THE PRINCIPLES OF THE DIAGNOSTICS, TREATMENT AND PREVENTION OF INFECTIOUS DISEASES

The principles of the infectious diseases diagnostics

In present time the diagnostics of the infectious diseases preserves the traditional characteristics. The methods of the distinction of the diseases are improved. The looking for new more effective methods are performed. The necessity of further elaboration of the methods of diagnostics of infectious diseases is connected with change of pathomorphology and clinic of infections.

The tendency to increase of number of asymptomatic, atypical, lindering forms of infectious diseases occurs. The frequency of mixed infections of bacterial and bacterial-viral etiology increases. These features are connected with change of all the factors,which participate in development of infectious disease (microorganism, macroorganism and conditions of environment). The courses of this transformation are the increase of common specific reactivity of the organism, massive vaccination and revaccination of the population, wide inculcation into practice of antibiotics and other chemical drugs, increasing nonspecific allergization of the organism.

The early, exact and maximally concretive diagnostics is the basis for effective therapy, prevention of complications and infavorable outcomes of the disease. The early diagnostics of the infectious diseases is basis of antiepidemic and prophylactic measures.

The diagnostics of infectious diseases is based on comprehensive and systemic examination of the patient, including anamnesis, epidemiological anamnesis, physical examination of the organs and systems, analysis of the results of laboratory and instrumental examination of the patient.

Anamnesis of the disease (Anamnesis morbi)

The physician must take the history actively and carefully. It is necessary to indicate features of the onset of the disease (an acute or gradual), presence of the fever, chill, degree of increase of the temperature, it's oscillations, duration, the character of the stool, localization and intensity of the pains (headache, abdominal pains, pains in the muscles and joints), violations of the sleep and other. The epidemiological amamnesis permits to receive data about place, circumstances and conditions of infection, and also about possible ways of the transmission of the agent. The data about contact of patient with other patients with same infection, about personal contact with animals (for example, professional), about stay in endemic or epizootic focus have especial value.

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The data about food of the patient, wounds after bites of the insects, traumas, operations, hemotransfusions have an important value too. Informations about transferred infections in last time, about prophylactic vaccination, use of immunoglobulines, glucocorticoides, antibacterial drugs are exceptionally important.

Clinical examination

There is the definite order of the clinical examination of the patients. At first, it is necessary to evaluate the common state of the patient (preservation or violation of the consciousness, excitement or brake action, adequacy of the behavior).

Due to examination of the skin it is necessary to mark pale skin or hyperemia, jaundice, humid or dry skin, and presence or absence of the rash. In presence of the rash it's localization, spread, and character (roseola, pethechias, papules or vesicula) are marked.

Then conjunctives, mucous membrane of the mouth's cavity are examinated. Due to some infectious diseases (diphtheria, scarlet fever, and infectious mononucleosis) the changes of the mucous membrane of the throat and tonsils are developed. In these cases the degree of hyperemia and edema of mucous membrane, presence of coats, it's localization, color and spread are marked.

In some infectious diseases the enlarged lymphatic nodes are observed. It may be enlarged of separate lymphatic nodes (tularemia) and multiple lymphatic nodes (brucellosis, infectious mononucleosis, HIV-infection). It is necessary to mark size of the lymphatic nodes, consistence, tenderness, motility.

There is the definite order of objective examination of the internal organs (cardiovascular system, respiratory system,, gastrointestinal tract, blood system, immune system, urinary system, nervous system).

The rule evaluation of haemogramma has great meaning in diagnostics of infectious diseases. The tests of haemogramma, connecting with clinics of the disease help in diagnostics of many infectious diseases (infectious mononucleosis, typhoid fever, viral hepatitis, HIV-infection and others). In leptospirosis, haemorrhagic fever with renal syndrome the analysis of urine may help too.

In infectious pathology the largest part of common symptoms are nonspecific. The high temperature, chill, vomiting, violation of the sleep, decrease of the appetite, weakness are observed almost due to all infectious diseases. These symptoms have not decisive meaning in diagnostics. Because, the pathognomonic symptoms have great value. These symptoms are specific symptoms only for one nosologic form.

The classic examples are Filatov-Koplik's spots in measles, crampic cough with reprises in whooping cough, opistotonus in tetanus, haemorrhagic star-like rash in meningoccemia, vesicular rash along turm of nerves in herpes Zoster, hydrophobia in rabies and other.

Besides common (nonspecific) and pathognomonic symptoms, there is a great group of signs with intermediate position. These signs are typical as for many

24 Infectious diseases

infectious diseases as for noninfectious diseases. So, enlarged liver may be in case of typhoid fever, epidemic typhus fever, malaria, acute or chronical viral hepatitis, sepsis, diseases of the blood, cirrhosis of the liver, acute and chronical heart's insufficiency. In typhoid fever, visceral leishmaniasis, diseases of the blood, sepsis enlarged spleen are observed. There is no enlarged liver and spleen in grippe. The different abdominal pains, diarrhea, cramps are symptoms from this group too.

In diagnostics the important moment is revelation of syndrome. Syndrome is combination of the signs, caused by united pathogenesis (intoxication, haemorrhagic, meningeal, colitis, hepatolienal, and syndrome of gastroenteritis, jaundice, cholesthasis and other). The different syndromes haye nonidentical meaning. So, syndrome of intoxication occurs due to all infectious diseases. Intoxicative syndrome plays the great role in evaluation of the severity of the course and prognosis of the disease.

In present time near 1,500 syndromes and more than 5,000 diseases are known. The identical syndrome may be due to different diseases. For example, meningeal syndrome is observed in subarachnoidal hemorrhage, serous and purulent meningitis, meningismis. Hemorrhagic syndrome occurs in viral hepatitis, leprospirosis, and meningococcal infection, hemorrhagic fevers, in diseases of the blood and other. The nosological form is characterized by few constant and typical syndromes. For example, colitis syndrome and syndrome of intoxication are observed in shigellosis. Symtomocomplex is combination of syndromes and symptoms, which typical for absolute majority cases of nosological form. Symptomocomplex has high specific, but it may be different in different periods of the disease. For example, there is combination of syndromes of intoxication, dyspeptic and other syndrome in prejaundiced period of viral hepatitis. Syndrome of jaundice, hepatolienal syndrome and sometimes syndrome of cholesthasis are observed in period of jaundice.

Laboratory methods

The different laboratory methods are used in diagnostics of infectious diseases (bacteriological, virological, parasitological, immunofluorescennt and others). The purpose of these methods is to establish etiology of the disease.

The bacteriological method includes sowing of the material on the nutritive mediums, isolation of the clean culture of the agent, it's identification.

The blood, urine, stool, cerebrospinal fluid may be material for the bacteriological investigation. For example, in typhoid fever the bacteriological method is used for isolation of agent from the blood, urine, stool (hemoculture, coproculture, urineculture). In meningococcal infection the blood and cerebrospinal fluid are the material for investigation. Besides that, smears from the pharynx and nose are investigated for isolation of the agent. Bacteriological method is used in diagnostics of cholera, shigellosis, salmonellosis, diphtheria,and other diseases.

Parasitological investigation is based on microscopy of the thick drop and blood's smears (malaria), smears of the blood and bone marrow (leishmaniasis),

The principles of the diagnostics, treatment and prevention of infectious diseases 25

smears of the blood and gland puncture (trypanosomomiasis), stool (amoebiasis and balantidiasis).

The virological method is more complicated. In virological diagnostics the culture of the tissues and hen's embryo are used.

The bacteriological and virological methods may be complete, accelerated and expressive. For example, expressive method is immunofluorescense method (Cooms's method). The method is based on specific fluorescence of the antigen-antibody complex. The primarily material is processed by specific fluorescent serum. The antigen-antibody reaction is basis of the serological methods of laboratory diagnostics of infectious diseases. The serological reactions are used for antibodies revelation in the blood serum of the patients. The investigations are performed with well-known antigens.

Reaction of agglutination,passive (indirect) hemagglutination,precipitation, and complement fixation have greatest spread.

In the last years immunofermentive method is used in specific diagnostics of parasitaric and viral infections. The new method of serological diagnostics is definition of belonging of antibodies to definite classes of immunoglobulines (IgM, IgG, IgA and other). This method helps to identificate primary infectious disease from repeated disease and infectious disease from artificial immunization. In diagnostics some infectious diseases skin's test with allergen is used. The examples are positive intraskin reaction to tularine (tularemia), brucelline, Burne's test (brucellosis) and others.

The laboratory-instrumental methods of nonspecific character occupy the considerable place in the diagnostics of infectious disease (biochemical, endoscopic, hystological, ultrsoundic).

The principles and methods of the infectious diseases treatment. The treatment of the infectious patients should be complex, etiotropic and pathogenetic, and also individually depending on the state of the patient, on seventy and period of the disease. In complex therapy of infectious diseases different remedies, directing to decrease of activity of the agent and neutralization its toxins, increase protective powers of the organism are used.

The remedies of specific action are used with purpose to increase protective powers of the organism. There are remedies, regulating immunogenesis (immuno-stimulating therapy) and remedies of nonspecific action (vitamins, preparations of the blood, preparations of pyrimidine - methyluracil, pentoxil).

In treatment of infectious diseases pathogenetic therapy is widely used. Pathogenetic therapy is directed to correct the violation of homeostasis (correction of water-electrolytic, protein balance, acid-alkaline state; liver, kidney, respiratory and cardiovascular failure and to decrease allergic manifestations).

In treatment of infectious diseases it is necessary to mention the form and period of the disease, severity of the course and features of the organism (age, reactivity, accompanied diseases and other).

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Some infectious diseases have declination to prolonged course and relapses. For these patients it is necessary to use special principles of the therapy (immuno-modulating therapy, interferones and other).

Chemotherapy of infectious diseases

The brilliant success in fighting of severe infectious diseases in many cases is connected with application of antibiotics.

In medical practice near 500 antibiotics are used. However, the application of antibiotics is accompanied by negative consequences: increase of antibiotic's resistant agents, depression of immunocompetentive system function, development of nonspecific sensibilization, increasing of endogenic infections mixed infections and superinfections.

The selection of antibiotic depends on the type of the agent. It is known, that the remedies of the penicillin group have high efficiency for gram-positive (streptococci, staphylococci, pneumococci) and gram-negative cocci (gonococci, meningococci, and also for agent of Siberian ulcer, leptospirosis. Cephalosporins have wide spectrum of the activity. They are effective such for gram-positive, as for gram-negative microorganisms.

The remedies of streptomycin group are more effective for gram-negative microorganism (plague, tularemia, and tuberculosis). Chloramphenicol is effective for many gram-negative and gram-positive bacteriums, rickettsias, spirochetas. Tetracyclines have wide spectrum of activity. They depress the growth of the majority of gram-positive and gram-negative bacterium's, rickettsias.

Aminoglycosides (monomicin, kanamycin and gentamicin) render the activity to majority of gram-positive and gram-negative microorganisms. This antibiotics are effective for resistant microorganisms to penicillin, chloramphenicol, tetracycline.

At the last decades the remedies of the new generation came into displacement of natural antibiotics: half-synthetic penicillins (ampicillin, oxacillin, amoxicillin); aminoglycosides (amikacin, tobramycin), tetracycline (doxycycline), rifampicins (rifampicin, rifadin). These antibiotics are characterized by acid-resistant, ferment-resistant wide spectrum of the activity.

Besides antibiotics, there are other kinds of medications that have influence on the agent of the disease. Derivates of nitrofuran (furazolidone, furodonine and furacillin) have a high antimicrobial activity. They are effective for many gramnegative and gram-positive bacteria - resistant to antibiotics and sulfonamides, and also for some protozoa (trychomonades, lamblia).

Sulfonamides don't lose their value. However, recently the decrease of their therapeutic action is observed connecting with appearance of the resistant forms of the microorganisms.

However, different complications may be due to treatment of infectious diseases by chemoremedies. There are 3 types of the complications in chemotherapy of infectious diseases: allergic, endotoxic and dysbacteriosis.

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Allergic reactions are observed more frequently. They are manifested by capillartoxicosis, catarrhic change of mucous membranes, dermatitis edema. Sometimes, anaphylactic shock arises. The development of allergic reaction doesn't depend from the dose and duration of application of the drug.

Endotoxic reactions arise, as a rule, after injection of the large shock doses of antibiotics. These reactions depend on intensive disintegration of the microorganisms with liberation of endotoxin.

In development of dysbacteriosis autoinfection arises due to reproduction of the microorganisms naturally living in it, for example some kind of gram-negative microorganisms and fungi from the Candida species.

Recently, antiviral remedies, interferon or inductors of endogenic interferon are used in the treatment of infectious diseases.

Serotherapy of infectious diseases

In treatment of some infectious diseases homological and heterological immune serums and immune gammaglobulines are used. Serums and gammaglobulines are used for treatment and for prophylaxis of the infectious diseases.

There are antibacterial and antitoxical serums. Antitoxical serums contain specific antibodies to toxins - antitoxins. The mechanism of the action of these serums is neutralization of toxins, producing by the agent. Antitoxical serums are serums against diphtheria,botulism,and tetanus.

The effect of the serum depends on the dose and date of its injection. The result will be better if the serum will be injected early because serum inactivates only toxins, circulating free in the blood. The duration of the toxin circulation in blood is 1-3 days, and then toxins connect with cells and tissues.

In treatment of some infectious diseases immune gammaglobulines are used, obtained from the blood serum of the donors (homological). These remedies have high concentration of antibodies. The balastic substances are absent in these gammaglobulines. Iinjection of the gammaglobulines is not accompanied by side reactions.

At the present time immunoglobulines are used in treatment of grippe,tick encephalitis, staphylococcous infection, anthrax and other diseases. Due to application of heterogeneous serum may be anaphylactic shock and serum's disease. The development of shock occurs immediately after injection of the serum. It is necessary to inject serum by divided doses for prevention of development of shock. The serum's disease develops in 5-12 days after injection of the serum. The clinical manifestations are fever, edema of mucous membranes, lymphadenitis, spotted-papular rash. The duration of the disease is 6-12 days. The prognosis is usually favorable. Sometimes the injection of the serum is accompanied by reaction only in the place of the injection. Hyperemia and edema without fever occur.

Pathogenetic therapy

The pathogenetic therapy is based on study of important characteristics of homeostasis and its violations in infectious diseases. In pathogenetic therapy it

.

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is necessary to allow for tests of acid-alkaline state, water-electrolytic balance, reological properties of the blood, and also disorder of microcirculation in the organs and tissues. The basic methods of pathogenetic therapy are desintoxication, rehydration, dehydration, and correction of the other violations of homeostasis.

In treatment of infectious diseases desintoxicative therapy is prescribed more frequently. Crystalloid solutions (Ringer's solution, threesalt, quartasalt acesalt and other) and colloid solutions (neohemodesis, polyglucin, reopolyglucin, albumin) are widely used.

The value of the pathogenetic therapy may be shown in the pattern of the infectious-toxic shock treatment.

The number of pathogenetic factors is known in the development of infectious-toxic shock. There are disorganization of blood circulation, violation of the microcirculation in the organs and tissues. Disorder of blood supply is accompanied by aggravation of provision of oxygen to cells, and also by difficulty in liberation of toxic products of metabolism from the cells.

Capillary system plays an important role in the development of shock. In shock damage of liver, functional insufficiency of kidney are observed.

Maintenance of homeostasis is ensured by dynamic balance of biologically active substances and their inhibitors (histamine, acetilcholine, catecholamines, proteolitic ferments, kallikreine-kinine system, cyclic nucleoproteins and prostaglandin's ensure maintenance of homeostasis.

In shock one of the more early reaction of the organism on damage is hyperfermentemia. Its biological meaning is concluded in supply of the organism with energy and destruction of damaging factors. Analysis of condition and level of ferments allows to consider pathogenetic based conclusion of proteolitic ferment's inhibitors in the therapy of shock.

One of the most important disorders of homeostasis is DIC-syndrome (synonyms - thrombohemorrhagic syndrome, coagulopathy of consumption, disseminated intravascular coagulopathies). The basis of this syndrome is diffusive coagulation of blood in small vessels, development of blockade of microcirculation in the organs (lungs, kidneys, liver and other), and deep disorders of the functions of these organs. Serious hypoxia and acidosis develop, leading unrarely to death. The formation of clots on the level of capillaries is connected with surplus quantity of thrombin. Transformation of fibrinogen into fibrin happens very quickly.

In the development of DIC-syndrome 3 clinical stages are differentiated:

-First stage is hypercoagulation of blood and formation of friable microthrombs and development of blockade of microcirculation in organs;

- Second stage is hypocoagulation. This stage is characterized by deep exhaustion of factors of coagulation. The clinical manifestations of the second stage are profuse bleedings;

- Third stage is outcome and residual appearances of DIC-syndrome.

-

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Infectious-toxic shock may be caused by viruses, rickettsia, fungi, gram-positive microorganisms (pneumococcus, streptococcus, staphylococcus) and gram-negative microorganisms (meningococcus). The most frequent reasons of infectious-toxic shock are infections of urinary tract (especially, in elderly age and in weakened patients), infections of respiratory tract due to bacterial pneumonia (especially, in condition of tracheotomy), complications of septic childbirth, septic abortions, peritonitis of different origin, pancreonecrosis, sepsis of any origin. In infectious clinics reasons of infectious-toxic shock are usually meningococcal infection, typhoid fever,salmonellosis,diphtheria,leptospirosis and other diseases. Besides hypotonia, toxinemia plays great role in clinic of infectious-toxic shock. Toxinemia leads to damage of liver, kidneys and heart. The compulsory development of DIC-syndrome is another important manifestation of infectious-toxic shock.

The basis of treatment of infectious-toxic shock -is complex of measures, including application of antibiotics and directed on improvement of blood circulation therapy. The duration of infectious-toxic shock is very serious, with high mortality (50 % of the patient die during the first 48 hours of the disease). That's why it is necessary to prescribe intensive therapy immediately. Broad spectrum antibiotics are prescribed. Steroid hormones have important value in the treatment of infectious-toxic shock. Hormones decrease general reaction of the organism on toxin, positively impact on hemodynamics. Treatment by glucocorticoids is conducted during 3-4 days, because depression of adrenocortical function does not arise.

Infusion therapy should be started with injection of crystalloid solutions: quartasalt, Ringer's solution, glucose-polarizing admixture (5 % solution of glucose with calcium chloride in dose 20-100 mg of 10 % solution per one liter of glucose). Besides salt solutions,, synthetic colloid solutions are used (neoheamodes, polyglucin, reopolyglucin in dose 0.4-0.8 L) with purpose of desintoxication and liquidation of hemodynamic disorders.

The basic principles of treatment of DIC-syndrome are heparinotherapy and transfusion of fresh frozen plasma. It is necessary to inject to patients 2,500-500 units of heparin in isotonic solution of sodium chloride, solution of native or fresh frozen plasma. In this case fresh frozen plasma is donator of plasminogen and antithrombin. Content of antithrombin in fresh frozen plasma is up to 200-250 % from norm. Daily dose of heparin is 10,000-15,000. Simultaneously reopolyglucin is transfused as desagregant. Inhibitors of proteolitic ferments are injected also (75,000-100,000 units trasilol or adequate dose of contrical).

Pathogenetic therapy is the basic principle of the treatment of hypovolemic shock. Hypovolemic shock (on the base of dehydration) is more frequently observed at cholera. Cholera is characterized by loss of fluid with stool and vomiting, which reaches in very small period. The loss of fluid may exceed up to 2 times the body mass of the patient. Hypersecretory processes are the main mechanism of diarrhea origin. They develop as a result of the exotoxin action -

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cholerogen on ferment adenylcyclase and accumulation of cyclic 3,5-adenosine-monophosphotase, leading to increase secretion of electrolytes and water. Deficit of potassium arises; reaching sometimes one third of it's content in the organism. Thickening of the blood, hypovolemia, hemodynamic insufficiency, metabolic acidosis, hypoxia and renal failure develop in consequence. The impetuous development of the disease already at the first 8-12 hours leads to dehydration, reaching 10 % from body's mass and more. The clinical manifestations of dehydration are pinched face, deeply sunken in the orbits, cold clammy skin. The skin is shriveled. The turgor of the skin decrease ("washwoman's hands"). A voice becomes hoarse. The general cyanosis, prolonged tonic muscles cramps are observed. The temperature is subnormal (34.5 °Ñ). There is no pulse. The arterial pressure is not determined. Anuria and hypovolemic shock develop.

The treatment of hypovolemic shock is conducted immediately. Treatment consists from 2 stages: primary rehydration for compensation loss of fluid and correction of continued fluid loss. Preliminarily heated solution up to 36-38 °Ñ is injected in stream with speed 70-120 mL in minute (up to 5-7 liters during 1.5-2 hours).

It is necessary to restore as a volume of circulating blood as a volume of extracellular liquid,because rehydration must be intensive. In hypovolemic shock it is necessary to use special salt solution: Phillips's solution ¹ 1 (threesault), Phillips's solution ¹ 2 (desault), quartasault, acesault and other. Ionic composition of these solutions is similar to composition of the patient's fluid loss.

It is prohibited to prescribe, the remedies with high molecular weight (polyglucin, reopolyglucin). These remedies restore a volume of circulating blood, but they don't liquidate dehydration of the organs and tissues. It is prohibited to inject heart's glycosides. The heart's glycosides increase shortenic ability of myocard, but the heart is empty. The exhaustion of myocard develops as a result. It may be death from heart's stop. It is prohibited to inject pressory amines (adrenaline, noradrenaline). These remedies increase arterial pressure and cause change of microcirculation. The kidneys may perish as a result. So, the treatment of cholera patients is concluded into injection of adequate quantity of fluid relatively to losses.

Dehydration may develop due to other infections (shigellosis, salmonellosis, toxical food-borne infections). However, in salmonellosis, shigellosis, toxical food-borne infections there is combination of the signs of damage of gastrointestinal tract (gastritis, gastroenteritis, or gastroenterocolitis), signs of general intoxication and dehydration. In this diseases pathogenetic therapy is performed in 2 directions, in dependence of predominated clinical manifestations (desintoxication and rehydration).

In meningitis and meningoencephalitis pathogenetic therapy is directed to elimination of the brain edema (dehydrative therapy) and intoxication. In case of generalized form of meningococcal infection pathogenetic therapy is performed

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simultaneously with etiotropic therapy. Its basis is intoxication treatment. Simultaneously dehydrative therapy is performed (lasix, mannitol).

In severe cases of meningococcal infection glucocorticoides are prescribed. Dose depends on dynamics of the basic symptoms and presence of complications. Usually, hydrocortisone in dose 3-7 mg/kg/day, prednisolon in dose 1-2 mg/ kg/day are prescribed.

Development of Waterhause-Fridrichsen's syndrome is possible at fulminant form of meningococcal infection, connected with hemorrhage into adrenal glands. In such cases the therapy is directed to the struggle with adrenal glands insufficiency (replacing therapy). The large doses of corticosteroid are prescribed.

Pathogenetic therapy is widely used in treatment of the patients with viral hepatitis. Due to investigations of the last years it was shown that activation of the processes of peroxide oxygenation of lipids plays the essential rose in the pathogenesis of viral hepatitis and leads to alteration of structure and functions of hepatocytes, thrombocytes and other cells membranes. Besides that, there is correlation between activation of peroxide oxygenation of lipids and duration of intoxication. Its worths to underline that simultaneously with activation of POL (peroxide oxygenation of lipids) the considerable depression of antioxydantic activity of the blood serum is marked.

The definition of the factors of intensification of the processes of peroxide

oxygenation of lipids in the patients with viral hepatitis  became the basis for

application of the remedies with antioxydantic mechanism of the action in complex

therapy. r

The degree of immunity development in considerable measure determines the possibility of formation of prolonged and chronic forms of the disease. Owing this the great quantity of works were performed last years on study of cell's immunity and its role in pathogenesis of acute viral hepatitis  according to the form, degree of gravity and period of the disease.

It was established that in patients with cyclic forms of acute viral hepatitis during of the process of the disease the secondary immune deficiency develops, with tendency to restoration of functions of immunocompetentive cells during period of reconvalescence. Decreased quantity of T-helpers and T-suppressors is observed. The subpopulation of T-suppressors was changed more than subpopulation of T-helpers. The correlation of tests of T-system of immunity and gravity of the disease course is marked. In patients with prolonged duration of acute hepatitis the strong decreasing of T-helpers is observed.

The determination of the considerable role of immune mechanisms in pathogenesis of viral hepatitis is pathogenic basis for application of immuno-correcting therapy.

The application of preparations of thymoid gland - thymalin, tactivin, synthetic peptide of thymus-thymogen may be used for to improvement of cell's interactions, disappearance of dysbalance in correlation of T-helpers and T-suppressors.

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The data about molecular mechanisms of damage of hepatocytes's membranes were received last years. Because the remedies with stabilizative action to hepatocyte's membrane are used (carsil, legalon and other hepatoprotectors) in complex therapy of acute viral hepatitis.

Pathogenetic therapy of acute viral hepatitis, directing to the struggle with intoxication, regulation of water-electrolyte balance, regulation kallekrein- kininic system, elimination of hemorrhagic syndrome is used in practice widely.

However, the application of different schemes of pathogenetic therapy with use modern desintoxicative methods, doesn't always conduct to favorable course and outcomes of acute viral hepatitis, it doesn't prevent development of complications (acute hepatic encephalopathy), formation of prolonged course and relapses.

For this reason the looking for chemotherapeutic remedies, preventing from replication of virus in hepatocytes is an actual question. The remedies with antiviral action were received last years: arabinozid-nucleotid A, amphotherycin B, virazol, aplizarin and other. However, the antiviral remedies application in treatment of viral hepatitis doesn't always are effective clinically, doesn't give complete elimination of viral antigens. Because, the application of these remedies is limited in clinical practice.

The application of interferon and remedies, stimulating its produce is perspective direction -owing this. Interferones are low molecular proteins depressing viruses reproduction. Leucocytaric and fibroblastic interferones may be produced practically by all cells. Immune gamma-interferon is produced by gamma-interferon immunocompetentive cells during immune response.

Interferon is the most important factor of nonspecific resistance. However, interferon has influence to differentiation and activation of effectoric cells of immune system. The activation of monocytes (macrophages) increases generation of peroxide radicals, increased phagocytes activity are observed under influence of interferon. Thus, at the present time interferon is used not only as antiviral remedy, but also as important regulator of interaction between cells.

It is established that there is decreased produce of interferon in patients with viral hepatitis B, especially in patient with severe duration of the disease. In fulminate course of acute viral hepatitis  interferon is no revealed in the serum of blood.

In accordance with opinion of many investigators, virus of hepatitis  is week inductor of interferon. The firm insufficiency of produce of interferon is one from decisive factors of crossing infectious process into chronic form. The application of interferon in infectious diseases may be possible in two directions: injection of ready-made interferon (exogenic interferon) and stimulation of synthesis of own interferon (endogenic interferon).

The decreased production of interferon in patients, decreased ability of virus hepatitis  (VHB) to induce interferon output, and also low cytotoxicity of natural killers are pathogenetic basis for interferontherapy application in patients with hepatitis  and C.

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The considerable effeciency of leucocytic interferon is marked in patients with medium and severe course of acute viral hepatitis B. The positive influence of interferon on clinical manifestations dynamics, decreasing of intoxication and improvement of biochemistric tests were observed.

The stimulation of endogenic interferon producing by organism is the most perspective direction. At the present time some hundreds inductors of interferon are known. The basic criteria of interferon inductors effeciency are their interferon-inducing and antiviral action. Some remedies are more effective in viral infections (larifan, ridostin, camedon, amixin, cycloferon and other).

Intensive therapy and reanimation

Many infectious diseases have declination to serious duration and complications development. It may happen at fulminant course of some infectious diseases (meningococcal infection, viral hepatitis  and other). The gravity of course depends on degree of violation of water - electrolyte balance, acid-alkaline state, blood coagulative system and other criterions of the patient state. The methods of intensive therapy and reanimation are inculcated in clinical practice last years. These methods are directed to restoration of vitalitive important functions of the organism altered due to acute violations. Intensive therapy is performed in the special department under control of express clinical laboratory investigations. Efficiency of this therapy is determined by intensive observation of the patient. The observation after a patient is performed continuously and through short intervals of the time with fixation of physiological parameters (registration of pulse, breath, arterial pressure, data of electrocardiogram, electroencephalography and other tests of the patient state).

The methods of intensive therapy are pharmacotherapy, artificial pulmonary ventilation, hyperbolic oxygenation, artificial hypothermia, oxygenation, hypothermic, different methods of extracorporal hemodialysis (hemosorbtion, perfusion of liver, abdominal hemodialysis, dialysis with help of artificial kidney apparatus and other).

Intensive therapy of infectious diseases includes antibacterial serums, immunoglobuiines, and different chemotherapeutic remedies. Intensive therapy is used for treatment of the patients with meningococcal infection, malaria, typhoid fever, salmonellosis, cholera, leptospirosis and other infectious diseases.

Prophylaxis of infectious diseases

At the last decades certain successes were achieved in fighting with infectious diseases, massive epidemics of most dangerous infectious diseases (epidemic typhus fever, plaque, smallpox, tick-borne relapsing fever and other). The struggle is realized successfully with diphtheria,poliomyelitis,measles,and many zoonozic infections. Undoubt success is achieved in malaria control. However, the deliverance of humanity from malaria requires time,considerable efforts and great expenses. More than billion cases of infectious diseases of gastrointestinal and respiratory tract are registered in the world every year. For example, grippe

34 Infectious diseases

is registered in some years in 10-15 % of population only of the countries of Europe and America. More than 75 millions of the people become ill by other acute viral diseases of the respiratory tract. Pandemic of grippe acquires character of the calamity and causes enormous economic detriment to all the countries. Every years multiple cases of streptococcous and staphylococcous infections, cholera, helminthiases, viral hepatitis, meningococcal infection and diseases caused by conditional pathogenic flora are registered in the world.

Thus,prophylaxis of infectious diseases is actual question. The measures of prophylaxis of infectious diseases may be conditionally divided on 2 groups: general and special measures. The general measures are state measures, directed on increase of material favorable condition, improvement of medical service, and conditions of work and rest of the population, sanitary-technique, hydrotechnic measures and also international measures in attitude to quarantine infections.

It is known about 3 links for development of epidemic process: the source of infection, ways of the transmission and susceptibility of the organism. The absence or rupture either of this links leads to cessation of epidemic process.

There are 3 groups of prophylactic measures:

1. The measures directing on the source of infection, its elimination.

2. The measures, directing on the mechanism of the transmission of infection. Their purpose is rupture pf the ways of transmission of infection.

3. The measures directing on increasing of unsusceptibility of population to infection.

Prophylactic measures, directing on the source of infection play an important role. It is known that when antroponozic infection the source of infection is a sick man or carrier of the agent. The source of infection is sick animal at zoonotic infections. Prophylactic measures of this group are diagnostic, isolative, medical and regimen-limitary measures. In some infectious diseases hospitalization into infectious hospital is obligatory (especially dangerous infections, typhoid fever,epidemic typhus,diphtheria,meningococcal disease). Incase of other diseases isolation may be at home if epidemiological and clinical contraindications are absent (shigellosis, escherihiosis, measles and others).

An important prophylactic measure is active revealing of carriers and their sanation. Revealing of carriers is performed in focuses of infection, among reconvalescents, and also among persons of food establishments, water pipe stations, and children's establishments. It is necessary to perform their bacteriological examination and treatment.

Isolation of persons, contacting with patient is necessary in case of especially dangerous infections (plague, cholera). The duration of isolation depends on maximal incubation period: in plague ~ 6 days, in cholera - 5 days. This measure is named observation. Observation is one of the quarantine measures. The word "quarantine" was originated from Italian word "quarantine" (quaranta gieri -40 days). At this historic period duration of incubation period was not known.

The principles of the diagnostics, treatment and prevention of infectious diseases 35

Because isolation of patients with plague and some other infectious diseases was 40 days.

The measures about sanitary guard of borders have an important meaning. In 1969 on Universal Public Health Assembly "International medical-sanitary rules" have been accepted. Infections, having international meaning are divided on 2 groups:

Diseases, which are submitted to these rules (plague, cholera, yellow fever).

Diseases for international surveillance (epidemic typhoid fever, tick-borne relapsing fever, grippe, poliomyelitis and malaria).

All countries-members of World Health Organization should report about

all cases of this diseases, and also perform proper antiepidemic measures. In

zoonozic infections prophylactic measures have one's own features. If the source

of infection are domestic animals, than it is necessary to perform sanitary-veterinary

measures about their health. If the source of infection are mice and rats it is

necessary to perform deratization.

In prophylaxis of infectious diseases an important measure is influence on mechanism of transmission of infection. Transmission of the agent from sick man to healthy man is realized with help of different factors (water, food, air, dust, soil and other). Prophylactic measures, directing on the second link of epidemic process are divided on 3 groups: sanitary-hygienic, disinfection and disinsection. The basic factors of transmission of the agent are food, water, rarely-flies, dirty hands in case of intestinal infections with fecal-oral mechanism of transmission of infection (typhoid fever, cholera, shigellosis). In prophylaxis of these infectious diseases general sanitary and hygienic measures have the most important value.

Prophylactic measure, directed on the ways of transmission is disinfection, which is performed in the focuses of infectious diseases, public place (railroad station, transport, and public toilets).

At infections of the respiratory tract (measles, rubella, diphtheria, scarlet fever,meningococcal infection,grippe) preventive measures are sanation of air, application of respirators. Disinfection is performed only due to scarlet fever and diphtheria,because the agents of the majority infections of respiratory tract are nonresistant in environment.

At transismissive infections the method of disinsection has the great meaning, directed on distruction of insects.

The measures, directed on the third link of epidemic process are increasing of general nonspecific resistance of the organism and also specific prophylaxis. Specific prophylaxis is directed on creation of artificial immunity (active or passive) against infectious diseases.

Specific prophylaxis is performed with help of vaccines, anatoxins serums, gammaglobulines. Vaccines and anatoxins create active immunity, serums and gammaglobulines - passive immunity. Vaccines are divided on living and killed vaccines.

36 Infectious diseases

Microorganisms with weakening of virulence are used for preparation of vaccines. In 1798 Edward Jenner proposed vaccine against smallpox, containing agent of cowpox. This agent has a little virulence for humans. Jenner called his new method of preventing smallpox "vaccination", from the Latin word "vacca", that is "a cow". In 1885 Paster proposed vaccine against rabies from weakening vaccine strain. Living vaccines are used for prophylaxis such infectious diseases, as tularemia, poliomyelitis, yellow fever, measles and other. These vaccines create tense and prolonged immunity (3-5-8 years).

Killed vaccines are divided on corpuscular and molecular (chemical). Killed vaccines are used for prophylaxis of intestinal infections. Efficiency of killed vaccines is less, than living vaccines. The duration of immunity is from 6 months till 12 months.

Anatoxins are also used for creation of artificial active immunity. Anatoxins have no toxic properties, but they preserve antigenic and immunogenic properties. At the present time anatoxins are used for prophylaxis of diphtheria, tetanus, botulism.

Artificial active immunity appears after injection of vaccine through few weeks. Artificial passive immunity develops more quickly. It is caused by injection of blood serum with ready antibodies (immune serums and immunoglobulines). There are preparations used for prophylaxis of tetanus, measles, tick-encephalitis and other infectious diseases.

Control questions:

1. Basic principles of anamnesis collection.

2. Principles of clinical examinations of infectious patients.

3. Value of additional methods of diagnostics.

4. The principles and methods of the infectious diseases treatment.

5. What are the remedies of specific action used for the treatment of the infectious diseases?

6. Basic principles of infectious diseases prophylaxis.

7. Groups of prophylactic measures and their characteristics.

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Date: 2014-12-21; view: 1508