RU2211706C1 - Method for immune therapy of viral respiratory diseases in calves - Google Patents

Abstract

FIELD: veterinary immunology. SUBSTANCE: the suggested method deals with intramuscular injection of hyperimmune serum containing specific antibodies to parainfluenza-3 and infectious rhinotracheitis viruses in titer not less than 1:1028 and 1:256, correspondingly, in mixture with glycopin as 0.2 %-solution at 5.0-6.0 ml/100.0 ml at the dosage of 1.5-2.0 ml at 24-h-long interval till complete recovery. EFFECT: higher efficiency of immune therapy. 3 ex, 4 tbl

Description

 The invention relates to veterinary immunology, relates to a method of immunotherapy and can be used to treat viral respiratory diseases of calves that occur as an associated infection of parainfluenza-3 / PG-3 / and infectious rhinotracheitis / IRT /.

 Among acute respiratory diseases of mixed etiology, calves are clearly nosologically delineated, these include PG-3 and RTI, which more often occur as an associated infection.

 Known methods for immunotherapy of viral respiratory diseases of calves using monovalent / live and inactivated / or multivalent vaccines / 1 /. Known methods of immunotherapy are based on complex measures, including intranasal vaccination of calves in the first weeks of life, their revaccination (parenterally) after 3-4 months, as well as vaccination of cows / 2 /. But with the complexity of the implementation, the known methods are ineffective, due to the presence in calves of colostral antibodies that block the antigens of the administered vaccines, thereby blocking the formation of immunity and exacerbating the infectious process. Live vaccines, in addition, have an immunosuppressive effect and can cause post-vaccination illness.

 There is also a method of immunotherapy of respiratory diseases of calves using the immune serum of animals-convalescents. The blood serum of animals-convalescents is a preparation containing antibodies to pathogens that form the virus-bacterial background of the livestock complex, however, the set of antibodies of blood serum of animals-convalescents and their titer do not always correspond to the complete set of antigenic structure of "local microflora", and in the manufacture of the drug and the complexity of the control does not ensure the stability and high quality of the finished forms, which reduces the effectiveness of therapeutic intervention using blood serum tnyh convalescent. In addition, the low varying activity of the blood serum of animals of convalescents requires mixing the sera of various donors with the use of the highest possible doses (at least 1.0 ml per 1 kg of live weight), which complicates the implementation of the known method.

 As a preferred analogue, a method for immunotherapy of viral respiratory diseases of calves using the immune serum of animal donors is considered / 3 /. Treatment-and-prophylactic immune sera are obtained by hyperimmunization of animals, they quickly provide the formation of passive immunity, but due to the low concentration of specific antibodies in the blood serum, the therapeutic effectiveness of the immune sera of animal donors is low. In addition, it is known that the virus affects mainly the cellular component of the immune system, and viral respiratory diseases are accompanied by secondary immunodeficiency states. So, the number of T- and B-lymphocytes decreases, lysozyme production is inhibited, phagocytosis is observed, bactericidal activity of blood serum is reduced, which is confirmed by our studies conducted in a farm that has long been dysfunctional in viral respiratory diseases of calves (table 1).

 The purpose of the invention is improving efficiency.

 This goal is achieved by the use of hyperimmune serum in a mixture with glycopine in the form of a 0.2% solution.

 Glycopin is a synthetic drug of natural origin (a common repeating fragment of the cell wall of all bacteria), the active principle of which is N-acetyl-glucoaminyl-N-acetyl-muramyl-alanyl-D-isoglutamine (GMDP). Currently, the nonspecific immunostimulating effect of GMDP, which activates the cells of the phagocytic system / 4 /, is known.

 GMDP under the pharmacopoeial name "lycopid" is used in medical practice for secondary immunodeficiency states / 5 /.

 The method is as follows.

 After diagnosis, hyperimmune serum is administered subcutaneously or intramuscularly to sick calves containing specific antibodies to PG-3 and IRT viruses in titers of at least 1: 1280 and 1: 256, respectively, in a mixture with glycopine in the form of a 0.2% solution based 5.0-6.0 ml per 100.0 ml of serum in a dose of 1.5-2.0 ml with an interval of 24-48 hours until complete clinical recovery.

 The novelty of the claimed method for immunotherapy of viral respiratory diseases of calves is the use of hyperimmune serum of animal donors in a mixture with glycopine. The mechanism of action of the drug mixture is based on counteracting the spread of the virus in the infected body and activating the cells of the phagocytic system, which leads to the stimulation of the synthesis of cytokines that enhance the formation of antibodies and increase the cytotoxic activity of macrophages and T-lymphocytes, which ensures the stability of the immunogenesis process and the balance of its regulatory mechanisms and indicates the presence in the claimed technical solution of "inventive step".

 The effectiveness of immunotherapy with the use of hyperimmune serum of animal donors in a mixture with glycopine in the form of a 0.2% solution was determined in the conditions of farms in the Nizhny Novgorod region with an incidence of respiratory diseases of up to 47.0% with a mortality rate of up to 18.0% with a tendency to stationarity. The etiological role of associations of PG-3 viruses and RTI has been established.

Clinically, the disease was characterized by an increase in body temperature to 41.3 ^o C, serous-mucous discharge from the nasal openings, depression of the general condition, conjunctivitis, cough, rapid breathing. In calves forcedly killed during the acute course of the lungs, red areas were found to be densified, signs of enphysema, hyperemia of the mucous membrane, mucopurulent exudate in the trachea and bronchi, and signs of hemorrhagic catarrhal gastroenteritis. The pharyngeal and bronchial nodes are enlarged. PG-3 and RTI viruses were isolated from pathological material.

 The essence of the method is illustrated by examples.

 Example 1. Efficiency, depending on the ratio of the components of the drug mixture and the dose, was determined on clinically sick calves 30-45 days of age with a confirmed diagnosis of associated infection with PG-3 and IRT in 4 series of experiments. In each series of experiments, according to the principle of analogues, 3 groups were formed, which were injected subcutaneously or intramuscularly with an interval of 24 hours until a complete clinical recovery of the drug mixture, consisting of hyperimmune serum containing specific antibodies against the PG-3 virus and an IRT in titers of at least 1: 1028 and 1: 256, respectively, and glycopine in the form of a 0.2% solution at the rate of 4.4, 5.0, 6.0 and 6.5 ml per 100.0 ml of serum. The condition of the calves during treatment was monitored by the results of a clinical examination. Recovery was judged by the disappearance of clinical symptoms. Dose-dependent efficacy, taking into account the different ratio of the components of the drug mixture of the claimed method are presented in table 2.

 As can be seen from table 2, stable results were obtained with the claimed ratio of components and doses of the drug mixture. Increasing the amount of a 0.2% glycopine solution in the drug mixture is impractical, since it led to a decrease in efficiency, and increasing the dose above the maximum decreased the effectiveness, which confirms the claimed parameters of the method.

 Example 2. The effect of the drug mixture at the optimal ratio of components and in the optimal dose was evaluated by the content of T and B lymphocytes (determined in the reaction of spontaneous rosette formation), the number of immunoglobulins of classes G and M (determined by the Mancini method / 1964 /), the functional activity of neutrophils blood (determined in the reduction reaction of nitros blue tetrazolium / Mayansky A.N. et al., 1979 /, bactericidal activity of blood serum (determined by the method of Smirnova O.V. and Kuzmina T.A., 1966), lysozyme activity of blood serum (op edelyali the method Dorofeychuk VG, 1968) before and after treatment. The results are shown in Table 3.

 The data in table 3 confirm the stimulating effect of the drug mixture on factors of cellular and humoral immunity, as well as indicators of natural resistance, which are as close as possible to the physiological norm, which indicates optimization of the resistance of the macroorganism.

 Example 3. Comparison of therapeutic efficacy claimed in comparison with known methods was carried out on calves 30-45 days of age with a diagnosis of associated infection with PG-3 and RTI, confirmed by virological studies with the isolation and identification of viruses PG-3 and RTI. 3 groups of patients with viral respiratory diseases of calves were selected according to the principle of analogues. Calves of the 1st group were treated in accordance with the invention, as in Example 2, calves of the 2nd group were treated in accordance with the prototype method, calves of the 3rd group were immunized with the TRIVAC multivalent vaccine in accordance with the Instructions for its use. The calves were monitored taking into account the number of calves recovered, the form of the disease, the duration of treatment and relapse. The results are presented in table 4.

 As can be seen from table 4, the hyperimmune serum of animal donors mixed with glycopene in the form of a 0.2% solution provided a higher percentage of recovery (93.4% compared to 87.5% - prototype and 80.0% - basic method) with a reduction in treatment time to 7 days compared with 12 (prototype) and 15 (basic method) days. Moreover, the number of calves with a mild form of disease increased (96.9% compared with 80.0 and 73.3%) in the absence of complications and relapses, which in the control groups were 10.0 and 25.0%. After recovery, the calves of the experimental group developed well, they had an appetite, restored reactions to external stimuli, they were mobile and active.

 The obtained clinical data showed that, in addition to clinical improvement, the claimed method provided positive dynamics of the immunogram — an increase in T and B lymphocytes, an increase in the functional activity of neutrophils, and the nature of the effect of the drug mixture is quite identical in both quantitative and qualitative parameters.

Sources of information
1. Urban V.P., Naimanov I.L. Diseases of young animals in industrial livestock. - M .: Kolos, 1984. - S. 192-196.

 2. Syurin V.N., Samuilenko A.Ya., Soloviev B.V. Fomina N.V. Viral diseases of animals. - M.: VNITIBP. - S. 248.

 3. Immunoprophylaxis of animal diseases. Per. with him. N.B. Chernykh - M .: Kolos, 1981. - S. 274-277.

 4. Guidance on the use of the drug glycopin for agricultural and small animals 13-4-2 / 1732 from 08.27.1999.

 5. High-belt A.I., Basova N.Yu., Shakhov A.G. Respiratory diseases in the Kuban // Veterinary medicine. - 2000. - 12. - S. 8-11 - prototype.

Claims (1)

 A method for immunotherapy of viral respiratory diseases of calves, including intramuscular administration of hyperimmune serum of animal donors, characterized in that the hyperimmune serum of animal donors containing specific antibodies to parainfluenza-3 viruses and infectious rhinotracheitis in titers of at least 1: 1028 and 1: 256 is introduced into mixtures with glycopine in the form of a 0.2% solution at the rate of 5.0-6.0 ml per 100.0 ml of serum in a dose of 1.5-2.0 ml with an interval of 24 hours until complete clinical recovery.

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