Scheme 12. Microbiological diagnosis of dysentery

Microscopic method with dysentery 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 test material is inoculated on Ploskirev and Endo media in Petri dishes, as well as on a selenite medium for accumulation, with which, after 16-18 hours, re-seeding is done on the indicated 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 Shigella colonies are subcultured on one of the polycarbohydrate media (Olkenitsky, Ressel, Kligler) to accumulate a pure culture. On the 3rd day, the nature of growth on a polycarbohydrate medium is taken into account, and the material is subcultured on differential media (Gissa and others) 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, "+" - the presence of a sign, "-" - the absence of a sign, "±" - a non-permanent sign.

Shigella, unlike Escherichia, are immobile microorganisms, they do not ferment lactose, decompose glucose without gas formation, and do not decarboxylate lysine. For serotyping, first put RA on the glass with a mixture of sera against the Shigella species and variants prevailing in the area, and then RA on the glass with monoreceptor specific sera. The sensitivity of the isolated culture to the polyvalent dysenteric bacteriophage and antibiotics is also determined. For epidemiological purposes, the fagovar and colicinovar 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 a chronic form), RNHA with erythrocyte shigellosis diagnosticums is used. Diagnostic titers: to Flexner's shigella in adults - 1:400, in children under 3 years old - 1:100, in children over 3 years old - 1:200, to other shigellas - 1:200. The reaction is, as a rule, 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 with dysentery - direct and indirect RIF, co-agglutination reaction, ELISA, RNGA with antibodies erythrocyte diagnosticums for the 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 frequent acute intestinal diseases in the world. The disease has been known since ancient times under the name of "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, in the next 15 years, the independence of this disease was established, which retained the name amoebiasis. 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 the 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. Saks.

Currently the genus Shigella includes more than 40 serotypes. All of them are short immobile gram-negative rods that do not form spores and capsules, which (grow well on ordinary culture media ax, do not grow on medium with citrate as sole carbon source; do not form H2S, do not have urease; the 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, do not ferment lactose (with the exception of Shigella Sonne), adonite, inositol, do not liquefy gelatin, usually form catalase, do not have lysine decarboxylase and phenylalanine deaminase. The content of G+C in DNA is 49-53 mol%. Shigella are facultative anaerobes, the temperature optimum for growth is 37 ° C, they do not grow above 45 ° C, the optimum pH of the medium is 6.7-7.2. Colonies on dense media are round, convex, translucent; in the case of association, rough R-shaped colonies are formed. Growth on the BCH in the form of a uniform turbidity, rough forms form a precipitate. Freshly isolated cultures of Shigella Sonne J4HO form colonies of two types: small round convex (I phase), large flat (Phase 2). The nature of the colony depends on the presence (I phase) or absence (II phase) of the plasmid with mm 120 MD, which also determines the virulence of Shigella Sonne.

O-antigens of different specificity were found in Shigella: common for the family enterobacteriaceae, generic, species, group and type-specific, as well as K-antigens; They do not have H antigens.

The classification takes into account only group and type-specific O-antigens. According to these features, the Shigella subdivided into 4 subgroups, or 4 species, and includes 44 serotypes. In subgroup A (species Shigella dysenteriae) Shigella not fermenting mannitol are included. The species includes 12 serotypes (1-12). Each stereotype has its own specific type antigen; antigenic relationships between serotypes, as well as with other types of shigella, are weakly expressed. To subgroup B (type Shigella flexneri) include shigella, usually fermenting mannitol. Shigella of this species are serologically related to each other: they contain type-specific antigens (I-VI), according to which they are divided into serotypes (1-6), and group antigens, which are found in different compositions for each serotype and by which serotypes are subdivided 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 does not have subserotypes, but it is divided into 3 biochemical types according to the characteristics of the fermentation of glucose, mannitol and dulcite.

To subgroup C (kind Shlgella boydll) include shigella, usually fermenting mannitol. Members of the group are serologically distinct from each other. Antigenic relationships 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 (species Shlgella sonnel included Shigella, usually fermenting mannitol and capable of slowly (after 24 hours of incubation and later) fermenting lactose and sucrose. View S. sonnei includes one serotype, however, phases I and II colonies have their own type-specific antigens. Two methods have been proposed for the intraspecific classification of Sonne's Shigella:

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 are mainly of epidemiological significance. In addition, Sonne's shigella and Flexner's shigella are subjected to typing for the same purpose by the ability to synthesize specific colicins (colicinogenotyping) and by sensitivity to known colicins (colicinotyping). To determine the type of colicins produced by Shigella, J. Abbott and R. Shannon proposed sets of typical and indicator strains of Shigella, and to determine the sensitivity of Shigella to known types colicins use a set of reference colicinogenic strains P. Frederick.

resistance. Shigella have a fairly high resistance to environmental factors. They survive on cotton fabric and paper 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 units, 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 (the introduction of one loop of a 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 white mice (development of pneumonia). The main pathogenicity factors of shigella can be divided into three groups:

1) factors that determine the interaction with the epithelium of the mucous membrane;

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

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

The first group includes adhesion and colonization factors: their role is played by pili, outer membrane proteins, and LPS. Adhesion and colonization are facilitated 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 Shigella chromosomal genes: ksr A (causes keratoconjunctivitis), cyt (responsible for cell destruction), as well as other genes that have not yet been identified. Protection of Shigella from phagocytosis is provided by surface K-antigen, antigens 3, 4 and lipopolysaccharide. In addition, Shigella endotoxin lipid A 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 exotoxins and Shiga-like exotoxins (SLT-I and SLT-II), whose cytotoxic properties are most pronounced in S.dysenteriae 1. Shiga- and Shiga-like toxins also 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 have been found in Flexner, Sonne and Boyd Shigella. Synthesis of LT in them 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 kD and consist of subunits A and B (the last of 5 identical small subunits). The receptor for toxins is the 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 which are associated with virulence. Shigella Sonne with 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 Flexner and Boyd Shigella. Shigella lipopolysaccharide is a potent endotoxin.

Features of epidemiology. The only source of infection is humans. No animal in nature suffers from dysentery. Under experimental conditions, dysentery can only be reproduced in monkeys. The method of infection is fecal-oral. Ways of transmission - water (predominant for Shigella Flexner), food, especially important role belongs to milk and dairy products (the predominant route of infection for Shigella Sonne), and contact-household, especially for the species S. dysenteriae.

A feature of the epidemiology of dysentery is the 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 XX 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 and almost disappeared. However, in the 1960s and 1980s 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 a change herd immunity and with a change in the properties of dysentery bacteria. In particular, the return S.dysenteriae 1 and its wide distribution, which caused the formation of hyperendemic foci of dysentery, is associated with the acquisition of plasmids by it, which 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 causative agent of dysentery penetrates, is cyclical: adhesion, colonization, the introduction of Shigella into the cytoplasm of enterocytes, their intracellular reproduction, destruction and rejection of epithelial cells, the 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 clinic 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 organism. However, many issues of the pathogenesis of dysentery remain unexplained, in particular: 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's dysentery.

Post-infectious immunity. As observations on monkeys have shown, after suffering dysentery, a strong and fairly long-term immunity remains. It is caused by antimicrobial antibodies, antitoxins, increased activity of macrophages and T-lymphocytes. A significant role is played by local immunity of the intestinal mucosa, mediated by IgAs. However, immunity is type-specific in nature, strong cross-immunity does not occur.

Laboratory diagnostics. The main method is bacteriological. The material for the study is feces. Pathogen isolation scheme: inoculation on the Endo and Ploskirev differential diagnostic media (in parallel on the enrichment medium, followed by inoculation on the 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 that do 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.

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

For serological diagnosis can be used: RPHA with appropriate erythrocyte diagnosticums, immunofluorescent method (in indirect modification), Coombs method (determination of the titer of incomplete antibodies). An allergic test with dysentery (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 infiltration with a diameter of 10-20 mm.

Treatment. The main attention is paid to the restoration of 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 a polyvalent dysenteric bacteriophage, especially tablets with a pectin coating, which protects the phage from the action of gastric HCl; in the small intestine, pectin dissolves, phages are released and show their action. For prophylactic 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 have also not been widely used. 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 childcare facilities, public places and in personal hygiene.

Microbiology of cholera

The WHO defines cholera as a disease characterized by acute, severe, dehydrating rice-water diarrhea resulting from infection with Vibrio cholerae. Due to the fact that it is characterized by a pronounced ability to widespread 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 East 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 the endemic focus of cholera here is explained by many reasons. Vibrio cholerae can not only remain in water for a long time, but also multiply in it under favorable conditions - temperatures above +12 ° C, the presence of organic substances. All these conditions are present in India - a tropical climate (average annual temperature from +25 up to +29 °С), abundance of precipitation and swampiness, high population density, especially in the Ganges delta, a large amount of organic matter in the water, continuous year-round water pollution with sewage and feces, low material standard of living and peculiar religious and religious rites of the population.

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

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 features 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 long, mobile ( V. cholerae- monotrichous, in some species two or more polar flagella); they grow well and quickly on ordinary media, chemoorganotrophs, ferment carbohydrates with the formation of acid without gas (glucose is fermented along 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., form acetylmethylcarbinol), do not have ureases, do not form H S. have lysine and ornithine decarboxylases, but do not have arginine dihydrolases.

Vibrio cholerae is very unpretentious to nutrient media. It multiplies well and quickly on 1% alkaline (pH 8.6-9.0) peptone water (PV) containing 0.5-1.0% NaCl, overtaking 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 V. cholerae. During growth, after 6-8 hours, it forms a delicate loose grayish film on the surface of the HP, which, when shaken, is easily destroyed and falls to the bottom in the form of flakes, the HP becomes moderately cloudy. To isolate Vibrio cholerae, various selective media have been proposed: alkaline agar, yolk-salt agar, alkaline albuminate, alkaline agar with blood, lactose-sucrose and other media. The best medium is TCBS (thiosulfate citrate-bromothymol sucrose agar) and its modifications. However, alkaline MPA is most often used, on which Vibrio cholerae forms smooth, vitreous-transparent with a bluish tinge, disc-shaped colonies of a viscous consistency.

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

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

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

Vibrios, similar in morphological, cultural and biochemical characteristics to cholera, were called and are called differently: paracholera, cholera-like, NAG vibrios (non-agglutinating vibrios); vibrios that do not belong to the 01 group. The latter name most accurately emphasizes their relationship to cholera vibrio. 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 replenished. Vibrio cholerae belongs to group 01. It has a common A-antigen and two type-specific antigens - B and C, according to which three serotypes are distinguished V. cholerae- Ogawa serotype (AB), Inaba serotype (AC) and Gikoshima serotype (ABC). Vibrio cholerae in the stage of dissociation has an OR antigen. For this reason, in order to identify V. cholerae O-serum, OR-serum, and type-specific Inaba and Ogawa sera are used.

pathogenicity factors V. cholerae :

1. Mobility.

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

3. Factors of adhesion and colonization, with the help of which the vibrio adheres to the 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 the substances that make up the mucus. Neuraminidase, splitting off sialic acid from epithelial glycoproteins, creates a "landing" platform for vibrios. In addition, it increases the number of cholerogen receptors by modifying tri- and disialogangliosides to monosialoganglioside Gm b which serves as a cholerogen receptor.

5. The main factor of pathogenicity V. cholerae is an exotoxin-cholerogen, which determines the pathogenesis of cholera. The cholerogen molecule has m.m. 84 kD 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 Sl serves to link fragments A and B. The peptide A t performs its own toxic function. It interacts with NAD, causes its hydrolysis, the resulting ADP-ribose binds to the regulatory subunit of adenylate cyclase. This leads to inhibition of GTP hydrolysis. The resulting complex GTP + adenylate cyclase causes ATP hydrolysis with the formation of cAMP. (Another way of accumulation of cAMP is the suppression by cholerogen of the enzyme that hydrolyzes cAMP to 5-AMP).

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

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

8. Endotoxin. Lipopolysaccharide V. cholerae has a strong endotoxic property. He is responsible for the 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 important component post-infection and post-vaccination immunity.

The ability of vibrios not belonging to the 01 group 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 adenylate- or guanylate cyclase systems, respectively.

Synthesis of cholerogen - the most important property V. cholerae. The genes that control the synthesis of A- and B-fragments of cholerogen 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 a positive control; mutations in this gene lead to a 1000-fold decrease in toxin production. The htx gene is a negative control; mutations in this gene increase toxin production by 3-7 times.

The following methods can be used to detect cholerogen:

1. Biological tests on rabbits. With the intra-intestinal administration of cholera vibrios to suckling rabbits (aged no more than 2 weeks), they develop a typical cholerogenic syndrome: diarrhea, dehydration and death of the rabbit. At autopsy - a sharp injection of the vessels of the stomach and thin
intestines, sometimes a clear liquid accumulates in it. But changes in the large intestine are especially characteristic - it is enlarged and full of a completely transparent, straw-colored liquid with flakes and gas bubbles. When V. cholerae is injected into the ligated area of ​​the small intestine in adult rabbits, the same changes in the large intestine are noted as in the case of infection of suckling rabbits.

2. Direct detection of cholerogen using immunofluorescent or enzyme immunoassay methods or passive immune hemolysis reaction (cholerogen binds to Gm1 of erythrocytes, and they are lysed when antitoxic antibodies and complement are added).

3. Stimulation of cellular adenylate cyclase in cell cultures.

4. Using a chromosome fragment as a DNA probe V. cholerae, carrier 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 (HDF-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 in Russia with other phages. The set of such phages (1-7) makes it possible to distinguish among V. cholerae 16 phage types. HDF-3 selectively lyses classic vibrios of the cholerae type, HDF-4 - El Tor vibrios, and HDF-5 lyses only cholerogenic (virulent) vibrios of both types and does not lyse non-cholerogenic vibrios.

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

resistance of cholera pathogens. Vibrio cholerae survive well at low temperatures: they remain viable in ice 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 remain for more than 1 year, in soil - from 8 days to 3 months, in fresh feces - up to 3 days, on boiled products (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 wet material - a week. Vibrio cholerae at 80 ° C die after 5 minutes, at 100 ° C - instantly; highly sensitive to acids; under the influence of chloramine and other disinfectants die in 5-15 minutes. They are sensitive to drying and direct sunlight, but they are well and long preserved and even multiply 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 0.3-0.4 mg / l of water in 30 minutes causes reliable disinfection from cholera vibrio.

Features of epidemiology. The main source of infection is only a person - a cholera patient or a carrier of vibrio, as well as water contaminated by them. No animals in nature get sick with cholera. The method of infection is fecal-oral. Ways of infection: a) main - through water used for drinking, bathing and domestic needs; b) contact-household and c) through food. All major epidemics and pandemics of cholera were of a water nature. Vibrio 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. The profuse diarrhea caused by Vibrio cholerae leads to intestinal cleansing of competing bacteria and contributes to the wide spread of the pathogen in the environment, primarily in sewage and in open water, where they are dumped. A person with cholera excretes a huge amount of the pathogen - from 100 million to 1 billion per 1 ml of feces, the vibrio carrier excretes 100-100,000 vibrios per 1 ml, the infecting dose is about 1 million vibrios. The duration of isolation of cholera vibrio in healthy carriers ranges from 7 to 42 days, and 7-10 days - in those who have been ill. A longer release is extremely rare.

A feature 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 sewage containing large amounts of organic substances, detergents and table salt, in the summer, Vibrio cholerae not only survives for a long time in them, but even multiplies.

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

In the event of cholera disease, a complex of anti-epidemic measures is carried out, among which the leading and decisive is the active timely detection and isolation (hospitalization, treatment) of patients in acute and atypical form and healthy vibrio carriers; measures are being taken to prevent 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, children's 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 non-slip hours to 6 days, most often 2-3 days. Once in the lumen of the small intestine, Vibrio cholerae due to mobility and chemotaxis to the mucous membrane are sent to the mucus. To penetrate it, vibrios produce a number of enzymes: neuraminidase, mucinase, proteases, lecithinase, some destroy the substances contained in the mucus and facilitate the movement of vibrios to epithelial cells. By adhesion, vibrios are attached 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 produce a large amount 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 organism. There are three types of the course of the disease:

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

2. less severe, or diarrhea without dehydration;

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

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

Post-infectious immunity durable, long-term, repeated diseases are rare. Immunity is antitoxic and antimicrobial, due to antibodies (antitoxins persist longer than antimicrobial antibodies), immune memory cells and phagocytes.

Laboratory diagnostics. Main and decisive method The diagnosis of cholera is bacteriological. The material for research from the patient is feces and vomit; feces are examined for vibrio-carrying; in persons who died from cholera, a ligated segment of the small intestine and gallbladder are taken for research; Of the objects of the external environment, water from open reservoirs and wastewater are most often examined.

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

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

2) the dishes 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) eliminate the possibility of contamination and infection of others.

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

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

Treatment patients with cholera should primarily consist in 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 substantiated treatment in combination with rational antibiotic therapy can reduce mortality in cholera to 1% or less.

specific prophylaxis. To create artificial immunity, various vaccines have been proposed, including those from killed strains of Inaba and Ogawa; 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 has diarrhea, abdominal pain, tenesmus, intoxication syndrome (weakness, fatigue, nausea). The diagnosis of dysentery is established by isolating the pathogen from the patient's feces, with 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.

Exciter characteristic

The causative agents of dysentery are shigella, currently represented by four species (S. dysenteriae, S. flexneri, S. boydii, S. Sonnei), each of which (with the exception of Sonne shigella) is in turn divided into serovars, which currently number over fifty. The population of S. Sonnei is homogeneous in antigenic composition, but differs in the ability to produce various enzymes. Shigella are immobile gram-negative rods, do not form spores, multiply well on nutrient media, and are usually unstable in the external environment.

The optimal temperature environment for shigella is 37 °C, Sonne rods are capable of reproduction at a temperature of 10-15 °C, can form colonies in milk and dairy products, can remain viable in water for a long time (like Flexner's shigella), resistant to antibacterial agents . Shigella quickly die when heated: instantly - when boiled, 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 obliterated form of dysentery are of the greatest epidemiological significance, especially those related to the food industry and public catering establishments. Shigella are isolated from the body of an infected person, starting from the first days of clinical symptoms, infectiousness persists for 7-10 days, followed by a period of convalescence, in which, however, the isolation 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 become chronic is observed with infection caused by Sonne bacteria. Dysentery is transmitted by the fecal-oral mechanism mainly by food (Sonne's dysentery) or water (Flexner's dysentery) route. When transmitting Grigoriev-Shiga dysentery, a predominantly contact-household transmission route is realized.

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 maintain post-infection immunity, which protects against re-infection for several years.

The pathogenesis of dysentery

Shigella enter 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 large intestine, partially penetrating into its mucous membrane and causing inflammatory reaction. The mucosa 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

The clinical classification of dysentery is currently in use. Its acute form is distinguished (it differs in its predominant symptoms into typical colitis and atypical gastroenteritis), 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 colitis variant of dysentery usually begins acutely, the body temperature rises to febrile values, symptoms of intoxication appear. Appetite is markedly reduced, may be completely absent. Sometimes there is nausea, vomiting. Patients complain of intense cutting pain in the abdomen, initially diffuse, later concentrated in the right iliac region and lower abdomen. The pain is accompanied by frequent (up to 10 times a day) diarrhea, bowel movements quickly lose their fecal consistency, become scarce, and pathological impurities are noted in them - blood, mucus, and sometimes pus ("rectal spit"). The urge to defecate is excruciatingly painful (tenesmus), sometimes false. The total number of daily bowel movements, as a rule, is not large.

On examination, the tongue is dry, coated with plaque, 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 mucosal defects usually heal completely within a month. The severity of the course of the colitis variant is determined by the intensity of the intoxication and pain syndrome and the duration acute period. At severe course there are disorders of consciousness caused by severe intoxication, the frequency of stools (like “rectal spitting” or “meat slops”) reaches dozens of times a day, pain in the abdomen is excruciating, 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 general intoxication syndrome: nausea, repeated vomiting. The course resembles that of salmonellosis or toxic infection. Pain in this form of dysentery is localized in the epigastric region and around the navel, has a cramping character, the stool is liquid and plentiful, there are no pathological impurities, with intense loss of fluid, dehydration syndrome may occur. Symptoms of the gastroenteric form are violent, but short-lived.

Initially, gastroenterocolitic dysentery also resembles food poisoning in its course, later colitis symptoms begin to join: mucus and bloody streaks in the feces. The severity of the course of the gastroenterocolitis 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. At present, cases of chronic dysentery in developed countries are rare. The recurrent variant is a 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, organic changes in the mucous membrane of the intestinal wall. Intoxication symptoms with continuous chronic dysentery are usually absent, there is constant daily diarrhea, stools are mushy, 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 an acute infection, subclinical - occurs when dysentery is transferred in an erased form.

Complications

Complications at 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 toxic shock, intestinal perforation, peritonitis. In addition, the development of intestinal paresis is likely.

Dysentery with intense prolonged diarrhea may be complicated by hemorrhoids, anal fissure, prolapse of the rectum. In many cases, dysentery contributes to the development of dysbacteriosis.

Diagnostics

The most specific bacteriological diagnosis. The pathogen is usually isolated from feces, and in the case of Grigoriev-Shiga dysentery, from blood. Since the increase in the titer of specific antibodies is rather slow, serological diagnostic methods (RNGA) have a retrospective value. Increasingly, the laboratory practice of diagnosing dysentery includes the detection of Shigella antigens in feces (usually performed using RCA, RLA, ELISA and RNGA with antibody diagnosticum), the complement binding reaction and aggregate hemagglutination.

Various laboratory methods are used as general diagnostic measures to determine the severity and prevalence of the process, to identify metabolic disorders. Stool is analyzed for dysbacteriosis and coprogram. Endoscopic examination (sigmoidoscopy) can often provide the necessary information for a 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 people with a severe infection, complicated forms. Patients are also hospitalized according to epidemiological indications, in old age, with concomitant chronic diseases, and children of the first year of life. Patients are prescribed bed rest with fever and intoxication, diet food(in the acute period - diet number 4, when diarrhea subsides - table number 13).

Etiotropic therapy of acute dysentery consists in the appointment of a 5-7-day course of antibacterial agents (antibiotics of the fluoroquinolone, tetracycline series, ampicillin, cotrimoxazole, cephalosporins). Antibiotics are prescribed for severe and moderate forms. Given the ability antibacterial drugs aggravate dysbacteriosis, in combination, eubiotics are used in a course for 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 with enzyme preparations(pancreatin, lipase, amylase, protease). According to indications, immunomodulators, antispasmodics, astringents, enterosorbents are prescribed.

To accelerate regenerative processes and improve the condition of the mucosa during the period of convalescence, microclysters 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. The appointment of therapeutic enemas, physiotherapy, bacterial agents to restore normal intestinal microflora is recommended.

Forecast and prevention

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

General measures for the prevention of dysentery include the observance of sanitary and hygienic standards in everyday life, in food production and at public catering establishments, monitoring the state of water sources, 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 examination is taken no earlier than 2 days after the end of treatment). Food industry workers and other persons equated to them are subject to discharge after a double negative result of 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 throughout the world. People of all nations and ages are sensitive to shigella. The highest incidence 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 of the population are registered.

Prevalence and susceptibility to shigellosis

• The most susceptible to infection are children and people with A (II) blood group and negative Rh factor. They are more likely to show symptoms of the disease.
• Citizens get sick 3-4 times more often than rural residents. This contributes to the overcrowding of the population.
• 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 the incidence is noted in the summer-autumn period.

Shigellosis has been known since the time of Hippocrates. He called the disease "dysentery" and united 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. Large 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 (Grigoriev-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 the enzymes they secrete.

Environmental sustainability

• 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, heating to 60 degrees can withstand 10 minutes.
• well withstand low temperatures up to -160 and exposure to ultraviolet.
• Resistant to acids, so acidic gastric juice does not neutralize them.

Shigella properties

• Penetrate into the cells of the mucous membrane of the large intestine.
• Able to multiply inside the epithelium (cells lining the inner surface of the intestine).


• Release toxins.
  • Endotoxin is released from the Shigella after they are destroyed. Causes disruption of the intestines and affects its cells. It is also able to penetrate into the blood and poison the nervous and vascular systems.
  • An exotoxin secreted by live Shigella. Damages the membranes of intestinal epithelial cells.
  • Enterotoxin. Increases the release of water and salts into the intestinal lumen, which leads to liquefaction of the stool and the appearance of diarrhea.
  • Neurotoxin - toxic effect on the nervous system. Causes symptoms of intoxication: fever, weakness, headache.

When infected with shigella, the ratio of bacteria in the intestine is disturbed. Shigella inhibit the growth of normal microflora and contribute to the development pathogenic microorganisms- develops intestinal dysbacteriosis.

Life cycle of shigella

Shigella live only in the human body. Once from the intestines of the patient or the 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 be carriers of the disease. On the paws of insects, bacteria remain viable for up to 3 days. Sitting on food, flies infect them. Even a small amount of Shigella is enough to cause illness.

Immunity after shigellosis unstable. Maybe reinfection the same or another species 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. From mucus, protective bacteria and their enzymes, a biofilm is formed that covers the inner surface of the intestine. In this environment, pathogenic microorganisms cannot gain a foothold and multiply. Therefore, even after the pathogen enters the body, the disease does not develop, and pathogenic bacteria leave the intestine along with feces.
• Involved in digestion. With the participation of microflora, the fermentation of carbohydrates and the breakdown of proteins occur. 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 the food mass through it, prevent constipation. Products secreted by bacteria improve the condition of the intestinal mucosa.
• Immunostimulating action. Substances secreted by bacteria - bacterial peptides - stimulate activity immune cells and synthesis of antibodies, increase local and general immunity.
• Antiallergic action. 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, antibiotic-like substances occurs.

Types of bacteria

• Mucosal microflora- These are bacteria that live in the thickness of the mucus on the intestinal wall between the villi and folds of the intestine. These microorganisms make up the biofilm that protects the gut. They attach to enterocyte receptors on the intestinal mucosa. Mucosal microflora is less sensitive to medications and other influences due to the protective film of intestinal mucus and bacterial polysaccharides.
• Translucent microflora- bacteria that have the ability to move freely in the thickness of 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 which 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, who has no manifestations of the disease.

Ways of transmission of shigellosis

• food. Shigella enter food through contaminated hands, washing with infected 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 typical for Flexner's dysentery.


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


• Contact household. If hygiene rules are not followed, a small amount of feces falls on household items, and from there to the mucous membrane of the mouth. The most dangerous in this regard are contaminated children's toys, bed linen and towels. It is possible to contract dysentery through sexual intercourse, 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 populate the lower sections of the large intestine. On the surface of bacteria there are special proteins that provide attachment to epithelial cells. They act on receptors and induce the cell to capture the bacterium. Thus, the pathogen penetrates the epithelium.
• Shigella secrete the enzyme mucin. With its help, they dissolve cell membranes and populate the deep layers of the intestinal wall. Inflammation of the submucosal layer begins.
• Bacteria disrupt the connections between intestinal cells, which contributes to their spread to healthy areas. The intestinal wall is loosened, the absorption process is disturbed, 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, the bacteria actively release toxins.

Symptoms of shigellosis

• Temperature increase. The onset of the disease is acute. A sharp increase in temperature to 38-39 degrees is an immune reaction to the appearance of Shigella toxins in the blood. Patients complain of chills and feeling hot.
• Intoxication. Signs of poisoning of the brain and spinal cord with toxins: loss of appetite, weakness, body aches, headache, apathy. Develops in the first hours of the disease.
• Increased stool (diarrhea). Diarrhea develops on the 2-3 day of illness. At first, the discharge is fecal in nature. Over time, they become more scarce, liquid, with a lot of mucus. With the development of erosions in the intestines, streaks of blood and pus appear in the feces. The patient is emptied 10-30 times a day. Defecation is accompanied by excruciating pain with tension of the inflamed rectum.
• Stomach ache appear with the introduction of shigella into the intestinal mucosa and the development of 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 side of the abdomen. Unpleasant sensations increase immediately before a bowel movement and weaken after a bowel movement.
• Nausea, sometimes repeated vomiting- the result of the action of the toxin on the vomiting center in the brain.
• False painful urge to defecate- tenesmus. A sign of irritation of the nerve endings of the intestine.


• Tachycardia and pressure drop- more than 100 heartbeats per minute. Blood pressure is reduced due to intoxication and fluid loss.

Forms of the course of dysentery

1. Light forms- 70-80%. The temperature is 37.3-37.8 ° C, the pain in the abdomen is insignificant, the stool is mushy 4-7 times a day.
2. Moderate forms- 20-25%. Intoxication, abdominal pain, temperature rises to 39°C, loose stools up to 10 or more times with blood and mucus, false urge to empty the bowels.
3. severe forms- 5%. The temperature is up to 40 ° C and above, the stool is mucous-bloody up to 30-40 times a day. Patients are severely weakened, suffer from severe pain in a stomach.

Diagnosis of shigellosis

Examination by a doctor

Collection of complaints. At the doctor's appointment, patients complain of:

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

• when pressing on the left side of the abdomen, pain is felt
• colon spasm - lump in the left lower abdomen
• spasm of the caecum - compaction in the right side of the abdomen

• The facial features are pointed, the skin is dry, the 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 circulatory disorders.
• Increased heart rate and lower blood pressure due to stimulation of cardio-vascular system sympathetic nerves.
• In severe forms, as a result of CNS 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 feces (bakposev). Material: a fresh sample of feces, a smear taken with a swab from the rectum, vomit right at the bedside of the patient is sown on nutrient media (selenite broth, Ploskirev's medium). The samples are placed in a thermostat for 18-24 hours. The formed 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 form small, colorless, transparent colonies. There can be 2 types:

   • flat with serrated edges
   • round and convex

   Individual Shigella do not stain with aniline Gram stains. 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 Shigella bacteria, they are placed in test tubes with Hiss medium. One of the types of serum containing antibodies to a certain type of Shigella is added to each. In one of the test tubes, agglutinate flakes form 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 the 5-7th day of illness, repeated after a week.

   

3. Serological methods.
   1. The reaction of indirect (passive) hemagglutination(RNGA), helps to detect Shigella antigens in feces and urine on the 3rd day of illness. A preparation containing erythrocytes is added to the material taken from the patient. They have antibodies on their surface. If a person is sick with shigellosis, then the red blood cells stick together and fall 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 ram erythrocytes are added to it. In patients with shigellosis, serum antibodies bind to antigens and attach complement. In a patient with shigellosis, when adding ram erythrocytes, blood cells remain intact in the test tube. In healthy people, the antigen-antibody complex is not formed and unbound complement destroys red blood cells.
4. Coprological examination of feces. Examination of feces under a microscope does not confirm shigellosis, but indicates inflammatory process in the intestine, characteristic of many intestinal infections.

   With shigellosis in the feces, they find:

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

Instrumental research: sigmoidoscopy

Indications for sigmoidoscopy

• latent course of dysentery without stool disorder
• excretion of blood and pus with feces
• diarrhea
• suspected rectal disease

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

Treatment of shigellosis

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

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

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

As the condition improves, the diet can be expanded. The menu includes: grated cottage cheese, soups on broths, boiled grated meat, rice porridge, stale white bread.

After 3 days after the cessation of diarrhea, you can gradually return to normal nutrition.

Body detoxification

1. Ready solutions for dehydration and detoxification shown to all patients with shigellosis. Plentiful drink compensates for the loss of fluid 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 illness
   Enterodes Regidron	Means for oral administration. The drug is diluted according to the instructions on the package. The amount of liquid drunk should be 50% higher than the loss with urine, stool and vomiting. Solutions are drunk in small portions throughout the day, every 10-20 minutes.	These funds replenish the supply of fluid and minerals - electrolytes, which are vital for the functioning of the body. They bind toxins in the intestines and help to eliminate them.
   Moderate form of the disease
   Gastrolit Orsol	The preparations 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 the content of sodium and potassium in the blood plasma. Glucose promotes the absorption of toxins. Replenish water supplies, thereby contributing to an increase in pressure. Improve the properties of blood, normalize its acidity. They have an antidiarrheal effect.
   5% glucose solution	The finished solution can be used in any form: orally or intravenously. The solution can be drunk in small portions no more than 2 liters per day.	Replenishes energy reserves necessary for cell activity. Improves the elimination of toxins, replenishes fluid loss.
   Severe intoxication (the patient has lost 10% of body weight) requires solutions for intravenous administration
   10% albumin solution	Intravenous drip at a rate of 60 drops per minute. Daily until 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 per day, 300-500 ml.	Bind toxins circulating in the blood and excreted in the urine.
   5-10% glucose solution with insulin	Intravenously	Replenishes fluid reserves, increases the osmotic pressure of the blood, providing better tissue nutrition. Promotes the neutralization of toxins, improving the antitoxic function of the liver. Covers the energy needs of the body.

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

2. Enterosorbents - Drugs capable of binding and excreting gastrointestinal tract various substances. They are used in any form of the course 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. Reduce the number of shigella in the body and relieve symptoms of intoxication (lethargy, fever). Reduce the amount of toxins entering the bloodstream and thereby reduce the load on the liver. Support normal microflora intestines.	Inside, 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.
   Enterodes		Inside, 5 g 3 times a day.
   Polysorb MP		3 g 3 times a day

   
   Important: between taking enterosorbent and any other drug must pass at least 2 hours. Otherwise, the enterosorbent will “absorb” medicine without letting it take effect. Enterosorbents are used 30-40 minutes before meals so that they do not absorb vitamins and other useful substances from food.
3. Corticosteroid hormones - substances produced by the adrenal cortex, which have an anti-inflammatory effect.
4. Plasmapheresis - procedure for cleansing blood plasma from toxins. A catheter is placed in a central or peripheral vein. A portion of blood is taken from the body and, using apparatuses of various designs (centrifuge, membrane), it is separated 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. During the procedure, sterile disposable instruments and membranes are used. Blood purification takes place under the control of medical equipment. The monitor monitors heart rate, blood pressure, 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 for 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 course of the disease.

Restoration of the 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 tap water, untested wells or springs
• wash fruits and vegetables thoroughly before eating
• do not consume spoiled fruit, in which bacteria multiply in the pulp
• do not buy cut watermelons and melons
• wash hands thoroughly after using the toilet
• keep flies away food products
• do not consume foods that have expired
• in countries with an increased risk of shigella infection, do not buy food that has not been cooked
• vaccination with dysenteric bacteriophage three times with an interval of 3 days:
  • family members where the patient is left at home
  • all who have been 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 bacillary 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, insufficient sensitivity, and the late appearance of positive results of many diagnostic methods, it is advisable to develop the diagnostic potential for detecting this infection.

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

Recognition of shigellosis infection in clinical practice encounters significant difficulties due to objective factors, which include the clinical pathomorphism of dysentery, an increase in the number of atypical forms of the disease, the existence of a significant number of infectious and non-infectious diseases that are similar to dysentery. clinical manifestations. Under the diagnosis of "clinical dysentery" in half of the cases, unrecognized diseases of a different etiology are hidden.

The greatest difficulty faced by physicians initial examination patient until the results of paraclinical diagnostic methods are obtained. Recognition of dysentery is also difficult in the presence of concomitant diseases of the gastrointestinal tract.

Since the beginning of the use of the etiological laboratory diagnosis of dysentery, quite a few methods have been proposed and tested. There are many classifications of methods for the etiological diagnosis of infections. Methodologically, the classification proposed by B.V. Punishment. With regard to the diagnosis of dysentery, the principles of methodologically sound classification were used by B.V. Karalnik, N.M. Nurkina, B.K. Erkinbekova..

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

Most researchers still believe that bacteriological research, which includes isolation in 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 isolation of shigella 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 for different authors depends not only on objective factors affecting the effectiveness of bacteriological examination, 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 sampling and delivery of material to the laboratory, the quality of nutrient 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 forms 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 the disease, the concentration of shigella in the feces is significantly reduced. T.A. Avdeeva found that the low content of shigella and the sharp predominance of non-pathogenic microorganisms in the feces practically exclude the possibility of bacteriological detection of dysentery bacteria.

It is known that bacteriological confirmation of shigellosis infection is most often successful when examining patients in the first days of the disease - the coproculture of the pathogen in the vast majority of cases is first isolated during the first study. Positive results of bacteriological examination are noted 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 an 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 with Sonne dysentery, less intense with Flexner dysentery and the least with Flexner VI dysentery; in the later stages of the disease, the highest concentration is maintained for the longest time in Flexner's dysentery, less long - Shigella Sonne and the least long - Shigella Flexner VI.

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

Since the frequency of positive RNF results is directly dependent on the degree of contamination of feces, the application 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 causes its special advantages over bacteriological examination in the late stages of the disease, as well as in the examination of patients with mild, asymptomatic and subclinical forms of infection, with a low concentration of the pathogen in the feces. RNF is also used in the examination of patients taking antibacterial agents, since the latter drastically reduce the frequency of positive results of the bacteriological method of research, but to a much lesser extent affect the effectiveness of the RNF. The sensitivity of the RNF is not absolute due to the existence of phage-resistant strains of shigella: the proportion of phage-resistant strains can vary over a very wide range - from 1% to 34.5%.

The great advantage of RNF is its high specificity. When examining healthy people, as well as patients with infectious diseases of a different etiology, positive reaction results were observed only in 1.5% of cases. RNF is a valuable additional method for diagnosing shigellosis infection. But today this method is rarely used because of its technical complexity. Other methods are immunological. With their help, a specific immune response is registered with respect to the pathogen or the antigens of the pathogen are determined by immunological methods.

Due to the severity of the processes of specific infectious allergy in shigellosis infection, allergological diagnostic methods were first used, which include an intradermal allergic test with dysentery (VPD). The drug "dysentery", which is devoid of toxic substances specific allergen shigella, was obtained by D.A. Tsuverkalov and was first used in clinical conditions when setting up 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 associated 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 various 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 16 to 60 years in 15 - 20% of cases and aged 3 to 7 years - in 12.5% ​​of cases. Even more often, non-specific 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. Given the above, we can say that this method is not very specific. Tsuverkalov's test is also not species-specific. 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 reaction of allergen leukocytolysis (ALC), the essence of which was the specific damage or complete destruction of actively or passively sensitized neutrophils upon contact with the corresponding AG. But this reaction cannot be attributed to the methods of early diagnosis, since the maximum frequency of positive results was observed on the 6-9th day of the disease and amounted to 69%. An allergen leukergia (ALE) reaction has also been proposed. It is based on the ability of leukocytes of a sensitized organism to agglomerate when exposed to a homologous allergen (dysentery). In view of the lack of evidence of the exact mechanisms of such tests, 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.

The detection of Shigella antigens in the body is diagnostically equivalent to the isolation of the pathogen. The main advantages of methods for detecting antigens over bacteriological examination, justifying them clinical application, is the possibility of detecting 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 antibiotic therapy.

One of the best methods for rapid diagnosis of dysentery was the immunofluorescent study of feces (Koons method). The essence of the method lies in the detection of 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, at the first stage, serum not labeled with fluorochrome (or globulin fraction of anti-shigella serum). At the second stage, fluorochrome-labeled serum is used against globulins of the anti-shigellosis serum used at 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 relationship of Enterobacteriaceae. different kinds. Therefore, this method is considered as indicative in the recognition of shigellosis infection.

Various reactions are used to detect shigella antigens without microscopy. These methods make it possible to detect pathogen antigens in feces in 76.5 - 96.0% of patients with bacteriologically confirmed dysentery, which indicates their rather high sensitivity. It is most advisable to use these methods in the late stages of the disease. The specificity of these diagnostic methods is highly estimated by most authors. However, F.M. Ivanov, who used RSK to detect shigellosis antigens in feces, received 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 the detection of specific antigens in the 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 features - the detection of antigenic substances in some cases is possible already from the first days of the disease, but with the greatest frequency and constancy it succeeds on the 10-15th day and even at a later date. According to B.A. Godovanny et al., the proportion of positive urine shigella antigens (RSK) after the 10th day of illness is 77% (the corresponding figure for bacteriological examination of feces is 47%). In connection with this circumstance, the study of urine for the presence of pathogen antigens has the value of a valuable additional method in 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 a highly active serum against S.flexneri VI, the S.flexneri I-V antigen is also detected, since the 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 blood and urine are higher in the first days of the disease and that the concentration of detected antigens is higher in moderate disease than in mild disease.

CM. Omirbayeva proposed a method for indicating the Shigella antigen, based on the use of formalized erythrocytes as a sorbent for antigens from the studied fecal extract, followed by their agglutination with immune sera. Evaluation of the specificity of this method, in our opinion, needs additional research, since fecal extracts contain significant amounts 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 for 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 found 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 the simplicity of setting up the reaction, the widespread use of this method is limited due to the need for special equipment.

Monoclonal antibodies, immunoglobulin fragments, synthetic antibodies, LPS silver staining, and other technological advances are recommended to enhance the sensitivity and specificity of various serological antigen detection methods.

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

T.V. Remneva et al. propose to use ultrasound to disintegrate antibody complexes with pathogen particles, and then determine the pathogen antigen in CSC 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 for antigen detection in acute dysentery is not justified due to its low sensitivity and specificity. We believe that the specificity of any method for indicating Shigella antigens can be significantly increased by using monoclonal antibodies to Shigella.

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

When conducting diagnostics by determining Shigella antigens from the very beginning of the disease, it is most effective, according to many authors, to examine the feces of patients. With the development of the disease, the possibility of detecting Shigella antigens in urine and saliva decreases, although they are found in faeces with almost the same frequency as at the beginning of the disease. It should be borne in mind that in the first 3-4 days of the disease, feces for antigen are somewhat more efficiently examined in RPHA. In the middle of the disease, RPHA and RNAb are equally effective, and starting from the 7th day, RNAb is more effective in the search 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 than antigens in faeces. Therefore, it is advisable to examine urine in RNAt. In the urine of women, in contrast to the urine of men, due to probable fecal contamination, Shigella antigens are equally often detected using TPHA and RNAb.

Although the antigen is significantly more often (94.5 - 100%) detected in those samples of feces from which it is possible to isolate Shigella 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 the antigen was found 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 to the maximum in dynamics. When focusing on a conditional diagnostic antibody titer, discrepancies in the specificity of such antibodies and the detected antigen can sometimes be observed. This discrepancy is due to insufficient diagnostic reliability of a single determination of the activity of serum antibodies. In this case, the etiological diagnosis should be based on the specificity of the detected antigen.

PCR method in terms of the task of direct detection of signs of the pathogen, it is close to the methods of indicating antigens. It allows you to determine the DNA of the pathogen and is based on the principle of natural DNA replication, including the unwinding of the DNA double helix, the divergence of DNA strands and the complementary addition of both. DNA replication may not begin at any point, but only in certain starting blocks - short double-stranded sections. The essence of the method lies in the fact that by marking with such blocks a segment of DNA specific only for a given species (but not for other species), it is possible to repeatedly reproduce (amplify) this particular region. Test systems based on the principle of DNA amplification, in most cases, make it possible to detect bacteria and viruses pathogenic to humans, even in cases where they cannot be detected by other methods. Specificity of PCR test systems (at right choice taxon-specific primers, exclusion false positive results and the absence of amplification inhibitors in bioassays) in principle avoids the problems associated with cross-reacting antigens, thus providing very high specificity. The determination can be carried out directly in 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 wide clinical practice, the most widely used among serological research methods are methods based on determining the level and dynamics of serum antibodies to the alleged causative agent of the disease.

Some authors have determined antibodies to Shigella in coprofiltrates. Coproantibodies appear much earlier than serum antibodies. The activity of antibodies reaches a maximum at 9-12 days, and by 20-25 days 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.H. Nikolaev et al. report an increase in the efficiency of deciphering the diagnosis and detecting convalescents by simultaneously determining serum and coproantibodies.

The 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 of unequal sensitivity of RA in various etiological forms of shigellosis infection. According to A.A. Klyucharev, antibodies in a titer of 1:200 and above are detected using RA only in 8.3% of patients with Flexner's dysentery and even more rarely with Sonne's dysentery. Positive results of the reaction are not only more often, but also in higher titers are observed with Flexner I-V and Flexner VI dysentery than with Sonne dysentery. Positive results of RA 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 illness 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 height of titers of antibodies detected with its help are directly dependent on the severity of the course of shigellosis infection. According to V.P. Zubareva, the use of antibiotic therapy does not reduce the frequency of positive RA results, 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 results of RA were obtained in 12.7% of cases, in 11.3% of cases group reactions were observed. Due to the antigenic relationship of Flexner I-V and Flexner VI bacteria, cross-reactions are especially often observed in the corresponding etiological forms of shigellosis infection.

With the advent of more advanced methods of serodiagnosis of shigellosis infection, RA has gradually lost its significance. The diagnostic value of the agglutination reaction (“Vidal's dysentery reaction”) (RA) in dysentery is estimated by various researchers ambiguously, however, the results of the work of most authors indicate a limited sensitivity and specificity of this method.

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

A comparative study of sensitivity in dysentery RPHA and agglutination reaction shows a 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 (1:320 - RPHA) are detected when using 4.5 times more often than in the titer (1:160 when setting up the agglutination reaction). With bacteriologically confirmed acute dysentery, a positive reaction of RPHA in diagnostic titers is noted during examination of 53-80% of patients.

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

There is a clear dependence of the frequency of positive results of RPHA and hemagglutinin titers on the severity and nature of the course of shigellosis infection. Relevant studies have shown that with erased and subclinical forms of infection, positive results of RPHA were obtained less frequently than with acute clinically pronounced dysentery (52.9 and 65.0%, respectively), while in titers of 1:200 - 1:400, only 4 responded, 2% of sera (with a clinically pronounced form - 31.2%), and with prolonged and chronic forms, positive results of RPHA were noted in 40.8% of patients, including only 2.0% in a titer of 1:200. There are also reports of different sensitivity of RPHA in certain etiological forms of shigellosis infection. According to L.M. Schmuter, the highest hemagglutinin titers are observed in Sonne dysentery and significantly lower titers in Flexner I-V and Flexner VI dysentery. Antibacterial treatment started in the early stages of the disease, due to a decrease in 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 shigellosis infection, which is associated with the possibility of group reactions. Cross-reactions are observed mainly in Flexner dysentery - between Flexner I-V and Flexner VI dysentery. Humoral immune response in many patients is poorly expressed. The possibility of cross-agglutination due to common antigens is also not excluded. However, the advantages of this method include the simplicity of setting the reaction, the ability to quickly obtain results, and a relatively high diagnostic efficiency. A 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".

In order to diagnose dysentery, it is also proposed to determine the level of specific circulating immune complexes represented by the S.sonnei O-antigen, connected to a specific antibody, using an indirect “sandwich version” of enzyme immunoassay due to its high sensitivity and specificity. However, the method is recommended to be used only with 5- days of illness.

In patients with dysentery, from the very beginning of the disease, a specific increase in the bacteriofixing activity of the blood due to the antigen-binding activity of erythrocytes is found. In the first 5 days of AII, the 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 by erythrocytes due to their C3v receptors (in primates, including humans) or Fcγ receptors (in other mammals) of the antigen-antibody immune complex.

Among the relatively new methods for recording a specific immune response at the cellular level, attention is drawn to the determination of antigen-binding lymphocytes (ASL) that react with a specific, taxonomically significant antigen. Detection of ASL is carried out by various methods - paired agglutination of lymphocytes with an antigen, immunofluorescence, RIA, adsorption of lymphocytes on antigen-containing columns, adhesion of mononuclear cells on glass capillaries, indirect rosette reaction (RNRO). It should be noted that such high sensitive methods registration of ASL, such as ELISA and RIA, adsorption of lymphocytes on antigen-containing columns is technically relatively complex and not always available for wide application. The works of a number of authors have shown the high sensitivity and specificity of RHRO for the detection of ASL in various diseases. A number of researchers have revealed 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 a 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 number of ASL falls, and if the effectiveness of treatment is insufficient, an increase or stabilization of this indicator is recorded. Sensitization to tissue, bacterial antigens, as well as to antibiotics can be quantified using the determination of ASL, which is of great diagnostic value. The ASL method has been used to a limited extent for diagnosing 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 wide spread of dysentery, insufficient sensitivity, and the late appearance of positive results of many diagnostic methods, it is advisable to develop the diagnostic potential for detecting this infection. Obtained in many infectious diseases data on high efficiency ASL method, the early appearance of its positive result determine the prospects for the study and application of this method in shigellosis.

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A.M.Sadykova

Dysentery laboratory diagnostics

Tү yin: Zhedel іshek infectionalaryn bakylauda, ​​dysentery naқty diagnostics en özu maselesi bolyp tabylady. Bacterial dysenteric dұrys қoyylғan diagnoses nauқaska vaқytynda em zhүrgizuge zhane epidemica қarsy sharalardy өtkіzu үshіn manyzdy. Obzordagy kөrsetіlgen mәlіmetter, dysentery ken taraluyn negіzdey otyryp, sezіmtaldyғynyn zhetkіlіksіzdіgі zhane kөp degen diagnosticslyқ аdіsterdіn оң nәtizhesіnің kesh anyқtaluyna baylanysty, wasps infektsionny anyktauda diagnostikalyk potentialdy maksatty turde damytu kerek ekenin korsetedі.

Tү hinds fromө zder: diagnostics, dysentery, antigenbaylanystyrushy adis.

A.M.Sadycova

Laboratory diagnostics of dysentery

Summary: Reliable diagnosis of diarhoea is one of the most important issue to control the accute intestinal infection. Exact diagnosis of bacteriosis diarrhoeas have vitae meaning for correct and accurate treatment of a patient and to take necessary antiepidemic measures as well. The members given in the survey, taking into concideration the widespread diarrhea, shows the lack of sensibility and late occurrence of positive results of many diagnostic methods. It is essential aimly to develop the diagnostic potential to design the infection.

keywords: diagnostics, dysentery, antigen binding lymphocytes method.