RU2180569C2 - Method to treat inflammatory diseases of small pelvic organs at chlamydial-herpetic ethiology - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: the method deals with treating a combined chlamydial-herpetic infection in women along inflammatory diseases of small pelvic organs. It is suggested to conduct preliminary immunotherapy with a combined immunoglobulin preparation together with alpha-2- recombinant interferon as suppositories for 7-10 d, antiviral preparations - since 3d-4th d of immunotherapy for 4-5 d, at 5th-6th d - an injection of antibiotics for 6-10 d; simultaneously, a hormonotherapy is conducted since 5th to 25th d of menstrual cycle for 3-6 mo. EFFECT: increased efficiency and shortened terms of therapy, increased inter-relapse period.

Description

 The invention relates to medicine and can be used in the treatment of concomitant chlamydial herpes infection in women with inflammatory diseases of the pelvic organs.

 Recently, among sexually transmitted infections (STIs), the frequency of chlamydial-viral associations in patients with inflammatory diseases of the pelvic organs (PID) has been increasing.

 The combined chlamydial herpetic infection develops slowly, proceeds without distinct clinical symptoms. In the examined women, subjective and objective symptoms prevail, characteristic of non-specific PID. Moreover, inflammatory processes are chronic and subacute in nature.

 In persons with chlamydial herpes infection, the immune system functions inappropriately. A full-fledged immune response is not formed or is formed too slowly, or immunopathological prevail over protective immune responses.

 With a combined infection of cell cultures, the competitive relations between microorganisms for the vital "territory of habitation" come to the fore. This contributes not only to the adaptation of chlamydia and herpes simplex virus (HSV) to intracellular parasitism, but also enhances the pathogenic properties of each of the members of this association, which leads to a high resistance of microorganisms to external influences, including antibiotics.

 In venereological practice, the methods of treating mono-infections with an etiopathogenetic approach are mainly used.

 There is a method of treating chlamydial infection of the urogenital tract in women, which involves hormone therapy with tricvilar-28 during the menstrual cycle, followed by joint hormone and antibiotic therapy during the second menstrual cycle. [Pat. RF 2128044, A 61 K 31/56, 35/74, 03/27/99, Bull. 9].

 There is a method of treating chlamydial infection of the urogenital tract in women with impaired reproductive function, in which hormone correction with estrogens and gestagens is performed, after which the antibiotic is administered subendometrically and orally for 7-10 days with the simultaneous use of proteolytic enzymes in a solution of dimethyl sulfoxide by phonophoresis. [Pat. RF 2114622, A 61 K 31/65, 38/24, 07/10/98, Bull. 19].

 A known method of treating chlamydial infection of the urogenital tract in women by combining antibiotic therapy with the use of immunotherapy using actovegin intramuscularly and locally. [Pat. RF 2108104, A 61 K 35/14, dated 10.04.98, Bull. 10].

 Recently, the drug acyclovir has been widely used to treat herpes. [STD, 2, 1995, p. 11-17, 48-49].

 With recurrent genital herpes, the effectiveness of long-term suppressive therapy (5 years) with acyclovir was studied. Despite the positive results of the study, the effectiveness of the cure cannot be recognized as sufficient, since the likelihood of the virus resistance to the drug is not excluded. This is due to tissue tropism, the ability of herpes viruses to multiply in infected cells and lifelong preservation in an implicit morphological and immunochemically altered form in nerve cells.

 A known method for the treatment of recurrent herpes, including the introduction of a multi-vaccine vaccine, followed by the introduction of Dibazole and Eleutherococcus. The term of the issue is 1.5-2.0 g. The course of treatment is 10 months. [A.S. USSR 1139436, A 61 K 31/00, dated 02.15.85, Bull. 6]. The method is long and does not provide intracellular inhibition of virus reproduction, since vaccination of a knowingly infected person is unable to qualitatively change the immune status.

 A known method for the treatment of herpes, comprising 3 stages.

 In the acute stage of infection or relapse, the use of acyclovir orally and topically in combination with antioxidants (vitamins C, E), interferon inducers (rheoferon), prostaglandin inhibitors (indomethacin).

 In remission, the use of immunomodulators (neovir, dibazole), adaptogens (lemongrass, golden root).

 2 months after the end of therapy - vaccination. [Safronova M.M. The principles of diagnosis and treatment of genital herpes. Clinical Pharmacology and Therapy, 1998, 1].

 The method is long and complex, moreover, it does not provide inhibition of reproduction of intracellular infection.

 A pronounced therapeutic effect was exhibited by the combined use of α-2-interferon (reaferon) and acyclovir in the treatment of experimental genital herpes in guinea pigs [STD, 2, 1995, p. 49].

 With recurrent herpes, good prophylactic results were achieved by intravenous administration of a solution of an immunologically active protein fraction of plasma or human serum containing IgG. [V.N. Serov, Bulletin of the obstetrician of the gynecologist 3, 1997, p. 42-44].

 Recently, the development of antibacterial and antiviral drugs based on immunoglobulins has been actively developing.

 Known drug for the treatment of viral, chlamydial and bacterial infections for rectal use, containing genetically engineered interferon and α-tocopherol acetate [Pat. RF 2057544, A 61 K 38/21, dated 10.04.96, Bull. 10].

 Of interest is the use of a complex immunoglobulin preparation (CIP) with a high content of IgM, IgA and IgG due to the processing of the protein ballast fraction [New drugs, vol. 3, 1993, p. 16; Pat. RF 2051054, A 61 K 39/395, dated 12/27/95. Bull. 36].

 Closest to the claimed method is an approach to the treatment of PID with polymicrobial etiology, providing for antibiotic therapy, while drug combinations are selected depending on the type of bacteria (gram-positive and gram-negative), the nature of the inflammatory process [STD, 2, 1994, p. 7-11]. However, the use of only antibacterial or antiviral therapy leads to the suppression of immunological reactions, intracellular adaptation of microorganisms, the transition of the infection to a latent state and a decrease in its antibiotic sensitivity.

 The technical result of the invention is to increase efficiency, accelerate the healing time, increase the relapse period.

 The technical result is achieved by the fact that the method of treatment of PID of chlamydial-herpetic etiology includes preliminary immunotherapy with interferons for 7-10 days, antiviral drugs - from 3-4 days of immunotherapy, for 5-6 days - the introduction of antibiotics; simultaneously hormone therapy from 5 to 25 days of the menstrual cycle for 3-6 months.

 As interferons, a complex immunoglobulin preparation with a high content of IgM, IgA and IgG and recombinant α-2-interferon is used.

 Distinctive features of the method are the following.

 Preliminary immunotherapy with a complex immunoglobulin preparation and recombinant α-2-interferon.

 One of the main means of protecting the body against viral and bacterial infections is its own system of interferons, which are the main effector mechanism of the cell-mediated immune response against infection. With inadequate immune system function, the use of recombinant α-2-interferon provides inhibition of the intracellular development of bacteria and stimulates antibacterial, antiviral immunity. The combined action of α-2-interferon and CIP causes a powerful antimicrobial and antiviral effect both intracellularly and in the extracellular environment of the body.

 The combination of antibiotic and antiviral therapy with immunotherapy while suppressing ovulation and regulation of the hypothalamic-pituitary-ovarian relationships using hormonal drugs provides a more pronounced antiviral and antichlamydial effect than using them separately without the use of immunotherapy.

 The time periods of the treatment stages have been established in clinical practice, their necessity and sufficiency is confirmed by the results of laboratory diagnostics (PIF, ELISA, PCR) and immunological reactivity indicators.

 The possibility of practical application of the proposed method is illustrated by an example of its specific implementation.

 Example. Patient E., 17 years old, was admitted to the hospital on January 12, 1999 with complaints of aching pains in the lower abdomen, itching and burning in the area of the external genitalia. Somatic history is not burdened. Menses from 13 years, after 28 days, 5 days, moderate, painless. Last monthly period 12/20/98. Sexual life from 14 years old, out of wedlock, for the entire period of 8 sexual partners. Pregnancy alone, ended in an artifact abortion. From the anamnesis it was found out: she got sick 2 days ago, when there were pains in the lower abdomen, the next day itching and burning sensations in the external genital area began to disturb, in connection with which she turned to the LCD, was sent and hospitalized in the clinic.

During the examination: the general condition is satisfactory, the pulse 78 in 1 min, body temperature 36.8 ^o C.

 The external genitalia are developed correctly; in the area of the posterior commissure, hyperemia, edema, pain on palpation, vesicles filled with transparent contents. Inspection in the mirrors: the mucous membrane of the cervix is eroded around the circumference of the cervical canal with a diameter of 1.5 cm. For vaginal examination: the body of the uterus is in a normal position, dense, limited mobility, and painless. Appendages on both sides are heavy, sensitive to palpation.

 Chlamydia was detected in smears from the urethra of the cervical canal by the PIF and PCR methods; in smears taken from the cervical canal and contents of the vesicles, HSV was detected by PCR, blood ELISA - the level of IgM HSV is positive.

 Immunogram indicators: the content of Ev-ROCK% is slightly reduced to 4.5% (in the control 5.8 ± 0.43%), the number of Ev-ROCK is a / h 0.11 (in the control 0.15 ± 0.01); the content of T cells with helper activity of 77% (in the control 51.2 ± 1.4); the content of T-suppressor cells 4% (in the control of 6.7 ± 0.71); the ratio Tx / Tc 19.2 (in the control of 6.72 ± 0.92); IgA content of 3.09 g / l (in the control 1.67 ± 0.07 g / l); the concentration of the CEC is 4.12 (in the control 3.2 ± 0.18).

 Diagnosis: Subacute bilateral salpingoophoritis, cervical erosion, chlamydia, genital herpes.

 The patient was prescribed treatment: CIP candles with α-2-interferon at 500,000 ME (1 candle) rectally, on the third day of immunotherapy, Valtrex (valciclovir) was prescribed - 500 mg 2 times a day, for 5 days (5 g course) ) On day 5, complete epithelization of the site of herpetic eruptions was noted. From the 5-6th day of immunotherapy, the introduction of an antibiotic with antichlamydia activity began: azithromycin (sumamed) - once in a dose of 500 mg for 6 days (3.0 g per course). In addition, the patient received vitamin therapy, physiotherapy, and candidiasis was prevented. On January 22, 1999 (the 5th day of the menstrual cycle), tri-regol was prescribed according to the scheme.

 On the 4-5th day after the start of therapy, an improvement in the general condition was noted, the itching and burning in the external genital area disappeared, on the 5th day the complete epithelization of the focus of herpetic eruptions was noted. On day 8, pain in the lower abdomen completely disappeared. On day 11, treatment was completed. Immunological parameters after treatment were: the content of Ev-ROCK% 6.0% (in the control 5.8 ± 0.43%), the amount of Ev-ROCK and / h 0.15 (in the control 0.15 ± 0.01); the content of T cells with helper activity of 51.4% (in the control 51.2 ± 1.4); the content of T-suppressor cells of 7.4% (in the control of 6.7 ± 0.71); the ratio of TX / TC 6.9 (in the control of 6.72 ± 0.92); the IgA content of 1.8 g / l (in the control of 1.67 ± 0.07 g / l); the concentration of the CEC 3.4 (in the control of 3.2 ± 0.18).

 The patient was discharged from the hospital with a complete clinical recovery. 21 days after the cancellation of antibiotics, the contents of the cervical canal and urethra were studied by the methods of unit investment funds and PCR - chlamydia was not detected. Control studies after 1.5 months by PCR - chlamydia were not detected, ELISA - only the IgG titer was detected, the IgM level of C.trachomatis is negative. At the same time, a study was conducted for the presence of HSV. PCR diagnosis - HSV was not detected, ELISA: HSV IgG level is positive, HSV IgM level is negative. During the control study, clinical symptoms and residual effects of the inflammatory process of the genitals were not found.

 Further monitoring of the patient for 1 year 4 months showed a complete absence of subjective and objective signs of the inflammatory process of the pelvic organs of chlamydial-herpetic etiology.

 Using the proposed method in a modern microsocial environment, a model of sexual behavior associated with risk factors such as an early age of the onset of promiscuity, the presence of several sexual partners, will improve the effectiveness of the treatment of chlamydial herpes infection.

Claims (1)

 A method for the treatment of inflammatory diseases of the pelvic organs of combined chlamydial-herpetic etiology, characterized in that they are immunotherapy with a complex immunoglobulin preparation with α-2-recombinant interferon in the form of suppositories for 7-10 days, antiviral drugs are prescribed starting from 3-4 days of immunotherapy within 4-5 days, on days 5-6 of immunotherapy, the introduction of antichlamydia antibiotics begins, within 6-10 days; at the same time, hormone therapy is carried out with monophasic, low-dose hormonal contraceptives: from 5 to 25 days of the menstrual cycle for 3-6 months.