RU2456020C1 - Method of preventing influenza and acute respiratory infections in children suffering bronchial asthma - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely pediatrics, may be used for preventing influenza and acute respiratory infections in children suffering bronchial asthma. For this purpose, 5 days before the scheduled influenza vaccination, Viferon is introduced in a child's body through rectum in the form of suppositories twice a day in the morning and in the evening, one suppository in a single dose for children aged 4 to 7 years old 150000 ME, 7 to 16 years - 500000 ME, and the second stage involves introducing the inactivated influenza vaccine.

EFFECT: use of the given method allows improving a clinical course of the post-vaccinal period ensured by reducing intercurrent ARIs in 4 times, and also decreasing the rate of influenza and ARIs of the other aetiology for the following epidemiological period in 2 times.

2 ex, 2 dwg

Description

The invention relates to medicine and can be used to prevent influenza and other acute respiratory infections (ARI) in children with bronchial asthma.

ARI, including influenza, occupy a leading place in the structure of the infectious morbidity of the population and cause great socio-economic damage. Children suffer from ARI more often than adults, and the incidence of severe and complicated forms of the disease is significantly greater.

Bronchial asthma (AD) is one of the most common chronic diseases. Epidemiological studies indicate that in recent years the number of patients suffering from allergic diseases has increased 5-10 times, and AD is observed in 5-15% of children under 18 years of age [1].

The problem of the prevention of influenza and other acute respiratory infections in children with AD at the present stage affects several aspects. On the one hand, respiratory pathogens contribute to the exacerbation of the disease, its severe course and themselves can play the role of causally significant allergens in the genesis of AD. On the other hand, repeated acute respiratory infections form a vicious cycle of immunological reactivity of the child's body with AD, which leads to a worsening and protracted course of episodes of a respiratory infection. According to the PREVIA study, a viral infection is detected in children with exacerbations of AD with a frequency of up to 85%, and there is a seasonal relationship between the frequency of ARI and the frequency of hospitalizations for AD [Bisgaard N. et al. American Journal of Respiratory and Critical Care Medicine, 2005; 171: 315-322]. According to other studies, viral infections are more often detected in AD patients during an episode of wheezing than during a period of no symptoms [Johnston SL et al. British Medical Journal, 1995; 310: 1225-1229; Johnston SL et al. American Journal of Respiratory and Critical Care Medicine, 1996; 154: 654-660; Pattemore PK et al. Clin Exp Allergy 1992; 22: 325-336].

A special approach to this category of children is required when carrying out preventive measures in relation to respiratory infections.

In this regard, the prevention of influenza and ARI in children with bronchial asthma is a socially and economically significant task.

Its solution will reduce the incidence of influenza and ARI in children with bronchial asthma, ease the course of each episode of a respiratory infection, ease the course of asthma and, as a result, reduce the frequency of hospitalizations of children with asthma, which will reduce the state's economic costs for treating children.

The most effective method adopted worldwide is the prevention of influenza through the use of influenza vaccines. It provides the creation of active immunity in vaccinated only against influenza pathogens, while the severity of the clinical manifestations of AD in children is affected by their wider spectrum: rhinovirus, coronavirus, parainfluenza, respiratory syncytial virus, etc. On the other hand, it is known that the complex of cytokines and the system of interferonogenesis are the regulators of the inflammatory reaction during exacerbation of AD. In children with AD, there is a disruption in the functioning of the interferon system, which is a pathogenetic prerequisite for the implementation of influenza and ARI, leading to the development of frequent exacerbations of AD and, in general, worsen the course of AD and the prognosis of the disease [4–6 Olga's patent].

A known method of preventing influenza in children [Center for Disease Control and Prevention. Prevention of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Wkly Rep. 2000; 49 (RR-03): 1-42], which consists in the fact that in the pre-epidemic period - no later than one month before the predicted rise in the incidence of influenza, they conduct active specific immunization of children by parenteral (subcutaneous or intramuscular) administration of a child inactivated influenza vaccine: for children from 3 to 14 years - 1 dose (0.5 ml) once. Children who have not previously had the flu and who have been vaccinated are advised to administer 2 doses of the vaccine with an interval of 4 weeks. Adults and adolescents over 14 years of age are given a single dose of the vaccine (0.5 ml).

However, the known method has several significant disadvantages. After vaccination of children with AD, there is a lack of formation or an insufficient level of formation of specific anti-influenza antibodies due to the peculiarities of the immunopathogenesis of this disease.

A specific immune response develops only to the components of the influenza vaccine, and therefore does not prevent the development of other non-influenza ARI etiologies.

In individual patients with AD with the initial changes in the immune status established in our studies and in studies of other authors (impaired phagocytic activity of neutrophils, decreased levels of secretory immunoglobulin A in the nasal secretion, immunoglobulins A and G in the blood serum), the immune response to the components of the vaccine is insufficient for the formation of protective specific immunity.

There is also known a method for the prevention of influenza and ARI in children, often bleating with acute respiratory diseases, including sequential immunization [Korovina N.A., Zaplatnikov A.L., Suzdalenkov A.V. Patent for the invention RU (11) 2223783 (13) C1; Zaplatnikov A.L. Clinical and immunological substantiation of immunotherapy and immunoprophylaxis of viral and bacterial diseases in children. Abstract. dis. Dr. med. Sciences., M., 2003]. At the first stage, no later than a month before the planned vaccination against influenza - in the pre-epidemic period of an increase in respiratory morbidity, the course application of ribomunil vaccine is prescribed in a dose of 1 inside daily for 4 days with an interval of 3 days during the first 3 weeks of administration and 1 dose inside daily for 4 weeks with an interval of 1 month for the next 2-5 months or course use of the bacterial vaccine IRS-19 according to the following scheme: 1 dose intranasally in each nostril 2 times a day, daily for 2 weeks. At the second stage, 1-3 months after the start of the use of the bacterial vaccine (September-November), the child is given a parenterally (subcutaneous or intramuscular) inactivated influenza vaccine in accordance with official recommendations on the age-related dosage regimen.

However, this method has not been tested in children with AD due to the high drug load, and the standard method using only the influenza vaccine is ineffective in children with AD and does not reduce the incidence of both influenza and other acute respiratory infections. The method with the sequential use of a bacterial vaccine (ribomunyl or IRS-19) and an influenza vaccine does not allow creating immunity against a wide range of viral pathogens that provoke or cause an exacerbation of AD. As a result, effective control over asthma is not possible.

Currently, there are no methods specially developed for children with AD for the prevention of influenza and ARI, including by vaccination.

The objective of the invention is to provide an effective method for the prevention of influenza and acute respiratory infections in children with bronchial asthma, which can simultaneously reduce the incidence of influenza and acute respiratory infections, to alleviate the course of bronchial asthma against their background and in the post-vaccination period.

The essence of the invention lies in the fact that the method for the prevention of influenza and acute respiratory infections in children with bronchial asthma is characterized by the fact that immunization is carried out sequentially in two stages, while at the first stage 5 days before the planned vaccination against influenza, the child is daily injected into the body viferon rectally in the form of suppositories twice a day in the morning and in the evening, one suppository in a single dose for children from 4 to 7 years old is 150,000 ME, from 7 to 16 years old - 500,000 ME, and at the second stage, the planned influenza vaccine is administered.

Using the invention allows to obtain the following technical result.

The first developed method for the prevention of influenza and other acute respiratory infections in children with AD is highly effective. It allows you to improve the course of the post-vaccination period by reducing intercurrent ARI by 4 times, and reduce the incidence of influenza and ARI of another etiology in the subsequent epidemic season by 2 times.

At the same time, acceleration of the timing of the creation of immunity against vaccine strains, an increase in the number of children with a protective titer of specific anti-influenza immunoglobulins is achieved.

The frequency and severity of subsequent ARIs are reduced, which helps to prevent the development of bronchial obstructive syndrome against their background.

The method allows to reduce the drug load on a patient with AD.

At the same time, the course of the underlying disease, bronchial asthma, is facilitated. This effect is achieved by reducing the number of asthma attacks, their severity against the background of acute respiratory infections. The inclusion of the component of the drug Viferon, additional to vaccination, is pathogenetically substantiated: the balance of cytokines is modulated, and, first of all, due to stimulation of the synthesis of gamma-interferon.

Using the method helps to restore balance in the cytokine system, activates the factors of innate immunity of children with AD, which increases the body's resistance to respiratory pathogens.

The proposed method allows to achieve epidemiological effectiveness in relation to a wide range of acute respiratory pathologies, including influenza.

All of the above as a whole allows improving the quality of life of children with chronic somatic pathology of asthma, especially with severe and moderate form.

Given the particular importance of interferon proteins, other factors of innate immunity in the prevention of exacerbations of AD with ARVI and the progression of the disease with repeated ARI, the method can be considered as a modern tactics for AD immunotherapy in children.

The anti-inflammatory (basic) therapy of AD used and introduced into practice at the present stage depends on the severity of the disease. The inclusion of Viferon as a component of a new method of vaccination against influenza is especially relevant and effective for children with severe forms of AD. Using the method will solve the important socio-economic problem of improving the quality of life of patients with AD.

The technical result is achieved due to the developed by the authors of a new technology for vaccination of influenza and ARI.

For the first time, a method has been developed for the prevention of influenza and other ARIs in children with bronchial asthma. It differs from previously known methods of vaccination in that it includes a complex sequential introduction into the body of children of the immunomodulator Viferon 5 days before the flu vaccine. The ability of the drug Viferon to positively affect the characteristics of immunopathogenesis in bronchial asthma, restore interferon formation and activate the immune system, eliminate imbalances in the cytokine system helps to increase the effectiveness of influenza vaccine prophylaxis, on the one hand, and on the other, alleviates the severity of AD.

The effectiveness of the doses and timing of the introduction of the specified drug to patients with AD during vaccination against influenza has been proven.

Numerous studies in our country and abroad have established that viral infection is a trigger factor in the development of asthma exacerbation, and a key element in the implementation of allergic inflammation is a feature of the cytokine complex and interferonogenesis. The manifestation of the features of AD immunopathogenesis consists in the altered activity of subpopulations of T-limocytocytes, which changes the activity of T-cells and B-unit of immunity. The mechanism consists in the selective activation of Th2-cell immunity, an increase in the production of the immunosuppressive cytokine IL-10, and a decrease in gamma-interferon formation [O.V. Zaitseva, S.V. Zaitseva. Bronchial asthma and respiratory infections in children. Bulletin of Pediatric Pharmacology and Nutrition, 2008, v.5, No. 1, p. 54-60].

Viferon® is an antiviral and immunomodulating drug, produced in the form of rectal suppositories and including recombinant α2-IFN and membrane-stabilizing components in therapeutically effective doses (RF patent No. 2024253).

Previously, Viferon® for the prevention of influenza and other acute respiratory infections in children with AD was used only as part of a comprehensive anti-inflammatory therapy for AD (2000 RF patent Zaitseva O.V., Malinovskaya V.V., Zaitseva S.V., Samsygina G.A.).

Considering the well-known adjuvant effects of interferon, which include activation of B cells, increased migration of myeloid dendritic cells to the injection site, increased antigen presentation, stimulated production of specific IgG, IgG2a and secretory IgA [Tovey MG, Bloch F., Launay O., 2006], to improve the results of influenza vaccination, as well as to expand the spectrum of controlled respiratory infections in children with AD, it is advisable to use an additional component in the form of a recombinant alpha2-interferon preparation to widely used anti-inflammatory drugs rippo vaccines. The basis for the use for this purpose of the preparation of recombinant alpha2-interferon, in addition to the proven adjuvant, are the pronounced immunomodulating effects of IFN.

The use of viferon in combination with subsequent vaccination against influenza is not obvious to specialists, because previously combined two stages of the introduction of vaccine preparations. Viferon is not a vaccine, but has pronounced antiviral and immunomodulating properties.

The authors found that viferon enhances the antiviral effect against a wide range of respiratory pathogens, corrects the characteristics of immunological interactions in children with bronchial asthma, enhances antibody formation and stimulates nonspecific resistance of the children's body.

The authors set themselves the task, on the basis of an additional rational component for the influenza vaccine, to improve the results of influenza and ARI vaccination in children with AD. Previously conducted by the authors of the study [T. Chebotareva An improved method for the prevention of influenza and other acute respiratory viral infections in children. Children's infections, 2004, No. 2, p. 34-37; T.A. Chebotareva, L.N. Mazankova, V.V. Malinovskaya, S.K.Karyaeva, V.V. Lazarev Clinical efficacy of the prevention of influenza and other acute respiratory viral infections in children living in the area of environmental problems, J. Pediatrics No. 6 , Volume 88, 2009., p.104-111],

Clinical studies, analysis and statistical processing of the data showed that the 5-day course of preliminary administration of viferon immediately before vaccination is optimal and sufficient to achieve the greatest effectiveness of both subsequent vaccination and the entire range of measures for the prevention of influenza and ARI, as it manages to show all the above effects and its longer use is inappropriate. The scheme of ionferotherapy by double rectal administration twice a day in the morning and in the evening was also worked out. Based on a large amount of clinical material, effective doses of viferon for patients with AD have been developed. A single dose for children from 4 to 7 years old was 150,000 ME, and for children from 7 to 16 years old - 500,000 ME.

The method is as follows.

In the pre-epidemic period of increasing respiratory morbidity in order to prevent influenza and acute respiratory infections, children with bronchial asthma are immunized in two stages sequentially.

At the first stage, 5 days before the planned vaccination against influenza, the viferon immunomodulator is administered rectally in the form of suppositories twice daily in the morning and evening, one suppository, into the child’s body.

A single dose for children from 4 to 7 years old is 150,000 ME, from 7 to 16 years old - 500,000 ME.

At the second stage, a routine influenza vaccine is administered.

The vaccine is administered parenterally (subcutaneously or intramuscularly) according to the following scheme: for children aged 3 to 14 years - 1 dose (0.5 ml) once. Children who have not previously had the flu and who have been vaccinated are advised to administer 2 doses of the vaccine with an interval of 4 weeks. Adults and adolescents over 14 years of age are given a single dose of the vaccine (0.5 ml).

Clinical example 1. Child L., 11 years old (observation map No. 5309) is observed with a diagnosis of bronchial asthma, atopic form, severe course. Pollinosis (rhino-conjunctival form). Allergic rhinitis.

The girl was born from pregnancy by IVF, which had the threat of termination, ARI at week 20, operative delivery by cesarean section at week 36 of pregnancy for emergency medical reasons (detachment of the placenta), the first of the triplets. Born with a weight of 1040 g / 42 cm. Apgar score 4/5 points. She screamed right away. From birth, she was breast-fed, nursed in the prematurity unit for 4 months. Psycho-motor development in the first year of life corresponded to the developmental parameters of small children. Vaccinated according to an individual schedule, without complications. Past diseases: perinatal damage to the central nervous system, frequent acute respiratory infections from the 2nd year of life, many times complicated by stenosing laryngotracheitis, obstructive bronchitis from 2 years old, bronchial asthma from 3.5 years old, chickenpox at 4 years old.

Allergic history: food allergy (citrus fruits, honey, nuts, apples, celery, kiwi) - Quincke's edema, bronchial obstruction. Household and epidermal allergies (house dust, hair and epidermis of cats, dogs, horses, guinea pigs) - allergic rhinitis, bronchial obstruction. Pollen allergy - spring trees (birch, alder, hazel), meadow herbs, poplar fluff - allergic rhinoconjunctivitis, bronchial obstruction.

Family history: mother's age at birth 27 years. Suffers from bronchial asthma, polyvalent allergy, smokes. Father's age at birth 26 years. Almost healthy. Relatives of the II degree of kinship - bronchial asthma, atopic dermatitis, allergic rhinitis, peptic ulcer of the stomach and 12 duodenal ulcer, pyelonephritis.

Anamnesis of the disease: from 1.5 years, ARI is often sick, which was complicated by the development of stenosing laryngotracheitis of the I-II degree. Repeatedly hospitalized in the infant department at the place of residence. DDU did not attend. From the age of 2, she began to suffer from obstructive bronchitis 6-8 times a year. The diagnosis of severe bronchial asthma was made in the allergology department of the Children's Clinical Hospital of St. Vladimir at the age of 3.5 years. From this age to the present, he receives basic therapy with inhaled corticosteroids. If necessary, bronchodilator therapy with ventolin through a nebulizer is performed. Attacks of bronchial obstruction are provoked by contact with causally significant allergens, physical and mental stress, acute respiratory infections, lives in a comfortable separate apartment, where hypoallergenic regimen is observed.

Status praesens: Girl of good physique, satisfactory nutrition (height 140 cm, weight 30 kg). HELL 100/65 mm Hg The skin is pale pink, clean. The mucous pharynx is pale pink, there are no deposits. Single cervical lymph nodes up to 0.6 cm are palpated, elastic, mobile, painless. Breathing through the nose is difficult, there is no discharge. The chest of the correct form, evenly participates in the act of breathing. In the lungs, vesicular breathing, no wheezing. Percussion-pulmonary sound. The area of the heart is not visually changed. The rhythm of the heart is correct, the heart sounds are loud. The boundaries of relative cardiac dullness within the age norm. The tongue is pink, wet. The abdomen is not swollen, soft, painless on palpation. Liver, spleen not enlarged. Physiological administration is normal.

The girl was examined by ENT: the conclusion is allergic rhinitis.

Chest x-ray - no pathology.

Prevention of acute respiratory infections in a child was carried out according to the proposed method in two stages.

At the first stage, 5 days before the scheduled vaccination, viferon in the form of rectal suppositories at a dose of 500,000 ME was administered 2 times a day daily for 5 days into the child's body.

At the second stage, an inactivated vaccine was vaccinated against influenza.

In the post-vaccination period, no changes in health status were noted: body temperature did not increase, local pain reaction did not exceed 1 day, and exacerbation of bronchial asthma was not observed. The volume of basic therapy did not change (fluticasone 500 mcg / day), there was no exacerbation of bronchial asthma, and no catarrhal phenomena were noted.

The data of clinical and laboratory examination before and after vaccination for 1 year are presented in tables No. 1, 2, 3; figure 1 - combined vaccination - vaccination of influenza with a preliminary 5-day intake of viferon in suppositories daily.

Table 1 Immunological data before and after influenza vaccine 1 month after vaccination Estimated Parameters Before vaccination After vaccination IgA 12.8 5.8 IgG1 8.8 12,2 IgG2 6.7 7.7 IgG3 1.28 1.43 IgG4 1.17 1.37 CEC 3% 29th thirty CEC 4% 68 51 CEC ratio 3% / CEC 4% 2,3 1.7 The titer of specific AT to vaccine influenza strains H1n1 0 160 H3N2 Wisconsin 80 160 H3N2 Brisbane 80 160

table 2 ARI before and after influenza vaccination Estimated Parameters Before vaccination After vaccination ARI episode frequency 6-8 times a year 1-2 times a year Duration of ARI episodes 12 days 4 days Fever duration 3 days 1-2 days Catarrhal symptoms 10 days Less than 2 days The development of bronchospasm Each episode of ARI Not developed The need for bronchodilator Reception daily Without bronchodilator therapies therapies Number of days to skip school Home training 10

Table 3 Data on spirography of influenza vaccine for ARI before and after Estimated Parameters Before vaccination After vaccination HPF data YELLOW expiratory% of due 52.42% 86.35% FEV1 46.8% 80.40% MOS 25 issue 54.88% 81.19% MOS 50 issue 62.90% 84.67% MOS 75 issue 60.85% 102.54% Conclusion Generalized obstruction of 1 degree The indicators are within normal limits. FEV1 46.8% 80.40% MOS 25 issue 54.88% 81.19% MOS 50 issue 62.90% 84.67% MOS 75 issue 60.85% 102.54% Conclusion Generalized obstruction of 1 degree The indicators are within normal limits.

Conclusion: Before vaccination, a decrease in pulmonary volumes and pronounced violations of bronchial patency of the central departments are noted.

After vaccine prophylaxis, an increase in pulmonary volumes and an improvement in bronchial patency to normal age values are noted.

As a result of the combination therapy (basic therapy of bronchial asthma and annual influenza vaccine prophylaxis), the severity of the underlying disease has decreased, and a moderate course of bronchial asthma with rare exacerbations that do not require inpatient treatment, which are stopped within 3-4 days at home with ventolin inhalation through a nebulizer, is being diagnosed. The patient increased exercise tolerance, indicators of external respiration function within normal limits. The volume of basic therapy was reduced to 250 mcg of fluticasone per day during the last year of observation.

Clinical example 2. Child P., 5 years old (observation map No. 24716) is observed with a diagnosis of Bronchial asthma, atopic form, mild course. Pollinosis (rhinoconjunctival form).

A girl from 1 pregnancy, with a threat of termination in the 1st and 3rd trimesters, nephropathy of the 2nd half, independent birth at the 41st week. She was born with a weight of 3800 g, height 53 cm. She screamed immediately. The Apgar score is 8/9 points. Applied to the chest on the first day of life. Discharged from the hospital on the 5th day. She was breast-fed for up to 2.5 months, and was transferred to artificial feeding in connection with the development of mastitis and hypogalactia in her mother. Early psychomotor development was age-appropriate. Vaccinated according to the calendar, without reactions. Allergic history: food allergy - Nutrilon breast milk replacer, tangerines (atopic dermatitis). Household sensitization not observed. Pollen allergy - meadow herbs in June (allergic rhinoconjunctivitis from 5 years). Past diseases: otitis media, frequent acute respiratory infections up to 4 years old, obstructive bronchitis from 2.5 years old, chickenpox.

Family history: mother's age at birth is 26 years old. Suffers from an allergy to metals, manifested by atopic dermatitis. The age of the father at the time of birth is 26 years old. Suffers from allergic rhinoconjunctivitis on the epidermis and hair of cats. Relatives of the II degree of kinship have cold and food allergies, manifested by itching and dermatitis.

Anamnesis of the disease: after registration in the DDU at the age of 2.5 years, acute respiratory infections started to hurt (up to 12 times a year), which were complicated by the development of obstructive bronchitis 3-6 times a year. At the age of 4 years, she was hospitalized in the allergology department of St. Vladimir's Children's Clinical Hospital, where she was diagnosed with bronchial asthma, mild course. After discharge from the hospital as a basic therapy, she received Intal for 4 months with a positive effect. The girl with her parents lives in a separate comfortable apartment, where hypoallergenic regimen is observed. Attacks of bronchial obstruction are provoked by acute respiratory infections, are stopped by taking bronchodilators (ventolin, salamol) for 3 days.

Status praesens: Girl of good physique, satisfactory nutrition (height 105 cm, weight 15.2 kg). HELL 90/60 mm Hg The skin is pale pink, clean. Zev - mucous pale pink, no raids. Single cervical lymph nodes up to 0.6 cm are palpated, elastic, mobile, painless. Free breathing through the nose. The chest of the correct form, evenly participates in the act of breathing. There is puerile breathing in the lungs, no wheezing. Percussion - a pulmonary sound. The area of the heart is not visually changed. The rhythm of the heart is correct, the heart sounds are loud. The boundaries of relative cardiac dullness within the age norm. The tongue is pink, wet. The abdomen is not swollen, soft, painless on palpation. Liver, spleen not enlarged. Physiological administration is normal.

The girl was examined by ENT: the conclusion is allergic rhinitis.

Chest x-ray - no pathology.

Prevention of acute respiratory infections in a child was carried out in stages:

Stage 1 - a 5-day course of viferon in the form of rectal suppositories in a dose of 150,000 ME 2 times a day until the planned vaccination; Stage 2 - vaccination of influenza with an inactivated vaccine.

In the post-vaccination period, no changes in health status were noted: body temperature did not increase, local pain reaction did not exceed 1 day, and exacerbation of bronchial asthma was not observed. The volume of basic therapy has not changed, the need for the use of bronchodilators has not been identified.

The data of clinical and laboratory examination before and after vaccination for 1 year are presented in tables No. 1, 2; figure 2 - before vaccination there is a decrease in pulmonary volumes to 78-80% of normal values. After vaccination, there is an increase in indicators from 85% to 100% of normal values.

Table 1
ARI before and after influenza vaccination Estimated Parameters Before vaccination After vaccination ARI episode frequency 10 times a year 3 times a year Duration of ARI episodes 10 days 4 days Fever duration 4 days 2 days Catarrhal symptoms 10 days Less than 2 days The development of bronchospasm Each episode of ARI Not developed The need for bronchodilator therapy Reception daily Without bronchodilator therapy The number of days to skip visiting the DDU per year 156 25

table 2 Immunological data before and after influenza vaccine 1 month after vaccination Estimated Parameters Before vaccination After vaccination Ira 12.7 6.2 IgG1 8 7.8 IgG2 2.7 4.8 IgG3 0.65 1.17 IgG4 0.95 1,2 CEC 3% 9 25 CEC 4% 32 39 CEC ratio 3% / CEC 4% 3,5 1,5 The titer of specific AT to vaccine influenza strains H1n1 0 160 H3N2 Wisconsin 40 320 H3N2 Brisbane 80 320

Clinical trials of the method were carried out during the pre-epidemic rise in the incidence of influenza and other acute respiratory infections at the clinical base of the Department of Pediatrics of the Moscow State Medical-Dental University. 108 children with mild, moderate and severe forms of asthma from 4 to 16 years old were vaccinated with the subunit influenza inactivated influenza vaccine. Vaccination was carried out once intramuscularly into the deltoid muscle in a dose of 0.5 ml. The second dose of the vaccine was not administered, because in the previous epidemic season, children were vaccinated against influenza. In addition to the influenza vaccine, 48 patients were prescribed Viferon® at a dose of 500,000 ME in suppositories, 1 suppository twice a day for 5 days prior to vaccination. Children receiving Viferon® were group I. 60 children who made up group II received suppositories similar in form to viferon (placebo). The formation of all groups was carried out by random sampling.

After vaccination was completed, intercurrent ARIs were recorded for 1 month, the development of which was assessed as a complicated course of the post-vaccination period. Long-term results of the clinical effect of vaccination were evaluated within 6 months.

Anti-influenza immunity was assessed by the level of specific class G immunoglobulins relative to four strains: H1N1, H3N2 (Wisconsin / 67/03), H3N2 (Brisbane / 10/08) and virus B (Sichuan). The study was carried out before vaccination and on the 30th day after vaccination by setting the reaction of inhibition of hemagglutination (RTGA). The results are processed by the method of variation statistics and correlation analysis.

The complicated course of the post-vaccination period was noted significantly more often in children who were vaccinated according to the standard method: in 43.5% of cases in group II compared with 9.3% of cases in group I, p <0.05.

The study also found that the incidence of ARI in children of group I in the epidemiological period is reduced by 2 times, compared with children of group II.

Along with this, the advantages of influenza vaccination were revealed in relation to the severity and duration of clinical manifestations of influenza in children with AD: diseases were recorded either in a mild form (42% of children in group I versus 14.2% in group II, p <0.05), or the severity of clinical symptoms was “cutting off" (1.8 ± 0.1 days in group I and 6.1 ± 0.7 days in group II, respectively, p <0.001). There was no relationship between the development of broncho-obstructive syndrome and influenza in any case in children of group I, while all children with influenza in group II developed broncho-obstructive syndrome against the background of the disease, while the cough after the disease persisted until 4-5 weeks

With the new method for the prevention of influenza and other acute respiratory infections, the protective titer of specific antibodies to vaccine strains is significantly faster formed; 1 month after vaccination, it is recorded in 92.5% of patients. The combined method of vaccination promotes effective control of AD, which improves the quality of life of patients and the prognosis of the course of the disease.

Thus, the presented clinical trial indicates the high efficiency of the combined method of influenza vaccination with the consistent use of the drug Viferon® and influenza vaccine.

Compared with the standard method of vaccination (the closest analogue) with the combined method of preventing influenza and other acute respiratory infections, there is a decrease in the number of intercurrent diseases in the post-vaccination period, a decrease in the incidence of acute respiratory infections, including in the subsequent epidemiological season by 2 times, a decrease in the severity of the clinical manifestations of influenza during the development of the disease after vaccination up to the "cutting off" nature of the duration of symptoms, a preventive effect in relation to the development of bronchial obstruction attacks against ARI in children with AD.

Claims (1)

A method for the prevention of influenza and acute respiratory infections in children with bronchial asthma, characterized in that they are immunized sequentially, while at the first stage 5 days before the scheduled vaccination against influenza, the drug viferon is administered rectally in the form of suppositories twice a day twice a day in the morning and in the evening, one suppository in a single dose for children from 4 to 7 years old is 15,000 ME, from 7 to 16 years old - 500,000 ME, and in the second stage, an inactivated influenza vaccine is administered.

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