The thesis for obtaining academic degree of Ph.D.Med. majoring in 14.01.20 – skin and venereal diseases. – P.L. Shupyk National Medical Academy of Postgraduate Education, Kiev, 2018.
The increase of genitourinal sexually transmitted diseases; their chronic course, frequent relapses, as well as reproductive and sexual dysfunction emerge as an important medical and social problem, which requires further research into the mechanisms of the infectious process, markers of clinical course, as well as the development of new treatment and prevention approaches. To achieve the objectives of this work, a comprehensive (clinical, biochemical, bacteriological, molecular, immuno-enzyme, sociological, statistical) research of 745 females and 395 males suffering from genital infections caused by C. trachomatis, U. urealyticum, M. genitalium.
Systemic and local molecular-cytokine profile in patients with these genitourinary infections is not determined by the etiology but by the type of inflammatory process. The concentration of intercellular adhesion molecules ICAM-1 and VCAM-1 and IL-8, as a rule, increases. The degree of increase depends on the intensity and chronology of inflammation. In the initial symptomatic process, ICAM-1 and VCAM-1 are increased in 5.5 and 3.9 times, respectively, and the IL-8 is not significantly different from norm; In a recurrent symptomatic process, ICAM-1 and VCAM-1 are increased in 5 and 4.3 times, respectively, and the IL-8 - in 1.5 times; at the latent course ICAM-1 and VCAM-1 increase in 4.7 and 3.3 times, respectively. There is an increase in the concentration of IL-1 β, IL-6, IL-8, IL-10, FNP, IFN-, respectively, in 2,5; 2; 2.2; 2.6; 2; 4,5 times, and a decrease in the concentration of IL-2 in 1,8 times. The maximum concentrations of IL-1β, IL-6, IFN-, FNP (increased by 3.4, 2.2, 5.7, 2.4 times, respectively) were in patients with primary and recurrent symptomatic infectious processes, and elevated in 2.7 times of IL-8 and in 3 times of IL-10 - in recurrent and latent.
Marker of complications in women is prolonged (more than 180 days) growth in ICAM-1 and VCAM-1 in serum. This leads to an epithelial-mesenchymal transition (EMT), tubal occlusion and cervical metaplasia in 17.2-19.2 % patients. The primary infection is the main factor of EMT: increased levels of MMP-9 and fibronectin in cervical lesions are found to be 1.5-fold more frequent with latent and relapsing infection than with the primary one. The type of pathogen does not significantly affect the development of EMT.
Marker of urethritis persistence in men is an increase in the production of IL-6 and IL-8 in urethra after the course of traditional antimicrobial therap. As ICAM-1 and VCAM, epithelial-mesenchymal transition seemls does not play any role in the pathogenesis of urethritis complications in men caused by chlamydia and mycoplasmas. Also, the presence of MMP-9 and fibronectin in urethral washes were not determined.
Based on clinical and molecular immunological markers of chronic infection and complications of urogenital infection caused by C. trachomatis, U. urealiticum, and M. genitalium, an effective method of complex treatment has been developed which, in addition to standard antimicrobial agents, includes pathogenetic therapy with lovastatin 40 mg per day, per os, 8 weeks. The use of lovastatin can increase the clinical efficacy of treatment in women by an average of 27 % compared with the traditional one, restores serum concentrations of ICAM-1 and VCAM-1 to the control group's indicators. In the primary infection, the normalization of the indicators occurs on the 60th day, with secondary infection - from 60 to 90 days, with latent - 60-120. The application of the developed method in women reduces the serum IL-8 concentration by 2.4 times, as well as reduces the local level of cytokines IL-1β, IL-6, IL-8, IL-10, FNP, IFN-α by 12.7 %, 14.6 %, 14.7 %, 17.8 %, 20.5 %, 17.7 %, respectively, and also increases the level of IL-2 by 14.6 %. In the case of persistent urethritis in men, the treatment method reduces the frequency of urethral discharge by 39.7 % and the discomfort in the urethra by 28 %, decreasing the concentrations of IL-6, IL-8, ICAM-1, and VCAM-1 in urethral washings by 37.9 %, 73.9 %, 66.1 %, 38.4 %.
The detection of low-intensity symptoms with the help of a specially developed questionnaire, as well as the determination of the molecules of intercellular adhesion of sICAM-1 and sVCAM-1 in blood serum, made it possible to increase the effectiveness of screening for Chlamydia and Mycoplasma infections. When predicting inflammatory syndromes in men and women, it is advisable to take into account the level of sICAM-1 and sVCAM-1 in serum. In men, it is also advisable to determine the level of IL-6 and IL-8 in urethral washings.
Key words: Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplsma genitalium, genital infections, intercellular adhesion molecules (sICAM-1, sVCAM-1), cytokines (IL-1β, IL-2, IL-
