Diphtheria Symptoms

Diphtheria is an acute infectious disease, which is based on the formation of fibrous films and the development of general intoxication.

Diphtheria is a dangerous disease that can be prevented. If your child was given three vaccinations in infancy and reinforced them in a year, and then every three years, there is almost no probability that he will get sick. How to use folk remedies for this disease look here.

Causes of

The cause of the disease are the corynebacteria of diphtheria. The source of infection is a sick person or bacterium carrier. Bacteria are transmitted by airborne droplets.

The source of infection is a sick person and carrier of a toxigenic corynebacterium diphtheria. The epidemiological danger of one patient with diphtheria is 10 times higher than that of one bacterium carrier. The frequency of carriage of toxic corynebacteria depends on the epidemic situation, in foci it can be 20-40%.Carriers of diphtheria are not dangerous.

Transmission mechanism - airborne, contact-household, food.

Seasonality - autumn-winter.

The index of contagiosity is 0.2.Children of all ages are ill, but the greatest susceptibility is typical for the age group from 3 to 7 years. At the same time, during the last epidemic( 1990-1999) in Rostov-on-Don, sick people prevailed among patients from 8 to 14 years old( 54%).Children of the first year of life are rarely ill, which can be explained by the presence of passive transplacental immunity in them.

Etiology of the .The causative agent of the disease Corynebacterium diphtheriae is a gram-positive rod, a distinctive feature of which is polymorphism, manifested in a variety of cellular forms. It is characterized by:

- uneven cell staining due to the presence on the one or both poles of the cell of the volute granules, which when painted according to Neisser or Lefler acquire a dark blue or black-blue color, contrasting sharply with the pale blue or light brown background of the cell;

- formation of various proteins and enzymes - diphtheria exotoxin, hydrolase, catalase, neuraminidase, hyaluronidase, hemolysin, necrotizing factor;

- significant stability in the external environment;

- the formation of clusters of closely fitting and tightly interwoven sticks, resembling wool or a bundle of pins( in stained smears from a thick suspension of microbial cells);

- pairwise arrangement of sticks at an acute or a right angle in thin smears.

According to the cultural, morphological and enzymatic properties of the corynebacterium, they are divided into 3 variants: gravis, mitis, intermedius. Currently, the most common pathological process is caused by a variant of gravis and much less often - mitis. Intrigue of each culture variant is circulating toxigenic and nontoxigenic( difteroids) strains.

Pathogenesis. Several stages are distinguished in the pathogenesis of diphtheria.

1. Introduction and reproduction at the entrance gate. Entrance gate for.diphtheriae are the mucous membranes of the oropharynx, the respiratory tract, the eyes, the genital organs, the skin. Fixation of the pathogen on epithelial cells is accompanied by the synthesis of proteases inactivating SIgA, which contributes to the breakthrough of the first line of the immune defense of the macroorganism. Then colonization of epithelial cells occurs and invasion of the pathogen into the underlying tissues, which is accompanied by the onset of an inflammatory process. In the inoculation zone, C. diphtheriae produces numerous damage factors that damage cells and facilitate the spread of bacteria in the body( hyaluranidase, neuramidaz, lecithinase, and DNAase).Evasion of the pathogen from protective mechanisms is provided by the antiphagocytic properties of C. diphtheriae, the ability to form catalase and SOD, which interfere with the action of peroxide radicals of phagocytic cells.

2. Development of fibrinous inflammation at the site of implantation. Penetrating into the mucous membrane represented by multilayered flat epithelium, the diphtheria bacillus produces exotoxin, which is fixed on the cell membranes and penetrates the cell, after which its local action on the body is realized. Under the influence of toxin, protein synthesis is suppressed, coagulation necrosis of the mucosal epithelium, expansion of blood vessels, an increase in their permeability, a slowing of the blood flow occurs. There is sweat exudate rich in fibrinogen, and its transformation into fibrin under the influence of thrombokinase released by necrosis of epithelial cells. A fibrinous film is formed, firmly welded to the underlying tissue. This type of inflammation is called "diphtheria."The increase in vascular permeability is the basis for the development of edema of the soft tissues of the oropharynx and subcutaneous tissue of the neck in toxic forms of the oropharyngeal diphtheria.

When the process is localized in the airways, where the mucous membrane is represented by a single-layered cylindrical epithelium, the fibrinous film is located superficially and is easily separated from the underlying tissues. This type of inflammation is called "croupier".

3. Toxinemia. The defeat of the oropharynx in a highly susceptible organism is accompanied by intensive reproduction of the corynebacteria. In this case, the products of their interaction with the epithelial, immune cells, the exotoxin that forms, as well as the disintegrating cells themselves, enter the blood.

The toxin absorbed into the blood interacts with specific receptors located on the membranes of the cells of the target organs( myocardiocytes, renal epithelium, peripheral nerves, cells of the cortical and medulla of the adrenal glands).The process of interaction of toxin with receptors is relatively slow and proceeds in the form of two stages. The first - reversible stage, lasting up to 30 minutes, is to create a weak connection of the poison with the receptors of the cell. In this case, the cell fully retains its viability, the toxin is easily neutralized by antitoxic serum. The second - irreversible stage is completed within 30-60 minutes. During this period, the structure of the cell does not undergo any changes, however, the addition of antitoxic serum does not protect the cells from subsequent death. Metabolism disorders, the violation of the function of vital organs are accompanied by the development of symptoms of intoxication, vascular disorders and underlie the formation of specific complications of diphtheria - II-III degree IIM, IIH III degree IIT, ICD, myocarditis, nephrosis, polyneuropathy.

The lesion of the mucous membrane of the trachea and bronchi is not accompanied by the absorption of exotoxin into the blood.

4. Development of the immune response. On the introduction of the pathogen the organism responds with a complex system of protective-adaptive reactions aimed at limiting its reproduction and subsequent elimination. First of all, the immune defense reaction involves the factors of the protection of the mucous membranes of the oropharynx, among which the important place is occupied by SIgA saliva. With imperfection of local defense factors, a specific immune response develops in the macroorganism. The leading role in antidiphtheria immunity belongs to antitoxic antibodies. However, other antigens of S. diphtheriae, which cause an antibacterial immune response, also participate in the antigenigenesis.

5. The outcome of the interaction of a microorganism and a macroorganism with diphtheria can be different and depends on the conditions of infection( premorbid background, age, grafting state, presence of mixed infection), biological properties of the pathogen and the characteristics of the macroorganism( susceptibility, degree of specific and nonspecific reactivity).

Pathomorphology of the .Pathohistological studies showed that the death of patients in the early stages of the disease( up to 3-5 days), the structure of the myocardium may not change. At the same time, the most likely causes leading to a worsening of cardiac activity are disturbances in the activity of its innervation apparatus, hypotension, uneven supply of the subendocardium, hydroionic disorders.

In case of death of the patient after 10-12 days, an alterative-parenchymal myocarditis is often found. The heart grows in size, becomes flabby, degenerative changes in muscle fibers are observed.

In addition to violations of the contractile activity of the heart for toxic diphtheria, vasodilation, capillary stasis, hemorrhages in internal organs, especially in the adrenal gland, are characteristic. In the latter, gross structural damage is found in combination with a sharp depletion of cortex by lipoids, ketosteroids, ascorbic acid. In the injured adrenal gland, an almost complete loss of the incretory function is observed.

People who died from diphtheria complicated by polyneuropathy tend to have local disturbances in the structure of nerve trunks, in the origin of which demyelination, which is associated with the inhibition of protein synthesis in oligodendrocytes, is of major importance. Loss of myelin leads to a marked decrease in the rate of conduction of nerve impulses, but remyelination is gradually taking place, which develops well and can be complete.

Kidney damage occurs in the acute period of toxic forms of diphtheria of the oropharynx. Morphological changes often do not correspond to functional changes. Thus, for those who died in the first days of the disease, pathohistological findings in the kidneys are weaker in comparison with the deceased in later periods. In this case, inflammatory edema, lymphocytic infiltration of interstitial tissue, degeneration of epithelial cells of distal and proximal tubules are observed.

According to the severity of the disease, diphtheria is classified into mild, moderate and severe.

At the location of inflammation, the disease can be divided into diphtheria of throat, larynx, nose, skin, navel, genitals, eyes. It is possible to develop combined forms. The most common form is the oropharyngeal diphtheria. Depending on the degree of prevalence and severity of the process, the disease is divided into sub-toxic, toxic and hypertoxic forms.

At present, the working classification of diphtheria proposed by N.I.Nisevich and VFUchaykin( 1990).

The incubation period for diphtheria lasts from several hours to several days, depending on the state of the body.

Diphtheria begins with general malaise, sore throat and temperature.

Then a sharp increase in body temperature, redness of the tonsils and a sore throat.

General intoxication is noted in the form of headache, weakness, decreased appetite and pallor of the skin. After a while on the tonsils begin to appear fibrinous films, which gradually thicken and swell. Such films are removed badly, exposing the bleeding mucosa.

Dirty-white spots formed on the tonsils can spread to the entire throat. Occasionally diphtheria begins with the larynx, in , then there is hoarseness and barking cough. Breathing becomes difficult and difficult. If a child has a sore throat and fever or other symptoms resembling croup, you should immediately call a doctor.

If diphtheria is suspected, the treatment is to administer serum and use other medications. The disease occurs one week after infection.

In severe cases, a large number of films lead to respiratory failure.

Clinic. An islet form is more common in children vaccinated against diphtheria( 31.4%) than unvaccinated( 17.2%).The main clinical symptoms of islet diphtheria of the oropharynx are:

- acute onset of the disease;

- short-term increase in body temperature to subfebrile or febrile digits;

- moderately expressed symptoms of intoxication;

- minor pain in the throat when swallowing;

- no response from the angular maxillary nodes;

- presence on the tonsils of island white patches of whitish-gray color with sharply outlined edges that rise above the mucous membrane( plus-tissue), which are difficult to remove, do not dissolve in water and do not trash between slides;

- mild hyperemia of the mucous membrane of the tonsils and their arches;

- a slight edema of the tonsils.

The frequency of localized membranous form of diphtheria of the oropharynx reaches 62%.Its main clinical symptoms are:

- acute onset of the disease;

- short-term increase in body temperature to febrile digits( 38-39 ° C);

- moderately expressed symptoms of intoxication;

- moderate pain in the throat when swallowing;

- moderate reaction from the angular-maxillary lymph nodes;

- the presence on the tonsils of filmy deposits of whitish, whitish gray or dirty-gray color with well-defined edges that rise above the mucous membrane( plus-tissue), which are difficult to remove, do not dissolve in water and do not trash between slides;

- mild hyperemia of the mucous membrane of the oropharynx;

- moderately pronounced swelling of the tonsils.

A common form of oropharyngeal diphtheria occurs in 4.8% of patients. The basic clinical syndrome is the presence in the oropharynx of filmy raids extending beyond the tonsils, whitish, whitish-gray or dirty-gray color with sharply outlined edges that rise above the mucous membrane( plus-tissue), which are difficult to remove, do not dissolve in water andrubbing between the slides. In this case, the following are observed:

- acute onset of the disease;

- increase in body temperature to febrile digits( 38-39 ° C);

- moderately expressed symptoms of intoxication;

- moderate pain in the throat when swallowing;

is a moderate reaction from the angular-maxillary lymph nodes;

is a moderately pronounced swelling of the tonsils.

The frequency of the subtotrophic form of the oropharyngeal diphtheria can reach 9.8%.Diagnose it allows the patient to have the following symptoms:

- acute, sometimes violent, onset of the disease;

- increase in body temperature to febrile digits( 38-39 ° C);

- marked symptoms of intoxication;

- significant sore throat when swallowing;

- pronounced reaction from the angular-maxillary lymph nodes( significant increase and soreness);

- presence of light pastosity of subcutaneous tissue over enlarged lymph nodes - marked hyperemia of the mucous membrane of the oropharynx;

- moderately pronounced swelling of the tonsils and soft tissues of the oropharynx( palatine arch, soft palate, tongue);

- presence on the tonsils and beyond the filmy deposits of whitish, whitish-gray or dirty-gray color with clearly outlined edges that rise above the mucous membrane( plus-

tissue), which are difficult to remove, do not dissolve in water and do not trash between subjectglasses.

Toxic forms of diphtheria of the oropharynx can take place in 11% of patients and are the most "recognizable", as they develop:

- rapid onset of the disease;

- fever to febrile digits( 39-40 ° C);

- pronounced symptoms of intoxication;

- intense pain in the throat when swallowing( sometimes painful trism);

- a pronounced reaction from the angular-maxillary lymph nodes( an increase of up to 4-5 cm and a sharp soreness);

- the presence of a painless edema of the subcutaneous tissue of the neck of a dough-like consistency, spreading, depending on the clinical form, to the middle of the neck, collarbone or to the chest( toxic oropharyngeal faeces of I, II, III degrees);

- pronounced, with cyanotic hue, hyperemia of the mucous membrane of the oropharynx;

- continuous swelling of the tonsils, soft tissues of the oropharynx( palatine arches, soft palate, tongue), hard palate;

- presence on the tonsils and beyond of the filmy deposits of whitish, whitish-gray or dirty-gray color with clearly outlined edges that rise above the mucous membrane( plus-tissue), which are difficult to remove, do not dissolve in water and do not trash between slides.

Malignant forms of diphtheria of the oropharynx - hypertoxic, hemorrhagic, gangrenous, are rare, but characterized by extreme severity of the flow. Thus, when hypertoxic form is observed:

- rapid onset of the disease;

- increase in body temperature up to 40 ° C;

- marked symptoms of intoxication( repeated vomiting, delirium, impaired consciousness, convulsions);

- edema and hyperemia of the oropharynx;

- a sharp increase and density of lymph nodes;

- a slower formation of fibrinous raids on the tonsils( appear at the end of the second day).

Rapid progression of edema of peritonsillar lymph nodes can outpace the growth of tonsils. The appearance of swelling of the subcutaneous tissue and its rapid progression coincides with the development of symptoms of infectious-toxic shock. The lethal outcome occurs in the first 2-3 days of the disease.

Hemorrhagic form is characterized by the development of infectious-toxic shock and DIC-syndrome on the background of signs of toxic diphtheria of the oropharynx II-III degree. At the same time on the 4-5th day of the disease, impregnation of fibrinous raids occurs with blood( get a black color), vomiting "coffee grounds", increased bleeding from injection sites, profuse bleeding.

For gangrenous forms, disintegration of raids with a pronounced putrefactive odor is characteristic. Usually this clinical variant joins a hemorrhagic form.

Characterizing the features of the flow of various clinical forms of diphtheria of the oropharynx, the following should be noted. Among the localized forms of diphtheria of the oropharynx, the islet form proceeds most favorably and can result in spontaneous recovery even in the absence of specific therapy. At the same time, in the case of membranous forms, in the case of late initiation of antitoxic serum treatment, polyneuropathy and / or myocarditis may develop.

Late diagnosis and lack of specific treatment can help to transfer the common form into a sub-toxic or toxic one.

The most serious prognosis is with the development of toxic diphtheria of the oropharynx II-III degree, since even in the case of timely diagnosis and adequate therapy, patients are not insured not only from the development of complications, but also from death.

The combined forms of diphtheria are spoken in cases where fibrinous inflammation develops in several organs. The most common diphtheria of the oropharynx is in combination with a lesion of the larynx( 3.4%) or nose( 0.9%).

The laryngeal diphtheria is in second place in the frequency of registration after diphtheria of the oropharynx. It should be remembered that diphtheritic croup rarely develops in isolation. In this regard, the severity of general infectious symptoms depends on the combination of which form of diphtheria is affected by the larynx.

For diphtheria of the larynx, first of all, the cyclicity in the development of the main symptoms of the disease is characteristic. Isolate catarrhal( stage croupous cough), stenotic, asphic stage. The duration of each of them is 2-3 days.

For the catarrhal stage is typical:

- increased body temperature;

- dry cough, which soon becomes "barking";

- hoarse voice.

Appearance of noisy breathing at rest marks the onset of the stenotic stage, which is accompanied by:

- psychomotor agitation of the child, fear;

- increasing inspiratory dyspnea;

- by the westernization of supple places of the chest and sternum( depending on the degree of stenosis and age of the child);

- aphonia;

- loss of pulse wave on inspiration.

For the asphyxic stage is typical:

- extremely difficult overall condition;

- the disappearance of psychomotor agitation, the occurrence of pathological sleep;

- pale gray skin color, cyanosis;

- dilated pupils;

- no response to injections;

- frequent shallow breathing;

- pronounced tachycardia, filiform pulse, drop in blood pressure;

- a violation of consciousness, convulsions.

Atypical( common) diphtheria croup can occur in two clinical variants - laryngotracheitis( cereal 2A) and laryngotra-hebronchitis( croup 2B).The symptomatology of laryngotracheitis does not differ significantly from typical croup. This circumstance makes the former particularly dangerous, since the raid in the trachea can suddenly peel off and cause asphyxia. Diphtheric laryngotraheobronchitis( 2B) is accompanied by signs not only of the upper obstruction, but also a pronounced bronchoobstructive syndrome.

The defeat of the nose, skin, genitalia, ear, and eye refers to the diphtheria of rare localizations. For diphtheria of the nose is characteristic:

- early age of patients;

- a gradual beginning;

- satisfactory overall condition;

- normal or short-term subfebrile body temperature;

- obstructed nasal breathing( characteristic "sniff");

- a sacred discharge from one nostril;

- ulceration of the skin of the upper lip.

According to the results of a rhinoscopy, two forms of diphtheria of the nose are distinguished - catarrhal-ulcerative and pleural.

Eye diphtheria often develops as a secondary disease with an existing nose or oropharynx infection. There are croupiform and diphtheritic forms of diphtheria of the eye. For croupiform form are characteristic:

- hyperemia and puffiness of the conjunctiva of the century;

- greyish-yellow, hard-to-remove coatings.

In the diphtheritic form,

is observed: sharp swelling and compaction of the eyelids;

- dirty gray raids, located not only on the conjunctiva, but also on the eyeball.

Despite serum treatment, ulcerative keratitis, panophthalmitis with complete loss of vision can be observed.

Genital diphtheria is more common in girls. On the large and small labia there appears a sharply limited, densely seated white or gray filmy coating. Around the films, the inflammatory reaction can be significantly expressed. In the absence of serotherapy, the development of a toxic form is possible.

Skin diphtheria is accompanied by the appearance on the skin of typical fibrinous-membranous lesions. However, there are also atypical forms occurring in the form of vesicles, pustules, impetigo.

In newborns born from seronegative mothers, diphtheria is accompanied by a navel lesion. At the same granulation of the umbilical ring is covered with a greyish-yellow coating, in the circumference of the navel there is hyperemia, edema. The body temperature rises, intoxication develops. Possible development of gangrene, inflammation of the peritoneum, thrombosis of veins.

Complications of

Unfortunately, in addition to the severe course of the disease, diphtheria has very serious complications. These include:

• myocarditis - inflammation of the heart muscle;

• kidney damage;

• infectious-toxic shock;

• polyradiculoneuritis;

• breathing disorders.

Specific complications in diphtheria are myocarditis, toxic nephrosis, polyneuropathy. The frequency of their occurrence, nature, severity of the course correlates with the severity of local manifestations, as well as with the timing of the introduction of antidiphtheria serum. In addition, it is possible to develop infectious-toxic shock, cerebral edema, acute renal failure, pneumonia. On the frequency of complications, the unconditional leader is the toxic forms of the oropharyngeal diphtheria.

Table

Frequency of complications in diphtheria in children, depending on the clinical form of

One of the modern features of diphtheria is the possible development of mixed infection, the frequency of which reaches 47% of the total number of cases. And in the role of associates are often golden staphylococcus, hemolytic or green streptococcus( 33%), pathogenic streptococcus( 28%), Candida( 10%), herpes simplex infection( 9.6%).

The presence of mixed infection leads to a more severe course of the disease and may make clinical diagnosis of diphtheria more difficult. So, activation of the cocci flora is accompanied by a change in the color of the raids( greenish, yellow), contributing to their easier separation.

Myocarditis is the most frequent and formidable complication of toxic diphtheria. The defeat of the cardiac muscle can develop both in the early( end of the first week) and late periods( 3 weeks) of the disease.

Severe myocarditis, as a rule, complicates the course of toxic diphtheria of the oropharynx II-III degree. In this case, the earlier myocarditis develops, the harder it is and the worse the prognosis. So, for a severe myocarditis are characterized:

- sharp deterioration of the general condition, weakness, anxiety, fear;

- increasing pallor of the skin;

- cyanosis;

- expansion of the borders of the heart;

- deafness of cardiac tones and rhythm disturbance( tachycardia or bradycardia, or extrasystole, or bigemia);

- abdominal pain;

- repeated vomiting;

- enlargement of the liver;

- changes in the ECG in the form of a decrease in the voltage of the P and T teeth, conduction disturbances, expansion of the ventricular complex, lengthening of P-Q intervals, atrial or ventricular extrasystole, concordant shift of the S-T interval, negative directionality of the T.

. Adverse predictors are painin the abdomen, nausea, vomiting, embryocardia, gallop rhythm.

The reverse development of myocarditis symptoms begins in 3-4 weeks. Duration of the course of severe forms 4-6 months, light and medium-heavy - 1-2 months. However, the patient can suddenly die from heart paralysis.

Mild and moderate forms of myocarditis usually develop at the end of the second - the beginning of the third week of the disease.

Toxic nephrosis, as a rule, develops in patients with toxic forms of diphtheria in the first days of the disease. The severity of kidney damage varies: from small albuminuria and leukocyturia to a high content of urine in the urine, red blood cells, leukocytes, cylinders, acute renal failure leading to an elevation in the blood of urea, creatinine. Recovery occurs within 2-3 weeks.

Polyneuropathy is a typical complication of diphtheria. Paralysis is early and late. So, during the first two weeks, the soft sky is most often affected, which is accompanied by:

- the appearance of a nasal speech;

- the flow of liquid food through the nose;

- the disappearance of reflexes from the soft palate;

- restriction of movements of a palatine curtain during phonation.

In toxic forms of diphtheria, the third, seventh, 9th, 10th, 12th pairs of cranial nerves may be involved in the process, resulting in the development of the paresis of the soft palate, paralysis of accommodation, strabismus, ptosis, lesion of mimic muscles. At the same time, pain along the nerve trunks can occur, followed by the attachment of the paresis of the muscles of the hands, legs, neck, back, chest, larynx, diaphragm.

At the 4th-5th week of the disease, late flaccid paralysis may occur. Dangerous for life is the defeat of the respiratory muscles, in which children experience superficial breathing, which occurs without the involvement of the muscles of the stomach, and a kind of impotent( "old") cough. If the patient is timely transferred to auxiliary hardware breathing and does not die, then recovery begins in 2-3 months.

Diagnosis of the disease is based on the analysis of manifestations and bacteriological examination( smear of mucus from the oropharynx on the corynebacterium).

The causative agent of diphtheria Corynebacterium diphtheriae, was isolated in its pure form by Loeffler in 1884. Corynebacterium diphtheriae is distinguished by polymorphism. In recent years, there has been a sharp increase in the incidence of diphtheria. Diagnosis of diphtheria is based on clinical and epidemiological data. To confirm the diagnosis, a bacteriological method of investigation is used, aimed at revealing the etiological factor - Loeffler's rods. The causative agent of diphtheria can be isolated after 8-12 hours in the event that the patient did not take antibacterial drugs. However, it should be borne in mind that when antibiotics( especially penicillin or erythromycin) are taken before taking a material for a bacteriological study, the growth of bacteria can not be obtained within 5 days( or there is no growth at all).In these cases, serological diagnostic methods are used.

When diagnosing diphtheria, epidemiological, clinical and paraclinical criteria should be considered. Among the latter, the most informative laboratory methods that allow deciphering the etiology of the disease are:

- bacteriological( direct isolation of the pathogen and determination of its toxigenic properties);

- immunological( testing of bacterial antigens);

- serological( detection of specific antibacterial and antitoxic antibodies).

Bacteriological diagnosis is aimed at isolating the causative agent of the disease and identifying its pathogenic features, including toxigenicity. Explore the film with tonsils, larynx, smears from the mucous membrane of the oropharynx, nose. The effectiveness of the bacteriological method depends on the length of the period between the intake of material and sowing. Positive results are high when sowing "at the patient's bedside" and are unlikely when sowing 2-3 hours after taking the material.

Immunological methods allow to test bacterial antigens( somatic, superficial) and toxins in saliva, mucus and film homogenates, serum and other pathological detachable( RO-agglutination, RIF, RNGA, ELISA and CPR).The toxicity of the strains is determined in the precipitation reaction in agar with horse antiserum, ELISA, DNA hybridization and biological methods.

Specific antibacterial and antitoxic antibodies are determined by the method of RA, RNGA, ELISA, etc.

Detection of antibacterial antibodies in RA, RNGA indicates the contact of the parasite host. ELISA allows you to determine the class-specific immune response. Detection of IgM antibodies is indicative of a disease, IgG antibodies - about the surviving antibacterial immunity after the disease or carrier, the detection of IgG in combination with a low IgM level indicates persistence.

Detection of antitoxin in serum may indicate the level of postvaccinal humoral immunity or, in some cases, the body's defense response to toxin as a result of infection with toxigenic strains.

To determine the intensity of postvaccinal immunity, biological methods are used based on the ability of a toxin to induce an inflammatory necrotic reaction( Remer is in the guinea pig model, Iersen is on rabbits).Biological tests are extremely rare.

The basic method for determining the antitoxin in the blood is the RNGA with commercial erythrocyte diagnosticums and the ELISA-based test system. The use of ELISA allows the determination of a class-specific immune response, which is very important for:

• monitoring the effectiveness of routine vaccination and revaccination;

• selection of persons for emergency vaccination in foci of diphtheria;

• differentiation in patients with diphtheria of an antitoxic immune response, postvaccinal, from the natural, due to the infectious process.

Laboratory methods are of great importance for the diagnosis of complications of diphtheria. So, for the early diagnosis of carditis, the following studies can be used:

- electrocardiography, phonocardiography, ultrasound of the heart;

- study of lactate dehydrogenase activity;

- study of the activity of creatinine phosphokinase;

- study of activity of aspartate aminotransferase;

- ionogram examination;

- measurement of blood pressure, CVP.

Diphtheria kidney damage can be documented in the study:

- a general urine test;

- determination of the urea content in the blood;

- definitions of the level of creatinine in the blood;

- ultrasound of the kidneys.

Differential diagnostics. The leading clinical syndromes in diphtheria include:

- a syndrome of pleural sore throat;

- swelling of the mucous membrane of the oropharynx;

- edema of the subcutaneous tissue of the neck.

Localized glandular diphtheria of the oropharynx, taking into account the syndrome "Angina pectoris", should be distinguished from infectious and non-infectious diseases accompanied by tonsillitis.

In this case, streptococcal angina differs from localized pharyngeal diphtheria of the oropharynx by the presence of the following symptoms:

- marked pain syndrome;

- significant symptoms of intoxication;

- diffuse bright hyperemia of all departments of the oropharynx;

- yellowish or greenish color of raids;

- lack of plus-fabric;

- loose, viscous consistency of raids;

- more significant increase and soreness of regional lymph nodes.

Symanovski-Vincent's angina is characterized by the presence of the following clinical signs:

- slightly pronounced symptoms of intoxication;

- normal or subfebrile body temperature;

- minor pain while swallowing;

- unilateral character of the lesion;

- absence of plus-cloth;

- transformation of "plaque" into crater-like ulceration;

- a weak reaction from the angular-maxillary lymph nodes.

Candidiasis of the tonsils is characterized by the presence of such clinical symptoms as:

- absence of symptoms of intoxication;

- absence of fever;

- white color of raids and their loose consistency;

- easy detachment of plaque and absence of mucosal bleeding after removal;

- absence of hyperemia of the oropharynx and edema of the tonsils;

- an indication in the history of long-term antibiotic therapy or the presence of an immunodeficiency state.

The defeat of the tonsils in secondary syphilis differs from the localized diphtheria of the oropharynx by the absence of intoxication, fever, prolonged course( weeks), more often unilateral nature of the defeat of the tonsils( less common papular syphilis are located on the hard and soft palate, gums, tongue), ankylosing lymph nodesmorbidity, the presence of exanthema.

Pharyngoscopic picture in infectious mononucleosis often resembles diphtheria of the oropharynx. In this case, a differential diagnosis allows accounting for such symptoms as:

- prolonged fever;

- an increase in postnatal and other groups of lymph nodes;

- hepatosplenomegaly;

- "curdled" nature of the raids( easily removed, do not leave a bleeding defect, triturate between slides);

- presence in the peripheral blood of wide-plasma mononuclear cells;

- detection of markers of EBV infection during the ELISA and PCR.

Anginous form of tularemia differs from the localized form of oropharyngeal diphtheria:

- sudden onset;

- marked symptoms of intoxication;

- prolonged febrile fever;

- presence of hepatosplenomegaly;

- late appearance( on the 3-5th day) of the overlays on the tonsils;

- presence of a minus-cloth;

- absence of edema of the tonsils;

- the formation of cervical bubo.

In view of the syndrome "Swelling of the mucous membrane of the oropharynx", the most commonly differential diagnosis is performed with the following diseases:

- paratonsillar abscess;

- the retropharyngeal abscess;

- allergic edema;

- burn of the mucous membrane of the oropharynx( chemical, thermal).

Treatment of diphtheria is carried out strictly in specialized hospitals. All patients are injected with antidiphtheria serum. In cases of severe intoxication, an infusion therapy is performed to purify the blood of toxins. In the case of a large number of films that interfere with breathing, they are quickly removed. To treat complications, antibiotics, anti-inflammatories and even hormones are prescribed. In the recovery period, the purpose of massage and physiotherapy is indicated.

In an acute period, patients must comply with strict bed rest, the duration of which depends on the clinical form of the disease. Dietotherapy provides for chemical and physical shchazhenie, the elimination of obligate allergens.

The neutralization of diphtheria toxin circulating in biological fluids by applying antitoxic antidiphtheria serum( APDS) is fundamental in the therapy of all clinical forms of diphtheria.

The specific therapy by administering the ADPC should begin immediately, as the antitoxin can neutralize only the circulating diphtheria toxin in the serum. The introduction of DPS in the late period( after the 4th day) of the disease is ineffective and does not significantly affect the duration of clinical symptoms of the localized form of diphtheria. There is no doubt about the need to introduce ARVD regardless of the timing of hospitalization of all patients with severe toxic forms of diphtheria.

Primary and course doses of APDs are determined by the clinical form of diphtheria. It is advisable to conduct specific serotherapy on the principles of minimum sufficiency.

Doses of antitoxic antidiphtheria serum for various clinical forms of diphtheria

Note: when combined diphtheria forms, the amount of ADPD administered is added together depending on the localization of the pathological process.

With a localized form, the intramuscular injection of serum is optimal, and with a toxic form, intravenous drip is more effective. The expediency of inclusion in the basic therapy of patients with toxic forms of diphtheria of ADPS administration by endolymphatic pathway is proved.

With a localized form, a single serum injection is used. However, if after 18-24 hours there is no positive dynamics or there is a worsening of the patient's condition and local inflammatory changes in the oropharynx, ADAP is re-introduced.

In the subtoxic form, indications for the reintroduction of ADPD include the following symptoms: the patient's arrival after

on the 3rd day of the disease, the absence of signs of reverse development of the raids( even in the form of their thawing and the beginning of rejection) by the time of re-introduction of serum, as well as the severity of changes in the subcutaneousneck tissue in the region of regional lymph nodes.

In case of toxic diphtheria of the oropharynx of I-III degrees, it is preferable to use a double administration of APDS.The indication for the third session of seroterapy is the increase of the plaque in the oropharynx and the edema of the subcutaneous cervical tissue during 10-12 hours after the second administration of DPD.

One of the most effective modern methods of treating diphtheria used in conjunction with APDS is extracorporeal detoxification( hemosorption, plasmapheresis).Indication for its appointment is the toxic form of diphtheria I, II, III degree.

Hemosorption( HS) is carried out in the acute period of the disease 2 hours after the end of the administration of APDS.The perfusion volume is 1.0 - 1.5 times the volume of circulating blood( BCC).The number of sessions is determined by the degree of severity, the dynamics of intoxication and local changes in the oropharynx. With toxic diphtheria I degree 2-3 sessions are enough, with toxic form II and III degree - 3-5 sessions. Clinical criteria for the end of the course of HS: stabilization of the edema of the neck and swelling of the soft tissues of the oropharynx, massive rejection of raids, reduction of intoxication.

In cases of a positive allergic reaction to intra- and subcutaneous administration of a heterogeneous ADPC and forced refusal to carry out etiotropic serum therapy, hemosorption remains the method of choice.

Plasmapheresis( PF), like HS, is used in patients with toxic forms of diphtheria, although it is inferior to the latter. Special efficacy of PF was noted in the treatment of late neurological complications. It is carried out in the acute phase of the disease in a volume of 1/3 bcc by a discrete method with a multiplicity of 2-3 sessions with an interval of 8-12 hours.

In order to more quickly eliminate the pathogens of diphtheria, all children should be prescribed antibacterial drugs. With localized forms, preference is given to antibiotics for internal use from the macrolide group - erythromycin, sumamed( azithromycin), clacidomycin( clarithromycin), rulid( roxithromycin), and protected aminopenicillin( amoxiclav), doxycycline, rifampicin. In toxic forms of diphtheria, the drugs of choice are aminopenicillins( amoxicillin, augmentin, amoxiclav, etc.), cephalosporins of the third generation( claphoran, cephobid, fortum, etc.), rifampicin, aminoglycosides( amikacin, netromycin).The duration of antibiotic therapy for localized forms of diphtheria is 5-7 days, with toxic and combined - 10-14 days or more.

The use of corticosteroids in severe forms of diphtheria is pathogenetically justified. Thus, in the toxic form of the I degree, prednisolone( or hydrocortisone or dexazone) is prescribed in a daily dose of 5-10 mg / kg( according to prednisolone), with toxic forms of II and III degrees - 15-20 mg / kg / day( mainly inform of dexazone).After stabilizing the edema of the neck, the dose of prednisolone is reduced to 2 mg / kg. The duration of the course depends on the severity of the disease, the presence of complications and an average of 5-7 days.

As a membrane-protective antioxidant inhibiting the processes of lipid peroxidation, the drug - epaden - is used: inside: for children under 3 years - 1 capsule 3 times a day, from 3 to 7 years - 1 capsule 4 times a day, 7 to 14years - 2 capsules 3 times a day, 7 days course.

Detoxification therapy for mild forms of diphtheria is limited to oral fluid administration. The development of severe forms requires the administration of infusion therapy with the use of solutions of dextrans( reopolyglucin 10 ml / kg) and crystalloids( 10% glucose solution, 0.9% sodium chloride solution).The volume of the injected fluid corresponds to the physiological age requirement of the child's organism with the possible earlier transfer to the enteral route of administration. When there are signs of circulatory insufficiency, the volume of the injected fluid decreases to 2 / 3-1 / 2 of the volume of physiological needs.

The choice of starting drug depends on the dominant syndrome: with severe intoxication, glucose-salt solutions are prescribed, with microcirculation disorders - rheopolyglucin, with the development of ITH-albumin, cryoplasm.

Therapy for infectious-toxic shock( ITSH) is conducted in accordance with modern approaches of intensive care and resuscitation.

With progression of signs of DIC-syndrome, freshly frozen donor plasma, heparin( under the control of coagulogram), antiplatelet agents( quarantil, trental) and proteolysis inhibitors( countercranial, tracerol, gordox) are used.

In the acute phase of the disease, in order to create optimal conditions for the operation of the myocardium, potassium-insulin mixtures, panangin, inotropic quick-acting drugs( dopamine 2.5 μg / kg / min, if necessary increase the dose to 5 μg / kg / min, dobrex) and drugs that reduce postnagruzku( captopril, renitek).

In case of circulatory failure, an angiotensin-converting enzyme blocker is used, enalapril 2.5-5.0 mg / day once for 7 days. With preservation of hemodynamic disorders, the course of enalapril is prolonged.

In the treatment of diphtheria heart lesions, energy-saving neoton( phosphocreatine) is used intravenously drip 1 g / day for 3-5 days with a subtitic form and 5-8 days for toxic forms.

To improve tissue nutrition, oxygen utilization is prescribed cytochrome, cocarboxylase, vitamins C, group B, PP, riboxin, potassium preparations.

In the treatment of children with combined severe forms of diphtheria of the oropharynx, larynx, trachea and bronchi, the following methods and medications can be used in addition to the administration of APDS:

- naso- or orotracheal intubation followed by sanation of the tracheobronchial tree( removal of films, mucopurulent secretions);

- aerosol therapy with proteolytic enzymes;

- bronchoscopy for indications;

- antihypoxants( cytomac, cytochrome C);

- eufillin;

- corticosteroids.

As for the lower tracheostomy in patients with descending croup, the most often indications for its superposition arise with late admission to the hospital. To resolve the issue of performing this manipulation, constant monitoring of the operating otolaryngologist is necessary.

In the acute period of the disease additionally prescribed drugs a-2-interferon( viferon, reaferon-EC-lipint, etc.), its inducers( tsikloferon, neovir, etc.), cytokines( leukinferon, etc.), immunoglobulins( intravenously drip,3-5 injections).

Local treatment consists in the treatment of tonsils:

- an intergen( recombinant a-2-interferon activity of 40 thousand ME in 1 g of ointment) - lubrication of raids with a cotton swab 3 times / day until the raids disappear;

- chymotrypsin( dilute 1 vial containing 5 mg of crystalline chymotrypsin in 5 ml of boiled water) - irrigation of tonsils 0.5-1.0 ml of solution 4-5 times / day until the raids disappear;

- bioantioxidant complex( BAC) - neovitin - in the form of a 50% glycerol solution by lubricating the tonsils 2 - 5 times / day until the raids disappear.

Symptomatic therapy involves the appointment of antipyretic agents( paracetamol, panadol, nurofen), antihistamines, multivitamins, physiotherapy( HF oropharynx and nose number 5, UHF on the tonsil area number 3-5).

Treatment of carditis should be conducted in conjunction with a cardiologist, under the supervision of regular ECG studies, with due regard to the timing of the disease, the severity of the heart and the severity of hemodynamic disorders. It is necessary to give maximum attention to the creation of optimal conditions for the work of the heart and to increase its energy supply. This purpose is served by the appointment of a protective regime, medical nutrition and medications.

Children with toxic diphtheria should comply with bed rest for 30 days, sometimes longer - up to 6-8 weeks.

The diet should be aimed at improving myocardial trophism, ie, contain a high-grade protein( low-fat fish and meat varieties, cottage cheese, kefir), unsaturated fatty acids in vegetable oils, and an increased amount of potassium due to fruits and vegetables. Patients should take food often( 5-6 times / day), with a uniform distribution during the day in order to prevent a mechanical obstruction to the work of the heart.

It is advisable in the early stages of the disease, before the appearance of signs of heart damage, to appoint neoton( 1 g in 50.0 ml of solvent intravenously drip daily for 3-8 days).

If there are signs of heart failure under cardiomonitor control, dopamine may be administered for a short period of time( from a few hours to 3-4 days).

In case of circulatory failure, a blocker of angiotensin-converting enzyme is used - enalapril - 2.5-5.0 mg / day once for 7 days. With preservation of hemodynamic disorders, the course of enalapril is prolonged.

During the period of convalescence, much attention is paid to the gradual expansion of the motor regime, to a fully balanced diet.

The basic principles of therapy of diphtheria polyneuropathies are consistency and continuity.

At the first stage, treatment should be aimed at preventing neurological complications, including the timely administration of adequate doses of ADPCs and hemosorption.

Vasoactive neurometabolites - trental, actovegin, instenon. With the prevalence of hemorrhoidal disorders in the acute period of the disease, trental should be given priority, in case of prevalence of hypoxic disorders - actovegin, autonomic symptoms - insthenone. The route of administration( iv, in / m, inward or by electrophoresis) is determined by the severity of the condition, and duration - by the severity of neurologic symptoms, averaging 3-6 weeks. In addition, the curative scheme includes:

- vitamins of group B( B1, B6, B12);

- dibasol;

- membrane-protective antioxidants - tocopherol acetate, vitamin C, epadene( inside of children under 3 years - 1 capsule 3 times a day, from 3 to 7 years - 1 capsule 4 times a day, from 7 to 14 years - 2 capsules3 times a day, the course for 6-8 weeks);

- dehydration agents( furosemide, diacarb, triampur) for 3-5 weeks.

In severe cases, with a rapid increase in bulbar disorders, a short course( 3-7 days) is prescribed glucocorticoid hormones at a rate of 1-2 mg / kg / day.

With the development of late polyneuropathies, it is advisable to include the plasmapheresis method( from 1 to 4 sessions) in the complex of therapeutic measures on the dates from the 15th to the 22nd day of the disease.

The prognosis of diphtheria depends on the severity of the course of the disease, the adequacy and timing of the initiation of treatment.

Diphtheria prophylaxis consists in routine immunization of the population with adsorbed diphtheria toxoid.

Nonspecific prevention of diphtheria involves the hospitalization of patients with any form of diphtheria and carriers of a toxigenic diphtheria bacillus. Carriers of nontoxigenic diphtheria microbes are not subject to isolation. Reconvalence of diphtheria before admission to the team is examined once. In the outbreak of contact, medical supervision is established for 7 days with daily clinical examination and a single bacteriological examination all at once in a single day.

Immunization of the contact is conducted according to the epidemiological indications taking into account the vaccination history. In children's institutions, immunization of contact persons with a well-known vaccination history is made after the study of the intensity of antidiphtheria immunity.

Specific prevention involves the introduction of vaccines containing diphtheria toxoid. The most common were complex vaccines:

- DTP, consisting of a mixture of corpuscular pertussis vaccine, diphtheria and tetanus toxoid;

- ADS-anatoxin, which is purified and adsorbed diphtheria and tetanus toxoid;

- ADS-M-anatoxin, characterized by a reduced content of antigens;

- AD-M-anatoxin containing only diphtheria antigen.

In addition to the above vaccines in Russia, it is allowed to use a number of foreign vaccines for the prevention of diphtheria: Tetrakok( Sanofi Pasteur, France), Bubo-M, Bubo-Kok( Russia), Infanrix( GlaxoSmithKline, England),"DT Vax"( Sanofi Pasteur, France), "Imovax DT Adult"( Sanofi Pasteur, France).

All vaccines are stored in a dry, dark place at a temperature of 2-8 ° C.Freeze-dried preparations are not suitable for use. Shelf life 3 years. Enter a single dose of 0.5 ml intramuscularly.

DTP vaccine is used for primary vaccination, starting at 3 months of age, three times at intervals of 1.5 months and the first revaccination 12-18 months after the completed triple vaccination.

ADS-anatoxin is used:

• for children who have contraindications to the introduction of DTP vaccine;

• for children who have recovered whooping cough( from 3 months to 6 years);

• for children aged 4 to 6 years, if for some reason the primary vaccination falls at this age.

In the latter case, the vaccination course consists of 2 vaccinations with an interval of 30 days. Revaccination is carried out once every 9-12 months after the second vaccination.

If a child who has experienced whooping cough earlier received 3 or 2 DTP vaccinations, the vaccination against diphtheria and tetanus is considered complete. In the first case, ADA revaccination is carried out 12-18 months later,

and in the second - 9-12 months after the last injection of DTP.If the child received one DTP vaccine, he is subject to a second vaccination with ADP followed by a booster in 9-12 months.

ADS-M apply:

• for planned age-related revaccinations of children 6 years, adolescents 16-17 years and adults without age restriction every 10 years( once in a dose of 0.5 ml);

• for vaccination of persons older than 6 years who were not previously vaccinated against diphtheria and tetanus, the course consists of two vaccinations with an interval of 30-45 days, with the first revaccination in 6-9 months, the second after 5 years, then every 10 years;

• as a substitute for DTP or ADP in children with severe temperature reactions( over 40 ° C) or complications for these drugs;

• in the focus of diphtheria.

AD-M is used for planned age-related revaccinations to persons who have received AS in connection with emergency tetanus prophylaxis.

Contraindications existing for vaccination. All vaccine preparations containing diphtheria toxoid are slightly reactogenic, so there are practically no contraindications to vaccination against diphtheria.

In children with mild manifestations of acute respiratory viral infection, vaccination can begin immediately after normalization of body temperature, and for moderate and severe forms of the disease - 2 weeks after recovery.

In all other cases, including patients with chronic diseases of the liver, kidneys, lungs, etc., as well as patients with hemoblastoses, immunodeficiencies, etc., vaccination is carried out in the remission period according to individual schemes.

Reactions to the introduction of diphtheria toxoids. Anatoxins are slightly reactogenic. Local reactions are manifested by flushing and condensation of the skin in individual grafted, short-term subfebrile and malaise are possible.

Complications of diphtheria toxoins. Children with a strong temperature reaction are febrile convulsions, very rarely described individual cases of anaphylactic shock, neurological reactions, a pronounced local allergic reaction.

It should be noted that the noted complications are mainly related to the use of DTP vaccine, i.e. with its pertussis component.

Preventive( specific) measures in the source of diphtheria. Children who are in close contact with the patient diphtheria, are subject to immediate vaccination or revaccination, depending on the vaccinal status.