Инвазивные инфекции группы А стрептококка: патогенез, риски и современные проблемы.

Group A streptococcal infections are a number of infections with Streptococcus pyogenes, a group A streptococcus (GAS). S. pyogenes is a species of beta hemolytic Gram positive bacteria that is responsible for a wide range of infections that are mostly common and fairly mild. If the bacteria enter the bloodstream an infection can become severe and life threatening, and is called an invasive GAS (iGAS). Infection of GAS may spread through direct contact with mucus or sores on the skin. Despite the emergence of antibiotics as a treatment for group A streptococcus, cases of iGAS are an increasing problem, particularly on the continent of Africa. There are many other species of Streptococcus, including group B streptococcus Streptococcus agalactiae, and Streptococcus pneumoniae, which cause other types of infections. Several virulence factors contribute to the pathogenesis of GAS, such as M protein, hemolysins, and extracellular enzymes.

Group A β hemolytic streptococcus can cause infections of the throat and skin. These may vary from very mild conditions to severe, life threatening diseases. Although it is not completely clear what causes different people to develop different diseases as a result of infection with the same pathogenic bacteria, it is suspected that host phenotypic and epigenetic factors are the source of such variation. Indeed, the many virulence factors of GAS can influence the epigenetics of the host. Furthermore, persons with suppressed or compromised immune systems may be more susceptible to certain diseases caused by GAS than other persons with intact immune systems. A 2019 study shows that GAS's evasion of immune detection is facilitated by protein S, an extracellular and cell wall associated protein that enables it to camouflage itself by binding fragments of lysed red blood cells. Humans may also carry the GAS either on the skin or in the throat and show no symptoms. These carriers are less contagious than symptomatic carriers of the bacteria. The two most prominent infections of GAS are both non invasive: strep throat (pharyngitis) where it causes 15–30% of the childhood cases and 10% of adult cases, and impetigo. Those at greatest risk include children with chickenpox; persons with suppressed immune systems; burn victims; elderly persons with cellulitis, diabetes, vascular disease, or cancer; and persons taking steroid treatments or chemotherapy. Intravenous drug users and homeless also are at high risk. GAS is an important cause of puerperal fever worldwide, causing serious infection and, if not promptly diagnosed and treated, death in newly delivered mothers. Severe GAS disease may also occur in healthy persons with no known risk factors. All severe GAS infections may lead to shock, multisystem organ failure, and death. Early recognition and treatment are critical. Diagnostic tests include blood counts and urinalysis as well as cultures of blood or fluid from a wound site. Severe Group A streptococcal infections often occur sporadically but can be spread by person to person contact. Close contacts of people affected by severe Group A streptococcal infections, defined as those having had prolonged household contact in the week before the onset of illness, may be at increased risk of infection. This increased risk may be due to a combination of shared genetic susceptibility within the family, close contact with carriers, and the virulence of the Group A streptococcal strain that is involved. Public health policies internationally reflect differing views of how the close contacts of people affected by severe Group A streptococcal infections should be treated. Health Canada and the US CDC recommend close contacts see their doctor for full evaluation and may require antibiotics; current UK Health Protection Agency guidance is that, for a number of reasons, close contacts should not receive antibiotics unless they are symptomatic but that they should receive information and advice to seek immediate medical attention if they develop symptoms. ).

Diagnosis is by a swab of the affected area for laboratory testing. A Gram stain is performed to show Gram positive cocci in chains. Then, the organism is cultured on blood agar. The rapid pyrrolidonyl arylamidase (PYR) test is commonly used, wherein a positive reaction confers a presumptive identification of group A beta hemolytic streptococci if the appearance and clinical context is consistent. GBS gives a negative finding on the PYR test test. There are also latex agglutination kits which can distinguish each of the main groups seen in clinical practice.

S. pyogenes infections are best prevented through effective hand hygiene. Difficulties in developing a vaccine include the wide variety of strains of S. pyogenes present in the environment and the large amount of time and number of people that will be needed for appropriate trials for safety and efficacy of the vaccine.

The treatment of choice is penicillin, and the duration of treatment is around 10 days. Antibiotic therapy (using injected penicillin) has been shown to reduce the risk of acute rheumatic fever. In individuals with a penicillin allergy, erythromycin, other macrolides, and cephalosporins have been shown to be effective treatments. In cases of streptococcal toxic shock syndrome, treatment consists of penicillin and clindamycin, given with intravenous immunoglobulin. For toxic shock syndrome and necrotizing fasciitis, high dose penicillin and clindamycin are used. Additionally, for necrotizing fasciitis, surgery is often needed to remove damaged tissue and stop the spread of the infection. No instance of penicillin resistance has been reported to date, although since 1985, many reports of penicillin tolerance have been made. The reason for the failure of penicillin to treat S. pyogenes is most commonly patient noncompliance, but in cases where patients have been compliant with their antibiotic regimen, and treatment failure still occurs, another course of antibiotic treatment with cephalosporins is common. The 30 valent N terminal M protein based vaccine as well as the M protein vaccine (minimal epitope J8 vaccine) are two vaccines for GAS that are currently getting close or becoming clinical studies, however, other vaccines using conserved epitopes are progressing.

Cases of GAS are still present today, but were also evident before World War I. This was shown by a training camp located in Texas, where a harmful strain of pneumonia complicating measles was caused by a strain of Streptococcus. Existence of streptococci strains was additionally found in World War II. An epidemic of streptococcal infection in the United States Navy during this war indicated that this type of disease was able to exist and spread in formerly unexposed individuals by environments that serological types of group A streptococci preferred. This number is quite large, often leaving the health care system encumbered, since 91 percent of patients infected with invasive GAS need to be hospitalized with 8950–11,500 episodes and 1050 1850 deaths taking place each year. ARF is often clinically diagnosed based on Jones Criteria, which include: pancarditis, migratory polyarthritis of large joints, subcutaneous nodules, erythema marginatum, and sydenham chorea (involuntary, purposeless movement). The most common clinical finding is a migratory arthritis involving multiple joints. Other indicators of GAS infection such as a DNAase or ASO serology test must confirm the GAS infection. Other minor Jones Criteria are fever, elevated ESR and arthralgia. One of the most serious complications is pancarditis, or inflammation of all three heart tissues. A fibrinous pericarditis can develop with a classic friction rub that can be auscultated. This will give increasing pain upon reclining. Further endocarditis can develop with aseptic vegetations along the valve closure lines, in particular the mitral valve. Chronic rheumatic heart disease mostly affects the mitral valve, which can become thickened with calcification of the leaflets, often causing fusion of the commissures and chordae tendineae. Other findings of ARF include erythema marginatum (usually over the spine or other bony areas) and a red expanding rash on the trunk and extremities that recurs over weeks to months. Because of the different ways ARF presents itself, the disease may be difficult to diagnose. A neurological disorder, Sydenham chorea, can occur months after an initial attack, causing jerky involuntary movements, muscle weakness, slurred speech, and personality changes. Initial episodes of ARF, as well as recurrences, can be prevented by treatment with appropriate antibiotics. It is important to distinguish ARF from rheumatic heart disease. ARF is an acute inflammatory reaction with pathognomonic Aschoff bodies histologically and RHD is a non inflammatory sequela of ARF.

Post streptococcal glomerulonephritis (PSGN) is an uncommon complication of either a strep throat or a streptococcal skin infection. It is classified as a type III hypersensitivity reaction. Symptoms of PSGN develop within 10 days following a strep throat or 3 weeks following a GAS skin infection. PSGN involves inflammation of the kidney. Symptoms include pale skin, lethargy, loss of appetite, headache, and dull back pain. Clinical findings may include dark colored urine, swelling of different parts of the body (edema), and high blood pressure. Treatment of PSGN consists of supportive care.

Obsessive–compulsive disorder and tic disorders are hypothesized to arise in a subset of children as a result of a post streptococcal autoimmune process. The PANDAS hypothesis is unconfirmed and unsupported by data, and two new categories have been proposed: PANS (pediatric acute onset neuropsychiatric syndrome) and CANS (childhood acute neuropsychiatric syndrome).