Modern therapy of H. pylori in children and adolescents

Infection with Helicobacter pylori (HP) is a global concern and widespread, including in our country. Share of HP infected people in developed countries is about 50% in less developed - to 80-90%.

The problem of pyloric helikobakterioza in pediatrics and is hot enough. Already in the newborn is found in the HP 5.4% of cases, and 13-15 years of infection for up to 58-72%. In 1994. International Agency for Research on Cancer has concluded that the effect of Helicobacter pylori "carcinogenic to humans" (group I carcinogen). This decision is based on the fact that Hp is an important etiopathogenetic factor in the development of peptic ulcer and chronic gastritis Hp-associated, which leads to the development of multifocal atrophic gastritis, gastric adenocarcinoma (55% - in less developed countries, 42% - as a whole), MALT - lymphoma.

Chronic HP-associated gastritis - the most common variant of gastritis. Infection with Hp occurs mainly in childhood and without treatment is a lifelong persistence of the microorganism. Depending on the virulence properties of Helicobacter pylori and genetic characteristics of microorganism infection outcomes H. pylori is different. Almost all infected individuals microorganism causes inflammatory changes in the gastroduodenal mucosa, which represent the actual substrate of the disease.

Major risk factors for infection Helicobacter pylori - low socio-economic status, most people crowding and poor sanitation. Most data suggest that the benefit of fecal-oral and oral-oral routes of transmission. Parents and siblings of infected children are likely also infected, as there is a definite family history, and if infected with the father and mother, the risk of infection in children is increased.

Helicobacter pylori - a spiral gram-negative bacterium and a width of 0.5 microns in length from 2 to 6.5 microns. The main features of it - multi-layer membrane, unipolar flagellum (one side) and expressed urease activity. The form of the organism and the presence of flagella allow it to penetrate the barrier of the gastric mucosa (GM). The high urease activity of H. pylori contributes greatly to its colonization and survival in hostile environments, as increases the resistance of microorganisms to low intragastric pH.

The damaging effect of Helicobacter pylori on the mucous membrane due to its property to provide enzymes (urease, proteases, phospholipases) and bacterial cytotoxins. Most pathogens are VacA-HP strain that produces vacuolating cytotoxin, leading to the formation of cytoplasmic vacuoles and loss of epithelial cells, and CagA-strain expressing the gene associated with cytotoxin. This gene encodes a protein mass of 128 kDa, which has a direct damaging effect on the coolant. The subsequent addition of local and systemic inflammatory response leads to a deeper damage to the walls of the gastric mucosa. H.pylori causes an increase in serum gastrin, which in turn increases the production of hydrochloric acid, this produces a specific inhibitory action of somatostatin, produced by D-cells of antrum on gastrinprodutsiruyuschie G-cells.

Excessive production of hydrochloric acid in the stomach, which, for a long time working on the mucous membrane of the duodenum (duodenal), leads to damage it, gives rise to lesions in the duodenum of gastric metaplasia. The peculiarity of Helicobacter pylori is the recognition and binding to receptors on cells of the gastric epithelium, by which it abuts tightly to the surface, as well as gastric epithelial cells ektopirovannogo throughout the gastrointestinal tract, such as the esophagus (Barrett's esophagus) and in the duodenum (gastric metaplasia in the parts).

Almost all infected people have histologic evidence of active hCG, but clinically symptomatic disease develops in only some of them. In patients with symptoms of antral gastritis only later more likely to develop duodenal ulcer, whereas in patients with symptoms of pangastrita, especially with mucosal atrophy and intestinal metaplasia are at high risk for gastric ulcers and adenocarcinoma.

Between gastritis caused by Hp and duodenal ulcer have a very close relationship. Almost 95% of patients infected with BU KDP Helicobacter pylori. HP infection is not only involved in ulcerogenesis, but also delays the repair of gastroduodenal ulcers, ie, reducing the quality of healing, is the leading cause of recurrent disease.

Diagnosis of H. pylori infection involves a series of tests to verify the association of disease with this organism.

The main methods of diagnosing Helicobacter pylori and the indications for their use

If the diagnostic endoscopy is indicated for the diagnosis, the most preferred method for detecting Helicobacter pylori is considered to be tissue biopsies and study of their urease activity. Rapid urease test - a method of detecting Hp in the material, which is based on the high urease activity of the microorganism. Sensitivity and specificity of this test exceeds 90%.

An alternative method for detection of H. pylori is the morphological study of fixed tissue obtained by biopsy as coolant. Microorganism found in the standard staining by various dyes (acridine orange, Giemsa stain, silver plated on Vartin - Starry), however, the sensitivity of this method varies greatly depending on the technique of fixation of the drug, the number of microorganisms in the preparation and experience of the doctor-histologist. The method allows not only to identify the HP, but also to quantify the degree of contamination. Sensitivity and specificity of the morphological methods reaches 90%.

Sowing of Helicobacter pylori (microbiological method) is often used for diagnosis in clinical practice, since it is quite expensive, fraught with some difficulties in carrying out, as well as time-consuming to execute. As a rule, it is used to identify the sensitivity of microorganisms to antibiotics in the treatment of resistant forms of disease.

Non-invasive detection methods include serum Hp, breathing tests and PCR - diagnostics. Antibodies to IgG or IgA, linking various bacterial antigens can be detected by enzyme immunoassay. Although the antibody levels decreased after successful treatment, it nevertheless remains elevated for quite a long time (up to 3 years). This kind of "serological scar" limits the application of serological tests for the evaluation of treatment and diagnosis of reinfection. Serological test is the method of choice for detecting Helicobacter pylori infection in community epidemiological studies. Sensitivity and specificity is 90%.

Urea breath test labeled with the isotope ¹³ C or ¹⁴ C is ideal for assessing the results of treatment and diagnosis of re-infection, since it is positive only in the presence of active infection. The widespread introduction into clinical practice with urea breath test would take it to the methods of choice for monitoring the effectiveness of treatment. Sensitivity and specificity of the breath test is more than 95%.

Determination of DNA HP (in the gastric mucosa, feces, saliva) by polymerase chain reaction, is the most accurate method of diagnosis of infection, especially in cases where the bacterium acquires a coccoid form (after a course of antibiotic therapy) and other diagnostic methods give false negative results.

Modern treatment of chronic diseases of the upper gastrointestinal tract (primarily peptic ulcer disease) includes - as a mandatory component - carrying Helicobacter pylori eradication in case of detection of microorganisms in patients with coolant. After eradication of infection in a month neutrophilic infiltration disappears completely epithelium and lamina propria of the mucous membrane, and at a later date disappears mononuclear infiltration. Thus, chronic gastritis neatrofichesky fully healed after the destruction of H. pylori.

In 2005, the Maastricht-3 Consensus adopted new standards for the treatment of patients with HP-associated kislotozavisimymi diseases, which were pre-emptive measures to respond to the growth of H. pylori resistance ═ with respect to the previously recommended standard therapy. The essence of the guidelines, as recommended by the European Working Group for the Study of HP (EHPSG) (Maastricht Consensus - 3):

- May increase the rate of eradication therapy to 14 days;

- The use of 7-day scheme is justified, if demonstrated their efficiency and profitability;

- There are no specific indications for eradication in children and adolescents (treatment is carried out, as in adults, with the calculation of doses of drugs on the basis of body weight).

As a first-line therapy is recommended to use ternary diagrams based on proton pump inhibitor (PPI) and two antibiotics. According to several studies, when used in HP eradication schemes of various PPIs at standard doses 2 times a day (esomeprazole 20 mg 2 times, rabeprazole 20 mg 2 times, lansoprazole 30 mg 2 times and omeprazole 20 mg 2 times), no significant differences in the frequency eradication, as well as the rate of cicatrization of ulcers have been identified.

The most viable option triple first-line therapy is protocol: omeprazole 20 mg в 2 times or other STIs at optimal dosages, clarithromycin 500 mg в 2 times, amoxicillin 1000 mg в 2 times a day for 7 - 10 days.

In the first-line therapy Maastricht-3 suggests the possibility of replacing amoxicillin for metronidazole (500 mg в 2 times), if the most common strains resistant to metronidazole HP does not exceed 40%. In our region, the frequency of antibiotic resistance in strains of HP to metronidazole varies from 40% to 55.5%, so the use of triple eradication protocols including this drug is not sufficiently effective.

An alternative scheme is kvadroterapiya, including: omeprazole 20 mg в 2 times or other STIs at optimal dosages, colloidal subcitrate / subsalitsillat bismuth 120 mg в 4 times, and metronidazole 500 mg в 2 times, tetracycline 250 mg в 4 times a day (which can be replaced furazolidone 100 mg в 4 times a day). Kvadroterapiya designed for 7 to 10 days and in some cases, therapy may be considered a second line. It is necessary to comply with age-dose preparations.

Conducted in our country studies in adults have shown that one of the protocols of choice is a 7-day triple eradication therapy PPI-amoxicillin-clarithromycin (eradication occurs in 80-81,5% of patients). It should be noted that when using a 14-day protocol eradication efficacy increased to 96.2%, ie, the probability of a successful treatment.

Creates prerequisites for improving adherence to treatment and results in significant economic benefits to the use of combination therapies that include all the individual components of therapy

A combination drug, the relevant recommendations of Maastricht-3, registered in the Republic of Belarus is PeptiPak (PeptiPac). In the same package, there are seven blisters each containing a set of daily drugs for eradication of line 1: omeprazole (Omepral) 20 mg в 2 times, clarithromycin (Klarikar) 500 mg в 2 times, amoxicillin (Amoksikar) 1000 mg в 2 times a day. Ease of distribution of the daily dose can observe compliance (a required interval between doses is 12 hours), which is important in achieving a positive treatment effect (if the patient receives only 75% of the prescribed drugs, the effectiveness of the scheme is reduced by 25%).

In appointing PeptiPaka children aged 12-15 daily dose of antibiotics is reduced 2-fold (clarithromycin 250 mg x 2 times, amoxicillin 500 mg x 2 times), omeprazole 20 mg once appointed. Adolescents over 15 years of drug is given in standard doses.

Failures in the treatment of HP infection is associated primarily with the level of primary resistance to antimicrobial agents within the regimen. Among other factors that reduce the effectiveness of eradication therapy are poor compliance, smoking, high basal acidity and a long reception prior antisecretory means low concentration of serum H. pylori IgG, high seeding the gastric mucosa by microorganisms HP, etc.

If unsuccessful elimination of HF circuits using the 1st and 2nd line treatment, further treatment is expedient to carry out after determining the sensitivity of the microorganism to the selected antibiotic.

Used in the treatment of antibiotics, bismuth preparations and STI inhibit bacterial activity Helicobacter pylori, which sometimes results in false-negative urease test, histology, bacterial seeding and breath test. Therefore, control of eradication is carried out by two methods no earlier than 4 weeks after treatment and 2 weeks after discontinuation of PPIs.

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