MODERN ASPECTS OF CORRECTION OF VAGINAL MICROBIOCENOSISVIOLATIONS IN WOMEN WITH GENITAL HERPES Текст научной статьи по специальности «Клиническая медицина»

References:

1. Бенюк В.А., Ластовецкая Л.Д., Щерба Е.А., Мельник В.В. Профилактика рецидивов хронического канди-дозного вульвовагинита у женщин в период ранней постменопаузы // Здоровье женщины., 2013, № 6( 80), с. 212-218

2. Кувита Ю.В., Бенюк В.А., Ластовецкая Л.Д., Щерба Е.А., Ковалюк Т.В. Лечение цервиковагинитов хламидий-но-кандидозной этиологии у женщин репродуктивного возраста // Сборник научных трудов Ассоциации акушеров-гинекологов Украины. - К.: Полиграф плюс, 2013 - с. 224-226.

3. Блинов Д.В. Вагинальные инфекции - от диагностики к рациональной комплексной терапии / Д.В. Блинов // Акушерство, гинекология и репродуктологии. - 2011. -Т.5, №4. - с. 44-47.

4. Радзинский В.Е. Коррекция нарушений биоценоза влагалища: марш на месте или движение вперед? / В.Е

Радзинский и соавт. / Репродуктивная эндокринология. -2014. - №4(18). - с. 92-100.

5. Вдовиченко Ю.П. Современные аспекты профилактики и лечения вульвовагинита смешанного генеза / Ю.П. Вдовиченко, П.Н. Баскаков, К.Н. Масленников // Здоровье женщины: Всеукраинский научно-практический журнал. - К.: Академия мед. наук Украины. - 2009. - №6. - с. 57-58.

6. Авкобян В.А. Урогенитальная хламидийная инфекция: 25 лет спустя / В.А. Авкобян // Репродуктивное здоровье женщины.-2007.-№4(33).-С.188-192.

7. Stary A. European guidelines for management of Chlamydial infection / A. Stary // Int. J. of STD and AIDS. -2001. - Vol. 12, Suppl. 3. - P. 30-34.

8. Szymankiewicz M. Wrazliwosc in vitro naflukonazolszczerow Candida parapsilosis izolowanych z roznych materialow klinicznych / М. Szymankiewicz // Micologialekarska. - 2007. - Vol.14, №1. - Р.37-40.

MODERN ASPECTS OF CORRECTION OF VAGINAL MICROBIOCENOSIS VIOLATIONS IN WOMEN WITH GENITAL HERPES

Vasyl Benyuk,

MD, Professor,

head of the Obstetrics and gynecology department №3 Bogomolets National Medical University - Kyiv, Ukraine

Оlena Shcherba,

PhD, assistant of the Obstetrics and gynecology department №3 Bogomolets National Medical University - Kyiv, Ukraine

Lily Lastoveckaya

PhD, associate Professor of the Obstetrics and gynecology department №3 Bogomolets National Medical University - Kyiv, Ukraine

Tetyana Kovalyuk,

PhD, assistant of the Obstetrics and gynecology department №3 Bogomolets National Medical University - Kyiv, Ukraine

Bu Weiwei

Obstetrics and gynecology department №3 Bogomolets National Medical University - Kyiv, Ukraine

ABSTRACT

The article presents modern aspects of correction of vaginal microbiocenosis violations in women with genital herpes. Proven clinical and laboratory efficiency of complex anti-inflammatory treatment of patients with recurrent genital herpes. It is established that the inclusion of «Depantol» and «Lavomax» in complex therapy reduces the treatment time and number of recurrences of genital herpes.

Key words: microbiocenosis of the vagina, genital herpes, treatment, Depantol, Lavomax.

Sexually transmitted diseases area key public health priority world wide due to the influence on the reproductive function and quality of life, accounting for 50-80% of total gynaecological morbidity. The frequency of their growing threatening, which is associated with increased sexual activity at a young age, disordered sex life, environmental degradation, a violation of vaginal microecology, intestinal dysbiosis, late referral for medical assistance, uncontrolled medications, particularly antibiotics and high dose of oral contraceptives etc. [1, 158; 2, 133; 3, 193; 4, 26; 5, 140; 10, 698; 11, 139].

It is known that the normal microflora of the genital tract, under certain conditions acquires pathogenic properties, and its representatives become causative agents of several diseases. Recent studies show that 95% of all vaginal discharge that

women turn to gynecologist associated with diseases such as candida or Gardnerella vulvovaginitis; cervicitis, caused by Chlamydia trachomatis, Herpes simplex or Neisseria gonorrhea. [1, 158; 7, 5; 8, 12, 9, 10].In the structure of diseases affecting women's reproductive health, a special role is played by viral infection.

Genital herpes (GH, HSV) is a common human disease that has an epidemic spread in the world. According to WHO, the herpes simplex virus infecting up to 90% of children and adults, and mortality due to herpes infection, takes the second place (15,8 %) after influenza (35,8%) [3, 193]. HSV cause a pathology of pregnancy and childbirth often lead to spontaneous abortions and intrauterine fetal death, or cause generalized infection in newborns. Indicates the link of genital

herpes and cervical/prostate cancer [5, 140; 6, 5; 7, 5].

Genital herpes (GH)is caused by the two most common serotypes - HSV-1 and HSV-2 (HSV-1, HSV-2). Recently, however, there is evidence that different types of HSV can move from one to another [6, 4]. The virus is transmitted primarily through sexual contact or acquired by the child from mother during passage through birth canal [6, 4; 7, 5]. Infection penetrates through the skin and mucous membranes. HSV enters the mucous membranes or broken skin with saliva, semen, or through contact with herpes lesions of the skin and mucous membranes of a sick person. After penetration, HSV persists in humans for life in the form of a latent infection [3, 193; 6, 5]. However, the state of commensals is not permanent. Herpes infection can be activated, turning in a clinically defined forms under the influence of debilitating factors of the body. HSV infects the skin and mucous membranes (most often on the face and in the genital area), Central nervous system (meningitis, encephalitis), eyes (conjunctivitis, keratitis) [3, 193; 7, 5; 9, 10].

Clinical manifestations of GH (HSV) in women is more pronounced than in men. Symptoms appear within 2-14 days after contact. First, there is General symptoms (fever, muscle aches, joint aches and headaches). After a few days appear local symptoms are characterized by painful vesicles, coalescing into clusters. They quickly open, revealing under an erosive surface. GH is often accompanied by secondary bacterial flora [6, 18]. The classic symptoms of HSV, are observed only in 20% of patients. A significant proportion of patients have minimal clinical manifestations, which can be neglected. The recurrence of the infection usually occurs in people with a specific combined immunodeficiency [3, 6, 19; 7, 5].

Today the treatment of GH continues to pose a challenge. With a wide arsenal of antiviral drugs, it is difficult to find a drug with a complex mechanism of action, i.e. the possibility of effect on different stages of the disease at the same time [1, 158; 3, 193; 6, 25; 7, 6]. The main objective in the treatment of HSV is not only the impact on the different stages of reproduction of HSV, but also improve anti-infective resistance of the organism. In this respect, it is worth considering the drug Tilorone (Tiloronum, Lavomax) that has antiviral and immunomodulatory properties. Is available in tablets of 125 mg. Tilorone stimulates the formation in the body of a-, P - and y - interferons. The main producers of interferon in response to the introduction Tiloron are cells of the intestinal epithelium, hepatocytes, T-lymphocytes and neutrophils. The drug stimulates stem cells in the bone marrow, depending on the dose increases antibody-development, reduces the degree of immunosuppression, restores the ratio of T-helper/T-suppressor. Effective to various viral infections, including herpes. The mechanism of antiviral action is associated with inhibition of translation of virus-specific proteins in infected cells, resulting in suppressed reproduction of viruses. Once inside Tiloron rapidly absorbed from the gastrointestinal tract. Bioavailability is 60%. About 80% of the drug is bound to plasma proteins. Excreted virtually unchanged in faeces (70%) and urine (9%). The half-life time is 48 hours. The drug is not biotransformed, and is not accumulated in the body.

For the topical treatment of the inflammatory process of the lower section of the female genital organs, deserves attention

combined drug Depantol (Depanthol), which has regenerative, antiseptic, and metabolic action. Vaginal suppositoria Depantol contain 0.1 g of dexpantenol and 0,016 mg of chlorhexidine bigluconate. Depantol stimulates the regeneration of the mucous membranes, normalizes cellular metabolism, enhances mitosis, and increases the strength of collagen fibers. Chlorhexidine bigluconate - antiseptic substance, active against most grampositive and gram-negative bacteria, protozoa, dermatophytes, yeast fungi, and herpes virus. Chlorhexidine bigluconate retains pharmacological activity in the presence of blood, pus and a number of secrets. The base of the suppositoria(polyethylene oxide) due to the high molecular weight has an osmotic and sorption action, stimulates the regeneration of the mucous membranes, normalizes cellular metabolism.

AIM.To assess the state ofvaginal microbiocenosis in women with recurrent genital herpes and to reduce the frequency of relapses through the use of comprehensive antiviral therapy.

THE MATERIALS AND METHODS.

We examined 87 women aged from 18 to 35 years and 67 patients with recurrent genital herpes (according to the inclusion criteria). The control group included 20 gynecologically healthy women. The main and control groups were representative by age and data of the obstetric-gynecologic and somatic history.

Diagnosis of HSV was carried out on the basis of the anamnestic, clinical and laboratory tests: microscopy study of the contents of the vagina and cervical canal, ELISA of serum for detection of antibodies and PCR of serum and cervical mucus to determine viral DNA of HSV-2. Conducted bacteriological examination of vaginal discharges.

In accordance with the objectives of the study, all patients with HSV before the appointment of therapy were divided into 2 groups, identical in age, symptoms and duration of the inflammatory process. I group included 35 patients who underwent comprehensive therapy, which includes antiviral medication Acyclovir (Aciclovir) 200 mg 5 times a day for 10 days. Also pathogenetic therapy consisted of oral antiviral and immunomodulatory drug, interferon inductors, Tilorone (Tiloronum, Lavomax). The drug was prescribed 0.125 g according to the scheme: during the first two days of 125 mg, then 125 mg every 48 hours. The course of treatment lasted 18 days. In addition, topically applied combined reparative, anti-inflammatory and antimicrobial drug Depantol (Depanthol) in the form of suppositories containing chlorhexidine bigluconate and dexpanthenol. Depantol appointed standard 1 vaginal suppositorium twice a day for 10 days, followed by appointment eubiotics (1 vaginal suppositorium on the night for 10 days).

32 patients of the II group underwent antiviral therapy, including Acyclovir orally 200 mg 5 times a day for 10 days followed by appointment of eubiotics.

Treatment efficacy was assessed by the dynamics of complaints, clinical symptoms, eradication of pathogens on the 5th and 10th day of treatment and after 1, 3, 6 months after the end of therapy, with a detailed evaluation of complaints, inspection data and results of laboratory and instrumental examination. Blood and secretions from the genital tract for the study of indicators was conducted in the same timeframe.

Statistical analysis was performed using the programs Statistica 6.0 and Excel 2007.

THE RESULTS OF THE STUDY AND THEIR

DISCUSSION.

The diagnosis of HSV in all cases has been confirmed by laboratory tests. Clinical manifestations of viral pathology were rather variable. Analysis of clinical manifestations showed that patients complained about discharge from genitalia - 42 women (62,7%), discomfort from the crotch - 29 (43,3%), itching - 35 (52,2%) patients. Less frequently observed increased passage of urine in 9 (13,4%) patients. While 49.2% (33 women) cases were characterized by the asymptomatic forms of herper virus vulvovaginitis.

Majority of the surveyed patients have the dysbacteriosis of the vagina, in which was observed a sharp decrease or complete absence of lactobacilli, abundant pleomorphic grampositive and gram-negative bacilli and coccal flora. Among conditionally pathogenic flora prevails peptostreptococci (43,3%), Corynebacterium vaginalis (56,7%), Staphylococcus epidermidis (65,7%) [table 1].

Thus, changes of the microbial biotope of the vagina in patients with HSV demonstrate a profound disturbance condition of habitat.

Analysis of the content ofantiherpetic specific immunoglobulins (IgM and IgG) in the serum has shown a significant increase of their concentration compared with the

Indicators of the vagina biotope in reproductive age wom<

control group (p<0.05) [table 2]. Study of lysozyme in patients showed significant decrease of its level in the cervical mucus (in 2.8 times), compared with the corresponding figure in blood [table 2].

Based on the comparison of the effectiveness of recurrent GHtherapy in reproductive agewomen we established that in

I group, patients who received comprehensive treatment, the complaints disappeared already at 2-3 days, whereas in group

II the decreasing of itching and discomfort were observed only for 5-6 days [Fig. 1]. Epithelization of erosions after rupture of the bubbles in Igroupoccurred on average 5-6 days to 8-9 days in II group [Fig. 1].

We also found a correlation between the state of humoral immunity and the dynamics of clinical manifestations of the pathological process in the course of the treatment. After complex treatment nonspecific resistance indices are significantly improved. Only in patients of group I IgG level showed no significant tendency to decrease [Fig. 2]. During treatment, we found a significant increase in the level of lysozyme in cervical mucus especially in patients of I group -by 2.3 times (p <0.05) [table 2].

Table 1

with recurrent genital herpes (in the dynamics of treatment)

Microorganisms Frequency of selection (abs., %)

Group

Before treatment, (n=67) After treatment Control group (n=20)

Group I (main), (n=35) Group II (comparison), (n=32)

>104CFU >104CFU >104CFU >104CFU

Lactobacillus spp. 10 (15,%) 25 (74,8%) 13 (40,6%) 15 (75%)

Enterococcus 27 (40,3%) 7 (20%) 11 (34,3%) 3 (15%)

Peptocostreptoccus spp. 29 (43,3%) 4 (11,4%) 8 (25%) 1 (5%)

St. Aureus 6 (9,0%) 2 (5,7%) 3 (9,3%) 1 (5%)

St. Epidermalis 44 (65,7%) 2 (5,7%) 3 (9,3%) 1 (5%)

Echerichia coli 46 (68,7%) 7 (20%) 19 (59,3%) 1 (5%)

Proteus 15 (22,4%) 0 5 (15,6%) 0

Enterobacter 17 (25,4%) 0 8 (25%) 0

Corynebacterium 38 (56,7%) 5 (14,3%) 13 (40,6%) 4 (20%)

Gardnerellavaginalis 50 (74,6%) 2 (5,7%) 19 (59,3%) 1 (5%)

Mobiluncus spp. 29 (43,3%) 2 (5,7%) 5 (15,6%) 1 (5%)

Candida 31 (46,3%) 2 (5,7%) 1 (3,1%) 2 (10%)

M. hominis 34 (50,7%) 2 (5,7%) 8 (25%) 1 (5%)

U. urealiticum 21 (31,3%) 2 (5,7%) 5 (15,6%) 1 (5%)

Table 2

The state of humoral immunity in women with recurrent genital herpes during the treatment

Indicators Groups

Before treatment After treatment Control group

Group I (main) Group II (comparison)

The content of IgM and G (S/CO)

Ig M in the serum 26,7±1,08* 8,7±0,4** 12,6±1,04* 1,33±0,16

Ig G in the serum 82,8±1,45* 35,6±1,2** 65,6±1,1* 6,4±0,9

The Content of IgA (S/CO)

In the serum 3,4±0,29* 2,1±1,5** 3,7± 1,1* 2,6±0,07

In cervical mucus 3,5±0,08* 4,8± 0,3** 3,9 ±0,1* 4,5±0,02

The content of lysozyme (g/l)

In the serum 0,017±0,02* 0,017±0,03** 0,013±0,02* 0,018±0,01

In cervical mucus 0,07±0,04* 0,15±0,01** 0,10±0,01* 0,17±1,1

Note. *- the difference statistically significant (p<0,05) with indicators of control group, ** - the difference statistically significant (p<0,05) with indicators of group II

Comparative aspects of the treatment prove that 88,6% of patients from I group (used combined therapy) have the lack of side effects, the eradication of pathogens during the control test, normalization of vaginal biotope [table1, Fig.2].

The nearest and remote results of the therapyeffectiveness showed that all women there was significant decrease of titers of specific immunoglobulins according to the ELISA on the

Fig. 1

The normalization of the vagina microflora on the results of bacterioscopic and bacteriologic studies of vaginal discharge during the 6 months survey I (main) group was distinguished

background of antiviral therapy one month after completion of treatment. In the group II with the use of the drug Acyclovir in the episodic mode, the recurrences decreased by 12.5%, while the use of complex therapy on the proposed method allowed to reduce the recurrence of HSV by 22.8%. It should be noted that in patients of I group (main) clinical manifestations of relapses were less severe, compared to II group.

in 76,4% of subjects, whereas in the treatment of drug Acyclovir as monotherapy at 43.9% of women from group II [Fig. 2].

5 days of treatment (group 1)

97,1

46,9

53,1

78,1

21,9

lOdays of treatment (group 1)

5 days of treatment (group 2)

lOdays of treatment (group 2)

complete epithelialization

i incompleteepithelialization

.Epithelization of herpetic elements in the treatment process, '

Fig. 2. Nearest and remote results of treatment efficacy in women with recurrent genital herpes.

Conclusions

Thus, changes in the surface epithelium of the cervix during exacerbation of genital herpes is caused by the reduction of protective functions, which creates conditions for the rapid development of vagina microbiocenosis disorders. The result is increased sensitivity to any damage that may cause development of background and precancerous processes of the cervix, and in the future - a malignant neoplasm.

We conducted comprehensive treatment of GH in reproductive age women with the inclusion of the immunomodulator and a local antiseptic. Our therapy is effective (in 88.6% of cases), leads to the increase of nonspecific resistance parametersof the organism, elimination of dysbiosis, which contributes to the normalization of vaginal microbiocenosis in women with recurrent GH.

References:

1. Бенюк В.О., Щерба О.А., Ластовецька Л.Д. Етюпа-тогенетичш тдходи до дiагностики та лжування канди-дозно-герпетичного вульвовапшту. // Здоровье женщины, №9(64),-2011р.- с. 158-160.

2. Бенюк В.О., Ластовецька Л.Д., Никонюк Т.Р., Мельник В.В. Бактериальный вагиноз и современные возможности его лечения у женщин репродуктивного возраста/здоровье женщины, №3(69),-2012р.- с.133-138.

3. Бенюк В.А. Опыт применения препарата Вальтро-вир у пациенток с рецидивирующим генитальным герпесом. // Здоровье женщины: Всеукраинский научно-прак-

тический журнал. - К.: Академия мед. наук Украины, 2009; 1: 193-195.

4. Краснопольский В.И., Серова О.Ф., Туманова В.А. и др. Влияние инфекций на репродуктивную систему женщин. // Российский вестник акушера-гинеколога. - 2004. -№5. - С. 26-29.

5. Штефор, 1.Б. Стан клггинного iмунiтету в жшок з вiрусною урогештальною шфекщею та мимовшьними ви-киднями // В^ник наукових дослвджень. - Тернотль, 2005. -N2. - С. 140-141.

6. Панченко Л.А. Герпес. Роль в патологии человека. Противовирусные препараты // Харьков: «Планета-Принт», 2014 - с. 204.

7. Осипова Л.С., Кононенко И.Я., Сольский С.Я., Юрчук Ж.Н., Асатова А.А. Генитальный герпес. Особенности течения и лечения в современных условиях //Украшсь-кий журнал дерматологи, венерологи, косметологи, 2012. - С.5 - 10.

8. Страчунский Л.С., Козлов С.Н. Современная антимикробная химиотерапия: руководство. М., 2002; 436.

9. Bren L. Genital herpes: a hidden epidemic // FDA Consum. - 2002. - Vol. 36, N2.-P. 10-16.

10. Brugha R. Genital herpes infection: a review. Int. J. Epidemiol. 1997; Vol. 26, № 4: 698-709.

11. Leitich H., Bodner - Adler B., Braunbauer M. et al. Bacterial vaginosis as a risk factor for preterm delivery: a meta -analysis .// Am.J. Obstet, Gynecol. - 2003.- 189.- 139-147.

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