streptococcal antigens. The causative agent of streptococcal infection
The genus Streptococcus includes: Streptococcus pyogenes (hemolytic) and Streptococcus pneumoniae (pneumococcus). Streptococci were first discovered by Billroth (1874), L. Pasteur (1879). They were studied by E. Rosenbach (1884).
Streptococcus pyogenes (hemolytic)
Morphology. Streptococci are cocci that have a spherical shape. The diameter of each coccus is on average 0.6-1 μm, however, they are characterized by polymorphism: there are small and large cocci, strictly spherical and oval. Streptococci are arranged in a chain, which is the result of their division in the same plane. Chain lengths vary. On a dense nutrient medium, the chains are usually short; on liquid ones, they are long. Streptococci are immobile, do not have spores (see Fig. 4). Freshly isolated cultures sometimes form a capsule. On ultrathin sections, a microcapsule is visible, under it there is a three-layer cell wall and a three-layer cytoplasmic membrane. Gram-positive.
cultivation. Streptococci are facultative anaerobes. Grow at a temperature of 37 ° C and pH 7.6-7.8. The optimal media for their cultivation are media containing blood or blood serum. On dense nutrient media, streptococcal colonies are small, flat, cloudy, grayish in color. On blood agar, some varieties of streptococci form hemolysis. β-hemolytic streptococci form a clear zone of hemolysis, α-hemolytic streptococci form a small greenish zone (the result of the transition of hemoglobin to methemoglobin). There are streptococci that do not give hemolysis.
On sugar broth, streptococci grow with the formation of parietal and near-bottom fine-grained sediment, while the broth remains transparent.
Enzymatic properties. Streptococci have saccharolytic properties. They break down glucose, lactose, sucrose, mannitol (not always) and maltose to form acid. Their proteolytic properties are poorly expressed. They coagulate milk, gelatin does not liquefy.
toxin formation. Streptococci form a number of exotoxins: 1) streptolysins - destroy red blood cells (O-streptolysin has a cardiotoxic effect); 2) leukocidin - destroys leukocytes (formed by highly virulent strains); 3) erythrogenic (scarlet fever) toxin - causes the clinical picture of scarlet fever - intoxication, vascular reactions, rash, etc. The synthesis of erythrogenic toxin is determined by the prophage; 4) cytotoxins - have the ability to cause glomerulonephritis.
Streptococci have various antigens. The cytoplasm of the cell contains an antigen of a specific nucleoprotein nature - the same for all streptococci. Protein type antigens are located on the surface of the cell wall. A polysaccharide group antigen was found in the cell wall of streptococci.
According to the composition of the polysaccharide group-specific antigen fraction, all streptococci are divided into groups, denoted by capital Latin letters A, B, C, D, etc. up to S. In addition to groups, streptococci are divided into serological types, which are indicated by Arabic numerals.
Group A includes 70 types. This group includes most streptococci that cause various diseases in humans. Group B includes mainly opportunistic human streptococci. Group C includes streptococci pathogenic to humans and animals. Group D consists of streptococci that are not pathogenic to humans, but this group includes enterococci, which are inhabitants of the intestinal tract of humans and animals. Getting into other organs, they cause inflammatory processes: cholecystitis, pyelitis, etc. Thus, they can be attributed to conditionally pathogenic microbes.
The belonging of the isolated cultures to one of the serological groups is determined using a precipitation reaction with group sera. To determine serological types, an agglutination reaction with type-specific sera is used.
Streptococci are fairly stable in the environment. At a temperature of 60 ° C, they die after 30 minutes.
In dried pus and sputum, they persist for months. The usual concentrations of disinfectants destroy them in 15-20 minutes. Enterococci are much more resistant, disinfectant solutions kill them only after 50-60 minutes.
Animal susceptibility. Cattle, horses, dogs, and birds are susceptible to pathogenic streptococci. From laboratory animals rabbits and white mice are sensitive. However, streptococci pathogenic for humans are not always pathogenic for experimental animals.
Sources of infection. People (sick and carriers), less often animals or infected products.
Transmission routes. Airborne and airborne dust, sometimes food, contact-household is possible.
Diseases can occur as a result of exogenous infection, as well as endogenously - with the activation of opportunistic streptococci that live on the mucous membranes of the pharynx, nasopharynx, and vagina. A decrease in the body's resistance (cooling, starvation, overwork, etc.) can lead to autoinfections.
Of great importance in the pathogenesis of streptococcal infections is preliminary sensitization - as a result of a previously transferred disease of streptococcal etiology.
When penetrating into the bloodstream, streptococci cause a severe septic process.
Diseases in humans more often cause β-hemolytic streptococci of serological group A. They produce pathogenicity enzymes: hyaluronidase, fibrinolysin (streptokinase), deoxyribonuclease, etc. In addition, a capsule, M-protein, which have antiphagocytic properties, are found in streptococci.
Streptococci cause various acute and chronic infections in humans, both with the formation of pus and non-suppurative, differing in clinical picture and pathogenesis. Suppurative - phlegmon, abscesses, wound infections, non-suppurative - acute infections of the upper respiratory tract, erysipelas, scarlet fever, rheumatism, etc.
Streptococci often cause secondary infections in influenza, measles, whooping cough and other diseases and often complicate wound infections.
Immunity. By nature, immunity is antitoxic and antibacterial. Postinfectious antimicrobial immunity is weak. This is due to the weak immunogenicity of streptococci and a large number of serovars that do not give cross-immunity. In addition, with streptococcal diseases, an allergization of the body is observed, which explains the tendency to relapse.
Prevention. It comes down to sanitary and hygienic measures, strengthening the overall resistance of the body. Specific prophylaxis has not been developed.
Treatment. Apply antibiotics. More often, penicillin is used, to which streptococci have not acquired resistance, as well as erythromycin and tetracycline.
The value of streptococcus in the etiology of rheumatic heart disease. The pathogenesis of rheumatic heart disease is not well understood. But a number of facts speak in favor of the role of streptococcus in the development of this disease:
1. In patients with rheumatic heart disease, B-hemolytic streptococcus is sown from the pharynx.
2. Rheumatism often occurs after suffering a sore throat, tonsillitis, pharyngitis, sensitizing the body.
3. Antistreptolysin, antistreptohyaluronidase - antibodies to streptococcal enzymes, toxins are found in the blood serum of patients.
4. Indirect confirmation of the role of streptococcus is the successful treatment with penicillin.
Recently, L-forms of streptococcus have been given importance in the occurrence of chronic forms of rheumatic heart disease.
Prevention of exacerbations of rheumatic heart disease is reduced to the prevention of streptococcal diseases (for example, in spring and autumn, a prophylactic course of penicillin administration is carried out). Treatment is reduced to the use of antibacterial drugs - penicillin.
The value of streptococcus in the etiology of scarlet fever. G. N. Gabrichevsky (1902) was the first to suggest that hemolytic streptococcus is the causative agent of scarlet fever. But since the streptococci isolated in other diseases did not differ from the causative agents of scarlet fever, this opinion was not shared by everyone. It is now established that scarlet fever is caused by group A streptococci that produce erythrogenic toxin.
In those who have been ill, immunity arises - persistent, antitoxic. Its tension is determined by setting the Dick reaction - intradermal injection of erythrogenic toxin. In those who are not sick around the injection site, hyperemia and edema occur, which is characterized as a positive reaction (lack of antitoxin in the blood serum). In those who have been ill, such a reaction is absent, since the antitoxin formed in them neutralizes the erythrogenic toxin.
Prevention. Isolation, hospitalization. Contact, weakened children are given gamma globulin. Specific prophylaxis has not been developed.
Treatment. Use penicillin, tetracycline. In severe cases, antitoxic serum is administered.
The purpose of the study: detection of streptococcus and determination of its serovar.
Research material
1. Mucus from the throat (tonsillitis, scarlet fever).
2. Scraping from the affected area of the skin (erysipelas, streptoderma).
3. Pus (abscess).
4. Urine (nephritis).
5. Blood (suspected sepsis; endocarditis).
Basic research methods
1. Bacteriological.
2. Microscopic.
Research progress
Second day of research
Take the cups out of the thermostat and inspect. In the presence of suspicious colonies, smears are made from a part of them, stained according to Gram and microscopically. If streptococci are found in the smear, part of the remaining colony is subcultured into test tubes on agar with serum to isolate a pure culture and on broth with blood in test tubes. By the end of the day, a 5-6-hour culture from broth or agar is subcultured onto Marten's broth with 0.25% glucose to determine the serological group in the Lensfield precipitation reaction. Test tubes and vials are placed in a thermostat and left until the next day.
Third day of research
The cultures are removed from the oven, the purity of the culture is checked on the agar slant, smears are made, Gram stained and microscoped. In the presence of a pure culture of streptococcus, they are sown on Hiss media (lactose, glucose, maltose, sucrose and mannitol), milk, gelatin, 40% bile and put in a thermostat.
Look through Martin's broth. In the presence of specific growth, a Lensfield precipitation test is performed to determine the serological group.
Setting up the precipitation reaction according to Lensfield. The daily culture grown on Martin's broth is poured into several centrifuge tubes, centrifuged for 10-15 minutes (3000 rpm).
The supernatant is poured into a jar with a disinfectant solution, and the precipitate is poured into a sterile isotonic sodium chloride solution and centrifuged again. To the precipitate collected from all centrifuge tubes, add 0.4 ml of 0.2% hydrochloric acid. Then the tube is placed in a water bath and boiled for 15 minutes, shaking occasionally. After boiling, the resulting suspension is again centrifuged. The antigen is then extracted into the supernatant, which is poured into a clean tube and neutralized with 0.2% sodium hydroxide solution to pH 7.0-7.2. Bromothymol blue (0.01 ml of a 0.04% solution) is added as an indicator. With this reaction, the color changes from straw yellow to blue.
Then, 0.5 ml of antistreptococcal group sera, which are prepared by immunizing rabbits, are poured into 5 precipitation tubes (see Chapter 19). Serum A is introduced into the 1st tube, serum B into the 2nd, serum C into the 3rd, serum D into the 4th, isotonic sodium chloride solution (control) into the 5th. After that, with a Pasteur pipette, the resulting extract (antigen) is carefully layered along the wall into all test tubes.
With a positive reaction in a test tube with homologous serum, a thin milky-white ring is formed at the border of the extract with serum (Fig. 38).
Fourth day of research
The results are recorded (Table 25).
Currently, deoxyribonuclease is being determined, as well as antistreptohyaluronidase, antistreptolysin-O.
test questions
1. What are the main methods of laboratory research for the detection of streptococci do you know?
2. What is the Lensfield precipitation reaction for?
3. Why should the antigen be transparent during this reaction? Describe the technique for staging this reaction.
Get antistreptococcal serum A, B, C, D and isotonic sodium chloride solution from the teacher. Set the precipitation reaction, show the results to the teacher and draw.
Nutrient media
agar with blood(see chapter 7).
Serum Agar(see chapter 7).
Hiss media(dry).
Meat peptone gelatin (MPG). To 100 ml of MPB add 10-15 g of finely chopped gelatin. Gelatin should swell when slowly heated in a water bath (at a temperature of 40-50 ° C). A 10% solution of sodium carbonate (baking soda) is added to the melted gelatin and the pH is adjusted to 7.0. It is then immediately filtered through a pleated filter. Filtration is slow. To speed up the process, filtration can be done in a hot autoclave. The filtered medium is poured into test tubes of 6-8 ml and sterilized. Sterilization is carried out either fractionally at a temperature of 100 ° C for 3 days in a row, or simultaneously at 110 ° C for 20 minutes in an autoclave. Cooling of the medium is carried out in test tubes placed vertically.
Milk preparation. Fresh milk is brought to a boil, put in a cool place for a day, freed from cream, boiled again. Leave for a day and remove the top layer. Skimmed milk is filtered through a layer of cotton wool, then alkalized with 10% sodium carbonate solution to pH 7.2 and poured into test tubes of 5-6 ml.
Bouillon Martin. An equal amount of peptone Marten (minced meat from pork stomachs exposed to hydrochloric acid) is added to the meat water. The resulting mixture is boiled for 10 minutes, alkalized with 10% sodium hydroxide solution to pH 8.0, 0.5 sodium acetate is added, boiled again and poured into sterile dishes. 0.25% glucose is added to Martin's broth.
Wednesday Kitt - Tarozzi(see chapter 34).
Streptococcus pneumoniae (pneumococcus)
Pneumococci were first described by R. Koch (1871).
Morphology. Pneumococci are diplococci in which the sides of the cells facing each other are flattened and the opposite sides are elongated, so they have a lanceolate shape resembling a candle flame (see Fig. 4). The size of pneumococci is 0.75-0.5 × 0.5-1 μm, they are arranged in pairs. In liquid nutrient media, they often form short chains, resembling streptococci. Prevmococci are immobile, do not have spores, form a capsule in the body that surrounds both cocci. The capsule contains a heat-resistant substance antiphagin (which protects pneumococcus from phagocytosis and the action of antibodies). When growing on artificial nutrient media, pneumococci lose their capsule. Pneumococci are gram positive. Gram-negative bacteria are found in old cultures.
cultivation. Pneumococci are facultative anaerobes. Grow at a temperature of 36-37 ° C and a pH of 7.2-7.4. They are demanding on media, since they cannot synthesize many amino acids, therefore they grow only on media with the addition of native protein (blood or serum). On agar with serum form small, delicate, fairly transparent colonies. On agar with blood, moist greenish-gray colonies grow, surrounded by a green zone, which is the result of the conversion of hemoglobin to methemoglobin. Pneumococci grow well in broth with the addition of 0.2% glucose and in broth with whey. Growth in liquid media is characterized by diffuse turbidity and dusty sediment at the bottom.
Enzymatic properties. Pneumococci have a fairly pronounced saccharolytic activity. They break down: lactose, glucose, sucrose, maltose, inulin with the formation of acid. Do not ferment mannitol. Their proteolytic properties are poorly expressed: they coagulate milk, do not liquefy gelatin, and do not form indole. Pneumococci dissolve in bile. Cleavage of inulin and dissolution in bile is an important diagnostic feature that distinguishes Streptococcus pneumoniae from Streptococcus pyogenes.
pathogenicity factors. Pneumococci produce hyaluronidase, fibrinolysin, etc.
toxin formation. Pneumococci produce endotoxin, hemolysin, leukocidin. The virulence of pneumococci is also associated with the presence of antiphagin in the capsule.
Antigenic structure and classification. In the cytoplasm of pneumococci there is a protein antigen common to the entire group, and in the capsule there is a polysaccharide antigen. According to the polysaccharide antigen, all pneumococci are divided into 84 serovars. Serovars I, II, III are the most common pathogens for humans.
Environmental resistance. Pneumococci belong to the group of unstable microorganisms. A temperature of 60 ° C destroys them in 3-5 minutes. They are quite resistant to low temperatures and drying. In dried sputum, they remain viable for up to 2 months. On a nutrient medium, they remain no more than 5-6 days. Therefore, when cultivating, it is necessary to do reseeding every 2-3 days. Conventional solutions of disinfectants: 3% phenol, sublimate at a dilution of 1:1000 destroy them in a few minutes.
Pneumococci are especially sensitive to optochin, which kills them at a dilution of 1:100,000.
Animal susceptibility. Humans are the natural host of pneumococci. However, pneumococci can cause illness in calves, lambs, piglets, dogs, and monkeys. Of the experimental animals, white mice are highly sensitive to pneumococcus.
Sources of infection. A sick person and a bacteriocarrier.
Transmission routes. Airborne, may be airborne.
entrance gate. The mucous membrane of the upper respiratory tract, eyes and ear.
Diseases in humans. Pneumococci can cause purulent-inflammatory diseases of different localization. Specific for pneumococci are:
1) lobar pneumonia;
2) creeping ulcer of the cornea;
The most common disease is croupous pneumonia, which affects one, less often two or three lobes of the lung. The disease is acute, accompanied by high fever, cough. It usually ends critically.
Immunity. After the illness, unstable immunity remains, since pneumonia is characterized by relapses.
Prevention. It comes down to sanitary and preventive measures. Specific prophylaxis has not been developed.
Treatment. Antibiotics are used - penicillin, tetracycline, etc.
test questions
1. Morphology of pneumococci. Cultivation and enzymatic properties.
2. What factors determine the pathogenicity of pneumococci and what protects pneumococci from phagocytosis?
3. What are the main gates of pneumococcal infection. What diseases are caused by pneumococci?
Microbiological research
The purpose of the study: detection of pneumococcus.
Research material
1. Phlegm (pneumonia).
2. Mucus from the pharynx (tonsillitis).
3. Discharge from the ulcer (creeping ulcer of the cornea).
4. Discharge from the ear (otitis media).
5. Pus (abscess).
6. Pleural punctate (pleurisy).
7. Blood (suspected sepsis).
1 (It is better to take morning sputum (with specific pneumonia, sputum has a rusty color).)
Basic research methods
1. Microscopic.
2. Microbiological.
3. Biological.
Research progress
biological sample. A little (3-5 ml of sputum) is emulsified in a sterile broth, 0.5 ml of this mixture is injected intraperitoneally to a white mouse. After 6-8 hours, the mice show signs of the disease. At this time, pneumococcus can already be detected in the exudate of the abdominal cavity. The exudate is taken with a sterile syringe. Smears are made from it, stained according to Gram and microscoped. To isolate a pure culture, the exudate is inoculated onto agar with serum. If the mouse dies or becomes ill, blood is cultured from the heart on serum agar to isolate a pure culture. Crops are placed in a thermostat.
An accelerated method for determining the type of pneumococcus(reaction of microagglutination). 4 drops of exudate from the abdominal cavity of an infected mouse are applied to a glass slide. Type I agglutinating serum is added to the first drop, type II serum to the second, type III to the third, and isotonic sodium chloride solution (control) to the fourth.
Type I and II sera are pre-diluted in a ratio of 1:10, and type III serum - 1:5. All drops are stirred, dried, fixed and stained with diluted magenta. With a positive result in one of the drops, microbial aggregation (agglutination) is noted.
Second day of research
The cultures are removed from the thermostat, examined, and smears are made from suspicious colonies. In the presence of gram-positive lanceolate diplococci in smears, 2-3 colonies are isolated on a slant of agar with serum to obtain a pure culture. Crops are placed in a thermostat. Smears are made from the broth, Gram-stained, and microscoped.
Third day of research
Crops are removed from the thermostat. Check the purity of the culture - make smears, Gram stain and microscope. If Gram-positive lanceolate diplococci are present in the isolated culture, the isolated culture is identified by inoculation:
1) on the Hiss media (lactose, glucose, sucrose, maltose), sowing is carried out in the usual way - by injection into the medium;
2) on the medium with inulin;
3) on the medium with optochin;
4) put a sample with bile.
Inulin test. The studied culture is seeded on a nutrient medium containing inulin and litmus tincture, and placed in a thermostat. After 18-24 hours, the crops are removed from the thermostat. In the presence of pneumococci, the medium turns red (streptococci do not change the consistency and color of the medium).
Determination of sensitivity to optochin. The isolated culture is seeded on 10% blood agar containing optochin 1:50,000. Pneumococci, unlike streptococci, do not grow on media containing optochin.
Bile test. 1 ml of the studied broth culture is poured into agglutination tubes. A drop of rabbit bile is added to one of them, the second test tube serves as a control. Both test tubes are placed in a thermostat. After 18-24 hours, lysis of pneumococci occurs, which is expressed in the clearing of a cloudy broth. In the control, the suspension remains cloudy.
A sample with bile can be placed on a dense nutrient medium. To do this, a grain of dry bile is applied to a colony of pneumococci grown in agar and serum plates - the colony dissolves - disappears.
Fourth day of research
The results are recorded (Table 26).
Note. to - the breakdown of carbohydrates with the formation of acid.
Currently, serological research methods (RSK and RIGA) are widely used to determine streptococcal antibodies. Determination of the group and serovar of the isolated culture is carried out using fluorescent antibodies.
Determination of pneumococcal virulence. Daily broth culture of pneumococcus is diluted with 1% peptone water from 10 -2 to 10 -8 , 0.5 ml of each dilution is administered to two white mice. The culture that caused the death of mice at a dilution of 10 -7 is assessed as virulent, at a dilution of 10 -4 -10 -6 it is considered moderately virulent. The culture that did not cause the death of mice is avirulent.
test questions
1. What methods of isolating a pure culture of pneumococci do you know?
2. Which animal is most susceptible to pneumococcus?
3. What reactions are put with the exudate of an infected mouse and for what purpose?
4. From which representatives of pyogenic cocci should pneumococcus be differentiated and by what test?
5. How to determine the virulence of pneumococci?
Exercise
Draw up a sputum examination scheme, indicating its stages by day.
Nutrient media
Serum Agar(see chapter 7).
Whey broth(see chapter 7).
agar with blood(see chapter 7).
Hiss media(dry).
Inulin test medium. To 200 ml of distilled water add 10 ml of inactivated bovine serum, 18 ml of litmus tincture and 3 g of inulin. Sterilize with flowing steam at 100°C for 3 consecutive days. Bile broth (see chapter 7).
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Streptococci are gram-positive cocci, mostly aerobes.
The classification of streptococci is based on the type of hemolysis they cause on blood agar and on the antigenic properties of the cell wall polysaccharide. According to the type of hemolysis, α-hemolytic, β-hemolytic and γ-non-hemolytic streptococci are distinguished. According to antigenic differences, 20 groups of streptococci are distinguished, designated by Latin letters from A to V (classification by R. Lancefield).
The most pathogenic streptococcus is α-hemolytic streptococcus group A - Streptococcus pyogenes. It causes sore throat, scarlet fever, erysipelas, impetigo and sepsis. Sensitization can cause erythema nodosum, rheumatism, and acute glomerulonephritis. In addition to the polysaccharide antigen, Streptococcus pyogenes also has other surface antigens (types M, T and R), they are used for epidemiological studies.
The M antigen is an important virulence factor; it is associated with the development of type-specific immunity; some streptococci that have the M antigen cause glomerulonephritis. Streptococcus pyogenes produces the following types of exotoxins.
Streptolysin O: damages cells by binding to cholesterol in membranes; has a cardiotoxic effect in many animals, possibly in humans; powerful antigen.
Streptolysin S: has hemolytic activity, its mechanism of action is unknown; does not have antigenic properties.
Deoxyribonuclease, streptokinase, hyaluronidase: may contribute to the spread of infection in tissues.
Erythrogenic (pyogenic) toxin: only some strains produce it; has antigenic properties.
Streptococcus viridans (α-hemolytic streptococcus) is the main causative agent of subacute infective endocarditis; anaerobic streptococci often cause surgical and postpartum sepsis.
Streptococcus pyogenes infections are common in temperate countries. Children are more often infected, the incidence increases in winter. The infection is often asymptomatic, up to 20% of children are bacteria carriers.
The source of infection is a bacteriocarrier or a patient (especially with an upper respiratory tract infection). Children are more likely to become carriers of infection than adults. A recovering person is more contagious than a carrier. In carriers, the infection is more often localized in the pharynx than in the nose, but in the latter case, the number of bacteria and their virulence is higher.
The most common route of transmission of infection is airborne: with saliva or sputum when coughing and sneezing. Another way is contact-household: through handshakes and household items. Consumption of contaminated foods (most often milk) can cause outbreaks of sore throats and scarlet fever.
The outcome of infection depends on the virulence of the bacteria and the resistance of the organism. With high antibacterial immunity, streptococci die or remain on the surface of the skin without causing harm. With a decrease in immunity or high virulence of streptococci, a superficial infection causes angina or impetigo, and a deeper infection causes lymphadenitis and sepsis. If bacteria produce a lot of erythrogenic toxin, and antitoxic immunity is reduced, scarlet fever develops.
Pathogen
1. Streptococci: pus smear (Gram stain). Streptococci are gram-positive bacteria of a round or oval shape with a diameter of 0.5-0.75 microns, interconnected in pairs or in chains of unequal length. They are immobile and do not form spores. May form a capsule in fresh culture; most streptococci are aerobes or facultative anaerobes, and only a few are obligate anaerobes or microaerophiles.
2. Culture on blood agar. Some aerobic streptococci produce soluble hemolysin, which causes a clear zone of hemolysis to form on fresh blood agar. This phenomenon is called hemolysis. The colonies are less than 1 mm in diameter and are surrounded by a clear, colorless zone, within which the erythrocytes are completely lysed. Hemolysis is especially pronounced when cultivating Streptococcus pyogenes under anaerobic conditions; in the presence of oxygen, hemolysis may not be. With α-hemolysis, the hemolysis zone is opaque and has a greenish tint.
Infections of the skin and mucous membranes
3. Streptococcal angina: lips. Lips become glossy and take on a cherry red hue. Weeping cracks are sometimes visible in the corners of the mouth.
4. Cervical lymphadenitis. The spread of infection from the palatine tonsils can cause purulent cervical lymphadenitis. In young children, swelling of the neck can be quite significant even with moderate changes in the tonsils. In such cases, mumps is sometimes misdiagnosed.
5. Catarrhal angina. Catarrhal angina can be both viral and streptococcal in nature, so it is difficult to judge the etiology without laboratory diagnostics. The picture shows that hyperemia spreads along the roof of the sky to the edematous uvula. In children under three years of age, local manifestations are mild, there are usually no raids. In the absence of treatment, the disease becomes protracted, subfebrile temperature persists for a long time. Diagnosis can be difficult with abdominal pain and vomiting.
6. Catarrhal angina. In older children and adults, the onset is acute and is manifested by sore throat, malaise, fever, and headache. The pharynx is inflamed, the tonsils are edematous, in more than half of the cases they are covered with a white or yellowish coating. The cervical and submandibular lymph nodes are enlarged and painful. In this age group, the disease usually resolves quickly.
7. Follicular tonsillitis. The severity of hyperemia of the mucosa is different, the tissues around the festering follicles are sometimes almost unchanged.
8. Peritonsillar abscess. The penetration of streptococci from the tonsils into the surrounding soft tissues leads to a rapid increase in edema, and often to suppuration. It becomes difficult to open the mouth, there is severe pain when swallowing, the voice becomes nasal. The front wall of the pharynx bulges, shifting the tongue in the opposite direction. In the future, an abscess is formed, as evidenced by the appearance of a yellow spot on the mucous membrane; in this place then there is an opening and emptying of the abscess. Antibiotics given early in the course of the disease can usually stop the infection from progressing and prevent abscess formation.
9. Angina Ludwig: front view. Phlegmon of the submandibular region (Ludwig's angina) is a very dangerous complication of tonsillitis, caries or lymphadenitis. Most often, Ludwig's angina is caused by streptococci, less often by mixed anaerobic flora.
10. Angina Ludwig: side view.
11. Angina Ludwig: bottom of the mouth. Inflammatory edema deforms the floor of the mouth and makes it difficult to swallow. Swelling of the larynx can develop suddenly and lead to asphyxia.
Scarlet fever
12. Pale nasolabial triangle and rash on the trunk. Scarlet fever is caused by strains of Streptococcus pyogenes that produce an erythrogenic toxin. The portal of infection is usually the pharynx, less commonly wounds, burns, and other skin lesions, such as vesicles in chickenpox. If the skin serves as the gate of infection, then they talk about wound scarlet fever. Infection of the birth canal can cause postpartum scarlet fever.
Scarlet fever begins with a high fever, sore throat, and vomiting. With a mild course, vomiting may be absent, sometimes there is no sore throat. The rash appears in the first 24-36 hours and spreads down the body from top to bottom. Bright red cheeks and chin contrast with a pale nasolabial triangle. Reddening of other areas of the skin is expressed to varying degrees, against this background, a small spotted spotted rash stands out. It is most noticeable around the neck and on the upper torso. On the distal parts of the extremities, the spots may merge. The pallor of the nasolabial triangle also occurs with other diseases, especially often with croupous pneumonia.
Complications of scarlet fever are divided into two groups: purulent-septic (rhinitis, sinusitis, otitis media and purulent lymphadenitis) and infectious-allergic (rheumatism and glomerulonephritis).
13. Spotted rash on the trunk. The rash is especially noticeable on the neck and chest, where it resembles reddened goose bumps.
14. Rash on thigh. A patchy rash on the extremities can be difficult to distinguish from rubella rash, but the characteristic appearance of the oral mucosa and pharynx allows a correct diagnosis.
15. Wound scarlet fever. In the absence of antitoxic immunity, absorption of the erythrogenic toxin from an infected wound or skin injury leads to scarlet fever. The typical rash occurs even when the streptococci do not spread beyond the wound.
16. Symptom Pastia. With a profuse rash, dark red pigmentation and petechiae often appear in skin folds, for example, in the folds of the elbows (Pastia's symptom). Pigmentation persists even after the rash fades.
17. Peeling on the brush. Peeling of the skin begins 4-5 days after the onset of the rash. First, small areas of peeling appear on the neck and upper body, and by the end of the second week, peeling extends to the hands and feet. The severity of peeling in different cases is not the same: the more abundant the rash, the stronger it is. When the rash is gone, flaking can help make the diagnosis, although it's not exclusive to scarlet fever. Peeling begins with the formation of small holes, surrounded by a rim of the epidermis, which then exfoliates and turns into scales.
18. Peeling on the brush. By the end of the second week, peeling begins around the nail folds, the thick epidermis of the palms and soles can peel off in large layers.
19. White strawberry tongue. During the first 1-2 days, the tongue is covered with a white coating, through which enlarged red papillae are visible. The sky is covered with dark red spots, sometimes individual petechiae are found on it. The pharynx is bright red, there is a white coating on the tonsils.
20. Red strawberry tongue. After a few days, the plaque peels off from the top and sides of the tongue. The picture shows a red glossy surface of the tongue with protruding papillae and islands of white plaque.
erysipelas
21. Butterfly. The development of erysipelas is often preceded by an upper respiratory tract infection. Degenerative changes in the skin, common in the elderly, also predispose to deep penetration of the infection. Erysipelas is usually localized on the face or on the legs: streptococci fall on them from the fingers. Penetrating through minor skin lesions, streptococci spread with lymph flow. Sometimes erysipelas occurs due to streptococcal infection of the surgical wound, trophic ulcer or umbilical wound in a newborn.
The incubation period does not exceed a week. The disease begins acutely: with fever and chills. Within a few hours, the patient experiences itching and burning in the affected area, then there is a sharp reddening of the skin, which spreads rapidly. The inflamed area has clear boundaries and rises above healthy skin. In the center of redness, a bubble may form, after opening which remains a bare weeping surface. Facial erysipelas often start on one cheek, then spread across the bridge of the nose to the other, taking on the shape of a butterfly.
22. Erysipelas of the face: acute period. In the acute period, the eyelids sometimes swell so much that the eye does not open, while the eyelashes stick together with pus.
23. Erysipelas of the face: recovery period. After the inflammation subsides, hyperpigmentation and flaking remain. These areas are especially sensitive to sunlight and cold for several months.
24. Phlegmonous erysipelas: acute period. The infection can penetrate into the subcutaneous tissues and cause phlegmon (phlegmonous erysipelas). Often a bubble is formed with serous-purulent contents, which is then opened. Necrosis of the affected tissues (gangrenous erysipelas) may develop.
25. Erysipelas of the legs: the period of recovery. The lower leg is edematous, the skin is hyperpigmented and flaky. Lymphangitis leads to chronic lymphostasis: this predisposes to relapses of erysipelas.
Streptococcal impetigo.
26. Impetigo on the face. Impetigo is a form of pyoderma, a highly contagious disease caused by both streptococci and staphylococci. Eczema, pediculosis, scabies and fungal infection predispose to the development of impetigo. Purulent blisters first appear on the face - around the mouth and nose - and very quickly spread to other parts of the body. The blisters dry up and form crusts. Streptococcal impetigo differs from staphylococcal impetigo in the golden color of the crusts.
27. Impetigo on the lower leg. Local application of antibiotics is ineffective, since the access of drugs is difficult due to thick crusts. Skin lesions with nephritogenic strains of streptococcus can cause acute glomerulonephritis.
28. Phlegmon. The penetration of streptococci through the skin and mucous membranes can lead to the development of phlegmon. The defeat of the lymphatic vessels leads to lymphangitis and lymphadenitis, and the penetration of streptococci into the bloodstream causes sepsis. With phlegmon, the inflamed area has less clear boundaries than with erysipelas, and is accompanied by suppuration.
29. Sepsis. The penetration of Streptococcus pyogenes into the bloodstream leads to metastatic lesions, for example, as in this case, to phlegmon. In the clinical picture of sepsis, the leading place is occupied by a violation of the general condition, so the defeat of individual organs fades into the background.
30. Abscess of the brain. The entry into the bloodstream of a small amount of low-virulence streptococci can cause only a slight violation of the general condition. However, they can settle in internal organs (such as the brain), leading to abscesses. Usually such streptococci are microaerophiles or anaerobes. Abscesses can be asymptomatic for a long time.
31. Subacute infective endocarditis. Streptococcus viridans (α-hemolytic streptococcus, viridans streptococcus) is part of the normal microflora of the mouth. In diseases of the teeth and gums, Streptococcus viridans can enter the bloodstream and cause infective endocarditis (especially on diseased valves). The only manifestation of infective endocarditis may be prolonged fever. The main diagnostic methods are blood cultures and echocardiography.
In subacute infective endocarditis, the vegetations on the valves are more massive, soft and loose than in rheumatism. The valves themselves are damaged to a lesser extent than in acute infective endocarditis (the most common causative agent of which is Staphylococcus aureus). Small emboli, detached from the outer layer of the vegetation, mostly settle in the kidneys and brain. They rarely contain bacteria, and therefore the heart attacks caused by them proceed without complications. (Arrows show vegetations.)
32. Subacute infective endocarditis: histological specimen of a heart valve. Vegetations consist of three layers: the outer one has an eosinophilic color and a granular structure. It is made up of fibrin and platelets. Streptococci are located in the middle layer, and the inner one is formed by an inflamed valve leaflet. The outer layer is a frequent source of small emboli (A - myocardium, B - valve leaflet, C - outer layer of vegetation).
33. Subacute infective endocarditis: subungual hemorrhages. The deposition of immune complexes in the walls of blood vessels can lead to hemorrhages in the conjunctiva, oral mucosa and under the nails. Small painful nodules form on the pads of the fingers and toes - Osler's nodules. Glomerulonephritis often develops.
Sensitization to streptococci
34. Erythema nodosum: localization of the rash. The rash in erythema nodosum consists of painful nodules 1-5 cm in diameter. The rash is usually localized on the shins; the hands and face may also be affected. Erythema nodosum is more common in young people. It is caused by sensitization, including to β-hemolytic streptococci. The general condition is disturbed to varying degrees; there is often fever and swollen lymph nodes.
35. Erythema nodosum. Initially, the nodes are red and painful, in the process of reverse development, they change color, like a bruise. The nodes do not ulcerate and do not leave scars.
36. Ring-shaped erythema. Erythema annulare is also caused by sensitization to streptococci. The rash looks like annular red spots, localized on the trunk. Erythema annulare is more common in children, sometimes against the background of a rheumatic attack.
Streptococcal infections are a group of infectious diseases caused by streptococci of various serological groups, with airborne and alimentary transmission of the pathogen, occurring with fever, intoxication, local suppurative processes and the development of post-streptococcal autoimmune (rheumatism, glomerulonephritis) complications.
ICD-10 codes
A38. Scarlet fever.
A40. Streptococcal septicemia.
A40.0. Septicemia caused by group A streptococcus.
A40.1. Septicemia caused by group B streptococcus.
A40.2. Septicemia caused by group D streptococcus.
A40.3. Septicemia caused by Streptococcus pneumoniae.
A40.8. Other streptococcal septicemias.
A40.9. Streptococcal septicemia, unspecified.
A46. Erysipelas.
A49.1. Streptococcal infection, unspecified.
B95. Streptococci and staphylococci as the cause of diseases classified elsewhere.
B95.0. Group A streptococci as the cause of diseases classified elsewhere.
B95.1. Group B streptococci as the cause of diseases classified elsewhere.
B95.2. Group D streptococci as the cause of diseases classified elsewhere.
B95.3. Streptococcus pneumoniae as the cause of diseases classified elsewhere.
B95.4. Other streptococci as the cause of diseases classified elsewhere.
B95.5. Unspecified streptococci as the cause of diseases classified elsewhere.
G00.2. Streptococcal meningitis.
M00.2. Other streptococcal arthritis and polyarthritis.
R23.3. Congenital pneumonia caused by group B streptococcus.
R23.6. Congenital pneumonia caused by other bacterial agents (streptococcus, with the exception of group B).
P36.0. Neonatal sepsis due to group B streptococcus.
P36.1. Neonatal sepsis due to other and unspecified streptococci.
Z22.3. Carriage of pathogens of other specified bacterial diseases (streptococci).
Etiology (causes) of streptococcal infection
The causative agents are non-motile facultative anaerobic gram-positive cocci of the genus Streptococcus of the family Streptococcaceae. The genus includes 38 species differing in metabolic features, cultural and biochemical properties, and antigenic structure. Cell division occurs only in one plane, so they are arranged in pairs (diplococci) or form chains of different lengths. Some species have a capsule. Pathogens are capable of growth at a temperature of 25–45 °C; temperature optimum - 35–37 °С. On dense nutrient media, they form colonies with a diameter of 1–2 mm. On media with blood, colonies of some species are surrounded by a zone of hemolysis. An obligate sign that characterizes all representatives of the genus streptococci is negative benzidine and catalase tests. Streptococci are stable in the environment; for many months they are able to persist in dried pus or sputum.
Exciters withstand heating up to 60 °C for 30 minutes; under the influence of disinfectants die within 15 minutes.
According to the structure of group-specific polysaccharide antigens (substance C) of the cell wall, 17 serological groups of streptococci are distinguished, denoted by Latin letters (A–O). Within groups, streptococci are divided into serological variants according to the specificity of protein M-, P-, and T-antigens.
Group A streptococci have a wide range of superantigens: erythrogenic toxins A, B and C, exotoxin F (mitogenic factor), streptococcal superantigen (SSA), erythrogenic toxins (SpeX, SpeG, SpeH, SpeJ, SpeZ, SmeZ-2).
Superantigens are capable of interacting with major histocompatibility complex antigens expressed on the surface of antigen-presenting cells and with variable regions of the β-chain of T-lymphocytes, causing their proliferation and a powerful release of cytokines, TNF-α and γ-interferon. In addition, group A streptococcus is capable of producing biologically active extracellular substances: streptolysins O and S, streptokinase, hyaluronidase, DNase B, streptodornase, lipoproteinase, peptidase, etc.
The cell wall of streptococcus includes a capsule, protein, polysaccharide (group-specific antigen) and mucoprotein layer. An important component of group A streptococci is protein M, which resembles the structure of the fimbria of gram-negative bacteria. The M protein (type-specific antigen) is the main virulence factor. Antibodies to it provide long-term immunity to re-infection, however, according to the structure of the M protein, more than 110 serological types are distinguished, which significantly reduces the effectiveness of humoral defense reactions. Protein M inhibits phagocytic reactions by directly acting on phagocytes, masking receptors for complement components and opsonins, and adsorbing fibrinogen, fibrin, and its degradation products on its surface. It has the properties of a superantigen, causing polyclonal activation of lymphocytes and the formation of antibodies with low affinity. Such properties play a significant role in the violation of tolerance to tissue iso-antigens and in the development of autoimmune pathology.
The properties of type-specific antigens are also possessed by the T-protein of the cell wall and lipoproteinase (an enzyme that hydrolyzes the lipid-containing components of the blood of mammals). Streptococci of different M-variants may have the same T-type or a complex of T-types. The distribution of serotypes of lipoproteinase exactly corresponds to certain M-types, but this enzyme is produced by about 40% of strains of streptococcus. Antibodies to T-protein and lipoproteinase do not possess protective properties. The capsule contains hyaluronic acid - one of the virulence factors. It protects bacteria from the antimicrobial potential of phagocytes and facilitates adhesion to the epithelium. Hyaluronic acid has antigen properties. Bacteria are capable of destroying the capsule on their own when they invade tissues, synthesizing hyaluronidase. The third most important factor of pathogenicity is C5a-peptidase, which suppresses the activity of phagocytes. The enzyme cleaves and inactivates the C5a component of complement, which is a powerful chemoattractant.
Group A streptococci produce various toxins. Antibody titers to streptolysin O are of prognostic value. Streptolysin S exhibits hemolytic activity under anaerobic conditions and causes surface hemolysis on blood media. Both hemolysins destroy not only erythrocytes, but also other cells: streptolysin O damages cardiomyocytes, and streptolysin S damages phagocytes. Some strains of group A streptococci synthesize cardiohepatic toxin. It causes damage to the myocardium and diaphragm, as well as the formation of giant cell granulomas in the liver.
The bulk of group B streptococcal isolates are S. agalactiae. In recent years, they have increasingly attracted the attention of medical professionals. Group B streptococci commonly colonize the nasopharynx, gastrointestinal tract, and vagina.
There are the following serological variants of group B streptococci: Ia, Ib, Ic, II and III. Bacteria of serovars Ia and III are tropic to the tissues of the central nervous system and respiratory tract; often cause meningitis in newborns.
Among other species, pneumococci (S. pneumoniae) are of great diagnostic value, causing the majority of community-acquired pneumonia in humans.
Epidemiology of streptococcal infection
The reservoir and source of infection are patients with various clinical forms of acute streptococcal diseases and carriers of pathogenic streptococci. The greatest danger from an epidemiological point of view are patients whose foci are localized in the upper respiratory tract (scarlet fever, tonsillitis). They are highly contagious, and the bacteria they secrete contain the main virulence factors, the capsule and protein M. Infection from such patients most often leads to the development of a manifest infection in susceptible individuals.
Patients in whom foci of streptococcal infection are localized outside the respiratory tract (streptococcal pyoderma, otitis media, mastoiditis, osteomyelitis, etc.) are not so contagious, which is associated with a less active release of the pathogen from the body.
The duration of the contagious period in patients with acute streptococcal infection depends on the method of treatment. Rational antibiotic therapy of patients with scarlet fever and tonsillitis frees the body from the pathogen within 1.5–2 days. Drugs (sulfonamides, tetracyclines), to which group A streptococci have completely or partially lost their sensitivity, form convalescent carriage in 40–60% of those who have been ill.
In communities where 15–20% of long-term carriers are present, streptococcus is usually constantly circulating. Carriage is considered dangerous for others with a microbial focus of more than 103 CFU (colony-forming units) per swab. The level of such carriage is significant - about 50% of healthy carriers of group A streptococci. Among cultures of the pathogen isolated from carriers, virulent strains are found several times less often than among strains isolated from patients. Carriage of streptococci of groups B, C and G in the pharynx is observed much less frequently than carriage of group A streptococci.
According to various data, for 4.5–30% of women, the carriage of group B streptococci in the vagina and rectum is typical. The localization of the pathogen in the body largely determines the route of its elimination.
Mechanism of transmission- aerosol (airborne), less often - contact (food route and transmission through contaminated hands and household items). Infection usually occurs through close contact with a patient or a carrier for a long time. The causative agent is released into the environment most often during expiratory acts (coughing, sneezing, active conversation). Infection occurs by inhalation of the resulting airborne aerosol. Overcrowding indoors and prolonged close contact exacerbate the likelihood of infection.
At the same time, it should be taken into account that at a distance of more than 3 m, this transmission path is practically impossible.
The transmission factors of the pathogen are dirty hands, household items and infected food. Additional factors contributing to the transmission of the pathogen are low temperature and high humidity in the room.
Group A streptococci, getting into certain food products, are capable of reproduction and long-term preservation of virulent properties. So, outbreaks of tonsillitis or pharyngitis are known when using milk, compotes, butter, boiled egg salads, lobsters, shellfish, sandwiches with eggs, ham, etc.
The risk of developing purulent complications of streptococcal genesis are exposed to the wounded, burned, patients in the postoperative period, as well as women in labor and newborns. Autoinfection is possible, as well as the transmission of group B streptococci, which cause urogenital infections, through sexual contact. In the pathology of the neonatal period, the transmission factors are infected amniotic fluid. In 50% of cases, infection is possible during the passage of the fetus through the birth canal.
The natural susceptibility of people is high. Antistreptococcal immunity is antitoxic and antimicrobial in nature. In addition, there is a sensitization of the body by the type of HRT, which is associated with the pathogenesis of many post-streptococcal complications. Immunity in patients who have had a streptococcal infection is type-specific. It is possible to re-disease when infected with another serovar of the pathogen. Antibodies to the M protein are found in almost all patients from the 2nd–5th week of illness and within 10–30 years after the disease. Often they are determined in the blood of newborns, but by the 5th month of life they disappear.
Streptococcal infections are ubiquitous. In areas of temperate and cold climates, the incidence of pharyngeal and respiratory forms of infection is 5-15 cases per 100 people. In southern regions with a subtropical and tropical climate, skin lesions (streptoderma, impetigo) are of primary importance, the frequency of which among children in certain seasons reaches 20% or more. Minor injuries, insect bites, and poor skin hygiene predispose to their development.
Nosocomial streptococcal infection is possible in obstetric institutions; children's, surgical, otolaryngological, eye departments of hospitals. Infection occurs both endogenously and exogenously (from carriers of streptococci among staff and patients) through invasive diagnostic and treatment manipulations.
Cyclicity is one of the characteristic features of the epidemic process in streptococcal infections. In addition to the well-known cyclicity with an interval of 2–4 years, there is a periodicity with an interval of 40–50 years or more. The peculiarity of this undulation is in the emergence and disappearance of especially severe clinical forms. A significant number of cases of scarlet fever and tonsillopharyngitis are complicated by purulent-septic (otitis, meningitis, sepsis) and immunopathological (rheumatism, glomerulonephritis) processes. Severe generalized forms of infection with concomitant deep soft tissue lesions were previously referred to as "streptococcal gangrene". Since the mid 80s. in many countries, an increase in the incidence of streptococcal infection has been noted, which coincided with changes in the nosological structure of diseases caused by S. pyogenes. Again began to register group cases of severe generalized forms, often ending in death [toxic shock syndrome (TSS), septicemia, necrotizing myositis, fasciitis, etc.]. In the United States, 10-15 thousand cases of invasive streptococcal infection are recorded annually, of which 5-19% (500-1500 cases) are necrotizing fasciitis.
The widespread use of laboratory methods of research has made it possible to establish that the return of invasive streptococcal diseases is associated with a change in the pathogen serotypes circulating in the population: rheumatogenic and toxigenic serotypes have replaced M-serotypes. In addition, the incidence of rheumatic fever and toxic infections (toxic tonsillopharyngitis, scarlet fever and TSS) has increased.
In Russia in the late 80's - early 90's. the predominance of serotypes of the pathogen involved in the occurrence of severe generalized forms of infection was noted. Currently, 6-8 million cases of respiratory streptococcal infections are registered annually in Russia.
The economic cost of streptococcal infections and their consequences is about 10 times greater than that of viral hepatitis. Among the studied streptococcosis, angina (57.6%), acute respiratory infections of streptococcal etiology (30.3%), erysipelas (9.1%), scarlet fever and active rheumatism (1.2%) and, finally, acute nephritis (0 .7%).
Diseases of primary streptococcal infection account for 50–80% of the seasonal incidence. The incidence of respiratory streptococcal infection has a pronounced autumn-winter-spring seasonality. The seasonal incidence rate is determined mainly by children attending preschool institutions.
The formation or renewal of organized teams and their numbers have a decisive influence on the timing of the seasonal increase in morbidity.
In organized collectives, updated once a year, a single seasonal increase in infection is observed. With a two-fold update, two-fold seasonal increases in the incidence are noted, especially characteristic of military groups. The first maximum incidence associated with the spring conscription is observed in June–July, the second, due to the autumn conscription, in December–January.
Measures to prevent streptococcal infection
In the absence of means of specific prevention of diseases transmitted by aerosols, with many erased and asymptomatic forms of infection, it is not so easy to reduce the incidence of streptococcal infection, therefore, anti-epidemic measures in organized groups are of particular importance.
The basis for the prevention of respiratory streptococcal infections in such groups is early and active diagnosis, isolation and full etiotropic treatment of patients. Preparations of the penicillin series prevent group diseases of scarlet fever and reduce the incidence of tonsillitis and streptococcal acute respiratory infections. To stop outbreaks of respiratory streptococcal diseases in organized groups, general emergency prophylaxis is carried out with penicillin preparations. To do this, all persons in contact with patients are given a single intramuscular injection of bicillin-5 (preschoolers - 750,000 IU, schoolchildren and adults - 1,500,000 IU) or bicillin-1 (preschoolers - 600,000 IU, schoolchildren and adults - 1,200,000 IU ). In military contingents belonging to high-risk groups for respiratory streptococcal infection, it is advisable to carry out emergency prophylaxis immediately after the formation of teams and before the start of the seasonal rise in the incidence (emergency preventive prophylaxis). In other groups, where seasonal rises in incidence are relatively low or not of a regular nature, an interrupting type of emergency prophylaxis can be used. In this case, it is carried out during the period of the epidemic rise in the incidence.
In organized children's and adult groups, hospital conditions, sanitary and hygienic measures (reducing the size of the team, its crowding, general sanitary measures, disinfection regimen) reduce the likelihood of airborne and contact-household transmission of the pathogen. Prevention of the alimentary route of infection is carried out in the same directions as with intestinal infections.
Activities in the epidemic focus
Decisive importance is attached to measures aimed at neutralizing the sources of infection (patients, convalescents, carriers) and preventing post-streptococcal complications. Treatment with penicillin drugs is carried out for ten days (WHO recommendations) - this is enough for the complete rehabilitation of patients as sources of infection and in order to prevent the development of post-streptococcal complications.
The pathogenesis of streptococcal infection
Most often, diseases occur after streptococci enter the mucous membranes of the pharynx and nasopharynx. Lipoteichoic acid, which is part of the cell wall, M- and F-proteins ensure the adhesion of the pathogen to the surface of the tonsils or other lymphoid cells. Protein M contributes to the resistance of bacteria to the antimicrobial potential of phagocytes, binds fibrinogen, fibrin and its degradation products. When streptococci multiply, toxins are released that cause an inflammatory reaction in the tissues of the tonsils. When streptococci enter the lymphatic tract through the lymph nodes, regional (angular) lymphadenitis occurs. Toxic components, penetrating into the blood, cause a generalized expansion of small vessels (clinically - hyperemia and punctate rash). An allergic component that disrupts vascular permeability is considered the cause of the development of glomerulonephritis, arthritis, endocarditis, etc. The septic component leads to the accumulation of the pathogen in various organs and systems and the development of foci of purulent inflammation. The presence of common cross-reacting antigenic determinants in group A streptococci (protein M, non-type-specific proteins, A-polysaccharide, etc.) and the sarcolemma of myofibrils of the heart and kidney tissues determines the development of autoimmune processes leading to rheumatism and glomerulonephritis. Molecular mimicry is the main pathogenetic factor of streptococcal infection in these diseases: antibodies to streptococcal antigens react with host autoantigens. On the other hand, protein M and erythrogenic toxin exhibit the properties of superantigens and cause T-cell proliferation, activating the cascade reaction of the effector link of the immune system and the release of mediators with cytotoxic properties: IL, TNF-α, interferon-gamma. Infiltration of lymphocytes and the local action of cytokines play an important role in the pathogenesis of invasive streptococcal infections (with cellulitis, necrotic fasciitis, skin lesions, internal organs). An important role in the pathogenesis of invasive streptococcal infection is assigned to TNF-α, LPS of its own gram-negative microflora and its synergistic interaction with the erythrogenic toxin S. pyogenes.
Clinical picture (symptoms) of streptococcal infection
Clinical forms of streptococcal infection. The clinical symptoms of streptococcal infections are diverse and depend on the type of pathogen, the location of the pathological process and the condition of the infected organism.
Diseases caused by group A streptococci can be divided into primary, secondary and rare forms. The primary forms include streptococcal lesions of the ENT organs (tonsillitis, pharyngitis, acute respiratory infections, otitis media, etc.), skin (impetigo, ecthyma), scarlet fever, erysipelas. Among the secondary forms, diseases with an autoimmune mechanism of development (non-purulent) and toxic-septic diseases are distinguished. Secondary forms of the disease with an autoimmune mechanism of development include rheumatism, glomerulonephritis, vasculitis, and toxic-septic diseases - metatonsillar and peritonsillar abscesses, necrotic lesions of soft tissues, septic complications. Rare forms include necrotic fasciitis and myositis; enteritis; focal lesions of internal organs, TSS, sepsis, etc.
Clinical and laboratory signs of invasive streptococcal infection
The fall in systolic blood pressure to the level of 90 mm Hg. and below.
Multiorgan lesions involving two or more organs:
- kidney damage: creatinine in adults is equal to or greater than 2 mg / dl, and in children twice the age norm;
- coagulopathy: platelet count less than 100×106/l; increased intravascular coagulation; low content of fibrinogen and the presence of its decay products;
- liver damage: the age norm of the content of transaminases and total bilirubin is exceeded two times or more;
- acute RDS: acute onset of diffuse pulmonary infiltration and hypoxemia (with no signs of heart damage); increased capillary permeability; widespread edema (presence of fluid in the pleural or peritoneal area); decrease in the content of albumin in the blood;
- common erythematous spotted rash with desquamation of the epithelium;
- soft tissue necrosis (necrotizing fasciitis or myositis).
Laboratory criterion - isolation of group A streptococcus.
Cases of streptococcal infection are divided into:
probable - the presence of clinical signs of the disease in the absence of laboratory confirmation or when another pathogen is isolated; isolation of group A streptococcus from non-sterile body media;
confirmed - the presence of the listed signs of the disease with the release of group A streptococcus from the usually sterile environments of the body (blood, CSF,
pleural or pericardial fluid).
There are four stages in the development of an invasive form of streptococcal infection:
Stage I - the presence of a localized focus and bacteremia (in severe forms of tonsillopharyngitis and streptoderma, blood cultures are recommended);
Stage II - circulation of bacterial toxins in the blood;
Stage III - a pronounced cytokine response of the macroorganism;
Stage IV - damage to internal organs and toxic shock or coma.
Young people get sick more often. The invasive form of streptococcal infection is characterized by a rapid increase in hypotension, multiorgan lesions, RDS, coagulopathy, shock, and high mortality. Predisposing factors: diabetes mellitus, immunodeficiency states, diseases of the vascular system, the use of glucocorticoids, alcoholism, chickenpox (in children).
A provoking moment can be a minor superficial injury, hemorrhage into soft tissues, etc.
Necrotizing fasciitis (streptococcal gangrene)
Confirmed (established) case:
- soft tissue necrosis with involvement of the fascia;
- systemic disease, including one or more signs: shock (drop in blood pressure below 90 mm Hg), disseminated intravascular coagulation, damage to internal organs (lungs, liver, kidneys);
- isolation of group A streptococcus from normally sterile environments of the body.
Supposed case:
- the presence of the first and second signs, as well as serological confirmation of streptococcal (group A) infection (4-fold increase in antibodies to streptolysin O and DNase B);
- the presence of the first and second signs, as well as histological confirmation of soft tissue necrosis caused by gram-positive pathogens.
Necrotizing fasciitis can be triggered by minor damage to the skin. External signs: swelling; erythema red, and then cyanotic; the formation of rapidly opening vesicles with a yellowish liquid. The process covers not only the fascia, but also the skin and muscles. On the 4-5th day, there are signs of gangrene; on the 7th–10th day - a sharp delineation of the affected area and detachment of tissues. Characterized by a rapid increase in symptoms, the development of early multi-organ (kidney, liver, lungs) and systemic lesions, acute RDS, coagulopathy, bacteremia, shock (especially in the elderly and people with concomitant diabetes mellitus, thrombophlebitis, immunodeficiency). A similar course of the process is also possible in practically healthy people.
streptococcal gangrene different from fasciitis of other etiologies. It is characterized by a transparent serous exudate, diffusely impregnating the flabby whitish fascia without signs of purulent fusion. Necrotizing fasciitis is distinguished from clostridial infection by the absence of crepitus and gas production.
Streptococcal myositis is a rare form of invasive streptococcal infection. The main symptom is severe pain that does not correspond to the severity of the external signs of the disease (swelling, erythema, fever, feeling of muscle strain). Characterized by a rapid increase in signs of local necrosis of muscle tissue, multiple organ lesions, acute distress syndrome, coagulopathy, bacteremia, shock. Lethality - 80–100%. TSS is a disease that poses a direct threat to life. In 41% of cases, the entrance gate of infection is a localized infection of soft tissues; lethality - 13%. Pneumonia is the second most common primary source of pathogen entry into the blood (18%); lethality - 36%. Invasive streptococcal infection in 8-14% of cases leads to the development of TSS (mortality - 33-81%). TSS caused by group A streptococcus is superior to TSS of other etiologies in terms of the severity of the clinical picture, the rate of increase in hypotension and organ damage, and the level of mortality. The rapid development of intoxication is characteristic.
Shock Symptoms occur after 4-8 hours and depend on the localization of the focus of the primary infection. For example, in the development of TSS associated with a deep skin infection involving soft tissues, the most common initial symptom is sudden intense pain (the main reason for seeking medical help). At the same time, objective symptoms (swelling, soreness) at the initial stages of the development of the disease may be absent, which causes erroneous diagnoses (flu, rupture of muscles or ligaments, acute arthritis, gout attack, deep vein thrombophlebitis, etc.). Cases of the disease with a fatal outcome in apparently healthy young people are described.
Severe pain, depending on its location, may be associated with peritonitis, myocardial infarction, pericarditis, pelvic inflammatory disease. Pain is preceded by an influenza-like syndrome: fever, chills, muscle pain, diarrhea (20% of cases). Fever is found in approximately 90% of patients; soft tissue infection leading to the development of necrotizing fasciitis in 80% of patients. In 20% of hospitalized patients, endophthalmitis, myositis, perihepatitis, peritonitis, myocarditis and sepsis may develop.
In 10% of cases, hypothermia is likely, in 80% - tachycardia, hypotension. All patients have progressive renal dysfunction, half of the patients have acute RDS. As a rule, it occurs already against the background of hypotension and is characterized by severe shortness of breath, severe hypoxemia with the development of diffuse pulmonary infiltrates and pulmonary edema. In 90% of cases, tracheal intubation and mechanical ventilation are necessary. More than 50% of patients experience disorientation in time and space; in some cases, coma may develop. In half of the patients who had normal blood pressure at the time of hospitalization, progressive hypotension is detected over the next 4 hours.
DIC often occurs.
Extensive necrotic changes in the soft tissues require surgical debridement, fasciotomy and, in some cases, amputation of the limbs. The clinical picture of shock of streptococcal genesis is distinguished by a certain torpidity and a tendency to persist, resistant to ongoing therapeutic measures (antibiotic therapy, administration of albumin, dopamine, saline solutions, etc.).
Kidney damage precedes the development of hypotension, which is characteristic only of streptococcal or staphylococcal toxic shock. Hemoglobinuria, an increase in creatinine by 2.5–3 times, a decrease in the concentration of albumin and calcium in the blood serum, leukocytosis with a shift to the left, an increase in ESR, and a decrease in hematocrit by almost two times are characteristic.
Lesions caused by group B streptococci occur in all age categories, but pathology of newborns dominates among them. In 30% of children, bacteremia is found (without a specific focus of primary infection), in 32-35% - pneumonia, and the rest - meningitis, often occurring within the first 24 hours of life. Diseases of newborns are severe, mortality reaches 37%. Meningitis and bacteremia are common in children, with 10–20% of children dying and 50% of survivors having residual impairment. Group B streptococci cause postpartum infections in puerperas: endometritis, urinary tract lesions, and complications of surgical wounds during caesarean section. In addition, group B streptococci can cause skin and soft tissue lesions, pneumonia, endocarditis, and meningitis in adults. Bacteremia is observed in elderly people suffering from diabetes mellitus, peripheral vascular disease and malignant neoplasms. Of particular note are streptococcal pneumonias that occur against the background of SARS.
Streptococci of serogroups C and G are known as the causative agents of zoonoses, although in some cases they can lead to local and systemic inflammatory processes in humans. Viridescent streptococci can cause bacterial endocarditis. Less significant, but incomparably more frequent pathology is carious lesions of the teeth caused by streptococci of the mutans biogroup (S. mutans, S. mitior, S. salivarius, etc.).
Diagnosis of streptococcal infection
Clinical diagnosis of streptococcal infections is often difficult.
The diagnosis of streptococcal pharyngeal and skin infections in all cases, except for scarlet fever and erysipelas, requires bacteriological studies with specific identification of the pathogen. For these purposes, express methods for identifying group A streptococci are used, with the help of which it is possible to diagnose an acute streptococcal infection within 15–20 minutes without first isolating a pure culture of the pathogen.
At the same time, the isolation of streptococci does not always indicate their involvement in pathology due to the widespread healthy carriage.
True infections caused by group A streptococci always initiate the development of a specific immune response, accompanied by a significant increase in antibody titer to one of the extracellular streptococcal antigens - streptolysin O, deoxyribonuclease B, hyaluronidase, or nicotinamide adenine dinucleotidease. These diagnostic methods are of practical importance in acute rheumatism and glomerulonephritis.
Along with the determination of the titer of antistreptococcal antibodies, the detection of circulating antigens (free or in immune complexes) plays an important role in establishing the role of streptococci in the formation of immunopathological processes. The basis of modern diagnostic methods is ELISA and the use of antisera to discrete antigens of group A streptococci.
Medical therapy
For the treatment of all diseases caused by group A streptococci, benzylpenicillin preparations are used, to which the pathogen remains highly sensitive. Most strains are also highly sensitive to erythromycin, azithromycin, clarithromycin, oxacillin, and oleandomycin.
In invasive streptococcal infections, benzylpenicillin is prescribed (intravenously or intramuscularly, 2.4 million units every 4 hours) and clindamycin (intravenously or intramuscularly, 0.6-1.2 g every 6 hours). Treatment of TSS with antibiotics is not always effective (mortality reaches 50%). Normal human immunoglobulin containing a wide range of neutralizing antibodies to streptococcal superantigens is effective.
DOMAIN → Bacteria; TYPE → Firmicutes; CLASS → Vasilli; ORDER → Lactobacillales;
FAMILY → Streptococcaceae; GENUS → Streptococcus; SPECIES → Streptococcus species (up to 50 species)
The main features of the genusStreptococcus:
1. Cells of spherical or oval (lanceolate) shape 0.5-2.0 microns. Arranged in a chain or in pairs.
2. Motionless, no dispute. Some species have a capsule.
3. Gram-positive. Chemoorganotrophs, demanding on nutrient media, facultative anaerobes
4. Ferment sugars to form acid, but this is not a reliable differentiator within the genus
5. Unlike staphylococci, there is no catalase activity and cytochromes.
6. Usually, erythrocytes are lysed. According to hemolytic properties: beta (complete), alpha (partial), gamma (none). Capable of forming L-shapes.
Antigenic structure of the genusStreptococcus:
Cell wall polysaccharide on the basis of which they are divided into 20 groups, denoted by Latin letters. Pathogenic species belong primarily to the A. group and less often to other groups. There are species without a group antigen.
Type-specific protein antigens (M, T, R). M-protein is possessed by pathogenic species. In total, there are over 100 serotypes, most of which belong to group A streptococci. The M-protein is located superficially in the form of filamentous formations braiding the cell - fimbriae.
Capsular streptococci have capsular antigens of various chemical nature and specificity.
There are cross-reactive antigens
Group A streptococci are part of the nasopharyngeal microflora and are not normally found on the skin. The most pathogenic for humans are hemolytic streptococci of group A, belonging to the species S. pyogenes
Group A streptococci cause infections at any age and are most common in children between 5 and 15 years of age.
Group A pathogenicity factors
1) Capsule (hyaluronic acid) → Antiphagocytic activity
2) M-protein (fimbriae) → Antiphagocytic activity, destroys complement (C3b), superantigen
3) M-like proteins → Bind IgG, IgM, alpha2-macroglobulin
4) F-protein → Microbe attachment to epithelial cells
5) Pyrogenic exotoxins (erythrogenins A, B, C) → Pyrogenic effect, increased HRT, immunosuppressive effect on B-lymphocytes, rash, superantigen
6) Streptolysins: S (oxygen stable) and
O (oxygen sensitive) → Destroy white blood cells, platelets, red blood cells. Stimulate the release of lysosomal enzymes.
7) Hyaluronidase → facilitates invasion by disintegrating connective tissue
8) Streptokinase (fibrinolysin) → Destroys blood clots (thrombi), promotes the spread of microbes in tissues
9) DNase → Demolymerizes extracellular DNA in pus
10) C5a-peptidase → Destroys the C5a component of complement, chemoattractant
The pathogenesis of infections caused byS. pyogenes:
It most commonly causes a localized infection of the upper respiratory tract or skin, but can infect any organ.
Most frequent suppurative processes: abscesses, phlegmon, tonsillitis, meningitis, pharyngitis, sinusitis, frontal sinusitis. lymphadenitis, cystitis, pyelitis, etc.
Local inflammation leads to leukocytolysis in the peripheral blood, followed by tissue infiltration with leukocytes and local pus formation.
Non-suppurative processes causedS. pyogenes:
erysipelas,
streptoderma,
impetigo,
scarlet fever,
rheumatoid infection (rheumatic fever),
glomerulonephritis,
toxic shock,
sepsis, etc.
Treatment of streptococcal infections:It is carried out primarily with antibiotics: cephalosporins, macrolides, lincosamides
Prevention of streptococcal infections:
General sanitary and hygienic measures, prevention and treatment of acute local streptococcal infections are important. To prevent relapse (rheumatic fever) - antibiotic prophylaxis.
An obstacle to the creation of vaccines is a large number of serotypes, which, taking into account the type-specificity of immunity, makes their production hardly realistic. In the future, the synthesis of M-protein polypeptides and the hybridoma route for its production.
Associated drugs are produced abroad for the immunotherapy of infections caused by opportunistic microbes - from 4 to 19 types. These vaccines include S.pyogenes and S.pneumoniae.
Immunoprophylaxis of pneumococcal infections - a vaccine from polysaccharides of 12-14 serovariants, which often cause diseases.
A vaccine against caries is being developed.
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