Scheme 12. Microbiological diagnosis of dysentery

Microscopic method for dysentery it is not used due to the morphological similarity of Shigella with other enterobacteria.

Bacteriological method is the main method of laboratory diagnosis of dysentery . The material under study is inoculated on Ploskirev and Endo media in Petri dishes, as well as on a selenite accumulation medium, from which, after 16-18 hours, reseeding is done on the specified dense nutrient media. Crops are grown in a thermostat at 37 0 C for 18 - 24 hours.

On the second day, the nature of the colonies is studied. Colorless lactose-negative smooth colonies of Shigella are subcultured onto one of the polycarbohydrate media (Olkenitsky, Ressel, Kligler) to accumulate a pure culture. On the 3rd day, the growth pattern on a polycarbohydrate medium is taken into account, and the material is also subcultured onto differential media (Gissa et al.) for biochemical identification of the isolated culture. The antigenic structure of the isolated culture is determined using OPA in order to identify it to the species and serovar levels. On the 4th day, the results of biochemical activity are taken into account (Table 14).

Table 14. Biochemical properties of Shigella

Designations: “k” – fermentation of the substrate with the formation of acid, “+” - presence of the characteristic, “-“ - absence of the characteristic, “±” - unstable characteristic.

Shigella, unlike Escherichia, are immobile microorganisms; they do not ferment lactose, decompose glucose without gas formation, and do not decarboxylate lysine. For serotyping, first RA is placed on glass with a mixture of sera against the species and variants of Shigella that are prevalent in the area, and then RA is placed on glass with monoreceptor species sera. The sensitivity of the isolated culture to polyvalent dysentery bacteriophage and antibiotics is also determined. For epidemiological purposes, phagovar and colicinvar of isolated Shigella are determined. One of the properties of Shigella is their ability to cause keratitis in guinea pigs(keratoconjunctival test)

Serological method. To determine antibodies in the blood of patients with dysentery (usually the chronic form), RNGA with erythrocyte shigella diagnosticums is used. Diagnostic titers: for Flexner's Shigella in adults - 1:400, in children under 3 years old - 1:100, in children over 3 years old - 1:200, for other Shigella - 1:200. The reaction is usually repeated with blood serum taken at least 7 days later; diagnostic value has an increase in antibody titer by four or more times.

Express methods for dysentery - direct and indirect RIF, co-agglutination reaction, ELISA, RNGA with antibodies erythrocyte diagnosticums for rapid detection of Shigella in the test material (usually in feces), as well as PCR.

Dysentery.

Dysentery is an infectious disease characterized by general intoxication of the body, loose stools and a peculiar lesion of the mucous membrane of the large intestine. It is one of the most common acute intestinal diseases in the world. The disease has been known since ancient times under the name “bloody diarrhea”, but its nature turned out to be different. In 1875 Russian scientist Lesh isolated an amoeba from a patient with bloody diarrhea Entamoeba histolytica, over the next 15 years, the independence of this disease was established, for which the name amoebiasis was retained. The causative agents of dysentery proper are a large group of biologically similar bacteria, united in the genus Shigelta. The pathogen was first discovered in 1888. A. Chantemes and Vidal; in 1891 it was described by A.V. Grigoriev, and in 1898. K. Shiga, using serum obtained from the patient, identified the pathogen in 34 patients with dysentery, finally proving the etiological role of this bacterium. However, in subsequent years, other pathogens of dysentery were discovered: in 1900. - S. Flexner, in 1915 - K. Sonne, in 1917 - K. Stutzer and K. Schmitz, in 1932. - J. Boyd, in 1934 - D. Large, in 1943 - A. Sax.

Currently genus Shigella includes more than 40 serotypes. All of them are short, immobile gram-negative rods that do not form spores or capsules, which (grow well on ordinary nutrient media ah, do not grow on a medium with citrate as the only carbon source; do not form H2S, do not have urease; Voges-Proskauer reaction is negative; glucose and some other carbohydrates are fermented to form acid without gas (except for some biotypes Shigella flexneri: S.manchester And ewcastle); As a rule, they do not ferment lactose (with the exception of Shigella Sonne), adonitol, inositol, do not liquefy gelatin, usually form catalase, and do not have lysine decarboxylase and phenylalanine deaminase. The G+C content in DNA is 49-53 mol%. Shigella are facultative anaerobes, the optimum temperature for growth is 37 ° C, they do not grow above 45 ° C, the optimal pH of the environment is 6.7-7.2. Colonies on dense media are round, convex, translucent; in case of association, rough R-shaped colonies are formed. Growth on MPB in the form of uniform turbidity, rough forms form a sediment. Freshly isolated cultures of Shigella Sonne J4HO form colonies of two types: small round convex (phase I), large flat (phase 2). The nature of the colony depends on the presence (phase I) or absence (phase II) of a plasmid with mm 120 MD, which also determines the virulence of Shigella Sonne.

In Shigella, O-antigens of different specificity were found: common to the family Enterobacteriaceae generic, species, group and type-specific, as well as K-antigens; They do not have N-antigens.

The classification takes into account only group and type-specific O-antigens. In accordance with these characteristics, the genus Shigella is divided into 4 subgroups, or 4 species, and includes 44 serotypes. In subgroup A (type Shigella dysenteriae) included Shigella, which does not ferment mannitol. The species includes 12 serotypes (1-12). Each stereotype has its own specific type antigen; antigenic connections between serotypes, as well as with other Shigella species, are weakly expressed. To subgroup B (type Shigella flexneri) include Shigella, which usually ferments mannitol. Shigella of this species are serologically related to each other: they contain type-specific antigens (I-VI), which are divided into serotypes (1-6), and group antigens, which are found in different compositions each serotype and according to which serotypes are divided into subserotypes. In addition, this species includes two antigenic variants - X and Y, which do not have typical antigens; they differ in sets of group antigens. Serotype S.flexneri 6 has no subserotypes, but is divided into 3 biochemical types based on the fermentation characteristics of glucose, mannitol and dulcitol.

To subgroup C (type Shlgella boydll) include Shigella, which usually ferments mannitol. Members of the group are serologically different from each other. Antigenic connections within the species are weakly expressed. The species includes 18 serotypes (1-18), each of which has its own main type antigen.

In subgroup D (type Shlgella sonnel) included Shigella, which usually ferments mannitol and is capable of slowly (after 24 hours of incubation and later) fermenting lactose and sucrose. View S. sonnei includes one serotype, but colonies of phases I and II have their own type-specific antigens. For the intraspecific classification of Shigella Sonne, two methods have been proposed:

1) dividing them into 14 biochemical types and subtypes according to their ability to ferment maltose, rhamnose and xylose;

2) division into phage types according to sensitivity to a set of corresponding phages.

These typing methods have mainly epidemiological significance. In addition, Shigella Sonne and Shigella Flexner are typed for the same purpose based on their ability to synthesize specific colicins (colicinogenotyping) and sensitivity to known colicins (colicinotyping). To determine the type of colicins produced by Shigella, J. Abbott and R. Shenon proposed sets of standard and indicator strains of Shigella, and to determine the sensitivity of Shigella to known types colicins use a set of reference colicinogenic strains of P. Frederick.

Resistance. Shigella has a fairly high resistance to environmental factors. They survive on cotton fabric and paper for up to 30-36 days, in dried feces - up to 4-5 months, in soil - up to 3-4 months, in water - from 0.5 to 3 months, on fruits and vegetables - up to 2 food, in milk and dairy products - up to several weeks; at 60 °C they die in 15-20 minutes.

Sensitive to chloramine solutions, active chlorine and other disinfectants.

Pathogenicity factors. The most important biological property of Shigella, which determines their pathogenicity, is the ability to invade epithelial cells, multiply in them and cause their death. This effect can be detected using a keratoconjunctival test (introduction of one loop of Shigella culture (2-3 billion bacteria) under the lower eyelid of a guinea pig causes the development of serous-purulent keratoconjunctivitis), as well as by infection of cell cultures (cytotoxic effect), or chicken embryos ( their death), or intranasally in white mice (development of pneumonia). The main pathogenicity factors of Shigella can be divided into three groups:

1) factors determining interaction with the epithelium of the mucous membrane;

2) factors that ensure resistance to humoral and cellular defense mechanisms of the macroorganism and the ability of Shigella to reproduce in its cells;

3) the ability to produce toxins and toxic products that determine the development of the pathological process itself.

The first group includes adhesion and colonization factors: their role is played by pili, outer membrane proteins and LPS. Adhesion and colonization are promoted by enzymes that destroy mucus - neuraminidase, hyaluronidase, mucinase. The second group includes invasion factors that promote the penetration of Shigella into enterocytes and their reproduction in them and in macrophages with the simultaneous manifestation of a cytotoxic and (or) enterotoxic effect. These properties are controlled by the genes of the plasmid with m.m. 140 MD (it encodes the synthesis of outer membrane proteins that cause invasion) and the chromosomal genes of Shigella: KSR A (causes keratoconjunctivitis), cyt (responsible for cell destruction), as well as other genes not yet identified. Protection of Shigella from phagocytosis is provided by the surface K-antigen, antigens 3, 4 and lipopolysaccharide. In addition, lipid A of Shigella endotoxin has an immunosuppressive effect - it suppresses the activity of immune memory cells.

The third group of pathogenicity factors includes endotoxin and two types of exotoxins found in Shigella - Shiga and Shiga-like exotoxins (SLT-I and SLT-II), the cytotoxic properties of which are most pronounced in S. dysenteriae 1. Shiga and Shiga-like toxins have also been found in other serotypes S. dysenteriae, they are also formed S.flexneri, S.sonnei, S.boydii, ETEC and some salmonella. The synthesis of these toxins is controlled by the tox genes of converting phages. Type LT enterotoxins are found in Shigella Flexner, Sonne and Boyd. Their LT synthesis is controlled by plasmid genes. Enterotoxin stimulates the activity of adenylate cyclase and is responsible for the development of diarrhea. Shiga toxin, or neurotoxin, does not react with the adenylate cyclase system, but has a direct cytotoxic effect. Shiga and Shiga-like toxins (SLT-I and SLT-II) have m.m. -70 kDa and consist of subunits A and B (the latter of 5 identical small subunits). The receptor for toxins is a glycolipid of the cell membrane.

The virulence of Shigella Sonne also depends on the plasmid with m.m. 120 MD. It controls the synthesis of about 40 outer membrane polypeptides, seven of them are associated with virulence. Shigella Sonne, having this plasmid, form phase I colonies and are virulent. Cultures that have lost the plasmid form phase II colonies and lack virulence. Plasmids with m.m. 120-140 MD were found in Shigella Flexner and Boyd. Shigella lipopolysaccharide is a strong endotoxin.

Features of epidemiology. The source of infection is only humans. No animals in nature suffer from dysentery. Under experimental conditions, dysentery can only be reproduced in monkeys. The method of infection is fecal-oral. Routes of transmission: water (predominant for Shigella Flexnera), food, especially milk and dairy products (predominant route of infection for Shigella Sonne), and household contact, especially for the species S. dysenteriae.

A feature of the epidemiology of dysentery is a change in the species composition of pathogens, as well as Sonne biotypes and Flexner serotypes in certain regions. For example, until the end of the 30s of the 20th century, the share S.dysenteriae 1 accounted for up to 30-40% of all cases of dysentery, and then this serotype began to occur less and less often and almost disappeared. However, in the 60-80s S.dysenteriae reappeared on the historical arena and caused a series of epidemics that led to the formation of three hyperendemic foci of it - in Central America, Central Africa and South Asia (India, Pakistan, Bangladesh and other countries). The reasons for the change in the species composition of dysentery pathogens are probably associated with changes herd immunity and with changes in the properties of dysentery bacteria. In particular, the return S.dysenteriae 1 and its widespread distribution, which caused the formation of hyperendemic foci of dysentery, is associated with its acquisition of plasmids that caused multidrug resistance and increased virulence.

Features of pathogenesis and clinic. The incubation period for dysentery is 2-5 days, sometimes less than a day. The formation of an infectious focus in the mucous membrane of the descending part of the large intestine (sigmoid and rectum), where the dysentery pathogen penetrates, is cyclical in nature: adhesion, colonization, introduction of Shigella into the cytoplasm of enterocytes, their intracellular reproduction, destruction and rejection of epithelial cells, release of pathogens into the lumen intestines; after this, the next cycle begins - adhesion, colonization, etc. The intensity of the cycles depends on the concentration of pathogens in the parietal layer of the mucous membrane. As a result of repeated cycles, the inflammatory focus grows, the resulting ulcers, connecting, increase the exposure of the intestinal wall, as a result of which blood, mucopurulent lumps, and polymorphonuclear leukocytes appear in the feces. Cytotoxins (SLT-I and SLT-II) cause cell destruction, enterotoxin - diarrhea, endotoxins - general intoxication. The clinical picture of dysentery is largely determined by what type of exotoxins is produced to a greater extent by the pathogen, the degree of its allergenic effect and immune status body. However, many questions of the pathogenesis of dysentery remain unclear, in particular: the features of the course of dysentery in children of the first two years of life, the reasons for the transition of acute dysentery to chronic, the significance of sensitization, the mechanism of local immunity of the intestinal mucosa, etc. The most typical clinical manifestations of dysentery are diarrhea, frequent urges - in severe cases, up to 50 or more times a day, tenesmus (painful spasms of the rectum) and general intoxication. The nature of the stool is determined by the degree of damage to the large intestine. The most severe dysentery is caused by S.dysenteriae 1, most easily - Sonne dysentery.

Post-infectious immunity. As observations of monkeys have shown, after suffering from dysentery, strong and fairly long-lasting immunity remains. It is caused by antimicrobial antibodies, antitoxins, increased activity of macrophages and T-lymphocytes. Local immunity of the intestinal mucosa, mediated by IgAs, plays a significant role. However, immunity is type-specific; strong cross-immunity does not occur.

Laboratory diagnostics. The main method is bacteriological. The material for research is feces. Pathogen isolation scheme: inoculation on differential diagnostic media Endo and Ploskirev (in parallel on enrichment medium followed by inoculation on Endo and Ploskirev media) to isolate isolated colonies, obtaining a pure culture, studying its biochemical properties and, taking into account the latter, identification using polyvalent and monovalent diagnostic agglutinating sera. The following commercial serums are produced:

1. To Shigella, which does not ferment mannitol: to S.dysenteriae 1 to 2 S.dysenteriae 3-7(polyvalent and monovalent), to S.dysenteriae 8-12(polyvalent and monovalent).

2. To Shigella fermenting mannitol:

to typical antigens S.flexneri I, II, III, IV, V, VI,

to group antigens S.flexneri 3, 4, 6,7,8- polyvalent,

to antigens S.boydii 1-18(polyvalent and monovalent),

to antigens S. sonnei I phase, II phase,

to antigens S.flexneri I-VI+ S.sonnei- polyvalent.

To detect antigens in the blood (including as part of the CEC), urine and feces, the following methods can be used: RPHA, RSK, coagglutination reaction (in urine and feces), IFM, RPGA (in blood serum). These methods are highly effective, specific and suitable for early diagnosis.

For serological diagnostics can be used: RPHA with the corresponding erythrocyte diagnostics, immunofluorescence method (indirect modification), Coombs method (determining the titer of incomplete antibodies). An allergy test with dysenterine (a solution of protein fractions of Shigella Flexner and Sonne) is also of diagnostic value. The reaction is taken into account after 24 hours. It is considered positive in the presence of hyperemia and infiltrate with a diameter of 10-20 mm.

Treatment. The main attention is paid to restoring normal water-salt metabolism, rational nutrition, detoxification, rational antibiotic therapy (taking into account the sensitivity of the pathogen to antibiotics). Good effect gives early use of polyvalent dysentery bacteriophage, especially tableted with pectin coating, which protects the phage from the action of HC1 gastric juice; In the small intestine, pectin dissolves, phages are released and exert their effect. For preventive purposes, the phage should be given at least once every three days (the period of its survival in the intestine).

Problem specific prevention. To create artificial immunity against dysentery, various vaccines were used: from killed bacteria, chemical, alcohol, but all of them turned out to be ineffective and were discontinued. Vaccines against Flexner's dysentery have been created from live (mutant, streptomycin-dependent) Shigella Flexner; ribosomal vaccines, but they also have not found widespread use. Therefore, the problem of specific prevention of dysentery remains unresolved. The main way to combat dysentery is to improve the water supply and sewerage system, ensure strict sanitary and hygienic regimes in food enterprises, especially the dairy industry, in child care institutions, public places and in maintaining personal hygiene.

Microbiology of cholera

According to WHO, cholera is a disease characterized by acute, severe, dehydrating diarrhea with rice-water-like stool, resulting from infection with Vibrio cholerae. Due to the fact that it is characterized by a pronounced ability to wide epidemic spread, severe course and high mortality, cholera is one of the most dangerous infections.

The historical homeland of cholera is India, more precisely, the delta of the Ganges and Brahmaputra rivers (now Eastern India and Bangladesh), where it has existed since time immemorial (cholera epidemics in this area have been observed since 500 years BC). The long existence of an endemic source of cholera here is explained by many reasons. Vibrio cholerae can not only survive in water for a long time, but also multiply in it under favorable conditions - temperatures above +12 ° C, and the presence of organic substances. All these conditions are available in India - tropical climate (average annual temperature from +25 up to +29 ° C), abundant precipitation and swampiness, high population density, especially in the Ganges River delta, a large amount of organic substances in the water, continuous year-round water pollution with sewage and excrement, low material standards of living and peculiar religious and cult rituals of the population.

The causative agent of cholera Vibrio cholerae was opened in 1883. during the fifth pandemic by R. Koch, however, vibrio was first discovered in the feces of patients with diarrhea back in 1854. F. Pacini.

V.cholerae belongs to the family Vibrionaceae which includes several genera (Vibrio, Aeromonas, Plesiomonas, Photobacterium). Genus Vibrio since 1985 has more than 25 species, of which the most important for humans are V.cholerae, V.parahaemolyticus, V.alginolyticus, dnificus And V. fluvialis.

Key characteristics of the genus Vibrio : short, not forming spores and capsules, curved or straight gram-negative rods, 0.5 µm in diameter, 1.5-3.0 µm in length, mobile ( V.cholerae- monotrich, some species have two or more polarly located flagella); grow well and quickly on ordinary media, chemoorganotrophs, ferment carbohydrates with the formation of acid without gas (glucose is fermented via the Embden-Meyerhof pathway). Oxidase positive, form indole, reduce nitrates to nitrites (V.cholerae gives a positive nitroso-indole reaction), break down gelatin, often give a positive Voges-Proskauer reaction (i.e., they form acetylmethylcarbinol), do not have urease, do not form H S. have lysine and ornithine decarboxylases, but do not have arginine dihydrolase.

Vibrio cholerae is very unpretentious to nutrient media. It multiplies well and quickly in 1% alkaline (pH 8.6-9.0) peptone water (PV) containing 0.5-1.0% NaCl, outpacing the growth of other bacteria. To suppress the growth of Proteus, it is recommended to add potassium tellurite 4 to 1% (PV) (final dilution 1:100,000). 1% PV is the best enrichment medium for Vibrio cholerae. As it grows, after 6-8 hours on the surface of the PV, it forms a delicate, loose, grayish film, which, when shaken, easily breaks down and falls to the bottom in the form of flakes; the PV becomes moderately cloudy. Various selective media have been proposed for the isolation of Vibrio cholerae: alkaline agar, yolk-salt agar, alkaline albuminate, alkaline blood agar, lactose-sucrose and other media. The best medium is TCBS (thiosulfate citrate-bromothymol sucrose agar) and its modifications. However, most often they use alkaline MPA, on which Vibrio cholerae forms smooth, glassy-transparent disc-shaped colonies with a viscous consistency with a bluish tint.

When sown by injection into a column of gelatin, vibrio after 2 days at 22-23 ° C causes liquefaction from the surface in the form of a bubble, then funnel-shaped and, finally, layer-by-layer.

In milk, vibrio multiplies quickly, causing coagulation after 24-48 hours, and then peptonization of the milk occurs, and after 3-4 days the vibrio dies due to a shift in the pH of milk to the acidic side.

B. Heiberg, based on the ability to ferment mannose, sucrose and arabinose, divided all vibrios (cholera and cholera-like) into a number of groups, the number of which is now 8. Vibrio cholerae belongs to Heiberg’s first group.

Vibrios, similar in morphological, cultural and biochemical characteristics to cholera, were and are called differently: paracholera, cholera-like, NAG-vibrios (non-agglutinating vibrios); vibrios not belonging to group 01. The last name most accurately emphasizes their relationship to Vibrio cholerae. As was established by A. Gardner and K. Venkatraman, cholera and cholera-like vibrios have a common H-antigen, but differ in O-antigens. According to the O-antigen, cholera and cholera-like vibrios are currently divided into 139 O-serogroups, but their number is constantly growing. Vibrio cholerae belongs to group 01. It has a common A-antigen and two type-specific antigens - B and C, which distinguish three serotypes V.cholerae- serotype Ogawa (AB), serotype Inaba (AS) and serotype Gikoshima (ABC). Vibrio cholerae in the dissociation stage has an OR antigen. In this regard, for identification V.cholerae O-serum, OR-serum and type-specific sera Inaba and Ogawa are used.

Pathogenicity factors V.cholerae :

1. Mobility.

2. Chemotaxis. With the help of these properties, the vibrio overcomes slime layer and interacts with epithelial cells. In Che" mutants (which have lost the ability to chemotaxis), virulence is sharply reduced. Virulence in Mot" mutants (which have lost mobility) either completely disappears or is reduced by 100-1000 times.

3. Adhesion and colonization factors, with the help of which vibrio adheres to microvilli and colonizes the mucous membrane of the small intestine.

4. Enzymes: mucinase, proteases, neuraminidase, lecithinase, etc.

They promote adhesion and colonization, as they destroy substances that make up the mucus. Neuraminidase, by cleaving sialic acid from epithelial glycoproteins, creates a “landing” site for vibrios. In addition, it increases the number of receptors for choleragen by modifying tri- and disialogangliosides into monosialoganglioside Gm b which serves as a receptor for choleragen.

5. The main factor of pathogenicity V.cholerae is an exotoxin-cholerogen, which determines the pathogenesis of cholera. The cholerogens molecule has a m.m. 84 kDa and consists of two fragments - A and B. Fragment A consists of two peptides - A1 and A2 - and has the specific property of cholera toxin. Fragment B consists of 5 identical subunits and performs two functions: 1) recognizes the receptor (monosialoganglioside) of the enterocyte and binds to it;

2) forms an intramembrane hydrophobic channel for the passage of subunit A. Peptide A 2 Cl is used to connect fragments A and B. The actual toxic function is performed by the peptide A t. It interacts with NAD, causes its hydrolysis, and the resulting ADP-ribose binds to the regulatory subunit of adenylate cyclase. This leads to inhibition of GTP hydrolysis. The resulting GTP + adenylate cyclase complex causes the hydrolysis of ATP with the formation of cAMP. (Another way of accumulating cAMP is the suppression of the enzyme that hydrolyzes cAMP to 5-AMP by cholerogens).

6. In addition to choleragen, Vibrio cholerae synthesizes and secretes a factor that increases capillary permeability.

7. Other exotoxins have also been found in Vibrio cholerae, in particular types LT, ST and SLT.

8. Endotoxin. Lipopolysaccharide V.cholerae has strong endotoxic properties. It is responsible for general intoxication of the body and vomiting. Antibodies formed against endotoxin have a pronounced vibriocidal effect (dissolve vibrios in the presence of complement) and are an important component post-infectious and post-vaccination immunity.

The ability of vibrios not belonging to group 01 to cause sporadic or group diarrheal diseases in humans is associated with the presence of enterotoxins of the LT or ST type, which stimulate either the adenylate or guanylate cyclase systems, respectively.

Cholerogen synthesis is the most important property V.cholerae. The genes that control the synthesis of the A- and B-fragments of cholerogens are combined into the vctAB or ctxB operon; they are located on the vibrio chromosome. Some strains of Vibrio cholerae have two such non-tandem operons. The function of the operon is controlled by two regulatory genes. The toxR gene provides positive control; mutations of this gene lead to a 1000-fold reduction in toxin production. The htx gene exerts negative control; mutations in this gene increase toxin production by 3-7 times.

The following methods can be used to detect cholerogens:

1. Biological tests on rabbits. When cholera vibrios are injected intraintestinal into suckling rabbits (no more than 2 weeks old), they develop a typical cholerogenic syndrome: diarrhea, dehydration and death of the rabbit. At the autopsy - a sharp injection of the vessels of the stomach and small
intestines, sometimes clear liquid accumulates in it. But the changes in the large intestine are especially characteristic - it is enlarged and filled with a completely transparent, straw-colored liquid with flakes and gas bubbles. When cholera vibrios are introduced into the ligated area of ​​the small intestine into adult rabbits, they experience the same changes in the large intestine as when suckling rabbits are infected.

2. Direct detection of cholerogens using immunofluorescent or enzyme-linked immunosorbent methods or a passive immune hemolysis reaction (cholerogen binds to Gm1 of erythrocytes, and they are lysed with the addition of antitoxic antibodies and complement).

3. Stimulation of cellular adenylate cyclase in cell cultures.

4. Using a chromosome fragment as a DNA probe V.cholerae, carrying an operoncholerogen.

During the seventh pandemic, strains were isolated V.cholerae with varying degrees of virulence: cholerogenic (virulent), weakly cholerogenic (low virulent) and non-cholerogenic (non-virulent). Non-cholerogenic V.cholerae, as a rule, they have hemolytic activity, are not lysed by cholera diagnostic phage 5 (CDF-5) and do not cause human disease.

For phage typing V.cholerae(including V.eltor) S. Mukherjee proposed corresponding sets of phages, which were then supplemented with other phages in Russia. The set of such phages (1-7) makes it possible to distinguish among V.cholerae 16 phagotypes. HDF-3 selectively lyses cholera vibrios of the classical type, HDF-4 - El-Tor vibrios, and HDF-5 lyses only cholerogenic (virulent) vibrios of both types and does not lyse non-cholerogenic vibrios.

Cholerogenic vibrios, as a rule, do not have hemolytic activity, are lysed by HDF-5 and cause cholera in humans.

Resistance of cholera pathogens. Vibrios cholerae survive well at low temperatures: in ice they remain viable for up to 1 month; V sea ​​water- up to 47 days, in river water - from 3-5 days to several weeks, in boiled mineral water they are stored for more than 1 year, in soil - from 8 days to 3 months, in fresh feces - up to 3 days, on cooked foods (rice, noodles, meat, cereals, etc.) survive 2-5 days, on raw vegetables - 2-4 days, on fruits - 1-2 days, in milk and dairy products - 5 days; when stored in the cold, the survival period increases by 1-3 days: on linen contaminated with feces, they last up to 2 days, and on damp material - a week. Cholera vibrios die at 80 °C in 5 minutes, at 100 °C - instantly; highly sensitive to acids; under the influence of chloramine and other disinfectants they die within 5-15 minutes. They are sensitive to drying and direct sunlight, but are preserved well and for a long time and even reproduce in open reservoirs and wastewater, rich in organic matter, having an alkaline pH and a temperature above 10-12 ° C. Highly sensitive to chlorine: a dose of active chlorine of 0.3-0.4 mg/l of water in 30 minutes causes reliable disinfection from Vibrio cholerae.

Features of epidemiology. The main source of infection is only a person - a person with cholera or a vibrio carrier, as well as water contaminated by them. No animals in nature suffer from cholera. The method of infection is fecal-oral. Routes of infection: a) main - through water used for drinking, bathing and household needs; b) contact and household and c) through food. All major cholera epidemics and pandemics were waterborne in nature. Vibrios cholerae have such adaptive mechanisms that ensure the existence of their populations both in the human body and in certain ecosystems of open water bodies. Profuse diarrhea, which is caused by Vibrio cholerae, leads to the cleansing of the intestines from competing bacteria and contributes to the widespread distribution of the pathogen in the environment, primarily in wastewater and in open water bodies where they are discharged. A person with cholera excretes the pathogen in huge quantities - from 100 million to 1 billion per 1 ml of excrement; a vibrio carrier excretes 100-100,000 vibrios per 1 ml, the infecting dose is about 1 million vibrios. Duration of isolation of cholera vibrio in healthy carriers ranges from 7 to 42 days, and 7-10 days for those who have recovered. Longer discharge is extremely rare.

The peculiarity of cholera is that after it, as a rule, there is no long-term carriage and persistent endemic foci do not form. However, as already mentioned above, due to the pollution of open water bodies with wastewater containing large quantities of organic substances, detergents and table salt, in the summer, Vibrio cholerae not only survives in them for a long time, but even multiplies.

Of great epidemiological significance is the fact that vibrios cholerae group 01, both non-toxigenic and toxigenic, can persist for a long time in various aquatic ecosystems in the form of uncultivated forms. Using the polymerase chain reaction, with negative bacteriological studies, veterinary genes of uncultivated forms were discovered in a number of endemic areas of the CIS in various water bodies V.cholerae.

When cholera diseases occur, a set of anti-epidemic measures is carried out, among which the leading and decisive one is the active timely identification and isolation (hospitalization, treatment) of patients with acute and atypical forms and healthy vibrio carriers; measures are being taken to suppress possible ways of spreading the infection; special attention is paid to water supply (chlorination of drinking water), compliance with the sanitary and hygienic regime at food enterprises, in child care institutions, and public places; Strict control, including bacteriological control, is carried out over open water bodies, immunization of the population is carried out, etc.

Features of pathogenesis and clinic. The incubation period for cholera varies from a few hours to 6 days, most often 2-3 days. Once in the lumen of the small intestine, cholera vibrios are directed to the mucus due to motility and chemotaxis to the mucous membrane. To penetrate through it, vibrios produce a number of enzymes: neuraminidase, mucinase, proteases, lecithinase, some destroy substances contained in mucus and facilitate the movement of vibrios to epithelial cells. By adhesion, vibrios attach to the glycocalyx of the epithelium and, losing mobility, begin to multiply intensively, colonizing the microvilli of the small intestine, and at the same time producing large amounts of exotoxin-cholerogen. Cholerogen molecules bind to monosialoganglioside Gm1 and penetrate the cell membrane, activate the adenylate cyclase system, and the accumulating cAMP causes hypersecretion of fluid, cations and anions Na +, HCO 3 ~, K +, SG from enterocytes, which leads to cholera diarrhea, dehydration and desalination body. There are three types of disease:

1. violent, severe dehydrating diarrheal disease, leading to the death of the patient within a few hours;

2. less severe course, or diarrhea without dehydration;

3. asymptomatic course of the disease (vibrio carriage).

In severe forms of cholera, patients develop diarrhea, stools become more frequent, bowel movements become more abundant, become watery, lose their fecal odor and look like rice water (a cloudy liquid with mucus residues and epithelial cells floating in it). Then comes debilitating vomiting, first with intestinal contents, and then the vomit takes on the appearance of rice water. The patient's temperature drops below normal, the skin becomes bluish, wrinkled and cold - cholera algid. As a result of dehydration, blood thickens, cyanosis develops, oxygen starvation develops, kidney function sharply suffers, convulsions appear, the patient loses consciousness and death occurs. The case fatality rate for cholera during the seventh pandemic ranged from 1.5% in developed countries to 50% in developing countries.

Post-infectious immunity durable, long-lasting, recurrent diseases are rare. Antitoxic and antimicrobial immunity is caused by antibodies (antitoxins last longer than antimicrobial antibodies), immune memory cells and phagocytes.

Laboratory diagnostics. Main and decisive method Diagnosis of cholera is bacteriological. The material for research from the patient is feces and vomit; feces are examined for vibrio carriage; from persons who died from cholera, a ligated segment of the small intestine and gall bladder are taken for research; Among environmental objects, water from open reservoirs and wastewater are most often studied.

When conducting bacteriological research The following three conditions must be met:

1) inoculate material from the patient as quickly as possible (vibrio cholera persists in feces for a short period of time);

2) the container in which the material is taken should not be disinfected with chemicals and should not contain traces of them, since Vibrio cholerae is very sensitive to them;

3) exclude the possibility of contamination and infection of others.

In cases where there are V.cholerae not 01-groups, they must be typed using appropriate agglutinating sera of other serogroups. Discharge from a patient with diarrhea (including cholera-like) V.cholerae not 01-group requires the same anti-epidemic measures as in the case of isolation V.cholerae 01-groups. If necessary, the ability to synthesize choleragen or the presence of choleragen genes in isolated cholera vibrios is determined using a DNA probe using one of the methods.

Serological diagnosis of cholera is auxiliary. For this purpose, an agglutination reaction can be used, but it is better to determine the titer of vibriocidal antibodies or antitoxins (cholerogen antibodies are determined by enzyme-linked immunosorbent or immunofluorescent methods).

Treatment for patients with cholera should consist primarily of rehydration and restoration of normal water-salt metabolism. For this purpose, it is recommended to use saline solutions, for example, of the following composition: NaCl - 3.5; NaHCO 3 - 2.5; KS1 - 1.5 and glucose - 20.0 g per 1 liter of water. Such pathogenetically based treatment in combination with rational antibiotic therapy can reduce the mortality rate in cholera to 1% or less.

Specific prevention. Various vaccines have been proposed to create artificial immunity, including killed Inaba and Ogawa strains; Cholerogen toxoid for subcutaneous use and enteral chemical bivalent vaccine, sos

is an acute intestinal infection caused by bacteria of the genus Shigella, characterized by the predominant localization of the pathological process in the mucous membrane of the large intestine. Dysentery is transmitted by the fecal-oral route (food or water). Clinically, a patient with dysentery experiences diarrhea, abdominal pain, tenesmus, and intoxication syndrome (weakness, weakness, nausea). The diagnosis of dysentery is established by isolating the pathogen from the patient’s feces; for Grigoriev-Shiga dysentery, from the blood. Treatment is carried out mainly on an outpatient basis and consists of rehydration, antibacterial and detoxification therapy.

General information

is an acute intestinal infection caused by bacteria of the genus Shigella, characterized by the predominant localization of the pathological process in the mucous membrane of the large intestine.

Characteristics of the pathogen

The causative agents of dysentery - Shigella, are currently represented by four species (S. dysenteriae, S.flexneri, S. boydii, S. Sonnei), each of which (with the exception of Shigella Sonne) in turn is divided into serovars, of which there are currently more than fifty. The population of S. sonnei is homogeneous in antigenic composition, but differs in its ability to produce various enzymes. Shigella is a nonmotile gram-negative rod, does not form spores, reproduces well on nutrient media, and is usually not very stable in the external environment.

The optimal temperature environment for Shigella is 37 ° C, Sonne bacilli are capable of reproduction at a temperature of 10-15 ° C, can form colonies in milk and dairy products, can remain viable for a long time in water (like Shigella Flexner), and are resistant to antibacterial agents. . Shigella quickly die when heated: instantly - when boiling, after 10 minutes - at a temperature of more than 60 degrees.

The reservoir and source of dysentery is a person - a sick or asymptomatic carrier. Patients with mild or erased forms of dysentery, especially those related to the food industry and public catering establishments, are of greatest epidemiological importance. Shigella is released from the body of an infected person, starting from the first days of clinical symptoms, infectivity persists for 7-10 days, followed by a period of convalescence, during which, however, the release of bacteria is also possible (sometimes it can last several weeks and months).

Flexner's dysentery is most prone to becoming chronic; the least tendency to chronicity is observed with infection caused by Sonne bacteria. Dysentery is transmitted via the fecal-oral mechanism mainly by food (Sonne's dysentery) or water (Flexner's dysentery) route. When transmitting Grigoriev-Shiga dysentery, the transmission route is predominantly through contact and household transmission.

People have a high natural susceptibility to infection; after suffering from dysentery, unstable type-specific immunity is formed. Those who have recovered from Flexner's dysentery can retain post-infectious immunity, which protects against recurrent disease for several years.

Pathogenesis of dysentery

Shigella enters the digestive system with food or water (partially dying under the influence of the acidic contents of the stomach and normal biocenosis intestines) and reach the colon, partially penetrating its mucous membrane and causing inflammatory reaction. The mucous membrane affected by Shigella is prone to the formation of areas of erosion, ulcers, and hemorrhages. Toxins released by bacteria disrupt digestion, and the presence of Shigella destroys the natural biobalance intestinal flora.

Classification

Currently, the clinical classification of dysentery is used. There are its acute form (differing in the predominant symptoms into typical colitic and atypical gastroenteric), chronic dysentery (recurrent and continuous) and bacterial excretion (convalescent or subclinical).

Symptoms of dysentery

The incubation period of acute dysentery can last from one day to a week, most often it is 2-3 days. The colitic variant of dysentery usually begins acutely, the body temperature rises to febrile levels, and symptoms of intoxication appear. Appetite is noticeably reduced and may be completely absent. Sometimes nausea and vomiting are noted. Patients complain of intense cutting pain in the abdomen, initially diffuse, later concentrating in the right iliac region and lower abdomen. The pain is accompanied by frequent (up to 10 times a day) diarrhea, stool quickly loses its fecal consistency, becomes scanty, and contains pathological impurities - blood, mucus, and sometimes pus (“rectal spit”). The urge to defecate is excruciatingly painful (tenesmus), sometimes false. The total number of daily bowel movements is usually not large.

On examination, the tongue is dry, coated, tachycardia, and sometimes arterial hypotension. Acute clinical symptoms usually begin to subside and finally fade away by the end of the first week, the beginning of the second, but ulcerative defects of the mucous membrane usually heal completely within a month. The severity of the colitis is determined by the intensity of the intoxication and pain syndrome and the duration acute period. At severe course disorders of consciousness caused by severe intoxication are noted, the frequency of stools (like “rectal spitting” or “meat slop”) reaches dozens of times a day, painful abdominal pain, and significant hemodynamic disturbances are noted.

Acute dysentery in the gastroenteric variant is characterized by a short incubation period (6-8 hours) and predominantly enteral symptoms against the background of a general intoxication syndrome: nausea, repeated vomiting. The course resembles that of salmonellosis or toxic infection. The pain in this form of dysentery is localized in the epigastric region and around the navel, has a cramping nature, the stool is loose and profuse, there are no pathological impurities; with intense loss of fluid, dehydration syndrome may occur. The symptoms of the gastroenteric form are violent, but short-lived.

Initially, gastroenterocolitic dysentery also resembles in its course a foodborne toxic infection; subsequently, colitic symptoms begin to appear: mucus and bloody streaks in the stool. The severity of the gastroenterocolitic form is determined by the severity of dehydration.

Dysentery of the erased course today occurs quite often. There is discomfort, moderate pain in the abdomen, mushy stool 1-2 times a day, mostly without impurities, hyperthermia and intoxication are absent (or extremely insignificant). Dysentery lasting more than three months is considered chronic. Currently, cases of chronic dysentery in developed countries are rare. The recurrent variant represents periodic episodes of the clinical picture of acute dysentery, interspersed with periods of remission, when patients feel relatively well.

Continuous chronic dysentery leads to the development of severe digestive disorders and organic changes in the mucous membrane of the intestinal wall. Intoxication symptoms in continuous chronic dysentery are usually absent, there is constant daily diarrhea, stools are mushy and may have a greenish tint. Chronic malabsorption leads to weight loss, hypovitaminosis, and the development of malabsorption syndrome. Convalescent bacterial excretion is usually observed after suffering an acute infection, subclinical - occurs when suffering from dysentery in an erased form.

Complications

Complications with the current level of medical care are extremely rare, mainly in the case of severe Grigoriev-Shiga dysentery. This form of infection can be complicated by infectious-toxic shock, intestinal perforation, peritonitis. In addition, the development of intestinal paresis is likely.

Dysentery with intense long-term diarrhea may be complicated by hemorrhoids, anal fissure, rectal prolapse. In many cases, dysentery contributes to the development of dysbiosis.

Diagnostics

Bacteriological diagnostics is extremely specific. The pathogen is usually isolated from feces, and in the case of Grigoriev-Shiga dysentery, from the blood. Since the increase in the titer of specific antibodies occurs rather slowly, serological diagnostic methods (RNGA) have retrospective significance. Increasingly, laboratory practice for diagnosing dysentery includes the identification of Shigella antigens in feces (usually done using RCA, RLA, ELISA and RNGA with an antibody diagnosticum), the complement binding reaction and hemagglutination aggregate.

As general diagnostic measures, various laboratory techniques are used to determine the severity and extent of the process and identify metabolic disorders. A stool test is performed for dysbacteriosis and coprogram. Endoscopic examination (sigmoidoscopy) can often provide the necessary information for differential diagnosis in doubtful cases. For the same purpose, patients with dysentery, depending on its clinical form, may need to consult a gastroenterologist or proctologist.

Treatment of dysentery

Mild forms of dysentery are treated on an outpatient basis, inpatient treatment is indicated for persons with severe infection and complicated forms. Patients are also hospitalized for epidemiological reasons, in old age, with concomitant chronic diseases, and children in the first year of life. Patients are prescribed bed rest with fever and intoxication, dietary food(in the acute period - diet No. 4, when diarrhea subsides - table No. 13).

Etiotropic therapy for acute dysentery consists of prescribing a 5-7-day course of antibacterial agents (fluoroquinolone, tetracycline antibiotics, ampicillin, cotrimoxazole, cephalosporins). Antibiotics are prescribed for severe and moderate forms. Taking into account ability antibacterial drugs to aggravate dysbacteriosis, eubiotics are used in combination for a course of 3-4 weeks.

If necessary, detoxification therapy is performed (depending on the severity of detoxification, drugs are prescribed orally or parenterally). Absorption disorders are corrected using enzyme preparations(pancreatin, lipase, amylase, protease). According to indications, immunomodulators, antispasmodics, astringents, and enterosorbents are prescribed.

To accelerate regenerative processes and improve the condition of the mucous membrane during the period of convalescence, microenemas with infusion of eucalyptus and chamomile, rosehip and sea buckthorn oil, and vinylin are recommended. Chronic dysentery is treated in the same way as acute dysentery, but antibiotic therapy is usually less effective. It is recommended to prescribe therapeutic enemas, physiotherapeutic treatment, and bacterial agents to restore normal intestinal microflora.

Prognosis and prevention

The prognosis is predominantly favorable; with timely complex treatment of acute forms of dysentery, chronicity of the process is extremely rare. In some cases, after infection, residual functional disorders of the large intestine (post-dysenteric colitis) may persist.

General measures to prevent dysentery include compliance with sanitary and hygienic standards in everyday life, in food production and catering establishments, monitoring the condition of water sources, and cleaning sewage waste (especially disinfection of wastewater from medical institutions).

Patients with dysentery are discharged from the hospital no earlier than three days after clinical recovery with a negative single bacteriological test (material for bacteriological testing is collected no earlier than 2 days after the end of treatment). Food industry workers and other persons equivalent to them are subject to discharge after a double negative result of a bacteriological analysis.

Fatigue, nausea). The disease is caused by bacteria of the genus Shigella and is transmitted by the fecal-oral route.

Statistics. Shigellosis is common in all countries of the world. People of all nations and ages are sensitive to Shigella. The highest incidence rates are in Asia, Africa and Latin America, in countries with low social culture and high population density. There are currently three major foci of infection: Central America, Southeast Asia and Central Africa. From these regions, various forms of shigellosis are imported to other countries. In the Russian Federation, 55 cases per 100 thousand people are registered.

Prevalence and sensitivity to shigellosis

• Children and people with blood type A (II) and a negative Rh factor are most susceptible to infection. They show more pronounced symptoms of the disease.
• City dwellers get sick 3-4 times more often than rural residents. Crowded population contributes to this.
• Shigellosis affects people with low social status who do not have access to clean drinking water and are forced to buy cheap food.
• An increase in incidence is noted in the summer-autumn period.

Shigellosis has been known since the time of Hippocrates. He called the disease “dysentery” and combined under this concept all diseases accompanied by diarrhea mixed with blood. In ancient Russian manuscripts, shigellosis was called “myt” or “bloody womb.” Severe epidemics raged in Japan and China in the 18th century. Major outbreaks that swept across Europe at the beginning of the last century were associated with wars.

Shigella (Structure and life cycle of bacteria)

Shigella are divided into groups (Grigoryev-Shiga, Stutzer-Schmitz, Large-Sachs, Flexner and Sonne), and those, in turn, into serovars, of which there are about 50. They are distinguished by their habitat, the properties of toxins and enzymes secreted by them.

Sustainability in the environment

• Shigella is resistant to a number of antibacterial drugs, so not all antibiotics are suitable for the treatment of shigellosis.
• When boiled, they die instantly; heat to 60 degrees is maintained for 10 minutes.
• Holds up well low temperatures up to -160 and exposure to ultraviolet light.
• They are resistant to acids, so acidic gastric juice does not neutralize them.

Properties of Shigella

• Penetrate into the cells of the mucous membrane of the large intestine.
• Capable of multiplying inside the epithelium (cells lining the inner surface of the intestine).


• Release toxins.
  • Endotoxin is released from Shigella after its destruction. Causes disruption of the intestines and affects its cells. It is also capable of penetrating the blood and poisoning the nervous and vascular systems.
  • An exotoxin produced by living Shigella. Damages the membranes of intestinal epithelial cells.
  • Enterotoxin. Increases the release of water and salts into the intestinal lumen, which leads to diluted stools and diarrhea.
  • Neurotoxin – has a toxic effect on the nervous system. Causes symptoms of intoxication: fever, weakness, headache.

When infected with Shigella, the ratio of bacteria in the intestines is disrupted. Shigella inhibits the growth of normal microflora and promotes the development pathogenic microorganisms– develops intestinal dysbiosis.

Life cycle of Shigella

Shigella lives only in the human body. Once from the intestines of a patient or carrier into the environment, they remain viable for 5-14 days. Direct sunlight kills bacteria within 30-40 minutes; on fruits and dairy products they can last up to 2 weeks.

Flies can carry the disease. On the legs of insects, bacteria remain viable for up to 3 days. Having landed on food products, flies infect them. Even a small amount of Shigella is enough to cause illness.

Immunity after shigellosis unstable. Maybe reinfection the same or another type of Shigella.

Normal intestinal microflora

Properties of microflora:

• Protective action. Bacteria that are part of the normal microflora secrete substances (lysozyme, organic acids, alcohols) that prevent the growth of pathogens. A biofilm is formed from mucus, protective bacteria and their enzymes, covering the inner surface of the intestine. In this environment, pathogens cannot gain a foothold and multiply. Therefore, even after the pathogen enters the body, the disease does not develop, and pathogenic bacteria leave the intestines along with the feces.
• Participation in digestion. With the participation of microflora, carbohydrates are fermented and proteins are broken down. In this form, it is easier for the body to absorb these substances. Without bacteria, the absorption of vitamins, iron and calcium is also difficult.
• Regulatory action. Bacteria regulate the contraction of the intestines and, by moving food mass through it, prevent constipation. Products secreted by bacteria improve the condition of the intestinal mucosa.
• Immunostimulating effect. Substances secreted by bacteria - bacterial peptides - stimulate activity immune cells and synthesis of antibodies, increase local and general immunity.
• Antiallergic effect. Lacto- and bifidobacteria prevent the formation of histamine and the development food allergies.
• Synthesizing action. With the participation of microflora, the synthesis of vitamin K, B vitamins, enzymes, and antibiotic-like substances occurs.

Types of bacteria

• Mucosal microflora- These are bacteria that live in the thickness of mucus on the intestinal wall between the villi and folds of the intestine. These microorganisms make up a biofilm that protects the intestines. They attach to enterocyte receptors on the intestinal mucosa. Mucosal microflora is less sensitive to medications and other influences, thanks to a protective film of intestinal mucus and bacterial polysaccharides.
• Luminal microflora- bacteria that are able to move freely in the intestine. Their share is less than 5%.

By quantitative composition

Methods of infection with Shigella

• Sick acute or chronic form. The most dangerous are patients with a mild form, in whom the manifestations of the disease are mild.
• Convalescent- recovering within 2-3 weeks from the onset of the disease.
• Carrier– a person who excretes Shigella and has no symptoms of the disease.

Methods of transmission of shigellosis

• Food. Shigella spreads to food through contaminated hands, washing with contaminated water, flies, or fertilizing vegetables with human feces. The most dangerous are berries, fruits and dairy products, as they are a good breeding ground for bacteria. Compotes, salads, mashed potatoes and other side dishes, liquid and semi-liquid dishes can also cause the spread of the disease. This method is the most common; it is characteristic of Flexner’s dysentery.


• Water. Shigella enters water with human feces and sewage, when washing infected clothes, and during accidents at wastewater treatment plants. From an epidemic point of view, large and small reservoirs and wells, as well as swimming pools and tap water in countries with low levels of sanitation, are dangerous. By consuming such water, using it to wash dishes, or swimming in bodies of water, a person ingests bacteria. At waterway transmission simultaneously infects a large group of people. Outbreaks occur during the warm season. Shigella Sonne is spread by water.


• Contact and household. If hygiene rules are not followed, a small amount of feces ends up on household items, and from there on the oral mucosa. The most dangerous in this regard are contaminated children's toys, bedding and towels. It is possible to contract dysentery through sexual contact, especially among homosexuals. The contact-household method is typical for Grigoriev-Shiga dysentery.

What happens in the human body after infection

Second phase includes several stages.

• The number of Shigella increases and they colonize the lower parts of the large intestine. On the surface of bacteria there are special proteins that ensure attachment to epithelial cells. They act on receptors and induce the cell to capture the bacterium. Thus, the pathogen penetrates into the epithelium.
• Shigella secretes the enzyme mucin. With its help, they dissolve cell membranes and colonize the deep layers of the intestinal wall. Inflammation of the submucosal layer begins.
• Bacteria disrupt the connections between intestinal cells, which promotes their spread to healthy areas. The intestinal wall loosens, the absorption process is disrupted, and a large amount of fluid is released into the intestinal lumen.
• Ulcerative colitis develops. Bleeding erosions and ulcers form on the intestinal mucosa. At this stage, bacteria actively release toxins.

Shigellosis symptoms

• Temperature increase. The onset of the disease is acute. A sharp increase in temperature to 38-39 degrees is the immune system’s reaction to the appearance of Shigella toxins in the blood. Patients complain of chills and a feeling of heat.
• Intoxication. Signs of poisoning of the brain and spinal cord by toxins: loss of appetite, weakness, body aches, headache, apathy. Develops in the first hours of illness.
• Frequency of bowel movements (diarrhea). Diarrhea develops on the 2-3rd day of illness. At first, the discharge is fecal in nature. Over time, they become more scanty, liquid, with a lot of mucus. With the development of erosions in the intestines, streaks of blood and pus appear in the stool. The patient empties 10-30 times a day. Defecation is accompanied by excruciating pain when the inflamed rectum is tense.
• Stomach ache appear when Shigella invades the intestinal mucosa and develops inflammation. This occurs 2 days after the onset of the disease. The first hours the pain is diffuse. When damaged lower section intestines, the pain becomes sharp, cutting, cramping. Mostly felt in the left half of the abdomen. Unpleasant sensations intensify immediately before defecation and weaken after bowel movement.
• Nausea, sometimes repeated vomiting– the result of the toxin’s effect on the vomiting center in the brain.
• False painful urge to defecate– tenesmus. A sign of irritation of the nerve endings of the intestines.


• Tachycardia and decreased blood pressure– the number of heartbeats is more than 100 per minute. Blood pressure is reduced due to intoxication and fluid loss.

Forms of dysentery

1. Light forms- 70-80%. Temperature 37.3-37.8 ° C, slight abdominal pain, pasty stool 4-7 times a day.
2. Moderate forms- 20-25%. Intoxication, abdominal pain, temperature rises to 39°C, loose stools up to 10 times or more with blood and mucus, false urge to have a bowel movement.
3. Severe forms- 5%. Temperature up to 40°C and above, mucous-bloody stools up to 30-40 times a day. The patients are severely weakened and suffer from severe pain in a stomach.

Diagnosis of shigellosis

Examination by a doctor

Collection of complaints. When visiting a doctor, patients complain of:

• temperature increase
• weakness and loss of strength
• loss of appetite, nausea
• diarrhea more than 10 times a day
• scanty, watery stool mixed with mucus and bright blood

• When pressing on the left side of the abdomen, pain is felt
• colon spasm - tightness in the left lower abdomen
• spasm of the cecum - compaction in the right half of the abdomen

• Facial features are pointed, skin is dry, eyes are sunken - the result of dehydration.
• Coated, dry tongue covered with a thick white coating. When you try to remove it, small erosions may be exposed.
• The skin is pale, lips and cheeks may be bright - the result of poor circulation.
• Increased heart rate and decreased blood pressure are a consequence of stimulation of cardio-vascular system sympathetic nerves.
• In severe forms, as a result of central nervous system poisoning, patients may experience delusions and hallucinations.
• Children may develop hoarseness and difficulty swallowing due to dehydration of the mucous membranes.

Laboratory research

1. Bacteriological examination of stool (bacteriological culture). Material: a fresh stool sample, a smear taken with a swab from the rectum, and vomit directly at the patient’s bedside are inoculated onto nutrient media (selenite broth, Ploskirev’s medium). Samples are placed in a thermostat for 18-24 hours. The resulting colonies are re-sown on media to obtain a pure culture and cultivated in a thermostat. The result will be ready on the 4th day.

   Shigella forms small, colorless, transparent colonies. There can be 2 types:

   • flat with serrated edges
   • round and convex

   Individual Shigella are not stained with aniline dyes using the Gram method. Under microscopy they look like colorless, motionless rods.

   To determine the species of Shigella, use agglutination reaction with species sera. After isolating a pure culture of bacteria, Shigella is placed in test tubes with Hiss medium. One type of serum containing antibodies to a specific type of Shigella is added to each. In one of the test tubes, agglutinate flakes are formed from glued Shigella and the corresponding antibodies.

2. Serological express methods diagnostics are designed to quickly confirm the diagnosis of shigellosis. They are highly accurate and allow you to determine the type of Shigella that caused the disease in 2-5 hours. The first study is carried out on days 5-7 of illness, repeated a week later.

   

3. Serological methods.
   1. Indirect (passive) hemagglutination reaction(RNGA), helps to detect Shigella antigens in feces and urine on the 3rd day of illness. A preparation containing red blood cells is added to the material taken from the patient. There are antibodies on their surface. If a person is sick with shigellosis, the red blood cells stick together and sink to the bottom of the test tube in the form of flakes. The minimum antibody titer confirming dysentery is 1:160.
   2. Complement fixation reaction (CFR)– used to detect antibodies to Shigella in the patient’s blood serum. During the study, antigens, complement and sheep red blood cells are added to it. In patients with shigellosis, serum antibodies bind to antigens and add complement. In a patient with shigellosis, when adding sheep erythrocytes, blood cells remain intact in the test tube. In healthy people, the antigen-antibody complex does not form and unbound complement destroys red blood cells.
4. Scatological examination of stool. Examination of stool under a microscope does not confirm shigellosis, but indicates inflammatory process in the intestines, characteristic of many intestinal infections.

   With shigellosis, the following is found in the stool:

   • slime
   • accumulations of leukocytes with a predominance of neutrophils (30-50 per field of view)
   • red blood cells
   • altered intestinal epithelial cells.

Instrumental studies: sigmoidoscopy

Indications for sigmoidoscopy

• latent course of dysentery without stool disorder
• discharge of blood and pus in stool
• diarrhea
• suspicion of rectal disease

• hyperemia (redness) of the intestinal wall
• looseness and vulnerability of the mucous membrane
• minor surface erosions
• cloudy mucus in the form of lumps on the intestinal wall
• atrophied areas of the mucosa - pale gray color, folds are smoothed

Treatment of shigellosis

• moderate and severe course of the disease
• severe concomitant diseases
• persons of decreed groups working with children or in food establishments
• children under one year old

Diet for shigellosis helps normalize stool and avoid exhaustion. In the acute period of the disease, it is necessary to adhere to diet No. 4, and after diarrhea stops, diet No. 4A.

On days when blood and mucus are present in the stool, meals should be as gentle as possible so as not to irritate the digestive tract. These are: rice water, pureed semolina soup, jelly, low-fat broths, crackers.

As your condition improves, your diet can be expanded. The menu includes: pureed cottage cheese, broth-based soups, boiled ground meat, rice porridge, stale white bread.

3 days after the diarrhea stops, you can gradually return to normal eating.

Detoxification of the body

1. Ready-made solutions for dehydration and detoxification indicated for all patients with shigellosis. Drinking plenty of fluids replenishes fluid losses after diarrhea and repeated vomiting. These funds replenish the stock minerals– electrolytes, which are vital for the functioning of the body. With the help of these solutions, the elimination of toxins is accelerated.

   A drug	Method of application	Mechanism of therapeutic action
   Mild form of the disease
   Enterodesis Regidron	Oral products. The drug is diluted according to the instructions on the package. The amount of fluid drunk should be 50% greater than losses through urine, stool and vomiting. The solutions are drunk in small portions throughout the day, every 10-20 minutes.	These products replenish fluid and minerals - electrolytes, which are vital for the functioning of the body. They bind toxins found in the intestines and promote their elimination.
   Moderate form of the disease
   Gastrolit Orsol	The drugs are diluted in boiled water and taken 2-4 liters per day. During the day, they are drunk in small portions of 20 ml and after each bowel movement, 1 glass.	Restore sodium and potassium levels in blood plasma. Glucose promotes the absorption of toxins. They replenish water reserves, thereby increasing blood pressure. Improves blood properties, normalizes its acidity. They have an antidiarrheal effect.
   5% glucose solution	The prepared solution can be used in any form: orally or intravenously. The solution can be drunk in small portions of no more than 2 liters per day.	Replenishes energy reserves necessary for cell activity. Improves the removal of toxins and replenishes fluid loss.
   Severe intoxication (the patient has lost 10% of body weight) requires intravenous solutions
   10% albumin solution	Intravenous drip at a rate of 60 drops per minute. Daily until the condition improves.	The drug contains donor plasma proteins. It replenishes fluid reserves and provides protein nutrition to tissues. Raises arterial pressure.
   Crystalloid solutions: hemodez, lactasol, acesol	Intravenously. 1 time a day, 300-500 ml.	They bind toxins circulating in the blood and are excreted in the urine.
   5-10% glucose solution with insulin	Intravenously	Replenishes fluid reserves, increases blood osmotic pressure, providing better tissue nutrition. Helps neutralize toxins, improving the antitoxic function of the liver. Covers the body's energy needs.

   When treating shigellosis at home, you can drink strong sweet tea or a solution recommended by WHO for dehydration. It contains: 1 liter of boiled water, 1 tbsp. sugar, 1 tsp. table salt and 0.5 tsp. baking soda.

2. Enterosorbents - Drugs that can bind and remove from gastrointestinal tract various substances. They are used for any form of the disease from the first days of treatment.

   A drug	Mechanism of therapeutic action	Mode of application
   Activated carbon	Bacteria adsorb toxins in the pores, bind them and remove them from the intestines. They reduce the number of Shigella in the body and relieve symptoms of intoxication (lethargy, fever). They reduce the amount of toxins entering the blood and thereby reduce the load on the liver. Support normal microflora intestines.	Orally 15-20 g 3 times a day.
   Smecta		The contents of 1 sachet are diluted in 100 ml of water. Take 1 sachet 3 times a day.
   Enterodesis		Orally 5 g 3 times a day.
   Polysorb MP		3 g 3 times a day

   
   Important: at least 2 hours must pass between taking the enterosorbent and any other drug. Otherwise, the enterosorbent will “absorb” medicine without allowing it to have its effect. Enterosorbents are used 30-40 minutes before meals so that they do not absorb vitamins and other beneficial substances from food.
3. Corticosteroid hormones - substances produced by the adrenal cortex that have an anti-inflammatory effect.
4. Plasmapheresis - procedure for cleansing blood plasma of toxins. A catheter is inserted into a central or peripheral vein. A portion of blood is taken from the body and, using devices of various designs (centrifuge, membrane), it is divided into blood cells and plasma. Plasma contaminated with toxins is sent to a special reservoir. There it is filtered through a membrane, in the cells of which large protein molecules with toxic substances are retained. After cleansing, the same volume of blood is returned to the body. Sterile disposable instruments and membranes are used during the procedure. Blood purification is carried out under the control of medical equipment. The monitor monitors pulse, blood pressure, and blood oxygen saturation.

Treatment with antibiotics and antiseptics

The drug is available in liquid form and in tablets with an acid-resistant coating that protects the bacteriophage from acidic gastric juice and in rectal suppositories. Take on an empty stomach 30-60 minutes before meals 3 times a day, 30-40 ml or 2-3 tablets. Candles: 1 suppository 1 time per day. The duration of the course depends on the form of the disease.

Restoration of intestinal mucosa and microflora

Treatment of dysbacteriosis after shigellosis is carried out with a complex of drugs.

Prevention of shigellosis

• use only boiled or bottled water for drinking
• do not drink water from taps, untested wells or springs
• wash vegetables and fruits thoroughly before eating
• do not consume spoiled fruits in which bacteria multiply in the pulp
• do not buy cut watermelons and melons
• wash your hands thoroughly after using the toilet
• keep flies away food products
• do not consume products that have expired
• in countries with an increased risk of Shigella infection, do not buy food that has not been heat-treated
• vaccination with dysentery bacteriophage three times with an interval of 3 days:
  • family members where the patient is left at home
  • everyone in contact with the patient or carrier

UDC 616.935-074(047)

A.M.Sadykova

Kazakh National Medical University

named after S.D. Asfendiyarov, Almaty

Department of Infectious and Tropical Diseases

Reliable diagnosis of dysentery is one of the urgent tasks of AEI surveillance. An accurate diagnosis of bacterial dysentery is important for the correct and timely treatment of the patient and for the implementation of the necessary anti-epidemic measures. The data presented in the review show that, given the widespread prevalence of dysentery, lack of sensitivity and late appearance of positive results of many diagnostic methods, it is advisable to develop the diagnostic potential for detecting this infection.

Keywords: diagnosis, dysentery, antigen-binding lymphocyte method.

Recognition of shigella infection in clinical practice encounters significant difficulties due to objective factors, which include the clinical pathomorphosis of dysentery, an increase in the number of atypical forms of the disease, the existence of a significant number of diseases of an infectious and non-infectious nature that are similar to dysentery clinical manifestations. In half of the cases, the diagnosis of “clinical dysentery” hides unrecognized diseases of a different etiology.

The greatest difficulties confront the doctor when initial examination patient until the results of paraclinical diagnostic methods are received. Recognition of dysentery is also difficult in the presence of concomitant diseases of the gastrointestinal tract.

Since the beginning of the use of etiological laboratory diagnosis of dysentery, quite a few methods have been proposed and tested. There are many classifications of methods for etiological diagnosis of infections. Methodologically, the classification proposed by B.V. is the most justified. Punisher. In relation to the diagnosis of dysentery, the principles of methodologically based classification were used by B.V. Karalnik, N.M. Nurkina, B.K. Erkinbekova..

Laboratory methods for diagnosing dysentery include bacteriological (isolation and identification of the pathogen) and immunological. The latter include immunological methods in vivo (Tsuverkalov allergy test) and in vitro. Immunological methods in vitro have one undoubted advantage over the Tsuverkalov test - they are not associated with the introduction of foreign antigens into the body.

Most researchers still believe that bacteriological research includes isolating pure culture the causative agent of the disease with its subsequent identification by morphological, biochemical and antigenic characteristics is the most reliable method for diagnosing shigellosis infection. The frequency of Shigella isolation from the feces of patients with clinical diagnosis“acute dysentery”, according to various authors, ranges from 30.8% to 84.7% and even 91.1%. Such a significant range among different authors depends not only on objective factors influencing the effectiveness of bacteriological research, but also on the thoroughness of the diagnosis (or exclusion) of “clinical dysentery”. The effectiveness of bacteriological research is influenced by such objective factors, as features of the course of the disease, the method of collecting and delivering the material to the laboratory, the quality of culture media, the qualifications of personnel, the timing of the patient’s contact with health workers, the use antimicrobials before taking material for research. A quantitative microbiological study of feces in acute dysentery shows that in any clinical form of infection, the most massive release of pathogens occurs in the first days of the disease, and starting from the 6th and especially from the 10th day of illness, the concentration of Shigella in the feces decreases significantly. T.A. Avdeeva found that the low content of Shigella and the sharp predominance of non-pathogenic microorganisms in feces practically exclude the possibility of bacteriological detection of dysentery bacteria.

It is known that bacteriological confirmation of shigella infection is most often possible when examining patients precisely in the first days of the disease - coproculture of the pathogen in the vast majority of cases is first isolated during the first examination. Positive results of bacteriological examination are observed only in the first 3 days of the disease in 45–49% of patients, in the first 7 days – in 75%. Tillett and Thomas also consider the period of examination of patients important factor, which determines the effectiveness of the bacteriological method for diagnosing dysentery. According to T.A. Avdeeva, in the first days of the disease, the most intense release of the pathogen is observed in Sonne dysentery, less intense in Flexner dysentery and the least in Flexner VI dysentery; in the later stages of the disease, a high concentration persists for the longest time in Flexner's dysentery, for a shorter period of time - Shigella Sonne, and for the least long time - Shigella Flexner VI.

Thus, although bacteriological examination of stool is the most reliable method for diagnosing shigellosis infection, significant disadvantages are the limitations of its effectiveness listed above. It is also important to point out the limitations of early diagnosis using the bacteriological method, in which the duration of the analysis is 3-4 days. In connection with these circumstances, the use of other laboratory diagnostic methods is of great practical importance. Another microbiological method for diagnosing dysentery is also based on the detection of living Shigella. This is a phage titer increase reaction (PTR), based on the ability of specific phages to multiply exclusively in the presence of homologous living microorganisms. An increase in the titer of the indicator phage indicates the presence of the corresponding microbes in the environment. Trial diagnostic value RSF for shigella infection was carried out by B.I. Khaimzon, T.S. Vilkomirskaya. RSF has a fairly high sensitivity. Comparison minimum concentrations Shigella in feces, captured by the bacteriological method (12.5 thousand bacteria in 1 ml) and RSF (3.0 - 6.2 thousand), indicates the superiority of RSF.

Since the frequency of positive RSF results is directly dependent on the degree of contamination of feces, the use of the method also gives greatest effect in the first days of the disease and in more severe forms of the infectious process. However, the higher sensitivity of the method determines its special advantages over bacteriological examination in the late stages of the disease, as well as when examining patients with mild, asymptomatic and subclinical forms of infection, with a low concentration of the pathogen in the feces. RSF is also used when examining patients who have taken antibacterial agents, since the latter sharply reduce the frequency of positive results of the bacteriological research method, but to a much lesser extent affect the effectiveness of the RSF. The sensitivity of RSF is not absolute due to the existence of phage-resistant strains of Shigella: the proportion of phage-resistant strains can vary widely - from 1% to 34.5%.

The great advantage of RSF is its high specificity. During examinations of healthy people, as well as patients with infectious diseases of other etiologies, positive reaction results were observed only in 1.5% of cases. RSF is a valuable additional method for diagnosing shigella infection. But today this method is rarely used due to its technical complexity. Other methods are immunological. With their help, a pathogen-specific immune response is recorded or pathogen antigens are determined using immunological methods.

Due to the severity of specific infectious allergy processes during shigellosis infection, allergological diagnostic methods were initially used, which included the intradermal allergy test with dysenterine (IDT). The drug "dysenterin", which is a deprived toxic substances specific allergen shigella, was obtained by D.A. Tsuverkalov and was first used in a clinical setting when performing an intradermal test by L.K. Korovitsky in 1954. According to E.V. Golyusova and M.Z. Trokhimenko, in the presence of previous acute dysentery or accompanying allergic diseases with skin manifestations (eczema, urticaria, etc.). positive results of VPD are observed much more often (paraallergy). Analysis of the results of VPD in different periods of acute dysentery shows that a specific allergy occurs already in the first days of the disease, reaches its maximum severity by the 7th – 15th day and then gradually fades away. Positive reaction results were obtained when examining healthy people aged from 16 to 60 years in 15–20% of cases and in people aged from 3 to 7 years – in 12.5% ​​of cases. Even more often, nonspecific positive results of VPD were observed in patients with gastrointestinal diseases - in 20–36% of cases. The introduction of the allergen was accompanied by the development of a local reaction in 35.5 - 43.0% of patients with salmonellosis, in 74 - 87% of patients with coli-0124-enterocolitis. A serious argument against the widespread use of VPD in clinical practice was its allergenic effect on the body. Considering the above, we can say that this method is not very specific. Tsuverkalov's test is not species specific either. Positive reaction results were equally frequent in various etiological forms of dysentery.

In addition to VPD, other diagnostic reactions were also used, with varying degrees of validity, considered as allergic, for example, the allergen leukocytolysis reaction (ALC), the essence of which was specific damage or complete destruction of actively or passively sensitized neutrophils upon contact with the corresponding antigen. But this reaction cannot be attributed to early diagnostic methods, since the maximum frequency of positive results was observed on days 6-9 of the disease and amounted to 69%. Allergen leukemia reaction (ALE) has also been proposed. It is based on the ability of leukocytes of a sensitized organism to agglomerate when exposed to a homologous allergen (dysenterin). Due to the lack of proof of the exact mechanisms of such tests and the insufficient correspondence of their results to the etiology of the disease, these methods, after a short period of their use in the USSR, did not subsequently become widespread.

Detection of Shigella antigens in the body is diagnostically equivalent to isolating the pathogen. The main advantages of antigen detection methods over bacteriological research that justify them clinical application, is the ability to identify not only viable microorganisms, but also dead and even destroyed ones, which is of particular importance when examining patients during or shortly after a course of antibacterial therapy.

One of the best methods for express diagnostics of dysentery was immunofluorescence examination of stool (Coons method). The essence of the method is to detect Shigella by treating the test material with serum containing specific antibodies labeled with fluorochromes. The combination of labeled antibodies with homologous antigens is accompanied by a specific glow of the complexes, detected in a fluorescent microscope. In practice, two main variants of the Koons method are used: direct, in which serum containing labeled antibodies against Shigella antigens is used, and indirect (two-stage), using non-fluorochrome-labeled serum (or the globulin fraction of anti-Shigella serum) in the first stage. At the second stage, a fluorochrome-labeled serum is used against the globulins of the anti-Shigella serum used in the first stage. A comparative study of the diagnostic value of two variants of the immunofluorescent method did not reveal large differences in their specificity and sensitivity. In clinical practice, the use of this method is most effective when examining patients in the early stages of the disease, as well as in more severe forms of infection. A significant disadvantage of the immunofluorescence method is its lack of specificity. The most important reason for the lack of specificity of the immunofluorescence reaction is the antigenic affinity of Enterobacteriaceae different kinds. Therefore, this method is considered as a guide for recognizing shigella infection.

Various reactions are used to detect Shigella antigens without microscopy. These methods make it possible to detect pathogen antigens in the feces of 76.5 - 96.0% of patients with bacteriologically confirmed dysentery, which indicates a fairly high sensitivity. It is most advisable to use these methods precisely in the later stages of the disease. Most authors rate the specificity of these diagnostic methods quite highly. However, F.M. Ivanov, who used RSC to detect shigella antigens in feces, obtained positive results when examining healthy people and patients with intestinal infections of other etiologies in 13.6% of cases. According to the author, the use of the method is more appropriate for identifying specific antigens in urine, since the frequency of nonspecific positive reactions in the latter case is much lower. The use of various research methods makes it possible to detect Shigella antigens in the urine of the vast majority of patients with bacteriologically confirmed dysentery. The dynamics of the excretion of antigens in the urine has some peculiarities - detection of antigenic substances in some cases is possible already from the first days of the disease, but with the greatest frequency and consistency it is possible on the 10th - 15th day and even later. According to B.A. Godovanny et al, the proportion of positive results for detecting shigella antigens in urine (SAC) after the 10th day of the disease is 77% (the corresponding figure for bacteriological examination of stool is 47%). In connection with this circumstance, urine testing for the presence of pathogen antigens is a valuable additional method for dysentery, primarily for the purpose of late and retrospective diagnosis.

According to N.M. Nurkina, if the antibody immunoreagent is obtained from polyclonal sera, positive indication results are possible if related antigens are present in the sample. For example, with an erythrocyte diagnosticum from highly active serum against S.flexneri VI, the antigen S.flexneri I-V is also detected, since Shigella of both subspecies have a common species antigen. Shigella antigens can be determined during the period of illness both in blood serum and in secretions.

Lee Won Ho et al. It has been shown that the frequency of detection of Shigella antigens and their concentration in the blood and urine are higher in the early days of the disease and that the concentration of detected antigens is higher in moderate cases of the disease than in mild ones.

CM. Omirbayeva proposed a method for indicating the Shigella antigen, based on the use of formalinized erythrocytes as a sorbent for antigens from the fecal extract under study, followed by agglutination with immune sera. Assessing the specificity of this method, in our opinion, requires additional research, since fecal extracts contain significant quantities of antigens of other bacteria that are not the causative agent of this intestinal disease.

A number of researchers propose enzyme immunoassay as a method of rapid diagnosis of acute dysentery, which, according to many authors, is considered highly sensitive and highly specific. In this case, the highest level of antigen is detected on days 1-4 of the disease. Despite the obvious advantages of ELISA, which include high sensitivity, the possibility of strict instrumental quantitative accounting, and ease of reaction setup, the widespread use of this method is limited due to the need for special equipment.

To enhance the sensitivity and specificity of various serological methods for detecting antigens, the use of monoclonal antibodies, immunoglobulin fragments, synthetic antibodies, LPS silver staining, and other technological improvements are recommended.

It is often not possible to detect the antigen of an infectious agent even when using highly sensitive reactions to detect pathogen antigens in biological substrates of the body, since a significant part of the antigenic substances is apparently found in the biosample in the form of immune complexes in the body. When examining patients with bacteriologically confirmed acute dysentery, positive results of antigen determination by RSC were noted, according to some data, only in 18% of cases.

T.V. Remneva et al. They propose to use ultrasound to disintegrate antibody complexes with pathogen particles, and then determine the pathogen antigen in the RSC in the cold. The method was used to diagnose dysentery; urine samples from patients with acute intestinal infections were used as research material.

The use of the precipitation reaction to detect antigen in acute dysentery is not justified due to its low sensitivity and specificity. We believe that the specificity of any methods for indicating Shigella antigens can be significantly increased by using monoclonal antibodies to Shigella.

The coagglutination reaction is also one of the methods for rapid diagnosis of shigellosis, as well as antigens of pathogens of a number of other infections. In case of shigellosis, pathogen antigens can be determined from the first days of the disease throughout the entire acute period, as well as within 1 - 2 weeks after the cessation of bacterial excretion. The advantages of the coaglutination reaction are the ease of making diagnostic kits, setting up the reaction, cost-effectiveness, speed, sensitivity, and high specificity.

When conducting diagnostics to determine Shigella antigens from the very beginning of the disease, it is most effective, according to many authors, to examine the feces of patients. As the disease progresses, the ability to detect Shigella antigens in urine and saliva decreases, although they are found in feces with almost the same frequency as at the onset of the disease. It must be taken into account that in the first 3–4 days of the disease, it is somewhat more effective to test feces for antigen in the RPGA. In the middle of the disease, RPHA and RNAb are equally effective, and starting from the 7th day, RNAb is more effective in searching for the Shigella antigen. These features are due to the gradual destruction of Shigella cells and their antigens in the patient’s intestines during the course of the disease. Shigella antigens excreted in urine are relatively smaller in size than antigens in feces. Therefore, it is advisable to examine urine in RNAt. In the urine of women, unlike the urine of men, due to probable fecal contamination, Shigella antigens are equally often detected using RPHA and RNAb.

Although the antigen is detected much more often (94.5 - 100%) in those fecal samples from which Shigella can be isolated than in those samples from which Shigella is not isolated (61.8 - 75.8%), with parallel bacteriological and serological (for antigen) in the study of fecal samples from patients with dysentery, in general, shigella was isolated only from 28.2 - 40.0% of samples, and antigen was detected in 65.9 - 91.5% of samples. It is important to emphasize that the species specificity of the detected antigen always corresponds to the specificity of serum antibodies, the titer of which increases as much as possible in dynamics. When focusing on a conditional diagnostic titer of antibodies, discrepancies in the specificity of such antibodies and the detected antigen can sometimes be observed. This discrepancy is due to the insufficient diagnostic reliability of a single determination of serum antibody activity. In this case, the etiological diagnosis must be made based on the specificity of the detected antigen.

PCR method in terms of the task of directly identifying the signs of a pathogen, it is close to the methods of indicating antigens. It allows the DNA of the pathogen to be determined and is based on the principle of natural DNA replication, including the unwinding of the DNA double helix, the divergence of the DNA strands and the complementary addition of both. DNA replication cannot begin at any point, but only in certain starting blocks - short double-stranded sections. The essence of the method is that by marking with such blocks a DNA section specific only for a given species (but not for other species), it is possible to reproduce (amplify) this particular section many times. Test systems based on the principle of DNA amplification, in most cases, make it possible to detect bacteria and viruses that are pathogenic for humans, even in cases where their detection cannot be detected by other methods. Specificity of PCR test systems (with making the right choice taxon-specific primers, excluding false positive results and the absence of amplification inhibitors in bioassays) in principle avoids problems associated with cross-reactive antigens, thereby ensuring very high specificity. The determination can be carried out directly on clinical material containing a live pathogen. But, despite the fact that the sensitivity of PCR can reach a mathematically possible limit (detection of 1 copy of the DNA template), the method is not used in the practice of diagnosing shigellosis due to its relative high cost.

In widespread clinical practice, the most widespread among serological research methods are those based on determining the level and dynamics of serum antibodies to the suspected causative agent of the disease.

Some authors have determined antibodies to Shigella in coprofiltrates. Coproantibodies appear much earlier than serum antibodies. Antibody activity reaches a maximum on days 9–12, and by days 20–25 they are usually not detected. R. Laplane et al. suggest that this is due to the destruction of antibodies in the intestine under the action of proteolytic enzymes. Coproantibodies cannot be detected in healthy people.

W. Barksdale et al, T.N. Nikolaeva et al. report an increase in the efficiency of deciphering the diagnosis and identifying convalescents through the simultaneous determination of serum and coproantibodies.

Detection of agglutinins in diagnostic titers is possible with bacteriologically confirmed dysentery only in 23.3% of patients. The limited sensitivity of RA is also manifested in insufficiently high titers of agglutinins detected with its help. There is evidence indicating unequal sensitivity of RA in various etiological forms of shigellosis infection. According to A.A. Klyuchareva, antibodies in a titer of 1: 200 and higher are detected using RA only in 8.3% of patients with Flexner’s dysentery and even more rarely in Sonne’s dysentery. Positive reaction results are not only more often, but also in higher titers observed with Flexner I-V and Flexner VI dysentery than with Sonne dysentery. Positive RA results appear from the end of the first week of the disease and are most often recorded in the second or third week. The first 10 days of the disease account for 39.6% of all positive reaction results. According to A.F. Podlevsky et al., agglutinins in diagnostic titers are detected in the first week of the disease in 19% of patients, in the second week - in 25% and in the third - in 33% of patients.

The frequency of positive RA results and the level of titers of antibodies detected with its help are directly dependent on the severity of the shigella infection. According to V.P. Zubareva, the use of antibacterial therapy does not reduce the frequency of positive results of RA, however, when antibiotics are prescribed in the first 3 days of the disease, agglutinins are detected in lower titers.

RA has limited specificity. When examining healthy people, positive RA results were obtained in 12.7% of cases, and group reactions were observed in 11.3% of cases. Due to the antigenic relatedness of Flexner I-V and Flexner VI bacteria, cross-reactions are especially often observed in the corresponding etiological forms of shigella infection.

With the advent of more advanced methods for serodiagnosis of shigella infection, RA gradually lost its importance. The diagnostic value of the agglutination reaction (“dysenteric Vidal reaction”) (RA) for dysentery is assessed ambiguously by various researchers, however, the results of the work of most authors indicate the limited sensitivity and specificity of this method.

Most often, the indirect (passive) hemagglutination reaction (IPHA) is used to determine antibodies. Detailed studies of the diagnostic value of the passive hemagglutination reaction (RPHA) for shigella infection were carried out by A.V. Lullu, L.M. Shmuter, T.V. Vlokh and a number of other researchers. Their results allow us to conclude that RPGA is one of the most effective methods for the serological diagnosis of dysentery, although it is not without some common disadvantages inherent in the methods of this group.

A comparative study of sensitivity in dysentery RPGA and the agglutination reaction shows the great superiority of the first method. According to A.V. Lullu, the average titers of RPHA in this disease exceed the average titers of RA by 15 times (at the height of the disease by 19-21 times), antibodies in high levels (1:320 - RPHA) are detected when used 4.5 times more often than in the titer (1:160 when performing an agglutination reaction). With bacteriologically confirmed acute dysentery, a positive RPHA reaction in diagnostic titers is noted when examining 53-80% of patients.

Hemagglutinins are detected from the end of the first week of the disease, the frequency of detection and antibody titer increase, reaching a maximum at the end of the second and third week, after which their titer gradually decreases.

There is a clear dependence of the frequency of positive RPGA results and hemagglutinin titers on the severity and nature of the course of shigella infection. Relevant studies have shown that with erased and subclinical forms of infection, positive results of RPGA were obtained less frequently than with acute clinically significant dysentery (52.9 and 65.0%, respectively), while only 4 responded in titers of 1:200 - 1:400. 2% of sera (with a clinically pronounced form - 31.2%) and with prolonged and chronic forms, positive results of RPGA were noted in 40.8% of patients, including in a titer of 1:200 - only 2.0%. There are also reports of different sensitivity of RPHA in certain etiological forms of shigellosis infection. According to L.M. Schmuter, the highest titers of hemagglutinins are observed in Sonne dysentery and significantly lower in Flexner I-V and Flexner VI dysentery. Antibacterial treatment started in the early stages of the disease, by reducing the duration and intensity of antigenic irritation, can cause the appearance of hemagglutinins in the blood serum in lower titers.

Like the agglutination reaction, RPGA does not always make it possible to accurately recognize the etiological form of shigella infection, which is associated with the possibility of group reactions. Cross reactions are observed mainly with Flexner type dysentery - between Flexner I-V and Flexner VI dysentery. The humoral immune response in many patients is weak. The possibility of cross-agglutination due to common antigens cannot be excluded. However, the advantages of this method include the simplicity of the reaction, the ability to quickly obtain results and relatively high diagnostic efficiency. Significant disadvantage this method is that the diagnosis can be established no earlier than the 5th day of the disease, the maximum diagnostic antibody titers can be determined by the 3rd week of the disease, so the method can be classified as “retrospective”.

For the purpose of diagnosing dysentery, it is also proposed to determine the level of specific circulating immune complexes represented by the O-antigen of S. sonnei, combined with a specific antibody, using an indirect “sandwich version” of an enzyme-linked immunosorbent assay due to its high sensitivity and specificity. However, the method is recommended to be used only with 5- 8th day of illness.

In patients with dysentery, from the very beginning of the disease, a specific increase in the bacteriofixing activity of the blood is detected due to the antigen-binding activity of erythrocytes. In the first 5 days of ACI, determination of the antigen-binding activity of erythrocytes makes it possible to establish the etiology of the disease in 85-90% of cases. The mechanism of this phenomenon is not well understood. It can be assumed that its basis is the binding of the antigen-antibody immune complex by erythrocytes through their C3b receptors (in primates, including humans) or Fcγ receptors (in other mammals).

Among the relatively new methods for recording a specific immune response at the cellular level, the determination of antigen-binding lymphocytes (ABLs) that react with a specific, taxonomically significant antigen attracts attention. Detection of ASL is carried out by various methods - paired agglutination of lymphocytes with antigen, immunofluorescence, RIA, adsorption of lymphocytes on antigen-containing columns, adhesion of mononuclear cells on glass capillaries, indirect rosette formation reaction (IRRO). It should be noted that such high sensitive methods registration of ASL, like ELISA and RIA, adsorption of lymphocytes on antigen-containing columns is technically relatively complex and is not always available for widespread use. The works of a number of authors have shown the high sensitivity and specificity of RNRO for detecting ASL in various diseases. A number of researchers have identified a close relationship between the content of ASL in the blood of patients with various pathologies and the form, severity and period of the disease, its transition to protracted or chronic form.

Some authors believe that by determining the level of ASL in the dynamics of the disease, one can judge the effectiveness of the therapy. Most authors believe that if it is successful, the amount of ASL falls, and if the effectiveness of treatment is insufficient, an increase or stabilization of this indicator is recorded. It is reported that using the determination of ASL, it is possible to quantify sensitization to tissue and bacterial antigens, as well as to antibiotics, which has important diagnostic value. The ASL method has been used to a limited extent for the diagnosis of dysentery.

The possibility of early detection of ASL, already in the first days after infection, is very important for early diagnosis and timely treatment, which is necessary for the clinician.

Thus, the data presented in the review show that, given the widespread prevalence of dysentery, lack of sensitivity and late appearance of positive results of many diagnostic methods, it is advisable to develop the diagnostic potential for detecting this infection. Data obtained for many infectious diseases high efficiency ASL method, the early appearance of its positive result determine the prospects for studying and using this method for shigellosis.

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A.M.Sadykova

Dysentery laboratories diagnostics

Tү yin: Zhedel іshek infectionslaryn baqylauda, ​​dysentery nakty diagnostics ең өзу мәсеLeсі мљселі віліп сайлади. Bacterials dysentery durys koyylgan diagnoses science uaqytynda we eat zhurgizuge zhane epidemic karsy sharalardy Otkіzu ushіn manyzdy. Review of corsetilgen malimetter, dysentery ken taraluyn nezhey otyrup, sesimtaldygynyn zhetkіlіksіzdіgі zhane kop degen diagnosticalyk adіsterdіn on natizhesіn ің cache anуқталуына балынысты, wasps are infected аnқtаuda diagnosticalyk poten- tiality maxatty tүrde damytu kerek ekenіn korsetedі.

Tү withө zder: diagnosis, dysentery, antigenbaylanystyrushy adis.

A.M.Sadycova

Laboratory diagnostics of dysentery

Resume: Reliable diagnosis of diarrhea is one of the most important issue to control the exact intestinal infection. Exact diagnosis of bacteriosis diarrhoea have vitae meaning for correct and accurate treatment of a patient and to take necessary antiepidemic measures aswell. The members given in the survey, taking into consideration the widespread diarrhoea, shows the lack of sensibility and late occurrence of positive results of many diagnostic methods. It is essential aimily to develop the diagnostic potential to desine the infection.

Keywords: diagnostics, dysentery, antigen binding lymphocytes method.