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on methodical conference
department of infectious diseases and epidemiology
„____” ____________ 200 р.
Protocol № _____
Chief of Dept., professor __________ V.D. Moskaliuk
METHODOLOGICAL INSTRUCTIONS
to a fifth year student of the Faculty of Medicine
on independent preparation for practical training
Topic: SHIGELLOSIS
Subject:
Major:
Educational degree and qualification degree:
Year of study:
Hours:
Associate professor
Infectious Diseases
Medicine
Specialist
5
2
Davydenko О.M.
2
Topic: SHIGELLOSIS
1. Lesson duration: 2 hours
2. Aims of the lesson:
3.1. Students are to know:
 Etiology and epidemiology of a shigellosis;
 Pathogenesis and pathological anatomy;
 Classification of a shigellosis;
 The clinical characteristic of different kinds of a shigellosis;
 Laboratory methods of examination at shigellosis;
 Complications, which are observed at a shigellosis;
 Differential diagnostics of a shigellosis;
 Medical tactics;
 Preventive and antiepidemic measures in the locus.
3.2. Students are to be able:
• to question a patient in order for obtaining of information on disease history and epidemiologic
anamnesis;
• to perform clinical examination of a patient;
• to formulate and to substantiate the diagnosis of shigellosis;
• to prepare a plan of additional patient examination;
• to evaluate results of laboratory examination;
• to determinate a dehydration stage;
• to make differential diagnosis to distinguish between similar diseases (gastric and intestinal
forms of salmonellosis, alimentary toxic infections, diseases caused by esherichia, viral enteritis,
cholera, mushroom poisoning etc.);
• to prescribe adequate pathogen and etiotropic treatment.
3.3. Students are to acquire the following skills:
 to conduct clinical examination of a shigellosis patient and other acute intestinal diseases;
 to formulate and substantiate a clinical diagnosis;
 to prepare a plan of paraclinic patient examination;
 to take samples of material (feces, vomit) for bacterioscopy and other quick analysis methods
and bacteriological examination for revealing of comma bacillus;
 to evaluate results of paraclinic patient examination;
 to organize hospitalization and treatment of a shigellosis patient;
 to plan and organize prophylactic measures against shigellosis;
 Veneering of the expedited report (form 058).
4. Advice to students.
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.
Etiology
The agents of shigellosis are regarded to genus Shigella, family Enterobacteriacea. 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 B (S. flexneri), group C (S. bojdii), group D (S. sonnei).
Each group is divided into serologic types and subtypes.
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All Shigellas are similar morphologically. They are small gram-negative rods, nonmotile
and nonencapsulated. Shigellas are facultative anaerobes. They grow well on the simple nutritive
mediums. Shigella contain thermostable somatic 0-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.
Epidemiology
The sources of infection are ill patients, persons in period of reconvalescence and
bacteriocarries. The patients with acute shigellosis are especially dangerous.
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. Foodstuffs, 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
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 a system has
leading meaning in pathogenesis of shigellosis.
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5.
Theory of intracellular parasitism. According this theory, all features of I the shigellosis
course are connected with parasitism of Shigella in the epitheliums 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-adenosinemonophosphates, increased secretion of electrolytes and water. The violation of water electrolytes balance is observed in gastroenteritic 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 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.
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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 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 Tsupressors 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, IgM. 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
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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.
Anatomic pathology
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 submucous layer of rectum. Small hemorrhages and erosions
are observed in the mucous membrane in the part of the patients. In rectoscopy mucous or mucoushemorrhagic 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 of 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.
Clinical manifestations
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 coarse. 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
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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 3839 °C 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 °C 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.
Gastroenteritic 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 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.
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
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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.
Diagnosis
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
Differential diagnosis is performed with the following diseases - salmonellosis, toxic foodborne 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.
Treatment
The complex of treatment is indicated, which depends on features of disease. In the first
days the diet N° 4, and diet N° 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.
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According to parameters of coprocytogram use mono or polycomponental fermental
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, abacterin, enterole-250 are indicated for elimination of intestinal dysbacteriosis i and restoration
of the normal biocenosis. Course of treatment is 2 weeks and long'er.
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
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.
Control questions:
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.
6.
Variants of shigellosis infection.
7.
Laboratory methods of shigellosis diagnosis.
8.
Criteria of shigellosis diagnosis.
9.
Differential diagnostics of shigellosis.
10.
Treatment of shigellosis.
11.
Prophylaxis of shigellosis.
THE LITERATURE
А. Basic:
Infectious disiseases /Edited by: prof. E. Nikitin, prof. M. Andreychyn.-Ternopil «Ukrmedknyga»,
2004.-364 p.
Б. Padding:
1. The Merck Manual of Diagnosis and Therapy.-Merck Sharp, 1987.-2696 p.
2. Reese R.E. A Practical Approach to Infectious Diseases-Boston-Toronto: Little,
Brown&Company, 1986.-782 p.
3. Ellner P.D., Neu H.C. Understanding Infectious Diseases – Mosby Year Book, 1992.- 343 p.