. sonnei bacteriologic carriage. [1, 2, 3, 4, 5, 12, 17, 21, 28].

Clinical features of shigellosis caused by different strains

S. dysenteriae 1 causes a severe disease course with pronounced intoxication, severe intestinal involvement, and exicosis. Grigoriev-Shiga dysentery is characterized by an acute onset, intense cramping abdominal pain, chills, fever up to 40⁰C, and tenesmus. On the first day of illness, the stool has a fecal character with visible blood, after which the volume of excrement decreases and an admixture of pus appears. Infectious-toxic shock (ITS), sepsis, and hemolytic-uremic syndrome may develop. Hypovolemic syndrome develops with copious stools and early onset of vomiting.

Regarding the clinical manifestations of shigellosis caused by S. flexneri, there is no consensus. Most researchers note a moderate-to-severe form of the disease with the development of symptoms of toxicosis and exicosis and a pronounced distal colitis syndrome. Thus, shigellosis caused by S. flexneri 2a, S. flexneri 3a more often proceeds severely, with sharply pronounced intoxication and colitis syndromes. ITS and damage to internal organs (pneumonia, myocarditis, toxic hepatitis, nephritis, polyarthritis) develop more frequently. Pneumonia, as the most frequent complication of shigellosis, can have a severe progressive course leading to acute cardiopulmonary failure. Formidable complications typical of dysentery in the past may be observed, such as exudative and perforative peritonitis, intussusception, erosive gastrointestinal bleeding, thromboendocarditis, and pulmonary embolism.

Manifestations of shigellosis caused by S. newcastle are similar to the course of Flexner shigellosis.

The clinical course of the disease caused by S. sonnei is more frequently recorded in older children and often manifests as a gastroenterocolitic variant of acute intestinal infection with a smooth course, rapid positive dynamics, and low mortality. There are many mild (subclinical) forms and bacterial carriage.

Shigellosis caused by S. boydii resembles S. sonnei shigellosis. It is characterized by a mild course with mildly expressed symptoms of intoxication and colitis syndrome.

In immunocompromised patients with shigellosis, pronounced fever may be absent, but large intestine involvement is typically total [19,20].

The course and outcome of shigellosis depend on the species of Shigella that caused the disease, the state of the macroorganism's natural resistance factors associated with lifestyle, nutrition, age, presence of concomitant diseases (especially alcoholism), complications, and the timeliness and adequacy of treatment. The condition of most patients improves within 48 hours, and complete recovery occurs in 7-10 days (without complications).

In general, the prognosis can be assessed as favorable in Sonne dysentery, more serious in Flexner dysentery, and relatively unfavorable in Grigoriev-Shiga dysentery.

Mortality is less than 1% among patients not belonging to the risk group and not requiring inpatient treatment, and exceeds 15% among patients from risk groups, with late-initiated treatment and inefficiency of antimicrobial drugs [1, 2, 3, 4, 7, 8, 12].

Complications of shigellosis

The risk of complications is highest in patients with dysentery caused by S. dysenteriae 1. However, there is a clear trend toward an increase in severe forms of Flexner dysentery. Among the most severe complications are:

• infectious-toxic shock and mixed shock (ITS + dehydration shock);

• perforation of intestinal ulcers with the development of peritonitis (from localized serofibrinoid to diffuse purulent forms), with intestinal bleeding;

• encephalic syndrome (fatal encephalopathy syndrome or Ekiri syndrome), which predominantly develops in children and immunocompromised patients in dysentery caused by S. sonnei, S. flexneri;

• acute adrenal insufficiency;

• bacteremia (detected in S. dysenteriae 1 dysentery in 8% of cases and extremely rarely when infected with other Shigella species in children under one year of age, debilitated, emaciated, and immunocompromised patients);

• hemolytic-uremic syndrome (developing a week after the onset of the disease and characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure);

• acute cardiovascular insufficiency (in severe course);

• myocarditis and thromboendocarditis;

• pulmonary edema and cerebral edema-swelling;

• thromboembolism of small and medium branches of the pulmonary artery;

• segmental thrombosis of the superior mesenteric artery.

Intestinal involvement in shigellosis can be complicated by intestinal hemorrhage, hemorrhagic imbibition of the ileal wall, toxic megacolon (toxic dilation of the colon), paresis, intestinal obstruction and intussusception, rectal prolapse, formation of intestinal or enterovesical fistulas, gangrene of the intestinal wall, pericolitis, peri- and paraproctitis, anal fissure, cicatricial stenosis of the intestine, etc.

Complications associated with the activation of secondary microflora may develop (pneumonia, otitis media, ascending urinary tract infection, liver abscesses, etc.).

Rare but probable complications include reactive arthritis and Reiter's syndrome (about 2% of patients expressing HLA B27). In recent years, the possible role of shigellosis in the development of irritable bowel syndrome has been discussed [1, 2, 3, 4, 7, 8, 12].

Acute intestinal amebiasis

The incubation period ranges from a few days to several months. The general condition and well-being of the patient in the initial period of the disease remain satisfactory; fever is absent. The first symptoms of gastrointestinal tract involvement are bloating and pain in the right iliac region, the appearance of abundant, mushy stools, 3–5 times a day, with a small amount of mucus and blood. Then the stool becomes liquid, increasing in frequency to 15–20 times a day, with a large amount of transparent glassy mucus impregnated with blood, resembling "raspberry jelly." The patient may experience agonizing tenesmus, burning, and pain in the distal large intestine, intensifying during defecation. The sigmoid colon is spastic and palpable as a thickened cord.

Typical changes in the intestinal mucosa for amebiasis form during the first 2 weeks. In the initial period of the disease, endoscopic examination (sigmoidoscopy, fibrocolonoscopy) reveals inflammatory changes in the rectum and sigmoid colon. On the second or third day from the onset of the disease, against the background of normal mucosa, areas of hyperemia (2–5 mm in diameter) are noted, some rising above the level of unchanged areas. From the fourth to fifth day of the disease, small nodules and ulcers are detected at the site of these hyperemic areas, surrounded by a hyperemic zone. From the 6th to the 14th day of the disease, ulcers up to 20 mm in size with undermined edges, filled with necrotic masses, are discovered.

The disease may be mild or subclinical; the acute period lasts no more than 4–6 weeks, followed by remission lasting from several weeks to 1 month or more. The main complications of intestinal amebiasis are intestinal perforation, peritonitis or abdominal abscess, amebic appendicitis, amebic strictures of the intestine, intestinal bleeding, and the formation of an ameboma.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnostic criteria

Diagnosis of shigellosis is made based on epidemiological and clinical anamnesis, clinical examination, laboratory and special examination methods, and is aimed at determining the nosology and clinical form, severity of the condition, identifying complications and indications for therapy [1, 2, 3, 4, 5]:

1) anamnesic data: consumption of food or water infected (or potentially infected) with Shigella 8–72 hours before the onset of the disease, contact with individuals having infectious diarrhea.

2) complaints and physical examination data: acute onset, high fever, pronounced symptoms of intoxication, colitis syndrome (lower abdominal pain, spasm, infiltration and tenderness of the sigmoid colon, tenesmus, false urges, non-fecal muco-hemorrhagic stool ["rectal spit"]).

3) laboratory investigations: isolation of Shigella from clinical material.

4) instrumental examination data are not used for routine diagnostics.

2.1 Complaints and Anamnesis

Comments: Infection can occur as a result of consuming water from open bodies of water or tap water contaminated with sewage; consuming dairy products with improper storage conditions and expiration dates; through contaminated hands and household items.

2.2 Physical Examination

Comments: gastrointestinal shigellosis is characterized by the development of varying degrees of dehydration.

Comments: abdominal palpation reveals a spastic, tonically tense large intestine, or in milder cases, only its distal part—the sigmoid colon. The latter is palpated as a dense, infiltrated, slightly mobile, sharply painful cord. Palpation often increases intestinal muscle spasm and provokes urges to defecate.

Comments:in severe cases, patients with shigellosis may develop infectious-toxic shock (ITS), while children may also develop dehydration syndrome

2.3 Laboratory Diagnostics

At the diagnostic stage:

Comments: The complete blood count (CBC) is characterized by moderate leukocytosis with a left shift of the leukocyte formula, monocytosis, and moderately accelerated ESR. Urinalysis in severe cases reveals minor proteinuria, microhematuria, cylindruria, and leukocyturia.

Comments: Coprograms reveal a normal or alkaline pH and absence of detritus, as well as mucus, pus, and an admixture of leukocytes and erythrocytes.

Comments: elevated amylase and urea levels, hypokalemia, hyponatremia, and hypocalcemia are noted. [1, 2, 3, 4, 5, 6].

Comments: the study is performed before initiating antibacterial therapy. Follow-up examination of patients with a confirmed diagnosis of dysentery is performed once, no earlier than 2 days after the completion of etiotropic treatment; for occupationally exposed groups (decreed groups), a two-stage examination is required [1, 2, 3, 4, 5, 6].

Comments: it is known that salmonellosis and campylobacteriosis can present with an invasive type of infection [58, 63].

Comments: Serological methods are used for the diagnosis of shigellosis when bacteriological test results are negative and for epidemiological investigations. They are not used for early diagnosis. They allow the detection of specific antibodies in the patient's blood (total or IgM, IgG to various Shigella species). A diagnostically reliable indicator is a 4-fold or greater dynamic change (increase or decrease) in the titer of specific antibodies in the patient's blood when tested in paired sera (the first blood sample is taken from the patient on days 6–8 of the disease, the second 10 days after the first). A single serological blood test in patients has no diagnostic value, as it does not allow differentiating an acute process from other forms of shigellosis course. [1, 2, 3, 4, 5, 6].

Comments: protozoa and parasites can be a cause of diarrhea [12, 13].

Comment: Confirmation of the diagnosis is provided by the detection of species-specific markers of Entamoeba histolytica or morphological confirmation of erythrophagocytosis by tissue forms (distinguishing the pathogen from the avirulent species – the morphological double E. dispar) [1-6, 51, 52].

2.4 Instrumental Diagnostics

Comments: The study is informative for diagnosing cardiovascular complications.

2.5 Other Procedures

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

Comments: care for children is determined by their age and the presence of comorbid conditions.

3.1 Conservative treatment

3.1.1 Etiotropic therapy

Comments: combination antibacterial therapy is used exclusively for patients with severe shigellosis (fluoroquinolones and aminoglycosides; cephalosporins and aminoglycosides); the duration of antibacterial therapy for moderate shigellosis is typically up to 5 days, and for severe cases, 5–7 days. Drugs are prescribed taking age limits into account. [1, 2, 3, 4, 12, 22, 30, 31]

Comments: In the Russian Federation, S. flexneri and S. sonnei are resistant to cefotaxime** (96.6% and 94.2%, respectively), tetracycline** (97.7% and 92.8%, respectively), chloramphenicol** (93.2% and 50.7%, respectively), ampicillin** (95.5% and 26.1%, respectively), and ampicillin/sulbactam** (95.5% and 23.2%, respectively). No resistance was detected to ciprofloxacin** or norfloxacin.

According to WHO data (2005), the majority of shigellae strains are resistant to ampicillin**, co-trimoxazole**, chloramphenicol**, and tetracycline**.

• Nitrofuran derivatives, aminoglycosides (gentamicin**, kanamycin**), 1st–2nd generation cephalosporins (cefazolin**, cephalothin, cefoxitin), and amoxicillin** penetrate the intestinal mucosa poorly

• Ciprofloxacin** is the drug of choice for the treatment of all adult patients presenting with "bloody diarrhea".

• Ciprofloxacin**, certain other fluoroquinolones, and ceftriaxone** are currently the only antimicrobial agents generally effective for treating multidrug-resistant Shigella strains; all drugs are prescribed with regard to age restrictions. [1, 2, 3, 4, 5, 9, 11, 12, 15, 16, 22, 24, 30, 31, 36, 37, 38, 39, 40].

• It is recommended to prescribe systemic antibacterial drugs to children with shigellosis during the acute and subacute phases of the disease [54, 55, 80, 81, 82, 83].

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

Comments: if indicated, systemic antibacterial drugs or intestinal anti-infective agents are prescribed in accordance with the instructions for use of the medicinal product and the susceptibility of the isolated strains; starting drugs include #azithromycin** orally 12 mg/kg/day on day 1, then 6 mg/kg/day for 4 days [54], ceftriaxone**, cefotaxime**. When susceptible Shigella strains are isolated, amikacin**, cefixime may be prescribed; Sulfamethoxazole+Trimethoprim**   [53, 54, 55, 58, 79, 80, 81, 82, 83].

3.1.2 Pathogenetic therapy

For children, the strength of recommendation is B (evidence level – 1).

For adults, the strength of recommendation is C (evidence level – 5).

Comments: the principles of oral rehydration include fractional administration of fluids and the use of solutions with an optimal composition (rehydration solutions for children are used with a reduced osmolarity of 200–240 mosm/l). Oral rehydration is carried out in two stages: Stage I — during the first 6 hours after the patient's admission, the water-salt deficit that developed before the start of treatment is eliminated. Stage II — maintenance oral rehydration, which is carried out throughout the rest of the illness in the presence of ongoing fluid and electrolyte losses. The effectiveness of oral rehydration is assessed by the following signs: a decrease in the volume of fluid losses; a reduction in the rate of body weight loss; the disappearance of clinical signs of dehydration; normalization of diuresis; and improvement in the general condition.

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

For children, for diosmectite**, the strength of recommendation is B (evidence level – 1).

For others, the strength of recommendation is C (evidence level – 5).

Comments: prescribed until diarrhea is relieved. The use of drugs that reduce gastrointestinal motility, slow down the passage of intestinal contents, and reduce the excretion of fluid and electrolytes with feces is not indicated.

Comments: antidiarrheal microorganisms are prescribed in accordance with the instructions, age, and strain composition of the drug. Clinical efficacy has been proven for Bifidobacterium animalis subsp. lactis, Lactobacillus acidophilus, S. boulardii CNCM I-745, Lactobacillus GG, and Lactobacillus reuteri. Antidiarrheal microorganisms are recommended to be prescribed in accordance with the instructions for use both in the acute phase of the disease and in the convalescent phase.

Comments: Dysentery bacteriophage or intesti-bacteriophage is prescribed after determining the sensitivity of the strain that caused the disease. Antimicrobial therapy is not indicated for transient or convalescent Shigella excretion.

Comments: pancreatin** in age-appropriate dosage orally 3 times a day during meals, course duration 10–15 days.

- During the convalescence period in patients with a slow subsidence of the inflammatory process in the intestinal mucosa, it is recommended to use oral infusions of chamomile flowers extract, alder cone infusion, and St. John's wort herb for astringent and anti-inflammatory purposes [2, 42].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

Comments: Antipyretic drugs in healthy children ≥3 months old are justified at temperatures above 39 °C. With a lower-grade fever (38–38.5 °C), temperature-lowering agents are indicated for children under 3 months, patients with chronic pathology, and in case of fever-related discomfort. Regular (scheduled) administration of antipyretics is undesirable; a repeated dose is administered only after a new temperature rise.

At the stage of outpatient, primary health care, and emergency medical care for persistent fever, a single administration of metamizole sodium in an age-appropriate dose is permissible [84, 85, 87, 88].

Management tactics for chronic shigellosis

Comments: In the early stages of the disease, when features of acute shigellosis persist during the exacerbation period, therapy differs little from the treatment of acute dysentery, but with mandatory enhancement of pathogenetic therapy (therapeutic nutrition, use of digestive enzymes, eubiotic preparations, agents stimulating reparative processes, astringent anti-inflammatory agents, and physiotherapeutic procedures). Strict adherence to the diet regimen is necessary both during the exacerbation period and the inter-relapse period. Therapeutic diet Table 4 should be taken as the basis, adjusted for concomitant diseases and individual intolerance to certain foods.

3.2 Diet therapy

Comments: Diet therapy helps accelerate reparative processes in the affected digestive organs in patients with shigellosis.

In infants, continuation of exclusive breastfeeding is recommended; in formula-fed infants with mild to moderate disease, the use of baby food products, infant formula, and for infants—lactose-free/low-lactose and fermented milk formulas with probiotics—is recommended; in severe disease and pronounced malabsorption syndrome, specialized therapeutic and dietary infant nutrition products and infant formulas based on partially hydrolyzed cow's milk whey proteins are recommended.

In children over 2 years of age and adults, a mechanically and chemically sparing diet is recommended. On the first day, the food volume is reduced by 25%, diet No. 4 is prescribed, as well as fermented milk products, liquid grain-free porridges (rice, corn, buckwheat), mucous soups; foods that enhance peristalsis and fermentation processes—whole milk, fresh vegetables and fruits, meat and chicken broths, fresh baked goods—are excluded from the diet [91].

The organization of therapeutic dietary nutrition for patients with shigellosis 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 medical and prophylactic 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".

3.3 Other Treatment

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

3.4 Surgical treatment

Not performed [1, 2, 3].

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Comments: gradual increase in dosed physical and mental loads, as well as the differentiated application of various intervention methods, are important

Comments: the speed 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

General approaches to prevention:

Comments: the necessity of their implementation, frequency, and scope are determined by Rospotrebnadzor specialists.

5.1 Specific prophylaxis of shigellosis

A separate unresolved problem is the development of a vaccine for the prevention of dysentery. The development of a dysentery vaccine has been declared a first-degree priority by the WHO. The developed live oral dysentery vaccines turned out to be insufficiently immunogenic and difficult to adapt for practical clinical use.

• There are no WHO-recommended vaccines effective in preventing shigellosis infection. Several candidate vaccines, mainly against S. flexneri, are currently in development. In the Russian Federation, only specific prevention for Sonne dysentery has been developed [1-4,29].

• It is recommended to administer vaccination with the dysentery vaccine** to adults and children traveling to areas with a high threshold of Sonne shigellosis incidence; to persons working in public utilities and public catering, and to staff of bacteriological laboratories and infectious diseases hospitals for specific prevention of Sonne dysentery [1-4,29].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

Comments: According to epidemiological indications, mass immunization of the population can be carried out in the event of a threat of an epidemic or outbreak (natural disasters, major accidents in water and sewer networks), as well as during an epidemic. Preventive vaccinations against Sonne dysentery should preferably be carried out before the seasonal rise of this infection. Immunity is species-specific and lasts for 1 year.

5.2 Nonspecific prophylaxis

5.2.1 Measures in the focus of infection:

Comments: patients not belonging to the above categories are allowed to work on the basis of a certificate of recovery and in the presence of a single negative result of bacteriological stool analysis.

Comments: if shigella excretion continues for more than 3 months after the disease, they are permanently transferred as chronic carriers to work not related to food products and water supply, and if transfer is impossible, they are suspended from work with the payment of social insurance benefits.

Comments: it is organized by the medical worker who established the diagnosis.

Comments: instructions on the procedure for their use and disinfection performance are provided by medical workers of the medical facility, as well as an epidemiologist or assistant epidemiologist of the territorial Rospotrebnadzor center

Comments: chamber disinfection is not performed.

Comments: the question of the necessity of studies, their type, scope, and frequency is decided by the epidemiologist or their assistant.

Comments: medical observation is established for 7 days from the moment of isolation of the source of infection (thermometry, stool examination, intestinal palpation; stool culture as indicated). When a dysentery patient is identified in an organized group, contacts are subjected to a control bacteriological examination. Chemoprophylaxis in persons in contact with the patient is not performed. The question of the need for examinations, their type, scope, and frequency is determined by an epidemiologist or their assistant). Emergency prophylaxis is not performed. Dysentery bacteriophage can be used (1–2 tablets of the drug per day).

5.3 Dispensary follow-up

Comments: Monitored are:

1. Convalescents with a bacteriologically confirmed diagnosis of shigellosis for 4-6 weeks.

2. Persons directly involved in the production, storage, transportation, and sale of food products and equivalent persons who have had dysentery with an identified species of pathogen; military personnel and bacterial carriers – observation for 3 months.

3. Persons with chronic dysentery, bacteriologically confirmed, or persons with persistently unstable stools who are food industry workers and equivalent persons are monitored for 6 months.

6. Organization of Medical Care

Primary accounting documents for disease information are drawn up: outpatient medical record (form no. 025/u); medical record (form no. 026/u) for registration and recording of a shigellosis patient. Registration of the case of the disease is carried out in the infectious diseases register (form no. 060/u) for recording and registration of a shigellosis patient.

The physician who registered the case of the disease sends an emergency notification (form no. 058/u): primary — orally, by phone, in the city within the first 12 hours, in rural areas - 24 hours; final - in writing, after the differential diagnosis and obtaining the results of bacteriological or serological examination, no later than 24 hours from the moment of their receipt for individual registration of the dysentery patient at territorial Rospotrebnadzor centers [1-4].

General approaches to the treatment of patients with shigellosis [1,2,3,4,12,16]

Treatment of patients with dysentery can be carried out not only in a specialized infectious diseases department, but also on an outpatient basis, as determined by clinical and epidemiological indications.

The principles of treatment of patients with shigellosis provide for the following tasks:

- relief of acute attacks of the disease;

- prevention of exacerbations, immediate relapses, and residual effects;

- completion of treatment for residual effects of shigellosis;

- prevention of distant relapses.

The choice of treatment tactics is influenced by the following factors:

- period of the disease;

- severity of the condition;

- patient's age;

- presence and nature of complications;

- availability and feasibility of treatment tactics in accordance with the required type of medical care.

Despite the planned nature of diagnostic and therapeutic measures for patients with shigellosis, care is of an emergency nature. A late start of combination therapy, including etiotropic therapy, leads to a more prolonged course of the disease, delayed diagnosis of complications, and may worsen the prognosis of the disease in a particular patient.

Comments: Persons subject to hospitalization in infectious diseases departments of medical institutions or infectious diseases hospitals include:

- those belonging to risk groups (infants in the first year of life, adults over 50 years of age, etc.);

- those suffering from moderate to severe forms of the disease;

- those with developing complications of the disease;

- those with protracted and chronic courses of shigellosis during periods of exacerbation and those suffering from severe comorbidities;

- contingented groups (food industry workers and equivalent persons);

- when there is a threat of the infection spreading at the patient's place of residence.

if the patient presents in a severe condition, it is necessary cito! to send them to an infectious diseases hospital on the day of presentation

• Shigellosis convalescents are recommended to be discharged from the hospital after the disappearance of clinical symptoms and a microbiological (cultural) examination of feces/rectal swab for microorganisms of the genus Shigella (Shigella spp.) [1, 2, 3, 4, 5, 6].

LOD 5Level of evidence C (reliability level of evidence - 5).

Comments: Criteria for hospital discharge:

o Patients who have had shigellosis without bacteriological confirmation are discharged from the hospital no earlier than 3 days after clinical recovery, normalization of body temperature and stool;

o Patients who have had shigellosis confirmed bacteriologically are discharged after clinical recovery, normalization of temperature and stool, and after a negative control bacteriological examination of feces for shigellae, performed no earlier than 2 days after the end of etiotropic treatment.

o All food handlers and equivalent personnel are discharged from the hospital after clinical recovery, normalization of temperature and stool, and after a double negative bacteriological examination of feces for shigellae. In case of a positive bacteriological result, the course of treatment is repeated.

o In protracted forms of dysentery with prolonged bacterial excretion and in chronic dysentery, discharge is carried out after the subsiding of exacerbation, disappearance of toxicosis, stable normalization of stool for 10 days, and a negative result of bacteriological examination.

o Patients who have had Shiga-Kitasato dysentery are discharged in the absence of shigellae in control examinations of feces and blood.

Medical care for patients with shigellosis is provided in the form of: − primary health care;

− emergency, including specialized emergency, medical care;

− specialized, including high-tech, medical care.

Medical care for patients with shigellosis can be provided in the following settings:

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

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

Primary health care includes:

1) primary pre-medical health care;

2) primary medical health care;

3) primary specialized health care.

Primary health care is provided in outpatient settings. Primary pre-medical health care in outpatient settings is provided in feldsher-midwife stations, maternity hospitals, primary and secondary vocational education institutions (hereinafter referred to as educational institutions) by nursing personnel.

Primary medical health care is provided by a district general practitioner or general practice physician (family physician) in outpatient settings. 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 practice physicians (family physicians), nursing staff of medical organizations or educational institutions), in the presence of medical indications, refers the patient for consultation to the infectious diseases office of a medical organization to receive primary specialized health care.

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.

7. Additional Information

The risk group for severe course and probability of an unfavorable outcome includes:

• infants in the first year of life

• adults over 50 years of age

• persons who have recently had measles

• children and adults with protein-energy malnutrition

• any patient with severe symptoms of dehydration (seizures, fainting, etc.), hypo- and hyperthermia.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Lira V. Arslanova, Candidate of Medical Sciences, Associate Professor at the Department of Infectious Diseases with the Course of Institute of Professional Education, Bashkir State Medical University of the Russian Ministry of Health.

2. Irina V. Barysheva, Senior Lecturer at the Department of Infectious Diseases with Courses of Epidemiology and Phthisiology, Peoples' Friendship University of Russia

3. Alena N. Burganova, Candidate of Medical Sciences, Associate Professor at the Department of Infectious Diseases with the Course of Institute of Professional Education, Bashkir State Medical University of the Russian Ministry of Health.

4. Damir A. Valishin, Doctor of Medical Sciences, Professor, Head of the Department of Infectious Diseases with the Course of Institute of Professional Education, Bashkir State Medical University of the Russian Ministry of Health

5. Golub Veniamin Petrovich, Candidate of Medical Sciences, Associate Professor at the Department of Infectious Diseases with Courses in Epidemiology and Phthisiology, RUDN University,

6. Aleksandr V. Gorelov – Academician of the Russian Academy of Sciences, Professor, Head of the Department of Infectious Diseases and Epidemiology, A.I. Evdokimov Moscow State University of Medicine and Dentistry of the Russian Ministry of Health; Deputy Director for Science, Central Research Institute of Epidemiology of Rospotrebnadzor; Chairman of the Board of the National Association of Infectious Disease Specialists named after Academician V.I. Pokrovsky

7. Galina M. Kozhevnikova, Doctor of Medical Sciences, Professor, Head of the Department of Infectious Diseases with Courses of Epidemiology and Phthisiology, Peoples' Friendship University of Russia, Board Member of the National Association of Infectious Disease Specialists named after Academician V.I. Pokrovsky

8. Sergey S. Kozlov, MD, PhD, Professor, Professor at the Department of Infectious Diseases (with a Course of Medical Parasitology and Tropical Diseases), Kirov Military Medical Academy of the Ministry of Defense of the Russian Federation; Professor at the Department of Adult Infectious Diseases and Epidemiology, Saint Petersburg State Pediatric Medical University of the Russian Ministry of Health.

9. Yury V. Lobzin – MD, PhD, Professor, Full Member of the Russian Academy of Sciences, President of the Pediatric Research and Clinical Center for Infectious Diseases of the Federal Medical-Biological Agency (FMBA) of Russia, Chief freelance pediatric infectious disease specialist of the Russian Ministry of Health and the FMBA of Russia, President of the NGO "Euro-Asian Society of Infectious Diseases"

10. Ksenia E. Novak, MD, PhD, Associate Professor, Associate Professor at the Department of Adult Infectious Diseases and Epidemiology, Saint Petersburg State Pediatric Medical University of the Russian Ministry of Health

11. Elena P. Tikhonova, MD, PhD, Professor, Head of the Department of Infectious Diseases and Epidemiology with a Postgraduate Course, Voyno-Yasenetsky Krasnoyarsk State Medical University of the Russian Ministry of Health,

12. Denis V. Usenko – MD, PhD, Head of the Educational Center, Leading Researcher at the Clinical Department of Infectious Pathology, Central Research Institute of Epidemiology of Rospotrebnadzor; Board Member of the Academician V.I. Pokrovsky National Association of Infectious Disease Specialists

13. Vladimir P. Chulanov, MD, PhD, Professor, 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, Professor at the Department of Infectious Diseases, I.M. Sechenov First Moscow State Medical University, Chief freelance infectious disease specialist of the Russian Ministry of Health; Board Member of the Academician V.I. Pokrovsky National Association of Infectious Disease Specialists

14. Liana R. Shaikhyullina, MD, PhD, Associate Professor at the Department of Infectious Diseases with a Course of Institute of Postgraduate Education, Bashkir State Medical University of the Ministry of Health of Russia.

15. Elena V. Esaulenko, MD, PhD, Professor, Head of the Department of Adult Infectious Diseases and Epidemiology, Saint Petersburg State Pediatric Medical University of the Russian Ministry of Health; Board Member of the Academician V.I. Pokrovsky National Association of Infectious Disease Specialists

16. Maria K. Bekhtereva – MD, PhD, Senior Researcher at the Research Laboratory of Intestinal Infections, Member of the Euro-Asian Society of Infectious Diseases; Association of Infectious Disease Physicians of Saint Petersburg and Leningrad Region

17. Svetlana V. Rychkova – MD, PhD, Associate Professor, Head of the Medical Care Organization Department, Pediatric Research and Clinical Center for Infectious Diseases of the FMBA, pediatrician

18. Aleksandr T. Podkolzin, MD, PhD, Deputy Director for Epidemiology at the Central Research Institute of Epidemiology of Rospotrebnadzor

19. Konstantin V. Kuleshov, PhD, Head of the Laboratory of Molecular Diagnostics and Epidemiology of Intestinal Infections, Central Research Institute of Epidemiology of Rospotrebnadzor

There is no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience of the clinical guidelines:

1. Infectious disease physician;

2. Physician (General Practitioner / Internist);

3. General practitioner;

4. Clinical pharmacologist;

5. Pediatrician;

6. District pediatrician;

7. Gastroenterologist

8. Preventive medicine physician;

9. Emergency/admitting department physician;

10. Epidemiologist.

11. Resident physician

12. 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 certainty and recommendation grades for diagnostic interventions

Table A1 – Levels of evidence certainty for diagnostic interventions

¹The accepted standard for clinical trials of diagnostic interventions is a cross-sectional study design, in which the investigational diagnostic method and the reference method (representing the "gold standard" for diagnosing the disease or condition under study) are applied to each included patient 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 interpreted by the researcher without knowledge of the results of the other method (blinding is recommended)

Table A2 – Scale for determining recommendation grades for diagnostic interventions

Table P3. Possible combinations of LCE and GGR 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 P4 - Levels of credibility of evidence for therapeutic, rehabilitation, and preventive interventions

Table P5 – 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

1. Federal Law No. 323-FZ of November 21, 2011, "On the Fundamentals of Protecting the Health of Citizens in the Russian Federation" (as amended on December 25, 2023);

2. Federal Law No. 326-FZ of November 29, 2010 (as amended on December 25, 2023) "On Compulsory Medical Insurance in the Russian Federation" (with rev. and add., effective from January 1, 2024);

3. Federal Law of the Russian Federation No. 52-FZ of March 30, 1999, "On the Sanitary and Epidemiological Welfare of the Population" (as amended on April 27, 2023);

4. Order of the Ministry of Health and Social Development of Russia No. 521n of May 5, 2012, "On Approval of the Procedure for Providing Medical Care to Children with Infectious Diseases", registered with the Ministry of Justice of the RF on July 10, 2012, registration No. 24867 (as amended on February 21, 2020);

5. Order of the Ministry of Health and Social Development of Russia No. 69n of January 31, 2012 (as amended on February 21, 2020) "On Approval of the Procedure for Providing Medical Care to Adult Patients with Infectious Diseases" (Registered with the Ministry of Justice of Russia on April 4, 2012, No. 23726);

6. Order of the Ministry of Health of Russia No. 804n of October 13, 2017, "On Approval of the Nomenclature of Medical Services", registered with the Ministry of Justice on November 7, 2017, registration No. 48808 (as amended on March 24, 2020);

7. Order of the Ministry of Health and Social Development of Russia No. 541n of July 23, 2010, "On Approval of the Unified Qualification Handbook of Positions of Managers, Specialists, and Employees", section "Qualification Characteristics of Employee Positions in the Healthcare Sector", registered with the Ministry of Justice of the RF on August 25, 2010, registration No. 18247 (as amended on April 9, 2018);

8. Order of the Ministry of Health of the RF No. 203n of May 10, 2017, "On Approval of Criteria for Assessing the Quality of Medical Care" (registered with the Ministry of Justice of Russia on May 17, 2017, No. 46740);

9. State Register of Medicines. Available at: https://grls.rosminzdrav.ru/

10. Clinical Nutrition Standards: Methodological Guide. 2017. Access: http://cr.rosminzdrav.ru/#!/manuals/adults//

11. Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 4 dated January 28, 2021 (as amended on May 25, 2022) "On Approval of Sanitary Rules and Norms SanPiN 3.3686-21 'Sanitary and Epidemiological Requirements for the Prevention of Infectious Diseases'" (together with "SanPiN 3.3686-21. Sanitary Rules and Norms...") (Registered with the Ministry of Justice of Russia on February 15, 2021, No. 62500)

12. Order of the Ministry of Health of the Russian Federation No. 330 dated August 5, 2003, "On Measures to Improve Clinical Nutrition in Healthcare Facilities of the Russian Federation."

13. Order of the Ministry of Health of the Russian Federation No. 395n dated June 21, 2013, "On Approval of Clinical Nutrition Norms."

14. 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 Clinical Nutrition."

Assessment of toxicosis severity in shigellosis

* The "white spot" sign tentatively allows assessment of microcirculation impairment: skin blanching is observed at the site of finger pressure, which disappears after 4–6 s (if the sign is negative)

Differential diagnosis of acute shigellosis from other acute diarrheal infections [1,2,4,5,10,11,14]

Differential diagnosis of acute shigellosis from surgical and certain other gastrointestinal diseases

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Shigellosis is an acute infectious disease caused by bacteria of the genus Shigella, is part of the group of acute intestinal infections (AII) and belongs to socially significant diarrheal diseases – about 30% of the population in industrialized countries suffer from diarrheal diseases annually, including bacterial dysentery. Every year, about 200 million cases of shigellosis are registered worldwide.

Factors contributing to the incidence of shigellosis include poor quality of drinking water, food, unsanitary living conditions, and improper waste disposal.

Causes of shigellosis

The disease develops when Shigella enters the body. There are several varieties of Shigella, but the most common are two – S. flexneri and S. sonnei, while S. dysenteriae 1 has the highest virulence.

The source of infection is exclusively a sick person or a bacterial carrier, especially those with a mild or subclinical form, as they actively interact with others. Recovered individuals also continue to shed the pathogen into the environment for a long time.

Transmission route is fecal-oral: bacteria are transmitted from an infected person via food, water, household items, and sometimes through vector insects such as flies and cockroaches. The infection is particularly spread by people whose work is related to food preparation, storage, and transportation, as well as employees of healthcare facilities, educational institutions, water supply facilities, etc. The incidence of shigellosis increases in the summer-autumn period, facilitated by increased consumption of vegetables and fruits, swimming in bodies of water contaminated with sewage, and seasonal migration. Shigella multiplies very rapidly in foods – salads, boiled meat and fish, minced meat, milk and dairy products, fruit compotes and kissels. During their multiplication in food, toxins accumulate. The ability of Shigella to cause disease upon entering the body is very high, so even a small amount of them is sufficient for a person to fall ill.

Bacteria are resistant to gastric acid and bile acids, and upon entering the intestine, they lose almost none of their dangerous properties. Shigellae penetrate the cells of the intestinal mucosa and release toxins, resulting in the formation of ulcers and erosions of the mucosa.

Symptoms of shigellosis

The clinical presentation of shigellosis depends on the affected section of the intestine and the strain causing the disease. The classic presentation is the colitis variant, involving the large intestine (observed in 60-80% of patients with acute shigellosis). The incubation period is 1-7 days (usually 2-3 days). The disease may begin with chills, headache, and abdominal discomfort, but most often manifests acutely with crampy pain in the lower abdomen or left iliac region. The patient experiences urgency to defecate, after which the pain subsides briefly. Stool frequency ranges from 3-5 to 10 times a day in mild cases, and up to 20-30 times in severe forms. Initially, stools are copious and fecal in character, but as defecation becomes more frequent, they take on the appearance of thick, transparent mucus, later mixed with blood and pus (known as a "rectal spit"). Abdominal pain is accompanied by fever ranging from 37 to 40^°C, headache, weakness, decreased appetite, and low blood pressure. In uncomplicated cases, the duration of the disease does not exceed 5-10 days.

The gastroenteritic variant begins acutely with nausea, vomiting, and upper abdominal pain, after which the clinical picture of colitis begins to predominate. In mild or inapparent cases, symptoms are short-lived and not very pronounced. Bacterial carriage is characterized by the absence of clinical manifestations for three months, while shigellae are still shed in the stool. The chronic form is diagnosed if symptoms persist three months after the acute illness. Chronic shigellosis can occur in a relapsing form with periods of exacerbations and remissions, as well as in a continuous form where colitis symptoms do not subside.

Diagnosis of shigellosis

Diagnosis of the disease is based on a thorough patient interview establishing a history of exposure in an acute diarrheal outbreak and contact with an infected person, swimming in and consuming water from natural bodies of water, consuming expired foods, and specific laboratory and instrumental methods.

If bacterial dysentery is suspected, an infectious disease specialist should be consulted. Treatment can be carried out at home or in a hospital setting. Hospitalization is recommended for children, individuals over 50 years of age, patients with severe and complicated forms, and when there is a risk of infection spread.

Treatment of shigellosis

Treatment depends on the severity of the disease, its complications, the patient's age, and comorbid conditions. Patients are prescribed a sparing diet excluding foods that irritate the gastrointestinal tract.

Depending on the type of disease and clinical picture, a patient with shigellosis may receive antibacterial therapy. Measures to replenish fluid loss are mandatory: oral rehydration with glucose-salt solutions for mild cases, and intravenous administration for moderate to severe cases. Enterosorbents are prescribed to neutralize toxins, and agents that relieve colonic spasms are used. During the recovery period, bifidobacteria and lactobacilli preparations, pancreatic enzymes, anti-inflammatory infusions, and physiotherapy may be prescribed.

Complications

Shigellosis can be very severe and lead to numerous dangerous complications. These include:

• infectious-toxic shock and mixed shock (due to intoxication and dehydration),

• perforation of intestinal ulcers with the development of generalized inflammation (peritonitis) or intestinal hemorrhage,

• fatal encephalopathy syndrome in children and debilitated patients,

• acute adrenal insufficiency,

• bacteremia — the entry of bacteria into the bloodstream and their dissemination throughout the body,

• hemolytic-uremic syndrome, accompanied by a decrease in red blood cell and platelet counts and acute renal failure,

• acute cardiovascular insufficiency,

• myocarditis (inflammation of the heart muscle) and thromboendocarditis (a syndrome characterized by the formation of mural thrombi in the heart against the background of endocarditis, inflammation of the inner lining of the heart wall),

• pulmonary edema and cerebral edema-swelling;

• thromboembolism of small and medium branches of the pulmonary artery;

• segmental thrombosis of the superior mesenteric artery, which can lead to impaired blood supply to a segment of the intestine.

In addition to the aforementioned complications, intestinal hemorrhage, hemorrhagic imbibition of the ileal wall, toxic megacolon, paresis, intestinal obstruction and intussusception, rectal prolapse, formation of intestinal or enterovesical fistulas, intestinal wall gangrene, pericolitis, paraproctitis, anal fissures, cicatricial stenosis of the intestine, etc., may develop.

Infectious complications may also arise due to the activation of secondary microflora.

Rare but possible complications include reactive arthritis and Reiter's syndrome.

Prevention of shigellosis

The most important method of prevention is compliance with sanitary and hygienic standards, such as hand washing, consuming only fresh foods, and thoroughly washing vegetables and fruits. One should avoid swimming in unverified bodies of water and drinking water from unverified sources.

In Russia, the Shigellvac dysentery vaccine has been developed. Vaccination is indicated for adults traveling to regions epidemiologically unfavorable for dysentery, food industry workers, municipal services personnel, and healthcare workers. Population vaccination may be carried out during the threat of an outbreak.

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

Appendix G1. Allgower Shock Index

Russian title: Allgower shock index

Original title (if available): ___ _______________ Source (official developer website, validation publication): [34, 35]: Type (underline):

- rating scale

- index

- questionnaire

- other (specify): ________________________ Purpose: Determination of blood loss volume

Content (template):

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: ____________________________________________________________

Appendix G2. Clinical Dehydration Scale (CDS)

Russian title: Clinical Dehydration Scale (CDS)

Original title (if available): Clinical Dehydration Scale

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

Type (underline): - rating scale

Purpose: assessment of dehydration severity in children

Content (template):

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