Myronchuk Y. Pathogenetic substantiation of imunocorection in complex treatment of children with new cases of tuberculosis

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0822U100925

Applicant for

Specialization

  • 222 - Медицина

07-09-2022

Specialized Academic Board

ДФ 17.600.051

Zaporizhzhya State Medical University

Essay

The dissertation is devoted to improving the effectiveness of antimycobacterial therapy (AMBT) in children with new cases of tuberculosis (TB) by studying the dynamics of immunological changes and activity of a specific process with the development of additional treatments to correct immunological changes and reduce specific process activity. To study the effectiveness of immunocorrective therapy in complex treatment aimed for correcting changes in immunological reactivity of the organism, a prospective study of clinical, laboratory (immunological, biochemical) and radiological features of a specific process in 79 children with new cases of TB was conducted. The study consisted of 3 fragments. The first part of the study was conducted: to study the nature of the body's immunological reactivity by indicators of cytokine profile (IL-2, IL-6, IL-4, IL-10) and immunoglobulin levels (Ig E, A, M , G) in children with new cases of TB ; to study the activity of a specific process according to neopterin; to determine the most informative diagnostic and prognostic indicators of immunological changes. To achieve this goal, 2 groups for the investigation were formed: the main research group consisted of 28 children with new cases of TB, the experimental group included 30 apparently healthy children. The age and sex of the groups were collated. The second part of the investigation is devoted to the study of immunological changes in cytokine profile (IL-2, IL -6, IL-4, IL-10) and levels of immunoglobulins (Ig E, A, M, G) in the process of AMBT (at the beginning of AMBT, at the end of IP AMBT and after SP AMBT) in children of the main observation group (28 children with new cases of TB), and monitoring the activity of a specific process according to neopterin. The third part of the investigation was conducted to study the exposure and the effectiveness of immunocorrective therapy in complex treatment in children with new cases of TB. Indicators of immunological reactivity of the organism against the background of immunocorrection in complex treatment were studied at the beginning of AMBT and after SP AMBT. For these purposes, 51 children with new cases of TB with immunological changes were included in the study, which were divided into 2 groups: 26 sick children who received immunomodulator azoximer bromide in combination treatment on the background of AMBT (main group) and 25 sick children who received only AMBT (control group). The groups were identical in age, sex, prescribed AMBT regimens, and severity of the specific process. In children with new cases of tuberculosis at the beginning of treatment, the features of the immunological reactivity of the body and the activity of a specific process is a significant disbalance of pro- and anti-inflammatory cytokines towards proinflammatory cytokines with predominance and high activity of Th1-type cellular immune response, which appears by significant increase of IL-2-contents by 3,8 times, a decrease in IL-4 by 3,1 times and IL-6 by 13,2 times, an increase in the ratio of IL-2 / IL-10 by 8 times, an increase in Ig E levels by 1,5 times, Ig A by 1,3 times, Ig G by 1,2 times and neopterin by 2,2 times. The manifestation of the local response to BCG vaccination is directly related to serum levels of IL-2 (r = 0,402; p <0,05) and Ig E (r = 0,670; p <0,001). At the end of the main course of antimycobacterial therapy in children with new cases of tuberculosis there is a pronounced disbalance of pro- and anti-inflammatory cytokines towards pro-inflammatory cytokines with predominance and high activity of Th1-type cellular immune response, manifested by significantly high IL-2 levels, 4 times higher than healthy individuals), the ratio of IL-2 / IL-10 (increase 13 times), Ig A (remains 1,5 times higher), Ig G tends to increase 1,2 times, in 71,4% of cases increased neopterin levels by 1,9 times. Scientific data on the features of the immunological reactivity of the organism and the activity of a specific process in children with new cases of tuberculosis at the beginning of treatment and at the end of the completion course of antimycobacterial therapy were supplemented. The most informative diagnostic and prognostic indicators of immunological changes and activity of a specific process in children with new cases of tuberculosis have been established. The expediency of using the immunomodulator azoximer bromide in the complex treatment of children with new cases of tuberculosis is substantiated.

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