ARI and "bacterial vaccines" to control them

Acute respiratory diseases are the most frequent pathology of childhood: every year children suffer from 2-3 to 10-12 ARI, which are caused by more than 150 pathogens and their variants. With the beginning of the visit to children's preschool institutions, respiratory morbidity sharply increases, so that in the first year of the visit, half of the children suffer 6 or more ARI, forming a group of "often ill children". And although in the 2-3 years of the visit the incidence declines, about 10% of children remain in the group of often ill children. As a rule, these are children with an allergic predisposition, which is manifested, in the main, by vivid manifestations of ARVI. Frequent acute respiratory diseases result in large economic losses.

Frequently ill children - not a diagnosis, but only an observation group; it includes underdeveloped children with specific nosological forms - relapsing bronchitis, incl. Obstructive, mild asthma, chronic tonsillitis and even chronic pneumonia and cystic fibrosis. So, before including the child in the group of dispensary observation for frequent morbidity, it is necessary to conduct a survey to exclude a specific pathology.

The lack of clear differences in the clinic of viral and bacterial ARI, the impossibility of express diagnosis of their etiology, the fear of missing a bacterial complication leads to excessive prescription of antibiotics to often sick children. However, antibiotics in ARVI do not have preventive efficacy, they only increase the incidence of bacterial complications.

In the arsenal of immunoprophylaxis there are vaccines against a number of pathogens ARD (Hib, pneumococcal, pertussis, diphtheria, influenza vaccines), however, against the main pathogens of acute respiratory viral infections, specific vaccines are not yet available.

Under these conditions, the creation of a large number of means for reducing respiratory morbidity can be explained. The annotations of these drugs usually emphasize their immunomodulatory effect, usually without a clear decoding. These are thymus preparations (T-activin, Timalin, etc.), and herbal remedies (dibazol, eleutherococcus, echinacea), and vitamins and trace elements, and homeopathic remedies (Aflubin, Anaferon), and stimulants (pentoxyl, diucifon, polyoxidonium) , and much more. Most of these funds, despite the increased advertising, do not have convincing evidence of effectiveness in reducing the respiratory incidence despite long-term use. And in respect of many of them, clear negative results were obtained. Moreover, the use of immunomodulators without special evidence is simply unacceptable. In this respect, drugs from the group of bacterial lysates are more acceptable, sometimes with the inclusion of more refined constituents of the microbial cell.

Indications for use

All drugs from the group can be used for the prevention of recurrent ARVI and related respiratory diseases (rhinitis, sinusitis, pharyngitis, tonsillitis, laryngitis, acute and recurrent bronchitis), incl. Often ill children and children with allergic pathology. Imudon is also indicated for diseases of the oral cavity and pharynx. It is possible to start using drugs in a healthy child and during a regular respiratory disease, continuing the course after recovery.

Characteristics of bacterial lysates

Bacterial lysates replaced microbial agents such as pyrogenal and prodigiozan, which were used as nonspecific immunostimulants. Prodigiozan in the form of drops in the nose was quite acceptable as a means of preventing ARD in kindergartens, which was shown in a controlled study in Lithuania and Estonia in the 1980s. The effectiveness of bacterial lysates, demonstrated in Europe in the 80-90s and somewhat later in Russia, was the basis of their recommendation as a safe means of nonspecific prevention of ARVI in children.

Although lysates are close to vaccines, the mechanism of their influence is different. By introducing these bacterial preparations, we mean the prevention of viral infections. And in assessing their effectiveness, it is not the decrease in the incidence of infections caused by the causative agents that enter them, but the overall respiratory incidence, that is assessed. Of course, in response to their administration, antibodies are also produced, for example pneumococci or klebsiella, but their role in preventing the corresponding infection is usually not considered.

It is proved that the action of these drugs is based on stimulation of the Th-1 type immune response, which is more mature, compared with the Th-2 type response with which children are born. The development of a Th-1 type response in a child occurs mainly under the influence of microbial stimulation, a deficiency of which in modern children is associated with a high level of hygiene, the relative scarcity of bacterial infections and the widespread unjustified use of antibiotics that suppress the commensal flora. An important role is played by the almost constant use of antipyretics at any temperature increase, which also suppresses the production of cytokines responsible for the Th-1 type response: γ-interferon, IL-1 and IL-2, TNF-α. Suppression of the Th-1 type response prevents the development of a more persistent response to infection and the formation of immunological memory.

Bacterial lysates stimulate the production of Th-1 cytokines of the type of response, they also increase the production of IgA, slgA, lysozyme in mucosal airways, simulate the activity of natural killers, normalizing the number of CD4 + cells upon their decrease, and also suppress the production of IgE and antibodies of this class. It is this action of lysates that is currently considered to be the main one that contributes to the formation of a mature immune response and a reduction in respiratory morbidity.

IRS 19 - bacterial lysate predominantly local action stimulates the production of endogenous lysozyme and SIgA, increases the phagocytic activity of macrophages (qualitative and quantitative enhancement of phagocytosis), indirectly normalizing the number of CD4 + cells when they decrease. The desensitizing effect of IRS 19 due to polypeptides that prevent the formation of sensitizing antibodies is also proved. When using IRS 19, the swelling of the mucous nasopharynx is also reduced, the exudate is liquefied and its outflow is facilitated.

Imudon increases the concentration of lysozyme, endogenous interferon, SIgA and antibodies of this class in saliva, including Candida albicans, the main pathogen of thrush and pharyngicosis. Imoudon quickly and effectively cuts the pain in the throat, normalizes the composition of the microflora of the oropharynx.

Preparations of predominantly general action, in addition to stimulating the formation of specific antibodies to the microorganisms included in their composition, activate the humoral activity characteristic of the Th-1 type response. Correction of the T-lymphocyte content (CD3, CD4, CD16, CD20), decrease in the level of immunoglobulin E has also been shown for VP-4 and Bronchominal. Ribomunyl also stimulates the function of T and B lymphocytes, the production of serum and secretory immunoglobulins, IL-1, alpha interferon. The drug has both a general action and local, increasing the level of secretory IgA. Lysates are included in the Program on ARI of the Union of Pediatricians.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]

Efficiency

A meta-analysis of the effectiveness of imported lysates shows that, in treatment groups, the incidence of ARI decreases in comparison with the placebo group by an average of 42% (95% of DI 40-45%). The use of VP-4 in frequently ill children led to a reduction in the duration of acute respiratory disease, a 3-fold decrease in morbidity, and a reduction in episodes of obstruction.

Controlled studies of a 6-month course of Ribomunile in frequently-ill children showed a reduction in the incidence of acute respiratory disease by 3.9 times, use of antibiotics 2.8 times. In placebo-controlled studies, a positive effect was achieved in 30-74% of children, the number of days of incapacity for work with parents was reliably reduced. Effective and 3-month course Ribomunila: in the first year the incidence of ARI decreased by 45.3%, and the need for antibiotic therapy - by 42.7%. In the second year the number of ARI per child was 2.17 + 0.25, in control - 3.11 + 0.47. These differences are smoothed by the end of 2 years.

It is shown that the use of IRS 19 leads to a reduction in the number of SARS. Thus, in patients with asthma treated with IRS 19, during the year, there were 3 times fewer episodes of ARVI (2.1 per 1 child) than in the previous year, while in the control group there were only 25% fewer (4.5 for 1 child). A good effect of IRS 19 was noted in adults as well as at the beginning of treatment in acute acute respiratory disease.

Imudon u often (more than 6 times per year) of ill children for the next 3 months. Compared with the previous 3 months. Reduced the frequency of acute respiratory viral infection by half, and exacerbations of chronic pharyngitis - by 2.5 times, the carrier of beta-hemolytic streptococcus decreased 3-fold, and the fungus Candida-4-fold. Despite the relatively high costs of bacterial lysates, they provide significant savings.

[12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22]

Methods of administration and dose

VP-4 is administered to children over 2.5 years of age by the nasal-oral route. The vaccine is diluted with 4 ml of saline. In this form it can be stored for 5 days at 2-6 °. The first 3 days of the vaccine is administered only nasally in a dose: 1 day - 1 drop, 2 days - 2 drops, 3 days - 4 drops. After 3 days, oral administration begins: at intervals of 3-5 days, 1 ml / day and 2 ml / day are first given, then 4 ml / day - 6 times. If the effect is insufficient, the course of oral techniques can be extended to 10 in a dose of 4 ml. Eating 1 hour before and 2 hours after the introduction of the vaccine.

Bronchomunal is prescribed by mouth, in the morning, on an empty stomach for one capsule for 10 -30 days. For preventive purposes - 1 capsule per day for 10 consecutive days per month; course - 3 months. (it is advisable to begin therapy every month on the same day). 1 capsule Bronhomunala P contains 3.5 mg for children 6 months to 12 years, for older children and adults 1 capsule contains 7 mg. Bronchovax is also available in capsules of 3.5 and 7 mg and is used similarly.

IRS 19 - Intranasal spray in 20 ml bottles (60 doses), prescribed for children from 3 months. 1 dose of 2 to 5 times a day for 2 weeks.

Imudon - tablets (0.05 g dry matter) for resorption with a pleasant taste should be kept in the mouth until it is completely absorbed (not chewing). Assign 6 tablets a day for acute (10 days) and chronic (more than 20 days) pharyngitis, with severe purulent inflammatory diseases of the oral cavity with bone damage

Bacterial lysates

A drug	Composition
VP-4, NIIVS them. THEM. Mechnikov RAMS, Russia	The cell-free multicomponent vaccine-antigens and the associated lipopolysaccharides of S. Aureus, K. Pneumoniae, Proteus vulgaris, E. Coli, and teichoic acid
Bronhovaks, OM form, Switzerland	Lyophilized lysate of 8 bacteria: S. Pneumoniae, H. Influenzae, K. Pneumoniae, C. Ozenae, S. Aurens, S. Viridans, St. Pyogenes, M. Catarrhalis
Bronchomunal Lek, Slovenia
Imoudon, Solvay Pharma, France	A mixture of lakes of 13 Bakeries: Streptococcus pyogenes group A, Enterococcus faecalis, Enterococcus faecium, Sptreptococcus sanguis, Staphylococcus aureus, K. Pneumoniae, Corynebacterium pseudodiphtheriticum, Fusobacterium nucleatum, Lactobacillus acidophilus, L. Fermentatum L. Hecticus, L. Delbrueckiis, Candida, albicans,
IRS 19, Solvay Pharma, France	Lysates of 18 bacteria: S. Pneumoniae (6 serotypes), S. Pyogenes (groups A and C), H. Influenzae, K. Pneumoniae, N. Perflava, N. Flava ,, M. Catarrhalis, Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis, Streptococcus group G, Acinetobacter
Ribomunil, Pierre Fabre, France	Ribosomal fractions of C. Pneumoniae (35 lobes), S. Pneumoniae (30 lobes), S. Pyogenes (30 lobes), H. Influenzae (5 lobes) + proteoglycans of the Klebsiella membrane part

Imudon is combined with antibiotics; when operating on the ENT organs, 8 tablets are given per day 1 week before and after the operation. It is recommended to carry out 2-3 courses per year.

Ribomunil is produced in tablets of 0.25 mg of ribosomal fractions and 0.375 mg of proteoglycans in the membrane part of Klebsiella pneumoniae (1/3 of a single dose) or respectively at 0.75 and 1.125 mg (1 single dose), and also in bags with 500 mg of granulate for preparation of a drinking solution. Dosage: 3 tablets (0.25 mg) or 1 tablet (0.75 mg) or 1 packet (after dilution in a glass of water) 4 days a week for 3 weeks in the first month of treatment, then the first 4 days of each month for the next 5 months.

Adverse reactions and contraindications

With the introduction of VP-4, it is possible to raise the temperature to subfebrile digits for 12-24 hours, nasal congestion, cough (at a temperature of 38.5 ° or other side effects, the administration is discontinued). Bryusomunal can cause dyspepsia. IRS 19 in rare cases can strengthen the rhinorrhea, it contributes to the elimination of pathogenic pathogens. There are no side effects for Imudon. Among the side effects of Ribomunil, hypersalivation is noted.

[23], [24], [25], [26], [27], [28], [29], [30]

Combined use with other vaccines

Ribomunil, IRS19 were successfully used in conjunction with influenza vaccines, which increased their effectiveness against ARI. Joint appointment of Ribomunil with measles vaccination reduced the frequency of ARI in the post-vaccination period; Ribomunyl accelerates the immune response to the inoculation, which indicates a pronounced immunomodulating effect.

[31], [32], [33], [34], [35], [36], [37], [38], [39]