RU2726070C1 - Method for pathogenetic correction of metabolic disorders in infectious mononucleosis caused by epstein-barr virus - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention relates to medicine and concerns a method for pathogenetic correction of metabolic disorders in infectious mononucleosis caused by Epstein-Barr virus, including drug-induced therapy, namely agents of etiotropic, pathogenetic, symptomatic therapy, wherein patient is prescribed azoxymer bromide preparation (Polyoxidonium) in dosage 12 mg sublingually 2 times a day in acute period of disease, 1–7 days of disease.EFFECT: invention provides effective control of infectious mononucleosis, eliminated development of serious complications and transition to chronic form, reduced length of hospital stay.1 cl, 2 ex

Description

The invention relates to medicine, in particular to infectious diseases, and can be used for effective and safe pathogenetic correction of metabolic disorders in various variants of infectious mononucleosis caused by the Epstein-Barr virus.

The relevance of the study of infectious mononucleosis (IMN) is due to the high circulation of the pathogen among the population of the whole world, the specific tropism of herpesvirus to immunocompetent cells, lifelong persistence of the virus in the body, latent course, and the development of serious complications leading to death. More than 95% of people worldwide are infected with the Epstein-Barr virus, mainly in the higher socio-economic groups of industrialized countries. In the past 15 years, the incidence of medical devices caused by the Epstein-Barr virus has increased 5 times not only in adults, but also in infants. This is due to both a true increase in morbidity due to exposure to various exogenous and endogenous factors, and an improvement in the laboratory diagnostic methods for this infection [Hjalgrim, N. Infectious mononucleosis, childhood social environment, and risk of Hodgkin lymphoma / H. Hjalgrim, K.E. Smedby, K. Rostgaard [etal.] // Cancer Res. - 2007. - No. 67 (5). - P. 2382-2388. Luzuriaga, K. Infectious mononucleosis / K. Luzuriaga, J. L. Sullivan // NEJM. - 2010. - No. 362 (21). - P. 1993-2000. Khodak, L.A. Modern features of infectious mononucleosis / L.A. Khodak, O.A. Rzhevskaya // International Medical Journal. - 2006. - No. 1. - S. 84.].

The choice of treatment for infectious mononucleosis depends on the clinical picture, the degree of symptoms, the severity of the disease, the presence of complications. Treatment of infectious mononucleosis according to clinical recommendations [Clinical recommendations (treatment protocol) for providing medical care to children with infectious mononucleosis. Developed by FSBI NIIDI FMBA of Russia. Approved at a meeting of the Profile Commission on October 9, 2013 - http://niidi.ru/dotAsset/a6816d03-b0d9-4d37-9b09-540f48e3ed43.pdf] includes:

1. Mode.

2. Diet.

3. Methods of drug treatment:

- means of etiotropic therapy (acyclovir, antibacterial drugs: Aminoglycosides, Macrolides, Cephalosporins of the 3rd and 4th generation, Glycopeptide structure antibiotics, Carbapenems)

- means of symptomatic therapy (Ibuprofen, Paracetamol, Diclofenac, Fluconazole, Nystatin, Glucocorticoids, Solutions affecting the water-electrolyte balance, Other irrigation solutions, Electrolyte solutions, adrenomimetics, anti-diarrheal microorganisms, absorbent intestinal drugs, m respiratory tract diseases, Selective beta ² adrenergic agonists, Benzodiazepine derivatives, sulfonamides, other systemic hemostatics).

- means of immunotherapy and immunocorrection (meglumine acridone acetate, tilorone, anaferon, normal human immunoglobulin).

4. Methods of non-drug treatment: - physiotherapeutic methods of treatment; - physical methods of temperature reduction; - sanitation of the upper respiratory tract (nasal passages); - aeration of the room; - hygiene measures.

The disadvantage of this method of treatment is the lack of impact on the content of lipid peroxidation products (LPO), as well as on the parameters of the oxidative-antioxidant system (AOS). None of the claimed drugs has a pronounced antioxidant effect.

There is such a thing as oxidative stress, it arises as a result of the accumulation of free radicals, prooxidants and reactive oxygen species, they are all harmful agents, and various pathological conditions develop when they act on cells, organs and systems. In infectious mononucleosis, oxidative stress is always pronounced, due to the development of an imbalance between the oxidative and antioxidant systems. All this leads to a protracted course of the disease, the development of a number of serious complications, to chronic infection or to a relapsing course. The therapy that exists at the moment and is presented in the clinical recommendations is mainly aimed at influencing the virus itself, it is not aimed at correcting the conditions caused by the action of the virus. The inclusion of a drug with immunomodulating, antioxidant and detoxifying effects in therapy will significantly reduce the duration of the disease, the frequency of complications, less often it will be possible to observe a transition to a chronic and relapsing course, this is very important for this pathology, since the Epstein-Barr virus is not only a lymphotropic virus and most importantly oncogenic and hepatotropic. With a recurring course, both oncological pathology and autoimmune processes can develop.

Closer analogues to the claimed invention was not found.

The objective of the invention is to develop an effective and safe method for the pathogenetic correction of metabolic disorders in infectious mononucleosis caused by the Epstein-Barr virus.

The problem is achieved in the proposed method for the pathogenetic correction of metabolic disorders in infectious mononucleosis caused by the Epstein-Barr virus, including drug therapy, namely, etiotropic, pathogenetic, symptomatic therapy with the additional use of immunocorrective and antioxidant drugs, the drug azoximer bromide (Dioxide) 12 mg sublingually 2 times a day in the acute period of the disease (1-7 day of illness).

Thus, the standard therapy for the disease includes the preparation of Azoximer bromide (Polyoxidonium), which has an immunomodulating effect, as well as pronounced antioxidant, detoxifying and membrane-protective properties, which is due to its polymer nature and chemical structure. Polyoxidonium neutralizes free radicals that cause the destruction of cells, tissues and organs, as a result of which the severity of the inflammatory process decreases. With its use, the production of anti-inflammatory cytokines, which are produced by cells of the monocyte-macrophage system (interleukin -1, 6, tumor necrosis factor-alpha and interferons), is enhanced. But activation occurs only at an initially low level of these cytokines, if their level is elevated, then Polyoxidonium does not have a stimulating effect, and even slightly reduces the level to normal. A number of studies (https://www.rmj.ru/articles/bolezni_dykhatelnykh_putey/Primenenie_immunokorrigiruyuschego_preparata_Polioksidoniy_pri_ostroy_infekcionno_vospalitelynoy_patologii_LORorganov/,

https://umedp.ru/articles/polioksidoniy_v_lechenii_i_profilaktike_zabolevaniy_lororganov_i_organov_dykhaniya.html,

https://cyberleninka.ru/article/n/immunomoduliruyuschaya-terapiya-v-lor-praktike/viewer, https://azimutmebel.ru/laringit/polioksidoniy-pri-laringite-u-rebenka/, http: // cdl .ru / novye-aspekty-primeneniya-polioksidoniya-v-profilaktike-i-lecheniya-zabolevaniy /), conducted with Polyoxidonium, showed that it can be used both before and after taking antibacterial and antiviral drugs, but its greatest effectiveness is registered with concomitant administration with etiotropic drugs.

The method is as follows.

An etiotropic, pathogenetic, symptomatic therapy is carried out for a patient with infectious mononucleosis, including antiviral, antipyretic and desensitizing drugs, vasoconstrictor drops in the nose, treatment of tonsils with antiseptic solutions, etc., if there are signs of bacterial flora joining, antibacterial drugs, and if hormonal complications appear, there is a short course. At the same time, the patient is given a sublingual preparation of azoximer bromide in a dosage of 12 mg for 6-10 days, twice a day with an interval of 12 hours.

A single dose of azoximer bromide is administered sublingually (sublanguage). Sublingual administration of the drug is convenient and safe for the patient, the therapeutic concentration of the drug administered in the body is quickly achieved. The drug is kept under the tongue until completely dissolved, the patient is warned about this before the start of therapy. Due to its chemical structure, azoximer bromide enhances the action of antiviral and antibacterial drugs. Due to the pronounced antioxidant and detoxifying effect, the level of lipid peroxidation products is reduced, as a result of which we correct oxidative stress, prevent massive damage to cells and organs and prevent complications.

The proposed method carried out pathogenetic correction of metabolic disorders in 60 patients.

The method is illustrated by specific clinical examples.

Example 1. Patient N., 17 years old, came to the clinic on the 3rd day of illness with complaints of febrile temperature, lymphadenopathy, severe nasal congestion, shortness of breath, sore throat, pasty face, severe weakness, lack of appetite.

Epidemiological history: there is no clear evidence regarding contact with infectious patients.

An objective examination of the state of moderate severity due to infectious-toxic syndrome (ITS), lymphoproliferative syndrome (LPS), tonsillar syndrome. The skin is pale. The pharynx is symmetrical, brightly hyperemic, hypertrophy of palatine tonsils of the 2nd degree, swelling of the tongue, significant fibrinous-necrotic overlays on the tonsils. Nasal breathing is very difficult. Lymph nodes are enlarged, mainly due to the posterior cervical group, painful on palpation. Breathing is carried out in all fields, vesicular, no wheezing. SpO2 97%. Heart tones are muffled, rhythmic. Heart rate 81 beats per minute. The abdomen is soft, accessible, the liver and spleen are palpation-enlarged +1 cm. Physiological functions are not disturbed. In the KLA: leukocytes 9.5 × 10 ⁹ / L, red blood cells 5.39 × 10 ¹² / L, hemoglobin 155 g / L, platelets 119 × 10 ⁹ / L, neutrophils 23%, lymphocytes 55%, monocytes 13%, ESR 14 mm / h, atypical mononuclear cells 15%

On day 5 of the disease, day 2 of hospitalization: the fever persists, pain when swallowing is severe, there are difficulties in breathing, organs are unchanged. In smears from the throat on the microflora, no diagnostically significant flora was revealed. ELISA for HIV is negative. ELISA revealed an AT class Ig M to a capsid AG VEB KP = 23.6. Identified AT class Ig G to early hypertension of EBV KP = 3.2. In the biochemical analysis of blood, there is an increase in ALT to 258 units / L, ACT to 163 units / L, CRP 21.50 mg / L.

On the 7th day of the disease, the 4th day of hospitalization, the patient's condition with positive dynamics, the fever stopped, sore throat is absent, breathing is not difficult, a massive discharge of fibrinous-necrotic plaque was observed in the throat. For organs unchanged. In a biochemical blood test: ALT up to 176 u / l, ACT up to 104 u / l. Ultrasound GBS: Hepatosplenomegaly, biliary dyskinesia.

On the 9th day of the disease, the 6th day of hospitalization, the temperature is within normal limits, the pharynx is mildly hyperemic, there is no plaque, in organs without changes, in the KLA: leukocytes 6.6 × 10 ⁹ / l, red blood cells 5.21 × 10 ¹² / l, hemoglobin 151 g / l, platelets 184 × 10 ⁹ / l, neutrophils 30% lymphocytes 58%, monocytes 10%, increased ESR 8 mm / h, atypical mononuclear cells 7%. In the biochemical analysis of blood, there is a positive dynamics of ALT 89 units / L, ACT 57 units / L.

The treatment was carried out in a hospital: acyclovir - 200 mg 5 times a day for 6 days, ceftriaxone - 1 g 2 times a day intramuscularly for 6 days, polyoxidonium - 12 mg 2 times a day sublingually 6 days, ursosan - 500 mg 2 times a day 6 days, treatment of tonsils with antiseptic solutions - 6 days, loratadine - 1 tablet 1 time per day - 6 days.

Discharged with recovery (improvement) on the 10th day of illness, 7th day of hospitalization.

Example 2. Patient Ch., 32 years old, came to the clinic on the 4th day of illness with complaints of febrile temperature, lymphadenopathy, headache of a pressing nature, dry cough, nasal congestion, sore throat, rash on the body, severe malaise, dryness mouth, lack of appetite.

Epidemiological history: there is no clear evidence regarding contact with infectious patients.

An objective examination of the condition is serious due to the infectious-toxic syndrome (ITS), respiratory, lymphoproliferative (LPS) and astheno-vegetative syndrome. Roseola rash throughout the body. The pharynx is symmetrical, brightly hyperemic, hypertrophy of the tonsils of the 3rd degree, fibrinous-necrotic overlays in the tonsils. Difficult nasal breathing. Lymph nodes are enlarged, mainly due to the posterior cervical group, sharply painful on palpation. Breathing is carried out in all fields, hard, no wheezing. Heart tones are muffled, rhythmic. Heart rate 73 beats per minute. The abdomen is soft, palpation is available, the liver is palpated +2 cm enlarged, the spleen is palpated +2.5 cm enlarged. Physiological functions are not broken. In the KLA: white blood cells 18.4 × 10 ⁹ / L, red blood cells 4.47 × 10 ¹² / L, hemoglobin 125 g / L, platelets 228 × 10 ⁹ / L, neutrophils 34%, lymphocytes 42%, monocytes 10%, increased ESR 22 mm / h, atypical mononuclear cells of 14%.

On day 6 of the disease, day 2 of hospitalization: complaints persist. In smears from the throat on the microflora, no diagnostically significant flora was revealed. ELISA for HIV is negative. ELISA revealed AT class Ig M to EBV. PCR for DNA to EBV - detected. In the biochemical analysis of blood, there is an increase in ALT to 414 units / L, ACT to 386 units / L, alkaline phosphatase 608 units / L, CRP 36.90 mg / L.

On the 8th day of illness, the 4th day of hospitalization, subfebrile temperature persists, severe sore throat when swallowing, hoarseness, breathing is difficult, in the throat of fibrinous necrotic plaque. No new rash has been observed. For organs unchanged. In the biochemical analysis of blood: ALT up to 401 units / L, ACT up to 298 units / L, alkaline phosphatase 578 units / L, CRP 28.34 mg / L. Ultrasound GBS: Hepatosplenomegaly, biliary dyskinesia. In the KLA: leukocytes 13 × 10 ⁹ / L, red blood cells 4.14 × 10 ¹² / L, hemoglobin 115 g / L, platelets 162 × 10 ⁹ / L, neutrophils 42%, lymphocytes 38%, monocytes 6%, increased ESR 12 mm / h, atypical mononuclear cells 16%.

On the 10th day of illness, the 6th day of hospitalization, subfebrile temperature persists, sore throat is insignificant, breathing is difficult, in the throat is discharge of fibrinous necrotic plaque. The rash has become less bright, merges. For organs unchanged. In the biochemical analysis of blood positive dynamics is observed: ALT up to 382 units / l, ACT up to 270 units / l, alkaline phosphatase 547 units / l, CRP 20.60 mg / l.

On the 12th day of illness, the 8th day of hospitalization, subfebrile temperature persists, sore throat is insignificant, in the throat is a massive discharge of fibrinous necrotic plaque. Lymph nodes, less painful. For organs unchanged. In the biochemical analysis of blood: ALT up to 234 u / l, ACT up to 147 u / l, alkaline phosphatase 478 u / l, CRP 12.3 mg / l.

On the 14th day of illness, the 10th day of hospitalization, the temperature returned to normal, there was no sore throat, tonsils in the throat cleared, according to the organs: liver and spleen palpation +1 cm, on the skin of the rash pale pink. In the KLA: white blood cells 9.8 × 10 ⁹ / L, red blood cells 4.25 × 10 ¹² / L, hemoglobin 117 g / L, platelets 183 × 10 ⁹ / L, neutrophils 39%, lymphocytes 45%, monocytes 6%, increase ESR 10 mm / h, atypical mononuclear cells 9%. In the biochemical analysis of blood: ALT up to 102 units / liter, ACT up to 68 units / liter, alkaline phosphatase 375 units / liter, CRP 1.6 mg / liter.

The treatment was carried out in a hospital: acyclovir - 200 mg 5 times a day for 7 days, cefotaxime - 1 g 2 times a day intramuscularly for 7 days, polyoxidonium - 12 mg 2 times a day, sublingual 10 days, ursosan - 500 mg 2 times a day 10 days, Infusion therapy with glucose-salt solutions - 3 days, treatment of tonsils with antiseptic solutions - 5 days, suprastin - 1 tablet 1 time per day - 7 days

Discharged with recovery (improvement) on the 14th day of illness, 10th day of hospitalization.

The proposed method allows you to more effectively control the course of infectious mononucleosis, to exclude the development of serious complications and the transition to a chronic form, as well as to reduce the length of the patient’s hospital stay.

Claims (1)

A method for the pathogenetic correction of metabolic disorders in infectious mononucleosis caused by the Epstein-Barr virus, including drug therapy, namely, etiotropic, pathogenetic, symptomatic therapy, characterized in that, in addition to immunocorrecting and antioxidant purposes, the patient is prescribed azoximer bromide preparation (Polyoxydonium 12) mg sublingually 2 times a day in the acute period of the disease, 1-7 days of illness.