The method of treatment of patients with tick-borne encephalitis

 

(57) Abstract:

The invention relates to medicine, namely to the treatment of infectious diseases, and can be used in the treatment of patients with tick-borne encephalitis with immunoglobulin. The method includes intramuscular immunoglobulin (IG) with a titre of antibodies to tick-borne encephalitis virus 1 : 160 or 1 : 320 and the use of non-specific therapeutic agents. A single dose of IG is determined at a feverish and meningeal forms of the disease at a dose of 0.2 ml/kg of body weight, severe focal form in a dose of 0.5 ml/kg of body weight. The calculated dose of immunoglobulin is administered simultaneously. The method reduces the likelihood of getting the disease in a more severe form, eliminates two of the disease and reduces the likelihood of chronicity of the process. 2 C.p. f-crystals.

The invention relates to medicine, namely to treatment by drugs, and can be used in the treatment of patients with tick-borne encephalitis with immunoglobulin.

There is a method of treatment of patients with tick-borne encephalitis (TBE), in accordance with which the patient is injected nonspecific therapeutic agent and intramuscularly administered immunoglobulin (IG) of a person with Titus the exposure dose, in accordance with generally accepted standards,... 6,0 3,0 ml two to three times a day for four to eleven days not less 36,0 ml of treatment, and without febrile stage of the acute period - dose...6,0 3,0 ml two to three times a day for six to twelve days not less 72,0 ml per treatment. When having a progressive disease course immunoglobulin is administered repeatedly in one dose...6,0 3,0 ml two to three times a day not less 24,0 ml per treatment.S., RF, N 1837230, A 61 K 39/395 G 01 N 33/53, 30.08.93.).

Closest to the present invention is a method of treatment of patients with EC, according to which the course is injected intramuscularly a human immunoglobulin with a titer of antibodies to tick-borne encephalitis virus not less than 1:80, with a single dose determine the rate of 0.1 ml per 1 to body mass. Patients with febrile form of infection immunoglobulin administered daily in a single dose for 3. . . 5 days to improve the overall condition. The average dose rate for an adult is not less than 21,0 ml of the drug. When meningeal form TBE immunoglobulin administered daily in a single dose with interval of time 10. . .12 h for at least five days prior to the improvement of the General condition of the patient on objective indicators (ischeznovenie what I term dose for an adult is not less than 70.0 ml Patients with focal forms of tick-borne encephalitis depending on the severity of the disease the drug is administered daily in a single dose with interval of 8... 12 hours not less than 5...6 days before temperature reduction and stabilization of neurological symptoms at an average exchange rate of the dose for an adult of at least 80... 130 ml of immunoglobulin. When a very severe form of the disease, a single dose can be increased to 0.15 ml per 1 to body mass. In the case of a two currents of tick-borne encephalitis immunoglobulin re-introduce the scheme of treatment depending on the nature of clinical manifestations (instructions for use of human immunoglobulin against tick-borne encephalitis. The Ministry of health of the Russian Federation, approved by the Chief state inspector of the RF Onishchenko gg, 08.09.99.).

The disadvantage of this method consists in the following. Application nizkotarifnogo (1:80) immunoglobulin reduces the effectiveness of the treatment, since the introduction it causes more intensive production Ig M antibodies (E. A. Cvetkova "Secondary immune deficiency and its role in the pathogenesis of viral infections". Republican collection of scientific works "natural focal infections and infestations", Omsk, 1984, S. 49 - 57; Cvetkova E. A., Konev B. N. and others "Fenomen "natural focal diseases of man." Materials jubilee scientific-practical conference dedicated to the 75th anniversary of Omsk research Institute of natural focal infections, Omsk, 1996, S. 46 - 60; centuries Pogodin and other Chronic tick-borne encephalitis", Novosibirsk: Nauka, 1986). The last cause of incomplete neutralization of the virus in the period when the formation of unstable dissociate immune complexes. This contributes to persistence of the virus increases the likelihood of chronicity of the process and the possibility of getting the disease in a more severe form. Carrying out a long treatment in both ways (from four to twelve days in a way equivalent, and five to six days in the closest to the proposed method) with a simultaneous increase in dose rate immunoglobulin (36 and 72 ml in the way the analogue and from 21 to 130 ml closest to the proposed method) can cause protein overload the body, especially with the introduction of vysokomarochnogo immunoglobulins with antibody titers of 1:160 and 1:320. In the method-analogue of this is aggravated by the fact that when determining the dose of immunoglobulin does not take into account the body weight of the patient. In addition, during the course of treatment already in secondary dose of the organism generates adaptive response to alien e decreases the rate of formation of active specific immunity of the body, consequently, increasing the likelihood of getting the disease in a more severe form, in some cases with a fatal outcome, and increases the likelihood of chronicity of the process. In addition, both methods do not exclude two disease that reduces the effectiveness of treatment.

Thus, identified as a result of a patent search close to the proposed known methods of treatment of patients with EC in the implementation does not allow for achievement of the technical result consists in increasing the effectiveness of treatment by increasing the rate of formation of active specific immunity, reduce the likelihood of getting the disease more severe, including fatal, two exceptions disease, reduce the likelihood of chronicity of the process.

The present invention solves the problem of creating a method of treatment of patients with tick-borne encephalitis, which allows to ensure the achievement of the technical result consists in increasing the effectiveness of treatment by increasing the rate of formation of active specific immunity, reduce the likelihood of getting the disease in more severe fosili process.

The essence of the invention lies in the fact that in the treatment of patients with tick-borne encephalitis, including intramuscular immunoglobulin with the titer of antibodies to tick-borne encephalitis virus 1:160 or 1:320 and the use of non-specific therapeutic agents, a single dose determined per kilogram of body weight and severity of the disease, the calculated dose of immunoglobulin is administered simultaneously with febrile and meningeal forms of the disease at the dose of 0.2 ml per 1 kg of body weight, and in severe focal form in a dose of 0.5 ml per 1 kg of body weight. If the calculated dose is greater than 10 ml, you enter one explored by multiple intramuscular injections, not exceeding 8-10 ml.

The technical result is achieved in the following way. Currently in the Arsenal of therapeutic agents in tick-borne encephalitis leading specific drug is a human immunoglobulin for intramuscular injection. This is facilitated by its pronounced therapeutic efficacy and the absence of allergic complications. The application of the proposed method vysokomarochnogo immunoglobulin (antibody titer of 1:160 or 1:320), in combination with the simultaneous introduction of PR is Abolina with antibody titers of 1:160 and 1:360 allows to reduce the phenomenon of persistence of TBE virus and may even be eliminated. This is because with the introduction of vysokomarochnogo immunoglobulin, particularly when the antibody titer of 1:320, in the body of the patient form stable immune complexes, in which the pathogen viral infection is neutralized. The result is a single large dose vysokomarochnogo immunoglobulin prevents the transition of the disease to more severe and reduces the risk of chronicity of the process. The result is warned chronization process and its further transition into a more severe stage. The value of a single dose 1 kg of body weight of the patient (0.2 and 0.5 ml/kg) obtained experimentally, is the best and takes into account the severity of the disease and protein loss during introduction due to the destruction or binding protein of muscle tissue. A one-time introduction the calculated dose immunoglobulin, as well as high titers of 1: 160 or 1: 320 allow you to create a sufficient concentration of antibodies in the blood of the patient in the shortest possible time from the onset of the disease and thereby increase the rate of formation of active specific immunity, which in turn reduces the likelihood of chronicity of the process and transition of the disease in a more severe form. In addition, as shown, a one-time introduction the calculated what the ranking, with the prototype several times reduces the dose of an administered drug, that completely eliminates the possibility of sensitization of the patient's body alien protein - protein overload. Thus the efficiency of immunoglobulin is not reduced, because the lack of protein overload eliminates the body's production as a result of adaptation to negative reaction to introduce a foreign body and as a consequence the production of corresponding antibodies. Due to the fact that the calculated dose in excess of 10 ml, injected simultaneously explored by multiple intramuscular injections, not exceeding 8...10 ml, enhances the permeability of an administered drug in the patient's body. This is because the inner layers of fabric is determined by homeostasis. While the receptor system of the surface layers of fabric have a high reactivity, the inner layers of tissue are more inert and their relaxation time more than superficial tissues (human Physiology edited by Pokrovsky C. M. and Korotko, F., M.: Medicine, 1998). Therefore, we can assume that at low doses (8...10 ml) receptor system of internal tissue layers do not have time to fix or fix late appearance in them of foreign bodies in the administration of the drug. This snijaia full penetration of the drug in the body and improves the effectiveness of its actions. At the same time due to the increased permeability reduces the loss of immune protein due to the destruction of or linking muscle tissue during penetration of it into the bloodstream. The application of the proposed method is non-specific therapeutic agents increases the effect of treatment of the primary drug - immunoglobulin, which just increases the effectiveness of the treatment.

From the above it follows that the proposed method for the treatment of patients with tick-borne encephalitis in the implementation ensures the achievement of the technical result consists in increasing the effectiveness of treatment by increasing the rate of formation of active specific immunity, reduce the likelihood of getting the disease more severe, including fatal, two exceptions disease, reduce the likelihood of chronicity of the process.

The method is implemented as follows. In the proposed method of treatment of patients with tick-borne encephalitis intramuscularly injected a human immunoglobulin with a titer of antibodies to tick-borne encephalitis virus 1:160 or 1:320 in a dose of 0.2 or 0.5 ml/kg of body weight depending on the form of the disease and the calculated dose of immunoglobulin is administered simultaneously. Complement is in kilogram of body weight and severity of the disease. The calculated dose of immunoglobulin is administered simultaneously. When feverish and meningeal forms of the disease at the dose of 0.2 ml per 1 kg of body weight, and in severe focal form in a dose of 0.5 ml per 1 kg of body weight.

As a non-specific therapeutic agents traditionally in the treatment of EC, in addition to the IG, include, depending on the condition of the patient leukocyte interferon, detoxification therapy, large doses of ascorbic acid, immunomodulating agents, cardiovascular drugs, ribonuclease; IFN (post-febrile period), metabolic therapy, glucocorticoids and other symptomatic therapy.

Comparative analysis of the dynamics of clinical indicators in patients with EC, past the proposed method of treatment, compared with the traditional method showed reduction in febrile period by 2.7 days; no two disease; more rapid regression of meningeal symptoms coming on 3-5 days earlier in a single dose rate of IG.

The effectiveness of the proposed method is confirmed by clinical observations of patients with different forms of acute tick-borne encephalitis - feverish (Example 1), meningeal (Example 2) and focal - encephalo analysis.

Example 1. Patient C., 38 years.

Tick bite 5.06.1998, in the region of the right shoulder. Pre-vaccination and seroprotection was not. 5 days after a tick bite temperature rise to 39.0oappeared General weakness, malaise. Did urgently.

Objectively admission: hyperthermia to 39.5o. Meningeal symptoms and focal neurological symptoms are not detected.

In the first hour of admission entered domestic immunoglobulin with the titer of antibodies to tick-borne encephalitis 1:160 at a dose of 0.2 ml/kg of body weight (0.2 ml x 65 kg =13 ml) simultaneously. Conducted detoxification therapy (up to 1.0 to 1.5 l of saline solution; intravenous ascorbic acid, 500 mg per day). 2 days after receipt of the temperature decreased to 37.0oC. then a day later fully normalized, decreased General weakness, to the end of the week in a normal condition. Received multivitamins. Discharged from hospital (2 weeks) in satisfactory condition with a diagnosis of acute tick-borne encephalitis. Febrile form.

Example 2. Patient D., aged 34.

Tick bite 13.07.1998, in the chest on the right. Pre-vaccination and seroprotection was not. H is IKI, however, temperature is not decreased, headache persisted, even after 2 days increased the intensity of the headache, she had nausea, vomiting, increased weakness, lethargy. Did urgently.

Objective: hyperthermia to 39.8o. In consciousness, sluggish, dynamiczny.

Revealed meningeal symptoms such as stiff neck up to 3 cm, bilateral moderate symptom of Cernica. Focal neurological symptoms are not detected.

Lumbar puncture, analysis of cerebrospinal fluid: lymphocytosis 160 cells, 80% lymphocytes, 20% neutrophils; protein 0.32 g/litre; sugar 3.2 mmol/L.

In the first hour after receipt entered simultaneously domestic immunoglobulin with the titer of antibodies to tick-borne encephalitis 1:320 in a dose of 0.2 ml/kg of body weight (0.2 ml x 80 kg = 16 ml). Conducted detoxification therapy (up to 2 - 2.5 liters of saline intravenous ascorbic acid up to 500 -1000 mg; desegregate and vascular therapy (pencilin, trental, aminophylline); metabolic therapy, multivitamin.

On the 3rd day after admission, the temperature decreased to 37.5o; 5-th day - normalized; by the end of the week had smoothed out meningeal symptoms, decreased headache after 10 days the norm is satisfactory condition with a diagnosis of acute tick-borne encephalitis. Meningeal form.

Example 3. Patient M., 68 years of age.

During may-June 1998 regularly drank raw goat milk. 03.06.98 was removed ticks from the body, but the bites denies. Pre-vaccination and seroprotection was not.

The incubation period of a given time from the time of removal of ticks to 8 days. Pain in acute 11.06.98, when there hyperthermia to 39.0o, headache, diffuse character, after 4 days noted weakness of the neck muscles, appeared difficulty when the conversation became sluggish dinamichnoy appeared difficulty contact with others due to severe drowsiness. Did urgently.

Objectively (at the time of admission): stunned, quickly depleted. Meningeal symptoms (stiff neck up to 4 cm, bilateral symptoms cherniga). Neurological symptoms: paresis of gaze to the left, the coarse horizontal nystagmus in extreme abduction of the eyeballs, the Central paresis of the VII cranial nerve left, deviation of the tongue to the left, reducing the strength in the neck muscles to 1 point, tremor of the fingers, reducing the force in the proximal hand to 3-4, legs - up to 4 points, diffuse hypotonia in the extremities, coordinatorsee violations. In connection with Albania disorders (dysarthria, dysphonia, dysphagia disappeared pharyngeal reflex), increased stun. The question arose about the need for artificial ventilation of the lungs.

Analysis of cerebrospinal fluid: lymphocytosis 240 cells (lymphocytes - 66%; neutrophils - 33%); protein - 0.45 g/l; sugar 3.6 mmol/L.

Introduced in the first hour of receipt of simultaneous domestic immunoglobulin rate of 0.5 ml/kg of body weight (0.5 ml x 60 kg = 30 ml). Was conducted of desintoxication, vascular and desegregate therapy. Within a few hours the patient's condition remained stable and hard, but the rise of human consciousness, bulbar disorders and attach breathing disorders did not happen. By the morning of the patient's condition has improved, recovered consciousness. By the end of the week decreased temperature-37.3o, improved overall health, decreased headache and dizziness. By the 10th day of disappeared meningeal symptoms. From the 3rd week of the disease regressed bulbar disorders, independently began to eat, increased strength in the muscles of the neck to 3-4 points. Limbs up to 4 points. On the background of active metabolic vascular therapy by the end of the month, decreased tremor in the limbs, regressed coordinatorsee violations.

Discharged from the CLASS="ptx2">

1. The method of treatment of patients with tick-borne encephalitis, including the use of non-specific therapeutic agents and intramuscular immunoglobulin, the dose of which is determined based on one kilogram of body weight and with regard to the form of the disease, characterized in that the use of immunoglobulin with the titer of antibodies to tick-borne encephalitis virus 1:160 or 1:320 in a dose of 0.2 or 0.5 ml/kg of body weight depending on the form of the disease and the calculated dose of immunoglobulin is administered simultaneously.

2. The method according to p. 1, characterized in that when feverish and meningeal forms of the immunoglobulin is administered at a dose of 0.2 ml/kg of body weight.

3. The method according to p. 1, characterized in that in severe focal forms of the immunoglobulin is administered at a dose of 0.5 ml/kg of body weight.

 

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