RU2155037C1 - Method of treatment of women with chronic urogenital candidosis - Google Patents

Abstract

FIELD: medicine, gynecology, dermatovenerology. SUBSTANCE: invention relates to treatment of women with torpent forms of urogenital candidosis. Method involves carrying out fractional plasmapheresis by taking off 400 ml of blood, its centrifugation (at 1500 rev/min for 15 min) followed by removal of supernatant plasma. Cycloferon is added to the remained cellular mass in the dose 1 mg/ml of leuko-erythrocyte mass. Obtained cellular mass is incubated at 18-24 C for 30 min at periodical stirring the mixture and then reinfusion of autogenic cellular mass is carried out by intravenous dropping route. Course of treatment is 4-5 seances, break is 2 days. Then antimycotic preparation diflucan is administrated in a single dose 150 mg. EFFECT: decreased time of immunocorrection, doses of preparation and treatment period. 2 tbl, 1 ex

Description

 The invention relates to medicine, in particular to dermatovenerology.

 Over the past decade, the frequency of urogenital candidiasis has almost doubled and amounts to 40-60% in the structure of inflammatory diseases of the female genital area. There is a tendency toward a predominance of recurrent, torpid-occurring forms of the disease (Serov V.N., 1997).

 The treatment of chronic recurrent candidiasis is a big problem in gynecology and dermatology, even despite the fact that oral preparations with high antifungal activity have now appeared. Known drug methods for the treatment of chronic forms of urogenital candidiasis in women, including antimycotic, desensitizing, immunostimulating therapy (V.L. Bykov // Pathology Archive - 1984 - N 12. - P. 75 - 82; Glazkova L.K., Egorova E. V., Minsker O.B. Fungal and some parasitic diseases of the female genital organs. - M., 1988. - P. 85).

 Known methods for treating chronic forms of urogenital candidiasis with systemic antimycotic drugs such as diflucan at a dose of 150 mg once a week for 3 to 4 weeks (N.M. Gerasimova, N.M. Tereshkina // Recommendations for the diagnosis, treatment and prevention of vulvovaginal candidiasis: Information sheet No. 1 of the Ural State Medical Academy, Department of Skin and Sexually Transmitted Diseases, Protocol No. 1 of January 24, 1997).

 The disadvantages of this method are the high doses of the antimycotic drug, as well as a high percentage of relapses (up to 60%). Given the complex pathogenetic mechanism of urogenital candidiasis, which is characterized by a long recurrent course, the appointment of only specific drugs, even highly effective ones, does not guarantee complete recovery.

 Mushrooms of the genus Candida belong to the conditionally pathogenic flora and cause disease only in conditions of a decrease in the body's resistance forces.

 Known methods for the treatment of candidiasis based on the notion that chronic recurrent candidiasis is based on the failure of local cellular immunity, its phagocytic link. There is a large arsenal of immunomodulating agents, however, due to the lack of methods of sufficiently effective immunostimulation, long-term (up to six months) prophylactic courses of itraconazole are prescribed to prevent relapse (Spinillo A., Colonna L. at al. Dept of Obstetrics and Gynecol, Univ of Pavia, IRCCS Policlinico S. Matteo, Italy. J. Reprod Med., 1997). The disadvantages of this method are the long duration of treatment, as well as large course doses of antimycotic drugs.

 Being complete antigens that are close in structure to human tissues, cause sensitization in the body. Candidiasis allergy leads to recurrence of the underlying disease, complicates its course (Sardyko N.V., Sobolev A.V., Pronina E.V., Zueva E.V. Allergy to mushrooms: Guidelines. - St. Petersburg, 1995 - 38 p.).

 In this regard, along with the use of antimycotic drugs, it is advisable to use methods that increase the defenses of the macroorganism - reduce allergic and autoallergic reactions, increase natural resistance and improve the general condition of the body (V.L. Bykov // Archive of Pathology - 1984 - N 12. - S. 75 - 82).

 For the above-mentioned effects in chronic urogenital, including fungal infections, the use of a new generation of immunomodulating preparation of an interferon inducer - cycloferon 250 mg iv or im from 10 to 15 injections (M.G. Romancev, F.I. Ershov et al. Immunodeficiency states: correction with cycloferon. NTFF Polisan, St. Petersburg, 1998) with simultaneous or subsequent etiotropic therapy (A.P. Remezev, V.A. Neverov Cycloferon: application in practice. Moscow - St. Petersburg, 1997). To conduct etiotropic therapy, the antimycotic drug Diflucan 150 mg once a week was used under the control of elimination of Candida genus from the body (Wood, A.G .; New England Journal of Medecine, 1994).

The disadvantages of this method are:
- the duration of the course of immunostimulating treatment with the subsequent use of diflucan (2 to 3 weeks). The duration of treatment is an average of 51 days;
- the occurrence of side effects, such as menstrual irregularities, painful ovulation, fever in 39.1% of cases.

 The objective of the invention is to increase the effectiveness of the treatment of chronic, torpid flowing forms of urogenital candidiasis in women, reducing the duration of treatment, reducing the dose of drugs.

The task is achieved by the fact that pre-conduct a sampling of 400 ml of blood, centrifuged it at 1500 rpm for 15 minutes, followed by removal of the supernatant plasma; cycloferon is introduced into the remaining cell mass at a dose of 1 mg per 1 ml of leuko-erythrocyte mass, the resulting cell mass is incubated at 18-24 ^° C for 30 minutes with periodic mixing of the mixture, and then the autogenic cell mass is reinfused intravenously 4- For 5 sessions, two days each and after the course of reinfusion of the autologous cell mass treated with cycloferon, the antimycotic drug Diflucan is prescribed at a dose of 150 mg once.

 The novelty of the method.

The course of reinfusion of autologous cell mass incubated extracorporeally with cycloferon provides:
1. improving tissue respiration and increasing cellular metabolism, eliminating specific sensitization in the body caused by candida fungi, increasing the overall reactivity of the body;
2. The introduction of cycloferon into the leuko-erythrocyte mass increases the bioavailability of the drug for acceptor cells and its activating effect on leukocyte membranes;
3. the introduction of 100 - 150 ml of a 9% physiological solution of NaCl is carried out to wash the cells of the leuko-erythrocyte mass and remove the residue of the drug, which determines the purity of the experiment;
4. The interval between the procedures is selected based on the period of the hyperreactive phase of the induction of interferon on stimulation by cycloferon.

 The essence of the method is as follows.

When making a diagnosis of chronic urogenital candidiasis in patients, exfusion of 400 ml of blood is preliminarily performed in hemacon 500/300 containers. After this, the blood is centrifuged at 1500 rpm for 15 minutes, followed by removal of the supernatant plasma (centrifugal plasmapheresis). Immunomodulator cycloferon is introduced into the remaining blood mass of the blood at a dose of 1 mg of the drug per 1 ml of leuko-erythrocyte mass, the mixture is incubated at a temperature of 18-24 ^° C for 30 minutes with periodic careful mixing of the mixture. Then, a 9% physiological solution of NaCl is injected into a hemocon with a leuko-erythrocyte mass to a volume of 500 ml. After that, centrifugation is carried out at 1500 rpm, followed by removal of the supernatant. After incubation, the leuko-erythrocyte mass is returned into the bloodstream of the patient intravenously. The course of treatment is from 4 to 5 sessions. The interval between procedures is two days, taking into account the removal of the drug from the body.

 After the procedure, to eliminate mushrooms from the body, patients take the antimycotic drug Diflucan in a dose of 150 mg once.

 The combination of preliminary centrifugal plasmapheresis with incubation of the cell mass with an immunomodulator cycloferon and subsequent administration of diflucan reduces the duration of treatment with cycloferon, avoids side effects, and reduces the dose of drugs.

 The time spent on operations of the proposed method are presented in table. 1.

 We have treated 18 patients with chronic continuously recurring forms of urogenital candidiasis; the results of treatment are given in table. 2, which presents the treatment indicators of the proposed method and the prototype.

 Clinical example.

 Patient K. with a diagnosis of chronic urogenital candidiasis, a continuously recurring course, levuride of the left hand - was admitted with complaints of intense itching in the vagina and perianal region, copious cheesy discharge from the vagina. From the anamnesis: the disease lasts 5 years, relapses of the candida process occur almost every menstrual cycle. Previously, a patient was treated with 150 mg diflucan once a week for urogenital candidiasis once a week for 4 weeks before elimination of candida fungi from the vagina. Relapse within 2 menstrual cycles.

 When entering the vagina, candida fungi were found. On examination: the vaginal mucosa is hyperemic, with a large number of curd masses.

The study of the immune status revealed a decrease in the T - cell immunity (CD ₃ - 47%, CD ₄ - 25%, CD ₈ - 10%, CD ₁₆ - 5%, a decrease in the phagocytic ability of neutrophils to 62%).

 The treatment was carried out: the patient underwent exfusion of 400 ml of blood. Blood sampling was performed in a single-use hemocon 300/500 system. After this, the blood was centrifuged at 1,500 rpm for 15 minutes, followed by removal of the plasma (centrifugal plasmapheresis). 2 ml of cycloferon was added to the remaining cell mass. The resulting mixture was incubated for 30 min with periodic, gentle stirring of the mixture. After incubation, the mixture was returned to the patient’s blood stream intravenously. The course of treatment was 5 sessions. With an interval between procedures of 2 days.

During treatment, the patient's condition improved significantly: itching in the vagina and perianal area stopped on the 3rd day (after 2 procedures), the number of discharge on the 5th day (after 2 procedures) decreased; in a vaginal examination, the disappearance of vaginal hyperemia was noted on the 8th day (after 4 procedures); the disappearance of levuride on the left hand was observed on the 12th day (after 5 procedures). After 5 procedures, normalization of cellular immunity indicators was noted (CD ₃ - 69%, CD ₄ - 39%, CD ₈ - 22%, CD ₁₆ - 14%, phagocytic activity of neutrophils to indicators corresponding to the norm - 82%).

 After 5 procedures, the patient took diflucan in a dose of 150 mg once. During mycological examination, no yeast-like fungi were found after a week. In this regard, a repeated dose of the drug was not prescribed.

 When observing the patient for six months, there were no exacerbations of urogenital candidiasis. In mycological studies (bacterioscopic and bacteriological) with a frequency of 1 time per month, fungi of the genus Candida were not found.

The positive effects of the proposed method:
1. This method of activation of leukocytes can effectively increase the immunoresistance of the patient’s body in the form of activation of indicators of the T-cell link of the immune system, specific indicators of phagocytosis of yeast-like fungi with neutrophils and reduce the dose of the immunostimulant and the dose of the antimycotic drug by 3 times.

 2. Re-infusion of autogenous cell mass with activated immunomodulator cycloferon can significantly reduce the sensitizing effect exerted on the body by yeast-like fungi.

 3. The frequency of side effects of the drug cycloferon is reduced by 4.5 times.

 4. The terms of treatment are reduced by 3 times.

Claims (1)

A method for the treatment of chronic urogenital candidiasis in women, including the use of an immunomodulating drug cycloferon, characterized in that it is pre-sampled with 400 ml of blood, centrifuged at 1500 rpm for 15 minutes, followed by removal of the supernatant plasma and the introduction of cycloferon into the remaining cell mass in a dose 1 mg of the drug per 1 ml leuco erythrocyte mass is carried out incubating the resulting cell mass at 18 - 24 ^o C for 30 min with occasional stirring and then carried rhein uziyu autologous cell mass intravenously after autologous reinfusion of treated cell mass cycloferon intervals for two days between treatments in the amount of 4 - 5 procedures prescribed antifungal drug Diflucan 150 mg once.

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