Causes and pathogenesis of streptococcal infection

Causes of Streptococcal Infection

Streptococcus causative agents are immobile facultative-anaerobic gram-positive cocci of the genus Streptococcus family of Streptococcaceae. The genus includes 38 species, differing in metabolic features, cultural-biochemical properties and antigenic structure. Cell division takes place only in one plane, so they are arranged in pairs (diplococci) or form chains of different lengths. Some species have a capsule. The causative agents are capable of growth at a temperature of 25-45 ° C; The temperature optimum is 35-37 ° C. On dense nutrient media, colonies with a diameter of 1-2 mm are formed. On media with blood, colonies of some species are surrounded by a hemolysis zone. Obligatory sign, which characterizes all representatives of the genus Streptococcus, is negative benzidine and catalase tests. Streptococci are stable in the environment; for months they can persist in dried pus or sputum. The causative agents can withstand heating to 60 ° C for 30 minutes: they are killed by disinfectants for 15 minutes.

According to the structure of group-specific polysaccharide antigens (Substance C) of the cell wall, 17 serological groups of streptococci, designated by Latin letters (A-0), are isolated. Inside the groups, streptococci are divided into serological variants for the specificity of protein M, P and T antigens. Group A streptococci have a wide spectrum 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 the antigens of the major histocompatibility complex expressed on the surface of antigen presenting cells and with the variable regions of the beta chain of T lymphocytes, causing their proliferation and powerful release of cytokines, TNF-α and γ-interferon. In addition, group A streptococcus is able to produce biologically active extracellular substances: streptolysins O and S, streptokinase, hyaluronidase, DNA-ase 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 streptococcus is the protein M, reminiscent of the structure of the fimbria of gram-negative bacteria. Protein M (type-specific antigen) is the main factor of virulence. Antibodies to it provide long-lasting immunity to repeated infection, however, more than 110 serological types are isolated in the structure of M protein, which significantly reduces the effectiveness of humoral defense responses. Protein M inhibits phagocytic reactions, directly acting on phagocytes, masking receptors for complement components and opsonins and adsorbing on its surface fibrinogen, fibrin and its degradation products. It has the properties of superantigen, causing polyclonal activation of lymphocytes and the formation of antibodies with low affinity. Such properties play an important role in the violation of tissue isoantigens tolerance and in the development of autoimmune pathology.

Properties of type-specific antigens are also possessed by the T-protein of the cell wall and lipoproteinase (an enzyme hydrolyzing the lipid-containing components of mammalian blood). Streptococci of different M variants may have the same T-type or T-type complex. Distribution of serotypes of lipoproteinase exactly corresponds to certain M-types, but this enzyme produces about 40% of Streptococcus strains. Antibodies to T-protein and lipoproteinase have no protective properties. The capsule contains hyaluronic acid - one of the factors of virulence. It protects bacteria from the antimicrobial potential of phagocytes and facilitates adhesion to the epithelium. Hyaluronic acid has antigen properties. Bacteria are capable of self-destroying the capsule when invading tissue, synthesizing hyaluronidase. The third most important factor of pathogenicity is C5a-peptidase, the suppressive activity of phagocytes. The enzyme cleaves and inactivates the C5a component of complement, which acts as a powerful chemoattractant.

Streptococcus group A produces a variety of toxins. Antibody titres to streptolysin O have a prognostic significance. Streptolysin S shows hemolytic activity under anaerobic conditions and causes superficial hemolysis on blood media. Both hemolysins destroy not only erythrocytes, but also other cells: streptolysin O damages the cardiomyocytes, and streptolysin S - phagocytes. Some strains of group A streptococcus synthesize cardiogeopathic toxin. It causes damage to the myocardium and diaphragm, as well as the formation of giant cell granules in the liver.

The main part of isolates of group B Streptococcus are S. Agalactiae. In recent years, they are increasingly attracting the attention of health professionals. Group B streptococci usually colonize the nasopharynx, the gastrointestinal tract and the vagina. The following serological variants of group B streptococcus are distinguished: la, lb, Ic, II and III. Bacteria of serovars 1a and III are pathogenic to the tissues of the central nervous system and respiratory tract; often cause meningitis in newborns.

Among other types of pneumococcus pneumoniae (S. Pneumoniae), which cause the majority of community-acquired pneumonia in humans, are of great diagnostic importance. They do not contain a group antigen and are serologically heterogeneous. According to the structure of capsular antigens, 84 serological variants of pneumococci are isolated.

[1], [2], [3], [4], [5], [6], [7]

Pathogenesis of streptococcal infection

Most often, the disease occurs after getting streptococci on the mucous membranes of throat and nasopharynx. Lipoteichoic acid, part of the cell wall, M- and F-proteins provide adhesion of the pathogen to the surface of the tonsils or other lymphoid cells. Protein M promotes bacterial resistance to the antimicrobial potential of phagocytes, binds fibrinogen, fibrin and its degradation products. When streptococci multiply, toxins are released, causing an inflammatory reaction of tonsil tissues. When streptococci enter the lymph nodes in the lymph nodes, regional (angular maxillary) lymphadenitis occurs. Toxic components, penetrating into the blood, cause the generalized enlargement of small vessels (clinically - hyperemia and spot rash). The allergic component, which breaks the permeability of the vessels, is considered the cause of the development of glomerulonephritis, arthritis, endocarditis, etc. The septic component leads to 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 streptococcus (protein M, non-specific proteins, A-polysaccharide, etc.) and 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 the host's autoantigens. On the other hand, the protein M and the erythrogenic toxin exhibit the properties of superantigens and cause proliferation of T cells, activating the cascade response of the effector link of the immune system and ejection of mediators with cytotoxic properties: IL, TNF-α, interferon-gamma. Infiltration of lymphocytes and local action of cytokines play an important role in the pathogenesis of invasive streptococcal infections (for cellulites, necrotic fasciitis, skin lesions, internal organs). An important role in the pathogenesis of invasive streptococcal infection is attributed to TNF-a, LPS of its own Gram-negative microflora and its synergistic interaction with the erythrogenic toxin of S. Pyogenes.

Epidemiology of streptococcal infection

The reservoir and source of infection are patients with various clinical forms of acute streptococcal disease and carriers of pathogenic streptococci. The greatest danger from the epidemiological point of view is! Patients who have foci localized in the upper respiratory tract (scarlet fever, angina). They are highly infectious, and the bacteria they release contain the main virulence factors - capsule and protein M. The infection from such patients most often leads to the development of a manifest infection in susceptible individuals. Patients whose foci of streptococcal infection are located outside the respiratory tract (streptococcal pyoderma, otitis, mastoiditis, osteomyelitis, etc.) are not so contagious, which is associated with less active excretion of pathogens from the body.

The duration of the infectious period in patients with acute streptococcal infection depends on the method of treatment. Rational antibiotic therapy of patients with scarlet fever and sore throat relieves the body of the pathogen within 1.5-2 days. Preparations (sulfonamides, tetracyclines), to which group A streptococci completely or partially lost sensitivity, form convalescence in 40-60% of patients who have recovered.

In collectives, where 15-20% of long-term carriers are present, streptococcus usually circulates constantly. It is believed that carriage is dangerous for others with a microbial focus of more than 10 ³ cfu (colony forming units) per tampon. The level of such carrier is significant - about 50% of healthy carriers of Group A streptococci. Among the exciter cultures isolated from carriers, virulent strains meet several times less often than the medium of strains isolated from patients. Streptococcus group B, C and G in the pharynx are observed much less frequently than the carriage of Group A streptococci. According to different data, for women, 4.5-30% of women typically carry group B Streptococcus in the vagina and rectum. Localization of the pathogen in the body largely determines the ways of its excretion.

The mechanism of transmission of infection - aerosol (air-drop), less often - contact (food and transmission through contaminated hands and household items). Infection usually occurs in close long-term communication with the patient or carrier. The causative agent is released into the environment most often with expiratory acts (coughing, sneezing, active conversation). Infection occurs by inhalation of the aerosol droplet that forms. The crowding of people in the premises and prolonged close communication aggravate the probability of infection. It should be borne in mind 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 - low temperature and high humidity in the room. Streptococcus group A, getting into certain foods, are capable of multiplying and prolonged retention of virulent properties. So, outbreaks of sore throat or pharyngitis are known with the use of milk, compotes, butter, salads from boiled eggs, lobsters, mollusks, sandwiches with eggs, ham, etc.

The risk of developing purulent complications of streptococcal genesis is affected by wounded, burned, patients in the postoperative period, as well as maternity and newborns. Possible autoinfection, as well as transmission of group B Streptococcus, causing urogenital infections, sexually. In pathology of the neonatal period transmission factors are infected amniotic fluid. In 50% of cases, infection is possible when the fetus passes through the birth canal.

The natural susceptibility of people is high. Antistreptococcal immunity is antitoxic and antimicrobial. In addition, there is a sensitization of the body according to the type of HRT, which is associated with the pathogenesis of many poststreptococcal complications. Immunity in patients who have suffered a streptococcal infection, type-specific. Perhaps a second disease when infected with another serovar pathogens. Antibodies to protein M are found in almost all patients from the 2-5th week of the disease and within 10-30 years after the disease. Often they are determined in the blood of the newborn, but by the 5th month of life they disappear.

Streptococcal infection is ubiquitous. In temperate and cold climates, the incidence of pharyngeal and respiratory forms of infection is 5-15 cases per 100 people. In southern regions with subtropical and tropical climates, skin lesions (streptoderma, impetigo) are of primary importance, the frequency of which among children in certain seasons reaches 20% or more. Small injuries, insect bites and non-compliance with skin hygiene rules predispose to their development.

Possible nosocomial streptococcal infection in obstetric facilities; children's, surgical, otolaryngological, eye departments of hospitals. Infection occurs both endogenous and exogenous (from carriers of streptococci among staff and patients) through invasive therapeutic and diagnostic manipulations.

Cyclicity is one of the characteristic features of the epidemic process with 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 the emergence and disappearance of particularly severe clinical forms. A significant number of cases of scarlet fever and tonsillopharyngitis is complicated by purulent-septic (otitis media, meningitis, sepsis) and immunopathological (rheumatism, glomerulonephritis) processes. Severe generalized forms of infection with concomitant profound lesions of soft tissues were previously designated by the term "streptococcal gangrene". Since the mid-80's. In many countries, the incidence of streptococcal infection has increased, coinciding with changes in the nosological structure of diseases caused by S. Pyogenes. Again, group cases of morbidity with severe generalized forms, often ending lethally [toxic shock syndrome (STS), septicemia, necrotic myositis, fascitis, etc.) began to be recorded. In the US, 10-15 thousand cases of invasive streptococcal infection are recorded each year, of which 5-19% (500-1500 cases) is necrotizing fasciitis.

The wide application of laboratory methods of investigation made it possible to establish that the return of invasive streptococcal diseases is associated with a change in the serotypes of the pathogen circulating in the population: rheumatogenic and toxigenic serotypes replaced M-serotypes. In addition, the incidence of rheumatic fever and toxicinfections (toxic tonsillitis, pharyngitis, and scarlet fever) has increased.

The economic damage caused by streptococcal infections and their consequences is about 10 times higher than that of viral hepatitis. Among the streptococcosis studied, the most important is angina (57.6%), acute respiratory tract 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 seasonal morbidity. The incidence of respiratory streptococcal infection has a pronounced autumn-winter-spring seasonality. Seasonal incidence rate is determined mainly by children attending pre-school institutions.

The timing of seasonal increase in morbidity is decisively influenced by the formation or renewal of organized collectives and their numbers.

In the organized collectives, updated once a year, one-time seasonal growth of infection is observed. With a two-fold renewal, two-time seasonal increases in morbidity are noted, especially those characteristic of military collectives. The first maximum morbidity associated with the spring appeal is observed in June-July, the second, due to the autumn appeal, in December-January.

[8], [9], [10], [11], [12], [13], [14], [15], [16],