Shigellosis is general infectious disease of human, caused by bacterium of genus Shigella.
Shigellosis is characterized by principal damage of mucous membrane of distal section of the large intestine. The disease is accompanied by symptoms of general intoxication,abdominal spastic pain, frequent watery stool with admixture of mucus and blood, and tenesmus.
The term "dysenteria" was used by Hippocrates to indicate a condition characterized by frequent passage of stool containing blood and mucus accompanied by straining and painful defecation.
In 1898 Shiga conclusively demonstrated that a bacterium was present in the stools of many patients with shigellosis and that agglutinins could be demonstrated in the serum of the infected patient. Two years later, Flexner found a similar but serological different organism in stool of other patients with shigellosis acquired in Philippines.
The agents of shigellosis are regarded to genus Shigella, family Enter'obacteriacea. There are approximately 50 serotypes of Shigella.
According to modern international classification genus of Shigella is divided into four groups: group A (S. dysentery), group Â (S. flexneri), group C (5. bojdii), group D (S. sonnet). Each group is divided into serologic types and subtypes.
All Shigellas are similar morphologically. They are small gram-negative rods, nonmotile and nonencapsulated. Shigellas are facultative anaerobias. They grow well on the simple nutritive mediums. Shigella contain thermostable somatic O-antigen, including group and standard antigens.
Depending on character of toxinoformation Shigella are divided into two groups. Shigella Grigoriev-Shiga's belongs to the first group. They produce strong exotoxin, having protein's origin, and also endotoxin. All other types of Shigella (Flexneri, Sonnei) are treated to the second group, they produce only endotoxin. Endotoxin consists of proteins and lipopolysaccharide. Protein part of endotoxin and exotoxin have expressive neurotropic action. Endotoxins has enterotropic action.
The sources of infection are ill patients, persons in period of reconvalescence and bacteriocarries. The patients with acute shigellosis are especially dangerous.
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The patients with acute shigellosis discharge the agent during all period of the disease, especially during period of expressive colitic syndrome. The persons with obliterated, light forms of the disease are dangerous too. These persons don't address for medical help and don't receive treatment. Because, these "atypical" cases of acute shigellosis have predominant epidemiological meaning. The patients with chronic shigellosis are dangerous for other persons, especially in the period of aggravation.
The mechanism and factors of the transmission of the infection. The mechanism of the transmission of the infection is fecal-oral. The transmission of the infection is realized through contaminated food-stuffs and water. Infection of food-stuffs, water, different objects happens due to direct contamination by infected excrements,through dirty hands and also with participation of flies. The factors of transmission have leading meaning in epidemiology of shigellosis. Depending on factors of transmission there are the next ways of contamination - contact, alimentary and water. Now, the alimentary way has more important meaning. Contamination over food-staffs may be through contaminated vegetables and berries with insufficient processing before use. Food-stuffs, prepared for use have the most important meaning in transmission of the infection (milk, milk products, especially, sour cream, meat stuffing and other meat products, bread, soft drinks, fruits, vegetables).
The susceptibility of human is high. It doesn't depend on sex or age. Shigellosis occurs as* in infants as in seniors. However, the morbidity of adult population is lower than children of early age.
Shigellosis is characterized by seasonal spread as the other intestinal infections. It is registered more frequently in summer and autumn.
Pathogenesis of shigellosis is complicated. It is studied insufficiently. In some cases the agents perish in the upper section of the gastrointestinal tract under the influence of acidic conditions. In other cases Shigella may pass through intestine, and it is excreted into environment without reply of the macroorganism.
Diverse theories of pathogenesis of shigellosis were pulled out in different years. The next theories are known:
1. Bacteriemic theory. Reproduction of the agent in the blood is the basis of pathogenesis of shigellosis according to this theory.
2. Toxico-infections Shiga's-Brauer's theory. Many positions of this theory don't lose one's own meaning in modern ideas about pathogenesis of shigellosis.
3. Allergic theory. According to this theory, shigellosis is general allergic infection disease.
4. Nervous-reflexious theory. According to this theory the damage of nervous system has leading meaning in pathogenesis of shigellosis.
5. Theory of intracellular parasitism. According this theory, all features of the shigellosis course are connected with parasitism of Shigella in the epithelium of mucous membrane of distal section of the large intestine.
In was established by investigations of the last years that secondary immune insufficiency plays considerable role in pathogenesis of shigellosis. At present time it is known that development and course of the different forms of shigellosis is connected with some factors. There are functional state of the organism; interaction of the human's organism, agent and environment; biological properties of the agent (toxigenecity, invasiveness, fermentic activity and other).
Bacteremia of short duration may be observed in decreased resistance, in entering of the large doses of the agent. However, bacteremia hasn't essential meaning in pathogenesis of shigellosis. Bacteremia is marked only in one third of the patients with Grigoriev's-Shiga's shigellosis.
Toxins, which are absorbed from the intestine, play an important role in pathogenesis of shigellosis. At first, toxins influence directly on the mucous membrane of the intestine and substances, disposing under mucous membrane (nervous endings, vessels, receptors). Second, toxins are absorbed and influence to different sections of central nervous system. Involvement of small intestine in pathological process from the first days of the disease is explained by toxinemia (violation of its motile, absorbing and digestive functions). The evidence of toxinemia is delivery of endotoxin into patient's blood serum from the first days of the disease and its delivery into urine.
Exotoxin of Shigella Grigoriev's-Shiga's and protein part of endotoxin possesses significant neurotoxic action. Neurotoxins influence on the central nervous system and peripheral gangiums of vegetative nervous system. It is manifested by severe intoxicative syndrome and violation of all types of the balance of substances.
Lipopolysaccharide part of endotoxin damages principally mucous membrane of distal section of large intestine, and in a less degree, other sections of gastrointestinal tract. It possesses cytotoxic action and causes activation of adenylcyclase.
Activation of adenylatecyclase leads to accumulation of cyclic 3,5-adenosine-monophosphates, increased secretion of electrolytes and water. The violation of water - electrolytes balance is observed in gastrointeritic variants of acute shigellosis course. It is necessary to allow for degree of dehydration of the organism. Dehydration of II-III degree develops in severe course of gastroenterocolitic and gastroenteritic variant of acute shigellosis. In severe (hypertoxic) form it may be development of hypovolemic shock and acute renal insufficiency.
Shigella toxins cause sensibilization of the mucous membrane of the intestine, render damaging action on it with development of inflammatory changes and erosions formation and ulcers in severe course of the disease.
Toxin stimulates discharge of biological active substances (histamine, serotonine, kinines, prostaglandines) into blood, causes violation of microcirculation of the blood in the intestine's wall, increases intensity of inflammatory process and disorders of functions of the intestine (motorics, absorbtion, secretion).
The violation of innervation of the intestine, microcirculation, electrolytic balance and inflammatory changes of mucous membrane are manifested clinically
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by sharp spastic pains in the stomach. Spasms of separate sections of the intestine lead to excretion of scanty stool ("fractional stool"). Spastic shortening of the muscles of sigmoid and rectum cause fecal urgency and tenesmus.
Allergic factor plays definite role in pathogenesis of shigellosis. Pathological process develops in large intestine after preliminary sensibility. However, it was shown experimentally, that shigellosis is not typical allergic disease.
However, intracellular parasitism was not confirmed due to biopsy of mucous membrane of the intestine in the patients with shigellosis. It is not expected, that phenomenon of intracellular parasitism plays certain role in shigellosis too.
In shigellosis, the invasion of Shigellas into epithelial cells is observed in large intestine, principally in rectum. It is caused by comparatively prolonged accumulation of intestinal content, toxins and bacteriums in the large intestine. They create favorable conditions for invasion of the agent into epitheliocytes. It is promoted by intestinal dysbacteriosis too. Intestinal dysbacteriosis develops inrarely under influence of antibioticotherapy. This therapy causes destruction of considerable part of symbiotic flora.
The disease may have prolonged or chronic course due to addition of supplementary factors of chronic process. The cases of formation of chronic shigellosis develops due to unfavorable premorbid state, delay of macroorganism functions replacement, decreased activity of immune system.
The recovery of the patients is prolonged in presence of damages at any portions of gastrointestinal tract (defects of masticatory apparatus, anomalies of intestinal tube, gastritis, ulcerous disease, appendicitis, pancreatitis, hepatitis, cholecystitis); presence of supplementary diseases (tuberculosis, brucellosis, malaria, helminthiases); state of endocrine system, dysbalance of vitamins. The factors, promoting to prolonged and chronic course of the disease, are late hospitalization of the patients, incorrect treatment, violation of alimentary regime after discharge of the patients from the hospital.
Immunity. In shigellosis postinfectious specific immunity is shaped and typed-specific.The investigations of humoral immunity revealed dependence of the level of blood serum immunoglobulins of the patients with shigellosis from gravity of the disease, kind of the agent, and also, from treatment. Antibodies play essential role in execution of functions of phagocytes. However, presence of antibodies can not be used for rendering of diagnosis and for estimate of complete sanation of the organism from the pathogen. In shigellosis humoral factors of immunity preserve the meaning only during one year.
Immunological examination reveales depression of the tests T-system of immunity with different course of acute shigellosis, which is more expressive in the patients with severe, moderate and lingering course of the disease.
Decrease of the tests T-system of immunity is appearance of short duration. It was mentioned a considerable decrease of functional activity and quantity of T-lymphocytes in the patients with lingering course of shigellosis and in chronic form of the disease.
Investigations of subpopulations of T- and B-lymphocytes were an important stage for deciphering of violation of immune system in shigellosis. These data allow to establish the most important links of pathogenetic process. Corrections of these links may be the most perspective.
Detailed analysis of subpopulations of immune system had proved the presence of secondary immune deficiency in shigellosis. So, decrease of T-supressors is observed in case of moderate and severe course of acute shigellosis. In chronic form of the disease the activity of T-supressors increases, but the level of T-helpers decreases.
However, the factors of cell immunity must be estimated according to humoral and especially, local immunity. It is possible, that absence of the local immune reaction is a risk factor of lingering, chronic forms of the disease development
and also for postdysenteric colites.
The local immune response of lymphoid tissue of intestine is promoted by antibodies — forming cells of mucous membrane-produced antibodies of classes IgA,
IgG> feM. The class of IgA has the leading role in the protection of the organism. Thus, the secondary immune deficiency in patients with different forms of
shigellosis is connected in general with violation of regulative and effectoric links of immune system. The causes of secondary immune deficiency development is inhibitory influence of antigenic-toxic complexes of the agent at immune system in infectious diseases.
It is known, that endotoxinemia is one of the mechanisms of pathogenesis of shigellosis. Toxins of the agent render depressive influence on hemopoesis, phagocytosis and cause the disorder of microcirculation. Correlation is marked between degree of intoxication, level of depression of cell immunity and natural resistance of the organism.
The study of different cells populations, their metabolic activity allow to determine their role in different forms of shigellosis. These investigations give a possibility of application of basic regulation of cell's functions with use immunocorrecting therapy for preventation of the formation of lingering, chronic forms of the disease and postdysenteric colites.
In shigellosis pathomorphologic changes are revealed, generally, in distal portion of the large intestine (sigmoid, rectum). There are 4 stages of inflammatory changes:
1. Acute catarrhic inflammation.
2. Fibrinous necrotic.
3. Ulcerous and folliclic-ulcerous.
4. Stage of formation of scars.
At present time fibrinous-necrotic and ulcerous damages occur rarely. Catarrhic inflammatory process is observed more frequently. It is confirmed by data of pathologoanatomic investigations due to biopsy of rectum. Catarrhic inflammation is characterized by edema, hyperemia of mucous membrane and
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submucous layer of rectum. Small hemorrhages and erosions are observed in the mucous membrane in the part of the patients. In rectoscopy mucous or mucous-hemorrhagic exudation is revealed on the surface of mucous membrane and in the intestine.
In microscopical investigation disorders of vessels are marked: increased permeability, local hemorrhages. Edema of strome and basal membrane leads to dystrophic changes of epithelium, in severe cases - to formation of ulcers and erosions. Hyperproduction of mucus is typical.
Fibrinous-necrotic changes are manifested by dirty, gray and dense coats on mucous of the intestine. The membranes consist of necrotic tissue, leukocytes and fibrin. Necrosis may achieve submucous and muscleous and fated submucous layer. Purulent damages and necrosis lead to formation oi ulcers. In shigellosis ulcers are superficial with dense borders.
The regeneration of epithelium begins on the 2-3 day of the disease in acute phase of catarrhic inflammation. However, complete anatomical recovery may be on 4-5 month after discharge the patient from the hospital even in mild course of shigellosis. Regeneration comes slowly in the destructive changes in the intestine, and disorders of vessels are preserved for a long time. Regeneration is combined frequently with focuses of inflammatory changes. In chronic shigellosis the morphological changes are characterized by multiple forms and flabby duration of inflammatory process.
There are the next clinical variants of acute shigellosis:
1. Colitic variant.
2. Gastroenterocolitic variant.
3. Gastroenteric variant.
Depending on gravity of the course of the disease there are mild, moderate and severe course of shigellosis, and also carriers.
Colitic symptomocomplex is typical for shigellosis. Incubation period lasts from 2 till 5 days, rarely - 7 days.
Mild course. Onset of the disease is acute. The temperate pains appears in the lower part of the stomach, principally, in the left iliac area. These pains precede act of the defecation. Tenesmus are observed in some patients. Stool is from 3-5 till 10 times a day. It contains mucus, sometimes - blood. Temperature is normal or subfebrile. Catarrhic inflammation of mucous membrane is observed at rectorhomanoscopy, sometimes erosions and hemorrhages.
Moderate course. Onset of the disease is acute or with short prodromal period. It is characterized by weakness, malaise, discomfort in the stomach. Then, spasmatic pain appears in the lower part of the stomach, tenesmus. At first, stool has fecal character. Then, mucus and blood appear in stool. Stool loses fecal character and has appearance of "rectal spit" (excretion of scanty stool -
"fractional stool"), with mucus and blood. Stool is accompanied by fecal urgency and tenesmus. Stool is from 10-15 times a day.
In patients with medium serious course of acute shigellosis temperature increases up to 38-39 °Ñ for 2-3 days. Subfebrile temperature is possible. The patients complain of weakness, headache. It may be collapse, dizziness. The skin is pale. Hypotonia, relative tachycardia are observed. Tenderness and condensation of sigmoid are revealed. In the peripheral blood leukocytosis and temperate neutrophylosis are observed. In coprocystoscopy erythrocytes (more then 30-40 in the field of vision) are revealed. In rectorhomanoscopy diffusive catarrhic inflammation, local changes (hemorrhages, erosions ulcers) are revealed. In patients with moderate course of acute shigellosis functional and morphological restoration may be prolonged - till 2-3 months.
Severe course. Onset of the disease is acute. Temperature is increased up to 39 °Ñ and higher. The patients complain of headache, harsh weakness, nausea, something vomiting. Strong abdominal spasmodic pains, frequent stool with smaller volume "without account", with mucus and blood are marked.
There are hypotonia, harsh tachycardia, breathlessness, skin cyanosis. Harsh tenderness at the left iliac area, especially in the area of sigmoid are marked during palpation of the stomach. It is possible pasesis of intestine. There are expressive leukocytosis neutrophylosis with shift to the left. ESR is accelerated. During microscopical examination of stool erythrocytes are marked through the field of the vision. In rectorhomanoscopy infusive catarrhic or fibrinous inflammation, presence of the local changes (erosions, ulcers) are marked. The functional and morphological restoration of intestine is longer than 3-4 months in patients after colitic variant of acute shigellosis.
Gastroenterocolitic variant of shigellosis. The principal feature of this variant of the acute shigellosis course is acute impetuous onset of the disease after short incubation period (6-8 hours). More frequent way of the transmission of the infection is alimentary. The factors of transmission are milk, milk products and other.
Intoxicative syndrome and symptoms of gastroenteritis are observed in the initial period. The manifestations of enterocolitis predominate in the period of climax. There are mild, moderate and severe course of gastroenterocolitic variant of acute shigellosis. During estimate of the disease course gravity it is necessary to allow for not only degree of intoxication and damage of gastrointestinal tract, but also degree of dehydration, because repeated vomiting and plentiful diarrhea are observed. It may lead to'dehydration of I-II-III degree.
Gastroenteric variant of shigellosis. The principal feature of this variant of the acute shigellosis course is predominance of clinical symptoms of gastroenteritis and presence of certain degree dehydration symptoms. Nowedays, besides clinically distinct sings of the disease, lingering and obliterated course of shigellosis is observed. Obliterated course is characterized by insignificant clinical manifestations. The great ratio of the patients do not apply to physician. Careful
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bacteriological examination of the patient with different gastrointestinal disorders of unknown etiology has large meaning for correct diagnostics. In these patients catarrhic inflammatory changes of mucous membrane of distal portion of rectum is revealed in the majority of cases during rectorhomanoscopy (Fig. 2).
Clinical recovery comes through 2-3 weeks in the majority of the patients with uncomplicated course of all variants of acute shigellosis. Complete functional and morphological restoration of gastrointestinal tract happens in 1-2 months and later. Relapses may arise in some part of the patients. The factors, promoting to relapses of the disease are the violation of diet, alcohol use, incorrect therapeutic tactics. The disease may have lingering course. Insufficient reactivity of the organism, sharp decrease of cell immunity in acute period of the disease promote to lingering course of shigellosis.
Lingering course of shigellosis. Shigellosis is estimated as lingering, if clinical manifestations of the disease are observed over 3-4 weeks. Declination to lingering course of the disease depends on gravity of the course of shigellosis in acute period. Colitic variant of severe course of acute shigellosis has prolonged course more frequently than moderate variant. The period of functional and morphological restoration of the intestine is over 3 months. In some patients lingering course is manifested only by persistent bacterioexcretion. Bacterioexcretion is combined with prolonged inflammatory process in rectum.
Bacterioexcretion. Dysfunction of intestine is absent at the period of examination and preceded 3 months in presence of bacterioexcretion (subclinical bacterioexcretion) or excretion of Shigella after clinical recovery (reconvalescent excretion) in this form of infectious process.
The principal methods of diagnostics of shigellosis are bacteriological and serological methods of investigation.
Excretion of coproculture of Shigella is more reliable method of confirmation of diagnosis of shigellosis. It is necessary to take the material for bacteriological investigation before beginning of the treatment.
Diagnosis may be confirmed by serological methods. Reaction of indirect agglutination with standard erythrocytic diagnosticum is used more widely. Diagnostic titer is 1:200 with increase of titer in 7-10 days.
Differential diagnosis is performed with the following diseases - salmonellosis, toxic food-borne infections, rotaviral gastroenteritis, amebiasis, balantidiasis, intestinal shistosomiasis, trichocephaliasis, enterobiasis, cancer of large intestine, appendicitis, ileus, hemorrhoids, diverticulitis, ischemic colitis, Crohn's disease, non-specific ulcer colitis, secondary colitis in patients with severe therapeutic pathology, radiation affections and poisonings with different chemical and biologic substances.
The complex of treatment is indicated, which depends on features of disease. In the first days the diet ¹ 4, and diet ¹ 2 (till clinical convalescence) are indicated.
At mild course of shigellosis etiotropic agents are not applied, at disease of average degree of gravity use basically preparations of nitrofuranes: furazolidon, nifuroxasid 0.1 gm 4 times per day. Use derivatives of 8-oxyquinoline - enteroseptol, intestopan, among other groups of preparations - intetrix, nalidix acid, ftalazol. At ambulatory treatment of shigellosis with moderate stage of gravity sulfanilamid preparations of prolonged action are indicated - phthazin, sulfadimethoxin.
In case of severe shigellosis course use antibiotics - ampicillin or a polymyxin; when there is no effect - ciprofloxacin or ofloxacin in combination with gentamicin or cefazolin are prescribed. Duration of course of etiotropic treatment at moderate course of shigellosis is 2 - 3 days, at severe case it lasts not longer than 4 - 5 days. A solution of regidron, in severe cases quartasault, lactosault are applying per os with the purpose of desintoxication and rehydratation. For the adsorption of bacterial toxins and metabolites from the intestine lumen and for their subsequent removing from the organism enterodes,coal microspherical sorbents, sillard P, smecta are used. Rectal pollination with sillard P in a dose 6 gm (1-3 procedures) is effective. There are proved methyluracil, pentoxyl, thymalin as natural factors of nonspecific protection of the organism and stimulators of regeneration. Calcy gluconate, dimedrol, suprastin, tavegil are indicated as pathogenetic treatment.
According to parameters of coprocytogram use mono or polycomponental fermentai preparations. At presence of plenty of fat drops in feces pancreatin, pancitrat, pancurmen, and at detection of a cellulose, amyl, muscular fibers -pansinorm, festal, mezym-forte, abomin, vobensim are applied.
There are indicated widely vitamins preparations, these are ascorbic acid, nicotinic acid, thiamin chlorid, riboflavin, pyridoxine hydrochloride, calcy pangamat, folic acid, rutin. It is better to use per os the balanced vitamin complexes -dekamevit, glutamevit.
Collibacterin, bifidumbacterin, bificol, lactobacterin, bactisubtil, linex, hilac forte, a- bacterin, enterole-250 are indicated for elimination of intestinal dysbacteriosis and restoration of the normal biocenosis. Course of treatment is 2 weeks and longer. Collectings of herbs and fruits of a bilberry, mint peppery, knot-herb ordinary, camomiles medicinal, herbs of a yarrow, centaury are helpful ordinary. Collecting with the shepherd's bag ordinary, grasses of St.-Johns wort are effective at hemocolitis. Fermentative and putrefactive processes reduces at lingering colitis, that is why collecting of grass of a sage-brush, a horsetail field, grasses of a yarrow ordinary, roots of snakeweed are applied.
Broths and juices of herbs, oil of dog rose for microclysters after a cleansing enema, 0.5 % solution of a colloid silver as medical clysters, insufflations of oxygen are used locally for stimulation of reparative processes in the mucosa of colon.
Prophylaxis of shigellosis includes complex of measures, directed to revelate the source of the infection, interrupt the ways of the transmission, increase of the organism resistance. Keeping the rules of personal hygiene and rules of food's cooking plays the principal role in prophylaxis of the disease. Sanitary education of population has an important meaning in shigellosis prophylaxis too.
1. Etiology of shigellosis.
2. Epidemiology of shigellosis.
3. Pathogenesis of shigellosis.
4. Anatomic pathology of disease.
5. Main clinical symptoms and signs of shigellosis.