DIPHTHERIA (grech, diphthera skin, a film) — the acute infectious disease with an airborne way of transfer of the activator which is characterized by inflammatory process in a pharynx, a throat, a trachea is more rare in other bodies with formation of fibrinous plaques and the phenomena of intoxication. Strikes children more often.
- 1 HISTORY
- 2 AETIOLOGY
- 3 The EPIDEMIOLOGY
- 4 The PATHOGENY AND PATHOLOGICAL ANATOMY
- 5 The CLINICAL PICTURE
- 6 The DIAGNOSIS
- 7 TREATMENT
- 8 The FORECAST
- 9 PREVENTION
- 10 Table 1. IDENTIFICATION KORINEBAKTERY on the basis of the COMPLEX of BIOCHEMICAL PROPERTIES
- 11 Table 2. AVERAGE DOSES (in ME) the SERUMS APPLIED. In the MEDICAL PURPOSES AT VARIOUS FORMS of DIPHTHERIA
the Classical description and association of various forms of a disease was made by Bretonno (R. of F. Bretonneau) in 1826; it gave it the name a diphtheria. A. Trusso offered nowadays standard name diphtheria. In 1883-1884 T.A.E.Klebs and F. Leffler opened and allocated in pure form a disease-producing factor. In 1892 — 1894 to E. Bering and at the same time E. R and Ya. Yu. Bardakh received antidiphtherial serum. Introduction to practice of a serotherapy was the most important milestone in the history of D. V 1902 S. K. Dzerzhgovsky proved a possibility of active immunization of the person against D. V of 1913 E. Bering developed a method of active immunization by mix of toxin and antitoxin. G. Ramone in 1923 offered immunization by a diphtherial anatoxin. In development and improvement of antidiphtherial inoculations the big contribution was made by P.F. Zdrodovsky.
The activator D. — Corynebacterium diphtheriae — belongs to the sort Corynebacterium (Lehmann, Neumann, 1896), group of korineformny bacteria (Bergey’s Manual of Determinative Bacteriology, 1974); morphologically represents polymorphic thin, slightly curved sticks 0,5 x 1,0 — 3,0 — 5,0 microns (the branching, segmented and kokkovidny forms — tsvetn meet. fig. A.1). At electronic and microscopic studying (fig. 1) the three-layered cell wall is visible, many strains have a microcapsule (E. I. Nekhotenova et al., 1963; I. S. Barban, 1964). In cytoplasm there are a nucleoid, intra cytoplasmic membranes — mesosom, vacuoles and also as an optional component — accumulations of polyphosphate, so-called grain of volutin or Babesh — Ernst. During the coloring of the fixed D.'s bacteria aniline dyes of grain paint metakhromatichesk in relation to cytoplasm; accumulations nucleinic to - t in cells give them stripe. D.'s bacteria of a grampolozhitelna. Thanks to cell fission in the form of a break and splitting they quite often are located at an angle to each other. Have no flagellums, do not form a dispute. Morphologically Cor. diphtheriae is indistinguishable from many strains of other korinebakteriya which are found on skin and mucous membranes of the person (so-called diphtheroids) and definition of types in a sort requires studying of a complex cultural and biochemical, signs.
On resistance to influence of environmental factors of a bacterium of D. do not differ from asporous pathogenic bacteriums. The activator D. is very sensitive to action of many antibiotics — penicillin, tetracycline, erythromycin. However, despite treatment by these drugs, D.'s bacteria can be in a nasopharynx of patients and carriers a long time.
The activator D. — a heterotroph (see. Heterotrophic organisms ). At its cultivation in simulated conditions mediums shall contain in quality of sources of carbon and nitrogen of amino acid — beta alanine, cystine, methionine, valine and some other [J. Mueller, 1938]. Optimum pH value 7,6; optimum temperature of cultivation 36 — 38 °. The microbe is a facultative anaerobe (see. Anaerobe bacterias ).
For growth of Cor. diphtheriae apply the mediums prepared on the basis of usual broths — beef-extract (see. Broth beef-extract ), Marten (see. Marten broth, peptone ), Hottingera, with addition 5 — 15% of serum or gemolizirovanny blood. At the end of 19 century E. Ra suggested to use the turned horse serum; F. Leffler before coagulation added to it 25% of the broth containing 1% of glucose. On a surface of dense blood or serumal mediums diphtheritic cultures develop macroscopically in 18 — 24 hours. Colonies are round, 0,5 — 1,0 mm in the diameter, dryish, creamy-yellow color, not merging even at continuous crops, sometimes crumble at a touch a loop. Cor. diphtheriae splits without gas with education to - t glucose and a maltose, occasionally sucrose, and some versions — starch, a glycogen and a dextrin. The most constant sign for all strains of Cor. diphtheriae is splitting of cystine with formation of H2S, and also lack of enzymes of urease and phosphatase. Ability korinebaktery D. and some other to recover metal tellurium from its salts also it is used for differential diagnosis. It is important that tellurites K and Na are not only substrate of recovery, but also inhibitors of the microflora which is found in a pharynx.
A major factor of virulence of the activator D. is exotoxin (see. Toxins ). In the complex defining pathogenicity of Cor. diphtheriae, in addition to toxin, enter hyaluronidase (see), a neuraminidase (see. Neuraminic acids ), superficially located lipid a cord factor, a factor In [O'Meara, 1941], and also hypothetical endotoxin [Frobisher (M. Frobisher), 1950], antiphagocytic factors. Their specific value, except toxin D., is not clear so far.
Diphtheritic toxin is protein about a pier. weighing 62 000 dalton. It is received in a crystal look in the 50th.
Force of toxin is determined by its local — necrotic or to the general — lethal action on a susceptible animal (Guinea pigs, rabbits). The minimum lethal dose of toxin — Dosis letalis minima (Dim) — represents the smallest amount of toxin causing death of a Guinea pig weighing 250 g on 4 — the 5th days at intra belly introduction. Toxin has specific immunogene properties which remain at formolation, but at the same time its poisonous properties are lost (see. Anatoxins ). Protective activity of toxin (anatoxin) not always matches its antigenicity what still P. Ehrlich pointed to.
The molecule of toxin consists of two fragments, one of which (A) is stable, has only enzymatic activity, and second (B) labilen and bears protective function.
Assume that the toxin synthesized intracellularly is emitted to the environment via channels in a cell wall of Cor. diphtheriae (V. M. Kushnarev et al., 1971). For synthesis of toxin the same conditions, as for growth of bacteria of D. are required, but glucose, a maltose and their metabolites, and also growth factors — nicotinic and pimelic to - you have additional value. Optimum reaction of the environment for toxin production at pH 7,8 — 8,0. In experiences of in vivo and in vitro transfer of a phage from a lysogenic and toxicogenic cell of Cor. diphtheriae to cultures of Cor, not toxicogenic and sensitive to this phage. diphtheriae and from other korinebakteriya leads to acquisition of lysogenicity by the last (see. Lysogeny ) and toxigenicity (see. Virulence ). The phenomenon of phage conversion of not toxicogenic diphtheritic strains opened in 1951 by V. Freeman in toxicogenic (see. Phage conversion ) it is treated as follows. The gene determining toksigenez is incorporated in a chromosome of one of diphtheritic moderate phages (the beta phage is most studied) therefore toxigenicity it is inherent in the lysogenic strains bearing moderated a phage.
Type of Cor. diphtheriae is heterogeneous. It is subdivided into toxicogenic and not toxicogenic versions, and also on various kulturalno-biochemical, serol, and fagotipa. Allocate two main of kulturalno-biochemical type: gravis and the metis, and also a number of intermediate forms — type intermedius [Anderson (J. S., Anderson) et al., 1931, 1933] and type minimus (Frobisher, 1946)., Most accurately types are differentiated in a form of colonies on the Wednesday by Mac-Lauda — option of a blood telluric agar. Colonies like gravis (tsvetn. the fig. A.3) in 48 — 72 hours of growth have to dia. 1,0 — 2,0 mm, wavy edges, differ radial ischercheniostyo and the flattened center, remind a flower of a daisy. Color them thanks to recovery of tellurium and its connection with at the same time formed hydrogen sulfide (H 2 S) serocherny, surface of colonies opaque. On broth representatives like gravis grow in a type of the crumbling film. Apprx. 90% of strains splits starch, a dextrin and a glycogen with education to - t. The second biotype — the metis — on a surface of a blood telluric agar creates the round, slightly convex, black, opaque colonies which are quite often surrounded with the roller with smooth edges, to dia. 1,0 — 2,0 mm (tsvetn. fig. A.4); on broth grows usually in a type of uniform dregs. The majority of strains does not ferment starch, a dextrin and a glycogen. Colonies like intermedius round and convex, more small, than at type the metis, have no roller, black, with a brilliant surface; relation to starch and other polysaccharides non-constant. All biotypes produce identical toxin though toxigenicity is inherent in type gravis. Designations of types were entered by the English authors (Anderson et al., 1931) believing what gravis is associated with heavier, and the metis — with easier forms of a disease. The subsequent observations could not confirm accurate communication between biotypes and forms of a disease of D., and also degree of their epidemiological danger.
Serol, heterogeneity of a type of Cor. diphtheriae is caused type-specific superficial thermolabile [Wong, the Tung tree (S. Wong, T. T’ung), from 1938 to 1940] and germostabilny (H. N. Kostyukova et al., 1970) antigens. In many countries of the world schemes serol were offered, to classification of bacteria of D. [Robinson, Piney (D. F. Robinson, A. Reepeu), 1936; L. P. Delyagina, 1950]. In the USSR since 1961 V. S. Suslova and M. V. Pelevina's scheme is accepted, in a cut the attempt to combine domestic and foreign classifications is made. However and this scheme does not allow to classify the most part of not toxicogenic strains (H. N. Kostyukova et al., 1972; M. D. Krylova et al., 1973, etc.).
More accurate marking of versions can be received by means of typing of diphtheritic cultures on their sensitivity to lytic action of phages (see. Lysotypy ). In the 60th schemes of a lysotypy Cor were created. diphtheriae from which the scheme A. Saragea with soavt is most distributed, (from 1962 to 1964). Gravis strains give in the Lysotypy easier, than the metis. There is a possibility of division of a look not only on sensitivity to phages, but also on lysogenic properties, and also on the basis of their bakteriotsinogennost [Thibaut, Frederik (J. Thibaut, P. Frederique), 1956; M. D. Krylova, 1969; etc.].
Due to the carrying out mass planned active immunization of the children's population is noted a sharp paleniye of incidence of. According to P. N. Burgasov (1974), D.'s incidence in 1972 in comparison with 1958 decreased by 369 times. Mortality from D. is considerably reduced (see. Immunization ); also some changed epidemiol, patterns.
A source of an infection is sick D. or the bacillicarrier of toxicogenic strains of the activator (see. Carriage of contagiums ).
After the postponed D. convalescents continue to allocate diphtheritic bacteria. At most of them during 3 weeks the carriage stops. Release of a convalescent from diphtheritic bacteria can be interfered by existence hron, patol, processes in a nasal part of a throat and decrease in the general body resistance. At some convalescents the long bacteriocarrier can be created (up to 3 months and more).
Special epidemiol, danger is constituted by patients with atypical forms D. if the true nature of a disease is not distinguished and patients timely do not isolate. The carriage of toxicogenic diphtheritic bacteria is observed also at healthy people. The number of such carriers in hundreds of times exceeds sick D. S number the largest frequency they are found among the persons communicating with sick D., and especially among children with patholologically the changed almonds, katara of a nasal part of a throat, hron, infections, hypovitaminoses and t. At falloff of number of sick D. also the frequency of a carriage of toxicogenic activators fell. And though bacillicarriers (especially healthy) allocate the activator quantitatively much less intensively, than patients, they are the main source of infection.
The activator D. is allocated from an organism of the patient or the carrier with pharyngeal and nasal slime. The main mechanism of transmission of infection — airborne; transfer of the activator through various objects (linen, clothes, ware, toys of the patient, household goods) plays a supporting role.
The disease arises only at absence at the infected subject of anti-toxic immunity against. Under natural conditions immunity is gained after the postponed D., and also in the course of a bacteriocarrier, i.e. by the hidden immunization; natural immunization before introduction of mass preventive inoculations caused progressive falling of a susceptibility with age and rather more rare incidence of the senior children and adults. At planned performing vaccination and a revaccination of the children's population against D. (see. Vaccination , Revaccination ) age composition of patients changed — the specific weight of diseases among teenagers increased; incidence among them decreases more slowly, than among children of earlier age. At very low level of incidence caused by inoculations its seasonal fluctuations noted in the past (rises in autumn and winter months) and frequency do not come to light (emergence of epidemics every 7 — 10 years). Sporadic incidence of D. is maintained at the expense of infection from carriers of toxicogenic strains of the activator and existence among the population at least of a small layer not vaccinated, defectively immunizirovanny and immunological inert or refractory children.
The PATHOGENY AND PATHOLOGICAL ANATOMY
the diphtheritic stick which Got into a human body settles in entrance infection atriums — on a mucous membrane of a pharynx, a nose, respiratory tracts and so forth.
The toxic form D. is considered as result of the changed reactivity of the organism which is in a condition of nonspecific sensitization (see). For the first time this situation is put forward on the basis a wedge, observations by A. A. Koltypin and his pupils of A. M. Bagashova (1944) and E. X. Ganyushina (1948). In development of this form immunodeficiency, inferiority of endocrine system have a certain value.
The most important defense reaction of an organism in response to influence of diphtheritic toxin is development antitoxin (see). This immune response in a complex with other protective mechanisms provides elimination of intoxication and development of postinfectious specific immunity (see).
Pathomorphologically D. is shown by a fibrinous inflammation on site of entrance infection atriums. There is a coagulative necrosis of an epithelium of a mucous membrane and the injured skin, and also expansion of blood vessels. Because of increase in permeability of a vascular wall there is a sweating of the liquid exudate containing fibrinogen. At contact with nekrotizirovanny fabric under the influence of the thrombokinase which is released at a necrosis of cells, fibrinogen is curtailed and turns into a grid of fibrin; the fibrinous film is formed.
If process develops on the mucous membrane covered by a single-layer cylindrical epithelium (e.g., in respiratory tracts), then only the epithelial layer is exposed to a necrosis; the formed film is unsteadily connected with the subject fabric and can separate rather easily from it. At development of process on the mucous membranes covered with a multilayer flat epithelium (e.g., in cavities of a pharynx, a throat), the diphtheritic inflammation develops, at Krom not only the epithelial cover, but also a connective tissue basis of a mucous membrane nekrotizirutsya (e.g., a diphtheritic angina). The thick fibrinous film is formed, edges it is hardly torn away from the subject fabrics. Nodes are involved in process also regional limf; they increase owing to a sharp plethora, hypostasis and proliferation cellular, preferential reticuloendothelial, elements. Quite often in the thickness of fabric focal necroses are formed. At a toxic form D. there is hypostasis of a mucous membrane of a pharynx, throat, and also hypostasis of cellulose of a neck in close proximity to struck limf, nodes. The serous inflammation with numerous cellular infiltrates is the cornerstone of this hypostasis.
Diphtheritic intoxication is characterized by defeat of nervous, cardiovascular systems, adrenal glands and kidneys. With big constancy changes in nodes of a sympathetic part of century of N of page where, in addition to vascular frustration, more or less expressed degeneration of ganglionic cells is found come to light. Defeat of peripheral nerves is shown by multiple toxic neuritis (see. Neuritis ). Damage of nervous covers is noted, and first of all a myelin cover — destructive changes in it quite often reach full disintegration and death of a myelin (fig. 2). In a myelin cover there is a proliferation of cellular kernels. To a lesser extent axial cylinders change; usually only a part them is exposed to deformation and disintegration.
At toxic D. changes in adrenal glands are found: in brain and cortical substance the sharp hyperemia, hemorrhages and destructive changes of cells up to a full necrosis and disintegration are noted.
Especially strongly the cardiovascular system suffers. Defeat of small vessels comes down hl. obr. to their paretic expansion with the phenomena of the stagnation reaching to staza (see), and to increase permeability (see).
The most profound degenerative changes are noted in a myocardium — parenchymatous regeneration of muscle fibers up to a full myolysis, glybchaty disintegration (fig. 3) or diffusion degenerative obesity. By method immunofluorescence (see) in big mononukleara and the struck myofibrils Electronic microscopic examination is found diphtheritic toksinony (see. Submicroscopy ) reveals the expressed changes of ultrastructure: the accruing destruction of mitochondrions, fatty dystrophy (see), and later focal destruction of myofibrils. Histochemical considerable disturbances in system of the intracellular enzymes defining activity of oxidizing processes [G.E. Burch], Gur and Pappengeymer are defined (R. S. Gour, A. M. by Pappenheimer, 1967) specify that pathogenic effect of toxin on fabric is connected with an inactivation of a desmoenzyme of the aminoacyl transferase II which is taking part in protein metabolism. Zelinger (G. Century of Saelinger, 1973) experimentally established a considerable delay of synthesis of protein in the myocardium affected with toxin. Thus, as a result of direct effect of the toxin suppressing activity of enzymatic systems there are deep disturbances of exchange processes in a myocardium. The expressed diffusion sclerosis of a myocardium can sometimes be an outcome of acute myocarditis (see. Cardiosclerosis ).
The CLINICAL PICTURE
the Incubation interval of D. lasts from 2 to 10 days. Depending on localization of process and its weight a big variety a wedge, forms of a disease is observed. On localization of process it is accepted to distinguish D. of a pharynx, a nose, a throat, a trachea and bronchial tubes, eyes, external genitals, skin and so forth. There can be a simultaneous damage of a pharynx and nose or pharynx and throat etc. These are the so-called combined forms. Each of these forms D. is subdivided on weight of a current.
Diphtheria of a pharynx
Diphtheria of a pharynx — the most frequent form; it is observed in 85 — 90% and more all cases of D. Razlichayut three main forms: localized, widespread and toxic.
The localized form is characterized by education on almonds of typical plaques in the form of white and grayish-white imposings with a smooth surface, accurately outlined edges; they densely sit on the subject fabric and do not act a tampon, out of limits of almonds do not pass (tsvetn. fig. 1). The mucous membrane of a pharynx is moderately hyperemic. Pain during the swallowing moderate or poorly expressed. Sometimes plaques have an appearance of the small plaques which are located preferential in lacunas of almonds (an ostrovchaty form). Regional (verkhnesheyny) limf, nodes are moderately increased and painful at palpation. Intoxication is expressed rather poorly, it is shown only by moderate temperature increase, a nek-eye disorder of health, small appetite, the weakness moderated by tachycardia.
The common form is shown by the plaques extending out of limits of almonds — on a mucous membrane of palatal handles, a uvula, and sometimes all palatine velum (tsvetn. fig. 2). Moderate pain during the swallowing. Reaction from regional limf, nodes approximately same, as well as at the localized form; their swelling and morbidity can be more expressed. Also the phenomena of the general intoxication are more expressed: temperature increases to 38 — 39 °, the general weakness, weakness, anorexia, headaches, frustration of a dream, sometimes is observed in the beginning vomiting.
The toxic form (toxic D.) in most cases begins violently: temperature rises to 39 ° above, headaches, the expressed weakness, frustration of a dream, anorexia, sometimes vomiting and an abdominal pain develop. The phenomena of excitement or the expressed slackness, an adynamia are occasionally noted. Sometimes in the presence of heavy process in a pharynx the general a wedge, displays of intoxication are expressed moderately, the health is broken a little. Moderate pain during the swallowing. In a pharynx — widespread plaques. On 2 — the 3rd day of a disease damage of a pharynx takes very characteristic form: the mucous membrane of a soft palate, a throat is edematous, but is hyperemic rather poorly; almonds are sharply increased and quite often almost adjoin with each other; their surface is covered by the thick hilly plaques of white and dirty-white color extending to a soft and hard palate (tsvetn. fig. 3). Language is laid over, lips dry, cracked. From a pharynx the specific unpleasant sladkovatognilostny smell is felt. Sometimes process extends to a nasal part of a throat and a nasal cavity; there are plentiful serous, serous and bloody allocations from a nose. Skin about nasal openings and on an upper lip ekskoriirutsya. Along with development of process in a pharynx or a bit later in the field of verkhnesheyny limf, nodes painful infiltrate of a plotnovaty consistence with indistinct contours appears. Over struck limf, nodes and in their environment on a bigger or smaller extent soft tissues (hypodermic cellulose) are edematous (fig. 4). Integuments over edematous fabrics keep normal coloring. Pressing in the field of hypostasis without serious consequences also does not leave poles; at tolchkoobrazny blow are shaken with a finger of fabric like jelly or jelly (the symptom of «jelly» described by S. D. Nosov in 1957). Prevalence of hypostasis of hypodermic cellulose corresponds to expressiveness of intoxication therefore are guided by it for division of toxic diphtheria into three degrees:
The I degree — spread of hypostasis to the middle of a neck, the II degree — to a clavicle, the III degree — is lower than a clavicle. In the first days of a disease deep intoxication at a considerable part of patients is not shown. Tachycardia, a hyperexcitability of heart and usually a little raised by the ABP are noted. Various serious consequences of intoxication (sharply expressed frustration from nervous and cardiovascular systems) develop by the end of the first or, more often, on the 2nd week and later.
At smaller expressiveness of the described symptoms allocate a subtoxic shape D. of a pharynx, at a cut there is no hypostasis of cervical cellulose, and only pastosity of fabrics in the field of cervical limf, nodes is noted. Intoxication at it is less expressed, toxic complications are observed much less often.
Other options of a toxic shape D. of a pharynx are rare, differ in a special zlokachestvennost. At a hypertoxical form, in addition to violently progressing local process inherent to a toxic form, very grave is observed intoxication (see) with catastrophically accruing decline of cardiovascular activity. Patients usually perish in the first 3 — 5 days from an onset of the illness. The hemorrhagic form is characterized by a symptom complex toxic II—III of degree in combination with the phenomena of hemorrhagic diathesis (see. Hemorrhagic diathesis ). A lethality at this form very high.
Diphtheria of airways, or a diphtheritic croup
its Specific weight was lost from 20 — 30% to 2 — 1% of cases below. This form is observed more often at children of early age.
Regarding cases damage of a throat develops or at the same time, or after D. of a pharynx or a nose (a secondary croup, the combined form). Process is localized on a mucous membrane of a throat or a throat and a trachea. If it extends in bronchial tubes, there is a very grave form D. — the widespread (descending) croup. The disease begins with moderate temperature increase, the increasing hoarseness of the voice, the rough barking cough soon losing the sonority and becoming hoarse. The hyperemia and puffiness of a mucous membrane of a throat is found; plaques can be absent still. The initial stage of a disease is called disfonichesky, catarral or a stage of croupous cough, proceeds on average apprx. days, is sometimes extended up to 2 and more days. The following stage — stenotic, at a cut the progressing phenomena of a stenosis of respiratory tracts are observed: characteristic pressure respiratory murmur, especially sonorous in an inspiratory phase, inspiratory retractions of a thorax (mezhreberiya, cartilages of the lower edges, the bottom of a breast, over - and subclavial hollows, a jugular pole) and tension of auxiliary respiratory muscles (grudino - clavicular and mastoidal, ladder, trapezoid and other muscles). Filmy plaques on a mucous membrane of an entrance of a throat, on true and predoor false voice folds, and sometimes and in a voice cavity are found (tsvetn. fig. 4). At the accruing difficulty of breath and the progressing exhaustion of the child there is a frustration gas exchange (see). Short attacks of suffocation with considerable concern of the patient are observed. Duration of a stenotic stage — from several hours to 2 — 3 days (on average 1 — 1,5 days).
Development of the third, asphyxial, stages is shown first of all by the expressed concern of the child. There is cyanosis of lips, face skin and extremities; face skin becomes covered then. Also at the beginning of this stage it is found paradoxical pulse (see) — loss of pulse wave at height of a breath as result of the considerable negative pressure in a chest cavity interfering emptying of heart at the time of a systole and to advance of blood in peripheral vessels. Symptoms of asphyxia quickly progress. There is a darkened consciousness, pulse weakens, becomes arrhythmic, the ABP falls. Quite often there come spasms and then death from asphyxia (see).
On character of a current, speed of changes of all stages it is necessary to distinguish violently progressing and slowly progressing croup. The first type occurs preferential at children to two-year age and often is followed by pneumonia; the second type has more favorable current.
The widespread (descending) diphtheritic croup proceeding on violently progressing type differs in special weight. Quickly arising disorders of gas exchange are shown usually not by cyanosis, but deathly pallor (asphyxia pallida). Breath sharply becomes frequent, the wedge, symptoms of a stenosis of respiratory tracts can be poorly expressed; the picture of a disease is similar to heavy pneumonia (see).
The signs helping to establish distribution of croupous process to the lower respiratory tracts are: a) expectoration of fibrinous tubular molds of bronchial tubes; b) emergence of a syndrome of the beginning obturation of bronchial tubes (sharp weakening or lack of respiratory noise and at the same time loud percussion sound over a part or the whole pulmonary share); c) radiological in roots of lungs the picture of a so-called shaggy hilus, i.e. strengthening of a shadow of the main vascular trunk with the powerful vascular tyazha which are fanlikely dispersing to the periphery is found.
Development of a stenosis of upper respiratory tracts at a diphtheritic croup is caused by a number of the factors of operating usually in a complex — filmy imposings, puffiness of a mucous membrane, the spasm of muscles of a throat which is patol, a perversion of a protective guttural reflex. In emergence of a guttural spasm at patients, it is long and repeatedly exposed to an intubation, a part is played by uslovnoreflektorny mechanisms. The stenosis of respiratory tracts at grain, leading to disturbance of ventilation and blood supply of lungs and to development of atelectases, promotes accession of pneumonia. Complications of a toxic origin (myocarditis, polyneuritis, nephrotic syndrome) at the isolated croup are observed seldom.
Diphtheria of a nose (diphtheritic rhinitis)
its Relative frequency decreased: it is observed at children of advanced age. Temperature happens subfebrile and even normal, but sometimes reaches 39 °. Nasal breath is at a loss, appear liquid serous, and then seroznokrovyanisty (sanious) and is purulent - bloody allocations from a nose. On skin nostrils have excoriations and cracks.
It is marked (tsvetn. fig. 6) swelling, a hyperemia of a mucous membrane, filmy plaques on sinks and a partition of a nose (a filmy shape D. of a nose). In other cases of a film in a nose are absent, on vospalitelno also surface erosions (a catarral and ulcer form) are visible to the changed mucous membrane only the dried-up discharge in the form of hemorrhagic crusts. Tendency to a long long current is characteristic. Of a nose (excepting its very rare toxic form) usually is not followed by the expressed intoxication.
The rare clinical forms which were found in the past In 1 — 5% nowadays almost disappeared. First of all it is necessary to carry D. of an eye proceeding in croupous and diphtheritic forms to them. The century, purulent discharges, sometimes with impurity of blood, fibrinous plaques on a conjunctiva or (more rare) than an eyeglobe is characterized a century by hypostasis. At a diphtheritic form all these phenomena are sharply expressed: the considerable hypostasis having the dense consistence, powerful dirty-white plaques which are densely soldered to the subject fabric; the expressed intoxication.
Of external genitals it was observed preferential at girls, it is frequent in combination with D. of other localization. It is characterized by a swelling of big and small vulvar lips, dirty-white plaques, ulcerations of a mucous membrane and skin and purulent discharges (tsvetn. fig. 5).
Very rare in the past, and nowadays at all not found forms — D. of skin, outside acoustical pass and wounds.
The clinical course of diphtheria at the persons which were exposed to active immunization usually considerably changes. Of a pharynx at them on the manifestations it is similar to lacunary quinsy (see), plaques of a rykhla, rather easily are removed and do not tend to distribution. It can be observed and a toxic form, however at it plaques are widespread a little. Of a nose takes usually catarral form with the scanty local phenomena and with tendency to a long sluggish current. Complications at vaccinated arise less often and proceed easier, the lethality is much lower, than at not vaccinated. On observations of a number of clinical physicians — N. I. Nisevich (1945), K. V. Lavrova (1961), N. P. Kudryavtseva (1964), V. I. Kachurets (1968), at the children who received a single unfinished inoculation, D., on the contrary, proceeds more hard. Perhaps, it is connected with the sensibilizing action of single administration of anatoxin.
Features of diphtheria at adults
D. at adults quite often accepts an atypical current. In this regard, and also owing to the late address to the doctor of many patients hospitalize in late terms. Gravis-kultury the activator D. at adults in comparison with children are allocated much less often. Perhaps, both rather smaller frequency of a toxic form and lower lethality is connected with it.
At adults in 90% cases proceeds in the localized form and in connection with an atipichnost of the manifestations is diagnosed as lacunary quinsy. At emergence of a croup the stenotic phenomena are poorly expressed, only rough, hoarse cough, hoarseness of a voice or a full aphonia, a nek-swarm difficulty of breath are observed. At untimely recognition (in the started cases) process extends to the lower respiratory tracts; the descending croup develops, from to-rogo the patient can die at the phenomena of suddenly developed asphyxia.
Complications are connected with the specific effect of toxin causing cardiovascular frustration neuritis (see) and polyneuritis (see), nephrotic syndrome (see). Complications are quite often combined with each other. Hl are observed. obr. at toxic D., especially II and III degrees, meet at a common form of D. of a pharynx much less often and is very rare at the localized shape D. of a nose and throat. Emergence of complications is also in direct dependence on terms of an initiation of treatment: the later the serotherapy is begun, the complications are observed more often.
Circulatory disturbances are possible in the first days of a disease. Tachycardia is noted at normal or even the raised ABP. On 3 — the 4th, and sometimes for the 2nd day of a disease the hypertension is replaced by quickly progressing falling of the maximum and especially minimum ABP. Tachycardia sharply amplifies, pulse becomes small, threadlike.
A wedge, changes from heart are usually small and changeable. However at an electrocardiographic research signs of damage of a myocardium come to light. At the accruing phenomena of a collapse there can come death. The early circulatory disturbance is caused by a combination of vascular and heart failure, and the first obviously dominates.
Myocarditis (see) clinically comes to light on 2 — 3rd week of a disease later. This complication often develops at toxic D. (according to various authors, at the II degree — in 20 — 70%, at the III degree — in 70 — 80%). An electrocardiographic research damage of a myocardium comes to light considerably more often than by means of usual a wedge, methods. The current of this complication depends on weight of damage of a myocardium. In addition to myocarditis (tsvetn. fig. 7), at D., as well as at other infectious diseases, is often observed so-called infectious heart — a syndrome of dysfunction of century of N of page.
A typical complication of D. are flaccid paralyzes as result of toxic defeat of peripheral nerves. They meet in 4 — 8% of cases. Quite often and most early (since the 2nd week) paralysis of a soft palate (a glossopharyngeal nerve, a vagus nerve) is observed. The speech accepts a nasal, nasal shade, liquid food during the swallowing follows in Nov, the palatine velum inertly hangs down, is not mobile at phonation; duration of these phenomena on average 2 — 4 weeks. At damage of ciliary nerves there is paralysis of accommodation (see. Accommodation of an eye ); patients badly distinguish the objects which are nearby (see. Diplopia ). At the same time squint (the taking-away nerve), a ptosis (third cranial nerve) can be observed. Also paralyzes of muscles of extremities and a trunk can develop in the late periods of a disease (on 4 — 6th week and later). The lost functions completely are recovered in 2 — 3 months, is more rare through more long terms. Big hazard to life is posed by paralyzes of muscles of a throat (the lower guttural nerve), intercostal muscles (intercostal nerves), diaphragms (a phrenic nerve), defeat of innervatsionny mechanisms of heart.
From kidneys in the first days even at easy forms D. are observed proteinuria (see) and cylindruria. At a toxic form often (in 50 — 60% of cases) the full picture of a nephrotic syndrome which is characterized by hl develops. obr. changes from urine: the expressed proteinuria (2 — 10 per milles and more), a cylindruria, sometimes with impurity of single erythrocytes. Specific weight of urine high, secretory function of kidneys is not broken. Hypostases are observed rather seldom, hl. obr. at a simultaneous circulatory unefficiency. At a favorable current of D. all phenomena from kidneys gradually disappear.
In addition to the complications caused by specific intoxication are observed various patol, processes, napr, the pneumonia, otitises, purulent lymphadenites caused by consecutive infection (a streptococcus, staphylococcus, a pneumococcus, etc.).
Pneumonia — a frequent complication of a croup, at Krom it is one of the main reasons for death; the hl develops. obr. at children of early age. Quite often it arises also at toxic D.'s patients, at the same time proceeds malosimptomno and is intravital not always is distinguished.
On V. S. Kuznetsov (1959) observations, adult patients in comparison with children have frustration from cardiovascular system more often; it is promoted by intoxications (nicotine, alcohol, infectious diseases etc.) postponed in the premorbidal period. Even at the localized shape D. of a pharynx a physical and electrocardiographic research damage of heart often comes to light; full normalization of function of the last happens in rather late terms.
At a toxic form of change from cardiovascular system are found in all patients; often myocarditis and a polyneuritis develops.
D.'s Recognition a pharynx is at a loss existence of atypical forms, especially at vaccinated children, and also strong likeness with other diseases. Can be mixed with follicular, lacunary and phlegmonous quinsy, fuzospirokhetozny quinsy of Simanovsky — Vincent (see. Quinsy ), with a mononucleosis (see. Mononucleosis infectious ), with quinsies arising at diseases of blood (see. Agranulocytosis , Leukoses ), etc. At recognition it is necessary to consider distinctiveness of D. of a pharynx: existence on almonds of the fibrinous plaques which are difficult separated from the subject fabric, moderately expressed hyperemia of a pharynx and pain during the swallowing, a little expressed reaction from regional limf, nodes; extensive plaques of diphtheritic character in a pharynx, hypostasis of cervical cellulose and the phenomenon of the general intoxication are typical for a toxic form.
As distinctiveness of a diphtheritic croup serve incremental frustration of a voice, the progressing cyclic current; the combination with filmy quinsy or rhinitis is typical.
The diphtheritic croup should be differentiated with the croup of other etiology which is especially arising at flu and other acute respiratory infections. It is necessary to differentiate with the stenoses of the lower respiratory tracts developing as a result of a prelum less often (hypertrophies of goitrous gland, increase tracheobronchial limf, nodes), and foreign bodys of a throat and trachea (see. Foreign bodys ).
Of eyes should be differentiated with filmy conjunctivitis (see. Conjunctivitis ), the caused adenoviruses, is more rare a pneumococcus, Koch's stick — Uiksa, etc.
Is investigated slime from a pharynx and a nose, and at suspicion on ekstrafaringealny forms — a discharge from wounds, ulcers, conjunctivas of an eye, generative organs etc. Capture of material is made on an empty stomach or not earlier than in 2 hours after meal or rinsing of a pharynx. Tampons with the studied material are brought to laboratory not later than in 3 hours after capture. Tests are sowed on a surface of the dense elective environment in a Petri dish. The direct bacterioscopy of the smears painted by aniline dye is possible (see. Bacteriological techniques ); the result of microscopy is regarded as preliminary.
At suspicion on D. of a nose or a bacteriocarrier the studied material, in addition to the dense environment, is sowed on semi-fluid Wednesday of enrichment, after an incubation the cut in the thermostat during 6 — 18 hours becomes seeding in a Petri dish with the elective environment (see. Mediums ).
On a surface of environments in cups in 24 — 48 hours there are well developed bacterial clumps of D. (tsvetn. fig. A.5), who use for release of pure growths for the purpose of the subsequent identification (see. Identification of microbes ). Establishment of belonging of culture to a sort of korinebakteriya carries out sya on the basis morfol, and cultural features; identification of a type of Cor. diphtheriae — on the basis of a complex biochemical, properties (ability to produce H2S on Wednesdays with cystine and inability to split urea). Biotypes gravis and the metis differ on fermentation of starch taking into account morphology of colonies. Toxigenicity is defined by in vitro method of precipitation in an agar on Oukhterlonya. Quantitative definition of degree of toxigenicity is possible on live models — Guinea pigs or 9-day chicken embryos. Considering variety of tests and need of obtaining the answer in the shortest possible time, the most rational is the following operations procedure: well developed suspicious colony which grew by surfaces of the elective environment in a cup is eliminated at the same time on Leffler's circle or Ru in a test tube (for receiving pure growth), on a surface of the environment for definition of toxigenicity (in the form of «plaque») and in a column of Wednesday with cystine. Whenever possible do eliminations of two or more colonies. In 24 hours the culture is studied in a microscope. At suspicion on belonging to a sort of korinebakteriya the result on the Wednesday with cystine is considered (test Pisa; tsvetn. the fig. A.2) is also put test on urease. At this stage (i.e. in 48 hours from the beginning of a research if the enrichment method was not applied) issue of the final answer is possible. To the same term precipitation lines on the Wednesday for definition of toxigenicity can appear; in case of their absence results are defined in one days (i.e. in 72 hours from the beginning of a research). The grown culture of bacteria of D. is used for definition of a biotype, a serotype and a fagotip.
Main mediums. Blood telluric agars (Klauberg-II environment) and its options contain, in addition to a nutritious basis — an agar on Hottinger's broth or a dry semi-finished product, 10 — 15% of gemolizirovanny blood (a ram, a Guinea pig, the person) and 0,03 — 0,04% of tellurite K. In 24 hours the opaque black, not merging, flat colonies are formed, in 48 — 72 hours their differentiation on biotypes is possible. From environments in which blood is replaced 10 — 20% of normal serum the environment of Tinsdeyl (1947) and its modification containing 0,12% of cystine were the most rational. Dark brown bacterial clumps of D. are surrounded with the same auras of sulphurous tellurium (tsvetn. fig. A.4). The Hinozolny circle of P. I. Buchin (1963) contains 5% of blood, 0,03% of cystine and inhibitors of growth of foreign flora — 0,002% of Chinosolum and 3% of NaCl, the water-blue indicator. Bacterial clumps of D. blue, Wednesday under them blue. For definition of toxigenicity of in vitro use the transparent agar mediums on Marten's broth with double concentration of meat water containing 20% of normal serum and 0,003% of cystine. On a surface of the environment in a Petri dish in the area of diameter the strip of filter paper moistened with drug of commercial diphtheritic antitoxin is imposed. On both sides from a strip of filter paper cause cultures of toxicogenic and not toxicogenic strains. Antitoxin, diffusing from a strip of filter paper on Wednesday, forms in it a number of cultivations. The toxin which is emitted with a growth of toxicogenic diphtheritic microbes also diffuses on Wednesday. In places where diphtheritic toxin and antitoxin meet in optimum concentration, there are white points of a flokkulyat which, merging, form precipitation lines («moustaches» or «arrows»). The accounting of results is made in 24 — 48 hour.
For detection of ability to split cystine the modified environment Pisa — a serumal agar of Marten with addition of 0,02% of cystine and 0,1% of a lead acetate as the indicator of the allocated H is used 2 S; crops are made by a prick. The accounting of results is made in 24 hours on the basis of blackening of the environment or lack of blackening on the course of a prick. Test on urease is put by seeding on broth with urea and the indicator phenol red or by entering of culture into 0,2 ml of the reactant containing 1% of urea and 0,02% of the indicator. Reddening of the environment or a reactant demonstrates availability of enzyme. Sakharolitichesky activity is defined in test tubes with 1% the peptone water supporting 0,5% of the examinee mono - di - or polysaccharide and 1% of the indicator of Andrade (see. Andrade indicator ). The accounting of a kislotoobrazovaniye is made in 24 hours on reddening of Wednesday.
Serological researches are based on detection of antibacterial antibodies since indicators of content of antitoxin change in connection with introduction in the very first days of anti-toxic serum. The agglutination test with diphtheritic culture, and also reaction of passive hemagglutination with use of somatic antigens of diphtheritic bacteria reveals in dynamics increase of antibacterial antibodies in credits 1: 80 and above on the 2nd week of a disease. Similar shifts are found also in carriers of toxicogenic strains that limits differential and diagnostic value of reactions.
Biochemical Cor properties. diphtheriae and close types of the korinebakteriya to it which are found on skin and mucous membranes of the person are provided in tab. 1.
At a severe form and existence of complications correctly organized mode and attentive leaving which are carried out in hospital conditions are of great importance.
In an initial stage of a disease, at a severe form, surely bed and guarding rest.
At easy forms D. (the localized shape D. of a pharynx, D. of a nose etc.) after disappearance of the acute phenomena children can get up for acceptance of food, collective occupations and unfatiguing games. At toxic D. even in the absence of complications of the patient contains in hospital with observance of a bed rest during the following minimum terms: at subtoxic and toxic D. of a pharynx of the I degree — to 21 — the 28th day, at toxic II of degree — till 40th day and at toxic III of degree — till 50th day of a disease. Strict long bed contents is offered also in the presence of myocarditis and a polyneuritis. In the first days at acute changes in a pharynx digestible liquid and semi-fluid food is appointed.
Holds a specific place serotherapy (see), the cut is the purpose elimination of specific intoxication. Diphtheritic anti-toxic serum in early terms of a disease — highly effective means. At easy forms (at D. of a nose localized by D. of a pharynx, the isolated croup in an initial stage) it is possible to be limited to single administration of serum and only in the absence of an overt effect to repeat an injection in the same or half dose next day.
At a common form, grain in the second and third stages and especially at subtoxic and toxic forms repeated administration of serum before considerable reduction of the phenomena of local process (plaques) is necessary; serum is entered in the doses lowered against initial twice, three times. The first introduction is carried out fractionally on the modified Bezredki's way (see. Bezredki methods ): in the beginning enter subcutaneously 0,1 ml, in 30 min. — 0,2 ml and later 1 — 1,5 more hour all other dose of serum. The dose of serum is established proceeding from weight of a disease (a wedge, forms) and terms which expired from the moment of a disease (see tab. 2).
Some authors [G. G. Ramon, 1933; M. P. Mukhamedov, 1942; N. P. Kudryavtseva; M. S. Zaluzhnaya, 1963] for the purpose of stimulation of active products of antitoxin recommend to enter along with serum the patient a diphtherial anatoxin (in a dose of 0,5 — 1 ml; in the acute period of a disease the first two injections at an interval of 5 — 6 days, a third — in a month). At earlier imparted children such treatment has bystry effect, stimulating products of antitoxin on the mechanism revaccinations (see). At toxic forms D. transfusion of odnogruppny blood (40 — 150 ml) or native plasma (60 — 150 ml) and its substitutes is in addition recommended. Apply intravenous injections hypertensive (25%) solution of glucose. Course of treatment of 7 — 12 days. Purpose of vitamins is necessary. Ascorbic to - that is appointed at the expressed intoxication on 300 — 600 — 1000 mg a day for 2 — 3 receptions within 7 — 10 days; further the daily dose decreases twice-three times. In the acute period ascorbic to - it is possible to enter that parenterally (intravenously, intramusculary) into 5 — 10% solution on 2 — 3 ml. Nicotinic to - that is appointed on 15 — 30 mg 2 times a day; in the first days of a disease — intramusculary or intravenously in 1% solution on 1 — 5 ml. Oryzamin (thiamin) is appointed inside or parenterally during 10 days. At easy forms appoint inside polyvitaminic drugs in usual doses.
In an initial stage of toxic D. the drugs raising a tone of vessels are shown. Appoint Cordiaminum, Corazolum; strychnine (in solution 1:1000 on 0,5 — 1,0 ml 3 times a day) within several weeks is widely applied. Also injections of 1% of solution of disodium salt adenosine triphosphoric to - you (0,3 — 1,0 ml) and cocarboxylase (50 — 100 mg) within 10 — 12 days are recommended.
In complex therapy of a pharynx by toxic D. apply glucocorticoid hormones (Prednisolonum, a daily dose of 2 — 3 mg on 1 kg of weight). Treatment of 5 — 7 days with a gradual dose decline.
At grain of any etiology, in addition to administration of serum, the complex of conservative methods of treatment is applied to fight against a stenosis of respiratory tracts (see. Croup ). At unsuccessfulness of conservative therapy resort to an operative measure. As the indication to it serve the symptoms characterizing the moment of transition of the second (stenotic) stage of a croup in the third (asphyxial): the resistant, sharply expressed phenomena of a stenosis, the expressed concern of the patient, paradoxical pulse, emergence at least slight, but not disappearing cyanosis. At diphtheritic stenoses it is applied intubation (see) or tracheotomy (see). Intubation — the bystry, technically simple, anemic operation which was less breaking fiziol, the act of breath, than tracheotomy. Indications to tracheotomy: extensive hypostasis and the bleeding plaques in a pharynx, deformation of a throat, the accompanying whooping cough with heavy tussive attacks, a low arrangement of films in a trachea. This operation should be preferred in conditions when at cough up tubes it is impossible to provide a repeated intubation quickly. Experience shows that extubation) it is reasonable to make the intubated patients in the 48th hour. After extubation, made in the specified time, at a considerable part of patients (on average at 40 — 50%) the phenomena of a stenosis do not renew. At other patients after the first extubation or after a vykashlivaniye of a tube later a nek-swarm time the symptoms of a stenosis forcing to repeat an intubation develop again. Some patients should be intubated repeatedly since after each extubation they have a recurrence of a stenosis. To avoid development of cicatricial stenoses of a throat, it is recommended not to delay treatment by an intubation more than 6 — 7 days and to make secondary tracheotomy.
At a diphtheritic carriage treatment by tetracycline or erythromycin in usual age doses is appointed. At the same time appoint ascorbic to - that. Erythromycin is applied in 4 times a day in daily doses: to children up to 2 years — 200 000, from 2 to 3 years — 300 000, from 4 to 7 years — 400 000, from 8 to 12 years — 600 000 PIECES. Duration of a course of treatment of 7 days, in the absence of effect in a week appoint the second year.
D.'s treatment at adults is carried out by the same principles with corresponding changes of a dosage of pharmaceuticals. Dosage of serum the same. In the presence of the accompanying diseases (the idiopathic hypertensia, stenocardias, atherosclerosis) should refrain from purpose of strychnine. Recovery at flaccid paralyzes and defeats of cardiovascular system at adults happens much more slowly, than at children. It would need to be considered at an extract from and definition of working capacity.
the Lethality at D. in connection with carrying out mass active immunization, improvement of methods of treatment and improvement of medical service of the population sharply decreased, and in some settlements reached zero. D.'s outcome depends on weight of a disease, age of patients, terms of the beginning of a serotherapy and full value of the carried-out treatment.
plays the Main role in fight against D. active immunization of children (see. Immunization ), high performance a cut is established by wide international experience. Progress of fight against D. is defined by the correct organization and the correct carrying out preventive inoculations. In the Soviet Union antidiphtherial inoculations are obligatory for all children's population. Primary immunization is made at the age of 5 — 6 months by the adsorbed pertussoid and diphtheritic and tetanic vaccine (AKDS), edges is entered intramusculary is triple on 0,5 bucketed ml in 30 — 40 days.
The revaccination is carried out by the same drug in a dose of 0,5 ml: the first in 1,5 — 2 after the finished vaccination, the second — in 6 years after the first. The third revaccination is carried out at the age of 11 years by the adsorbed diphtheria tetanus vaccine (ADS) in a dose of 0,5 ml. Persons are more senior than 12 years which are positively reacting to a Schick's test, revaccinations on epid, to indications are subject. At a part immunizirovanny soon after an inoculation short-term postinoculative reactions — local are observed (reddening, swelled, small infiltration, morbidity on site of an injection) and the general (small temperature increase, a febricula, sometimes rashes and hypostases of the allergic nature). Patients and the weakened children transfer inoculations worse, at them also processes of development of immunity therefore active immunization in such cases is temporarily contraindicated are suppressed. The children who are subject to immunization shall undergo pilot medical survey surely. Existence of antidiphtherial specific immunity is defined by a Schick's test.
Its essence consists in intradermal administration of active diphtheritic toxin in number of 1/40 Dlm (toxin gets divorced so that the specified dose contained in 0,1 ml of cultivation). The result of reaction is estimated later 72 — 96 hours; the positive reaction indicating lack of immunity to D. is shown by reddening and infiltration of skin on the site with a diameter not less than 1 cm. Introduction even of a small dose of diphtheritic toxin can reveal allergic reaction of an organism (see. Allergy ). Therefore it is recommended to reduce whenever possible indications to its use and not to put it to children with allergic the changed reactivity.
The second important protivoepid, an action — fight against a diphtheritic bacteriocarrier (see. Carriage of contagiums ). Identification of a carriage with the help bacterial, researches is made on epid, to indications in children's collectives (day nursery, kindergartens, sanatoria, hospitals) and families. The revealed healthy carriers of toxicogenic diphtheritic bacteria are isolated (see. Isolation of infectious patients ) also sanitation is exposed. Release from a carriage can be promoted by actions for increase in the general resistance of an organism (broad aeration, the healthy good nutrition, purpose of vitamins) and sanitation of a nasopharynx in the presence in it patol, processes.
In epid, the center the following events are held:
1. The revealed sick D. immediately would place in infectious; patients with suspicion on D. are also subject to hospitalization (in the diagnostic boxed department). After recovery the had D. is written out on condition of a negative take double bacterial, the research conducted at an interval of the 2nd day. The convalescent who is written out from-tsy is allowed in child care facility at a negative take of additional double inspection on a carriage.
2. Visit of child care facilities in which all children are imparted against D. is allowed to carriers of toxicogenic diphtheritic bacteria in 30 days after establishment of a carriage. Carriers of not toxicogenic strains of diphtheritic sticks of isolation are not subject.
3. In the apartment of the patient after his isolation final is made disinfection (see). 4. All children and adults communicating with the patient are subject to survey by the doctor for the purpose of identification of the erased forms D. and to inspection on a bacteriocarrier. Children, and also the adults servicing children's collectives, institutions and catering establishments are allowed in child care facilities (or to work at the relevant enterprises) only after bacterial, the inspection excluding a toxicogenic carriage and after carrying out disinfection in the center. 5. For epid, medical observation within 7 days after isolation of the patient is established by the center.
Table 1. IDENTIFICATION KORINEBAKTERY on the basis of the COMPLEX of BIOCHEMICAL PROPERTIES
Table 2. AVERAGE DOSES (in ME) the SERUMS APPLIED. In the MEDICAL PURPOSES AT VARIOUS FORMS of DIPHTHERIA
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