A method for the treatment of hemorrhagic fever with renal syndrome

 

(57) Abstract:

The invention relates to medicine, namely to infectious diseases, in particular to the treatment of hemorrhagic fever with renal syndrome (HFRS). For this set of patients prescribed the drug yodantipirin in the early stages of the disease, not later than the 5th day of the disease, oral - in the first four days of 0.2 g (2 tablets) 3 times a day for the next 5 days 0.1 g (1 tablet) 3 times a day. The General course of 9 days. This treatment is performed on the background of standard therapy, including isotonic solution of glucose and sodium chloride, ascorbic acid, antihistamines, disaggregants, diuretics. The method provides a reduction in the duration of periods and individual symptoms. 6 table.

The invention relates to medicine, namely to infectious diseases, in particular to the treatment of hemorrhagic fever with renal syndrome (HFRS) in the early stages of the disease.

The generally accepted method of treatment of HFRS is pathogenetic therapy aimed at reducing intoxication, the restoration of the currency circulating blood, improved rheology and microcirculation, decrease vascular permeability, normalization of acid-base status is preventing the rise of the severity of the disease. In this treatment, there is no impact on the etiological factor of the disease is a virus, immunological reactivity of the organism, and the interaction of these two factors play a role in the pathogenesis of HFRS.

Despite advances in modern medicine, the treatment of hemorrhagic fever with renal syndrome remains an actual problem. We are searching for the treatment of HFRS with inductors of interferon.

In the literature there is only reported attempt immunotherapy HFRS-timagenes, combining properties of the stimulator cell immunity and inductor interferonbeta. However, the expected therapeutic effect compared with the control group received no (Clinical and immunological monitoring of the effectiveness of thymogen in HFRS. C. I. Roshchupkin et al., 1989, S. 181-182).

In patent literature, and the open publication of information on the application of yodantipirin for treatment of patients with HFRS us could not be found.

The technical result - the reduction in the duration of periods and individual symptoms of the disease.

The proposed method of treatment is as follows: for the treatment of HFRS patients prescribed the drug iodine is 3 times a day, in the next 5 days 0.1 g (1 tablet) 3 times a day. The General course of 9 days. This treatment is performed on the background of standard therapy, including isotonic solution of glucose and sodium chloride, ascorbic acid, antihistamines, disaggregants, diuretics.

Yodantipirin (1-phenyl-2,3-dimethyl-4 iteration) belongs to the group of nonsteroidal anti-inflammatory drugs, pyrazolone derivative, has anti-inflammatory, antiviral and immunostimulating and interferonogenna properties. The drug is an active inducer of alpha - and beta-interferons, significantly increases the activity of fibroblasts and induces their anti-virus resistance, delaying the entry of the virus into the cell due to the stabilizing action on biological membranes, significantly stimulates the production of antibodies. Clinical study of the drug as a means for the treatment and prevention of tick-borne encephalitis, influenza and other acute respiratory viral infections in adults. Obtained good clinical results, which allowed us to recommend yodantipirin for wide use (Current issues of natural focal infections, 1998, S. 244-245). Yodantipirin economically available, the five-assess the effectiveness of therapy, patients were divided into two groups. The first group of 67 patients received only common pathogenetic therapy and constituted the control group. The second of the 74 patients in addition to conventional therapy received yodantipirin. The object of study became patients with moderate and severe form of the disease, as in the mild form is not expressed immunopathological and clinical manifestations of the disease.

As criteria for the effectiveness of therapy, we used the following indicators: 1) clinical duration of fever, pain, duration of oliguria, 2) biochemical - peak levels of urea and creatinine, 3) dynamics of some indicators of immune subpopulations CD3. CD4CD8lymphocytes, phagocytic index, b-lymphocytes, 4) dynamics of interferon status - serum IFN alpha-IFN.

Assessing the positive effect of immunomodulatory therapy, we primarily relied on clinical performance criteria.

As can be seen from table 1, patients with moderate over HFRS receiving yodantipirin, duration of symptoms such as fever, oliguria, pain in the lower back, the abdomen was significantly less, che is inina in the experimental group. In patients with a severe form of HFRS, treated with the test drug, duration of fever, lower back pain, also significantly differed. The difference in the duration of oliguria, abdominal pain and headache patients of both groups was observed. Peak values of creatinine were significantly lower in the experimental group, and urea had no significant difference (table 2).

Yodantipirin as we developed the regimen is well tolerated, side effects and allergic reactions have not been reported. Although it should be noted that his oral application may be limited in patients with severe vomiting.

The results obtained in the study CD3CD4CD8lymphocytes, phagocytic index, b-lymphocytes, showed that the dynamics of indicators of cellular immunity depended on the severity of HFRS patients.

As can be seen from tables 3 and 4, immunological parameters in olimpijski period was not significantly different in the groups. In politicheskoi period there was an increase in the relative number CD3, CD4lymphocytes in moderate and severe form of HFRS. As for level CD8lymphocytes, obtained PAH, and, if severe in the experimental group the rate was significantly lower than in the control. Phagocytosis of neutrophils in the experimental group in politicheskoi period was characterized by high rates phagocytic index. Revealed significantly higher values of b-lymphocytes. In the convalescence period at moderate form of the relative number of subpopulations CD3CD4CD8lymphocytes remains significantly higher in the experimental group and approaches the performance of healthy persons. Indicators phagocytic index and b-lymphocytes in this period was not significantly different in the groups. When severe, we saw a General trend towards normalization of cellular immunity, but there was no statistically significant difference in both groups.

Thus, in General, the analysis of the above characteristics of cellular immunity in the two study groups of patients, we can speak about the presence of immunomodulatory effect yodanthipirina in patients with moderate and severe disease.

In early appointment yodanthipirina was significantly rapid increase in the activity of the IFN system.

As can be seen from table 5, when moderate form Gpsies.com periods have been identified. At discharge, the level of serum IFN in the experimental group was significantly lower than in the control. Increase the ability of leukocytes to the production of alpha-IFN came later to the period of convalescence in the experimental group.

In severe form of HFRS level of serum IFN during all periods of the disease remained high in both groups and did not differ significantly. The level of alpha-IFN was reduced in comparison with the same indicator in patients with moderate to severe form of the disease. During convalescence the level of alpha-IFN had a tendency to increase, which was more pronounced in the experimental group, however, performance was not significantly different (table 6).

High titers of serum IFN in the midst of illness, seems to be connected with high interferonogenna activity of blood cells and other systems involved in the pathological process, also with high interferonogennoy activity of the viral hemorrhagic fever with renal syndrome.

In oligarchism period there was a decline in the ability of leukocytes to produce alpha-IFN, probably this is due to the depressing effect of HFRS virus for the production of alpha-IFN. Improving the ability of leukocytes to produce alpha-IFN in the recovery period Sopki.

Thus, early appointment yodanthipirina contributed to a greater increase interferoninducible ability of leukocytes in moderate and severe form of HFRS, but in moderate form, this ability was more pronounced.

Examples of specific applications of the proposed method of treatment.

Example 1.

Patient P. , aged 30, was on treatment in the 8th ward KIB 4 from 5 October to 26 October 1999. Clinical diagnosis: Hemorrhagic fever with renal syndrome, moderate severity.

The diagnosis is confirmed by serological method (the increase in antibody titer and virus hemorrhagic fever with renal syndrome in paired sera 1:256-1:1024).

Admitted to the hospital on the 4th day of the disease. History: the disease began acutely with rise in temperature to 39oWith, chills, headache. On the 3rd day of the disease appeared pain in the lumbar region, nausea, weakness. The house took antipyretics. October 4, went to a local doctor and 5 October hospitalized.

Epidemiological history: Periodically went to the garden area, notes the infections (HFRS) among the neighbors in the garden. Chronic diseases in anamnesis no.

When objectivesthe, body temperature 38,8oC.

Hyperemia of the face, neck, upper half of the body, the injection of the sclera. Enanthema the soft palate. On the lateral surfaces of the body petechial rash.

The vesicular breathing, muffled heart sounds, tachycardia up to 96 beats per minute, AD=120/60 mm RT. senior palpation of the abdomen - mild pain in the area of the projection of the kidneys, severe tenderness effleurage lumbar region.

Patient scheduled infusion therapy, hypertonic glucose, ascorbic acid, antisense drugs. 6 October (on the 5th day of the disease) the patient is assigned yodantipirin 0.2 g (2 tab.) 3 times a day, and on October 10, 0.1 g (1 tab.) 3 times a day. The General course of 9 days.

October 6, the patient's condition remained heavy, kept the temperature to 38.9oWith pain in the lumbar region, was a decrease of urine. The next day the temperature dropped to 37,3oAnd since October 8, it was normalized. Gradually decreased manifestations of intoxication and pain. Daily diuresis 6 October amounted to 800 ml, 7 October - 850 ml, 9 October - 900 ml, and 10 October, about 2 liters, then noted the development of polyuria to 3.2 liters per day, continue overvoltage condition.

Laboratory data from 6 October.

The CBC - hemoglobin 162 g/l, erythrocytes 5,31012/l, leukocytes 6,5109/l, stab 3%; segmented 70%, lymphocytes -13%, eosinophils 2%, monocytes 12%, platelets 69109/l, erythrocyte sedimentation rate 5 mm/h, PETIT 89%, clotting time 4' 15".

Biochemical blood test: creatinine 132 Ámol/l, urea of 8.2 mmol/l, ALT 26 U/l, ACT 30 U/l, bilirubin total of 4.8, thymol test 2,7.

Urinalysis: relative density 1018, protein 0,66%0, hyaline cylinders - single.

October 8 (7-day sickness) - azotemia (creatinine 280 Ámol/l, urea 14.1 mmol/l), urine analysis - relative density 1010, protein 3.3% of0, erythrocytes 0-1 in the field of view.

After 9 days of treatment (15 October) - creatinine 110 Ámol/l, urea 6.0 mmol/L. urinalysis: relative density 1014, protein negative, the epithelium 0-1 in the field of view.

Indicators of immunity

In olimpijski period: CD343,4%, CD429%, CD830%, b-lymphocytes 14%, phagocytic index of 40%.

In politicheskii period (after the end of treatment yodantipirin): CO350%, CD434%, CD830%, lymphocytes 10%, phagocytic index 56%.

The rate of interferon status:

In olimpijski period: serum IFN 87 IU/ml, alpha-IFN 130 IU/ml

In politicheskii period (after the end of treatment yodantipirin): serum IFN-130 IU/ml, alpha-IFN-175 IU/ml.

In the convalescence period: serum IFN 87 IU/ml, alpha-IFN 260 IU/ml

As can be seen from the above observations, the purpose of yodantipirin in the complex treatment of the patient severe form of HFRS has had a positive impact on the clinical course of disease, cellular immunity and performance interferonogenesis.

Example 2.

Patient N., 43 year history 8768, was hospitalized in 4 KIB, Ufa from 6 October to 1 November 1999.

Clinical diagnosis of Hemorrhagic fever with renal syndrome, severe. Complication - ITSH-11 degrees, DIC syndrome. The diagnosis is verified by serological method: in paired sera in the IAF, the increase in antibody titer to the virus hemorrhagic fever with renal syndrome 1:16-1:1024.

He entered on day 3 of illness. Ill sharply with the increase of body temperature up to 40oWith, chills, lower back pain, also experienced blurred vision and intermittent nasal bleeding. After inspection, the part is a drain in Demsky area notes the cases of HFRS among neighbors on the garden plot.

Complaints at admission: body aches, back pain, weakness, dizziness, headache, blurred vision, nausea.

Objectively: the state of the heavy, sluggish, hyperemia of face, neck, upper third of the chest, bleeding in the sclera, skin, breast petechial hemorrhagic rash. In the lungs weakened vesicular breathing, respiratory rate 22 / minute. Muffled heart sounds, regular rhythm, pulse 110 beats per minute, blood pressure 100/70-90/70 mm RT. senior Language dry, white furred. Abdomen palpation soft, painful in the area of the projection of the kidneys. Symptom tapping on the lumbar region is positive on both sides.

Given the severity of the condition, the patient was hospitalized in the intensive care unit. Appointed infusion therapy - 10% glucose with insulin, 4% sodium bicarbonate solution, prednisolone 90 mg intravenously, antisense drugs. From 7 October (on the 4th day of illness) assigned yodantipirin at a daily dosage of 0.6 g, and from 11 October to 0.3 g per day. Total duration of therapy for 9 days.

Laboratory data from 6 October:

General>/l, stab 4%, segmented 76%, lymphocytes 10%.

Urinalysis: relative density 1060, protein 3.3% of0, erythrocytes 4-6 field of view, the cylinders in large quantities.

Creatinine levels 103,2 Ámol/l, urea of 6.3 mmol/L.

October 7, the patient's condition remained severe, was observed hypotension 80/70 mm RT. Art., daily diuresis was 450 ml.

On the day of the appointment yodanthipirina there was a decrease in body temperature up to 37.4oAnd the next day its normalization. On the 6th day of the disease, October 9, daily diuresis was 350 ml, vomiting was observed up to 5 times a day, pain in the abdomen.

Thus, the duration of febrile period was 4 days, oliguria 4 days. The highest level azotemii was celebrated on 13 October, on the 10th day of the disease (creatinine 428 Ámol/l, urea 24 mmol/l), but daily diuresis on this day was already 3 liters.

After therapy yodantipirin laboratory findings were as follows.

Complete blood count: hemoglobin 122 g/l, erythrocytes 3,81012/l, leukocytes 8,8109g/l, erythrocyte sedimentation rate 10 mm/h, platelets 325109g/l, lymphocytes 42%, stab 4%.

Urinalysis: relative density 1005, white is/l, urea 5.0 mmol/l

These immunological indexes:

Olimpijski period - CD337%, CD424%, CD825%, lymphocytes 11%, phagocytic index 49%.

Politicheskii period - CD339%, CD424%, CD826%, b-lymphocytes 15%, phagocytic index of 32%.

The convalescence period - CD343%, CD429%, CD831%, b-lymphocytes 17%, phagocytic index 52%.

The patient was discharged in satisfactory condition under the supervision of your GP.

As can be seen from the above example, the assignment yodantipirin in the complex treatment of the patient severe form of HFRS has had a positive impact on the clinical course of disease and indicators of cellular immunity.

Yodantipirin, apparently, having antiviral activity, affects the level of viraemia, as evidenced by a more rapid decrease in temperature. One of the mechanisms of action of yodantipirin is to delay the penetration of the virus into the cell and the induction of interferon synthesis, antibodies, resulting in the interruption of the pathological process.

On the basis of our data we can conclude that the dynamic evaluation of changes in the indicators of cellular immunity and interferonovy positive effect when using yodantipirin allows pathogenetically to justify the expediency of its application in complex therapy of patients with moderate and severe forms of HFRS inducers of interferon.

A method for the treatment of hemorrhagic fever with renal syndrome immunokorrigiruyuschy drug on the background of standard therapy, characterized in that as immune correcting drug use yodantipirin in the early stages of the disease, not later than the 5th day of the disease and for 9 days, and during the first 4 days at a daily dose of 0.6 g, in a subsequent dose of 0.3,

 

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