RU2348402C2 - Method of patients' preventive vaccination - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: for preventive vaccination, vaccine injection is preceded with Tilorone therapy. Tilorone is introduced once a day according to dosage regimen as follows: 1st day - 250 mg, 2nd day - 125 mg, further triduan - 125 mg. Course doze is at least 1250 mg.

EFFECT: higher efficiency of preventive vaccination ensured by higher longevity of protective antibody titre and lower rate of postvaccinal complications due to presented maximal immunomodulatory properties of Tilorone introduced at the specified regimen.

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Description

The invention relates to medicine and can be used for prophylactic vaccination.

In recent years, the toxic load has significantly exceeded the one in which the human body evolved. New diseases have appeared, well-known chronic processes take a protracted course and are poorly suited to traditional methods of prevention, treatment and rehabilitation. Everywhere, an increase in the specific gravity of congenital pathology, infectious and chronic somatic diseases, and a decrease in the effectiveness of vaccination prophylaxis were noted. Among the organized adult population, even after the planned preventive vaccination, epidemic upsets of infectious diseases very often arise. Under these conditions, the epidemiological situation for the spread of infectious diseases can be designated as moderately tense. The vaccination calendar for various populations is designed to create a high-quality immune layer.

Given the high proportion of young people among patients with diphtheria, an analysis of the intensity of anti-diphtheria immunity was performed in 101 practically healthy patients with similar socio-economic and living conditions. In the study of immunity, it was found that only 31 patients (30.6%) had a protective antibody titer.

In the immune status in adults who did not have a protective titer of antibodies, a decrease in CD3 and CD4 was most often detected in 75.4% of patients (in 46 patients), IgA and IgM concentrations in 29.5% (18), and an increase in IgE in 18% patients (in 11 patients).

Thus, although patients did not have clinical signs of secondary immune deficiency (VIN), laboratory tests revealed signs of immune status disorders that led to frequent post-vaccination complications. The problem of the immunopathogenic effect of prophylactic vaccines is that an undesirable immune response may not be noticed. The objective reasons for this phenomenon are due to the so-called “drift” of the immune response in an unpredictable direction.

For example, patient P., 52 years old, considered herself practically healthy and carried out routine vaccine prophylaxis with anatoxin ADS-M (adsorbed diphtheria-tetanus toxoid with a reduced content of antigens) during the period of epidemiological troubles in 1994. 7 days after vaccination, the patient rose to 38.7 ° C, swelling of the lips, eyelids, abundant rashes such as “urticaria”. In the blood test - eosinophilia 7%, leukocytosis, lymphocytosis. From the anamnesis it was found that earlier after a preventive vaccination there was the same reaction that the patient forgot about, and the local doctor who carried out the vaccination did not do a clinical blood test before vaccination, did not collect an allergy history.

Thus, the issue of preventing the undesirable consequences of preventive vaccinations is very relevant.

A known method for the prevention of complications caused by vaccination of children with a chronic recurrent infection (patent RU 2228756, publ. 2004.05.20, A61K 31/522), in which acyclovir is prescribed for the first 5 days, cycloferon, alvitil and imudon b for 2 weeks before vaccination. preventive doses.

Cycloferon and imudon are immunomodulators.

The purpose of this known method is the prevention of recurrence of herpes infection, in which 2 immunomodulators are used, but this method has not been used to prevent post-vaccination complications and create intense post-vaccination immunity. In the materials of the description of the invention there is no data on the duration and severity of post-vaccination immunity.

The objective of the invention is to develop a method of prophylactic vaccination of patients.

The technical effect that can be obtained by using this invention is to reduce the incidence of post-vaccination complications, taking into account the pathogenesis of the development of the immune response in patients and increase the effectiveness of preventive vaccination, because the average duration of treatment decreases with exacerbation of chronic foci of infection, conditions are created for a longer preservation of the protective titer of antibodies in the post-vaccination period (more than 3 years).

To solve this problem, a prophylactic vaccination method is proposed by administering a vaccine to produce antibodies, in which, before the vaccine is administered, an immunomodulator, in particular, tilorone, is administered, followed by vaccination during the recovery period of the altered immune response indicators. In this case, the effectiveness of immunization is assessed by the dynamics of the increase in antibody titer and the duration of its preservation at the level of the protective titer. The restoration of altered indicators of the immune response is understood to mean the normalization of the Th1 / Th2 ratio, the production of interferons and immunoglobulins, which is especially important in immunocompromised patients and patients with allergopathology.

The prophylactic vaccination method proposes to take an anamnesis before administering the vaccine to patients, conduct clinical blood tests and identify chronic diseases, allergic reactions and changes in the blood test (leukocytosis or leukopenia, eosinophilia, lymphocytosis or lymphopenia) to undergo a course of therapy with an immunomodulator, in particular tilorone .

Such a course of tilorone therapy can be carried out, for example, according to the following scheme: 1st day - 250 mg once a day; 2nd day - 125 mg once a day; then after two days on the third - 125 mg once a day, only 1250 mg (for example, 10 pieces of tablets or capsules of 125 mg). Then administer the vaccine, for example, after 10 days.

Tiloron is the first synthetic low molecular weight interferon inducer effective for oral use (immunomodulator), also has antiviral and antimicrobial activity (“Tiloron: profile of biological activity. I Pharmacological properties.” Interactive Antropolia, No. 1 (7) 2006, pp. 18-23-23 )

Tiloron has synonyms: Amixin, Lavomax.

Clinical and immunological examination was carried out in 178 patients who considered themselves to be practically healthy. The average age of vaccinees was 34.4 ± 1.2 years. In clinical, laboratory and functional examinations, 73.0% (n = 130) of the patients before the planned preventive vaccination revealed chronic foci of infection of various localization (chronic tonsillitis, chronic rhinosinusitis, sinusitis, chronic bronchitis, gastroduodenitis, adnexitis, infections of the genitourinary system).

When determining indicators of humoral immunity in 78.9% of cases, an increase in the titer of antibodies of the IgM class to opportunistic microorganisms was noted during the exacerbation and IgG class in the period of remission. However, the avidity of these antibodies was significantly reduced, which exacerbated the chronic foci of infection.

A post-vaccine immune response study was conducted in 145 patients with confirmed clinical and laboratory signs of secondary immune deficiency (VIN).

Group I - 47 patients - ADS-M revaccination was carried out according to the generally accepted technique.

Group II - 48 patients - ADS-M revaccination was carried out after taking cycloferon according to the scheme: 1st day - 300 mg once a day, 2nd day - 150 mg once a day, then two days later on the third - 150 mg once a day, only 1500 mg (per course - 10 tablets of 150 mg). The vaccine was administered 10 days after the course of cycloferon.

Group III - 50 patients - ADS-M revaccination was carried out after taking tilorone according to the scheme: 1st day - 250 mg once a day, 2nd day - 125 mg once a day, then two days later on the third 125 mg once a day, only 1250 mg (per course - 10 tablets or capsules of 125 mg). The vaccine was administered 10 days after the course of tilorone.

Studies of the immune status and tension of anti-diphtheria immunity (according to RPHA - passive hemagglutination reaction) were carried out: before vaccination 3 weeks, 6, 12 months and 36 months after administration of ADS-M. The concentration of immunoglobulins was determined by Mancini, total IgE - by ELISA.

3 weeks after revaccination, negative changes in the immune status characteristic of VIN persisted in group I in 26 patients, in group II in 19 patients and in group III in 14 patients. After 12 months, changes were recorded in group I in 11 patients, in group II in 8 patients, in group III. in 5 patients.

A protective titer of anti-diphtheria antibodies (> 1:40 and 1:80) was established after 3 weeks in group I in 19 patients, in group II in 26 patients and in group III in 31 patients; after 6 months it was established in group I in 29 patients, in group II in 31 patients and in group III in 41 patients. In group II, the intensity of immunity was 1.1 times higher than in patients of group I, in group III - 1.8 times higher than in patients in group I, and remained at a fairly high level after 6, 12 and 36 months .

Local reactions after vaccination were observed in 9 patients in group I, in 3 patients in group II, and in 2 patients in group III. Systemic post-vaccination reactions within 12 months of observation were not observed.

After the course of tilorone, the average duration of treatment of patients with exacerbation of chronic foci of infection decreased by 4.6 ± 0.4 days, and humoral immunity indicators normalized in 76.7 ± 2.1% of patients. Remission for more than 12 months was observed in 10.6 ± 1.2% of patients, in 19.9 ± 1.1% - up to 12 months, in 42.2 ± 2.3% - up to 6 months, their quality of life significantly improved ( p <0.05).

In the group of patients (n = 50), who were prescribed a course of tilorone before the vaccine, the most stable positive clinical and immunological parameters of the post-vaccination response were obtained.

The possibility of implementing the method is confirmed by the following examples when vaccinating with ADS-M, but is not limited to them.

Example 1. Patient K.R.P. 28 years old has been observed in the hospital since birth. In childhood, ARVI was often sick, 3 times suffered a sore throat. DTP vaccinations were carried out according to the plan, the post-vaccination period was uneventful. From the age of 12, he began to smoke actively, at 23, chronic obstructive bronchitis was diagnosed with an exacerbation frequency of up to 3-4 times per year, mainly in the autumn-winter period.

In 1999, with the introduction of tetanus toxoid after domestic foot injury, the patient had a local and general reaction (hyperemia, swelling, pain at the injection site, as well as an increase in temperature on the 2nd day after the administration of toxoid to 37.6 ° C, headache, muscle pain, joints).

In 2004, planned revaccination was planned. Before vaccination, the titer of anti-diphtheria antibodies by RPGA was 1:20, no clinical, instrumental or laboratory signs of exacerbation were detected. 10 days before vaccination, tilorone was prescribed according to the scheme:

1st day - 250 mg (2 capsules) after meals once a day; 2nd day and 3rd day - 125 mg (1 capsule) once a day; then 125 mg (1 capsule) once a day two days later on the third. In total, 1250 mg per course (for example, 10 pieces of tablets or capsules of 125 mg each). On the 10th day from the start of treatment, revaccination of ADS-M with toxoid 0.5 ml s / c in the right subscapular region was performed (series 973-2).

There were no reactions to vaccination or signs of exacerbation of a chronic disease. Vaccination efficacy was confirmed after 12 and 36 months with a high titer of specific anti-diphtheria antibodies (1: 1280 and 1: 640).

Example 2. Patient I.A.A., 27 years old, from childhood suffers from atopic dermatitis with frequent exacerbations (5-6 times a year), chronic tonsillitis, chronic adnexitis. Clinical and laboratory examination before the planned vaccine prophylaxis did not reveal the activity of the chronic inflammatory process. The titer of specific anti-diphtheria antibodies before planned revaccination was 1:10. 10 days before revaccination, the patient received tilorone according to the scheme (10 capsules per course) and on the 10th day from the start of treatment with tilorone, toxoid ADS-M was introduced 0.5 ml s / c in the right subscapular region (series from 973-2).

The post-vaccination period was uneventful. A high titer of anti-diphtheria antibodies was maintained for 24 and 36 months (1: 640 and 1: 320), during the observation period after revaccination there was only 1 exacerbation of atopic dermatitis and chronic adnexitis. The average duration of exacerbation decreased from 14 to 8 days.

Example 3. Patient O.A.V., 28 years old, with a verified diagnosis of chronic obstructive bronchitis, chronic tonsillitis. In childhood, all vaccinations were carried out according to the plan. At 18 years after the planned revaccination of ADS-M, the patient experienced long-term subfibril temperature (more than 30 days and leukopenia (L-3.6-4.2 g / l), antibodies to the herpes simplex virus were detected.

Before the planned revaccination, clinical, laboratory and instrumental signs of exacerbation of chronic foci of inflammation were not detected. There were no antibodies to the herpes simplex virus. Tension of specific anti-diphtheria immunity was minimal - 1:20, L - 4.6 g / l. The patient was prescribed tilorone according to the scheme (10 capsules per course), and on the 10th day from the start of tilorone therapy, the toxin ADS-M was introduced 0.5 ml sc in the right subscapular region (series from 987-4).

The post-vaccination period was uneventful, there were no exacerbations of chronic foci of inflammation for 12 months, the tension of post-vaccination anti-diphtheria immunity after 36 months was 1: 1280, L -5.2 g / l.

Those. it was shown that tilorone contributes to the long-term preservation of the protective titer of antibodies in the post-vaccination period.

Thus, the dynamics of the post-vaccination immune response in chronic inflammatory diseases made it possible to achieve stable clinical and laboratory parameters and conduct routine preventive vaccination.

The use of an immunomodulator of Tiloron before the introduction of the vaccine on the example of ADS-M has proven its effectiveness.

Previously, the use of an immunomodulator, in particular tilorone, for prophylactic vaccination was not known.

The data obtained give reason to recommend tiloron before any routine vaccination and revaccination to all patients with chronic diseases, allergic reactions and changes in the blood test.

Claims (1)

A method for prophylactic vaccination of patients, comprising administering a vaccine to produce antibodies after an immunomodulator treatment course, characterized in that tilorone is administered as an immunomodulator once a day according to the scheme: 1st day - 250 mg, 2nd day - 125 mg, then in two days on the third - 125 mg; course dose - not less than 1250 mg.