A method of treating destructive and progressive forms of tuberculosis caused by drug-resistant strains of mycobacterium tuberculosis

 

(57) Abstract:

The invention relates to medicine. A method for treatment of destructive and progressive forms of tuberculosis caused by drug-resistant strains of Mycobacterium tuberculosis with the introduction of Roncoleukin at a dose of 500 thousand ME through a day, treatment 3 procedures. The invention increases the efficiency of the treatment.

The invention relates to medicine, namely to Phthisiology, and can be used for the treatment of destructive and progressive forms of tuberculosis caused by drug-resistant (LU) strains of Mycobacterium office (ILO).

It is known that in Russia since the second half of the 80-ies recorded adverse trend in TB: there was a significant increase in the incidence of tuberculosis has increased the number of patients with acutely progressive, destructive and generalized forms, decreased the effectiveness of previously used drugs in connection with the emergence of drug-resistant strains of Mycobacterium tuberculosis (1).

Tuberculosis is a chronic disease pathogenetic features which depend on the relationship between macro - and microorganism the Development of TB infection leads to changes in the negative character in the immune system of the patient, and when the progression of a marked inhibition of T-systems, especially in terms of proliferative response to PHA and PPD, accompanied by the overproduction of antibodies and decreased cellular response (2) and IL-2. Progressive course specific infection caused, as a rule, the presence in the body of the patient LOU MBT strains that dictates the need for the appointment of up to five anti-TB drugs in high therapeutic doses; thus, ongoing long-term, massive polychemotherapy is not conducive to the normalization of the immune status of the patient, but on the contrary may lead to secondary immunological failure (3).

Previously used in the treatment of tuberculosis immunomodulatory tools, such as the adjuvant, T-activin, allowed to achieve efficiency in the treatment of these patients (4 - prototype), but they are not selective, and the entire spectrum of lymphocytes, whereas now clear inappropriateness of activation in destructive and progressive forms of tuberculosis of certain subpopulations, particularly T helper 2, and, in addition, these drugs are foreign proteins of animal origin.

Currently, through genetic engineering, created a new class of immunomodulators recombinant interleukins, which contributes to a more focused impact on components of the immune response. IL-2-Roncoleukin* (recombinant IL-2, manufactured by BIO, St. Petersburg) acts on T cells, enhancing their proliferation and subsequent synthesis of IL-2. He directed affects the growth, differentiation and activation of T-lymphocytes, macrophages, oligodendroglia cells, epidermal Langerhans cells, its presence depends on the development of cytological activity of natural killer cells and cytotoxic T-lymphocytes (5, 6). Cytokines are products of immune cells and at the same time, immunocompetent cells are targets of cytokines (7, 8). In the experiment on the model of tuberculosis caused by Mycobacterium bovis, is sensitive to anti-TB drugs, it is shown that tuberculostatic therapy in combination with recombinant IL-2-ronkoleykin found its high therapeutic efficacy (9).

A distinctive feature of pic is mi strains of Mycobacterium tuberculosis, is the introduction on the background of chemotherapy Roncoleukin at a dose of 500 thousand ME, the introduction is carried out in a day, treatment 3 procedures.

The method is as follows:

1. The drug is administered intravenously at a dose of 500 thousand ME.

2. As a solvent used 0.9% solution of sodium chloride in the amount of 500.0 ml

3. The drug is injected through the day, the course of treatment is 3 injections.

4. For puncture is used cubital vein.

5. The speed of the drug 10-14 drops per minute.

6. Roncoleukin (recombinant IL-2) is assigned to the background of the application of anti-TB drugs.

Examples of clinical use.

Example 1. Patient P. , 1972, R., I. B. 115/517. Was admitted to the hospital on December 18, 1998 , issued 16 March 1999, the Patient has a diagnosis of disseminated tuberculosis in both lungs in the phase of infiltration and degradation of MBT(+) (progression), suffers a specific process since 1994, the course is undulating, in the last year or progressive. The patient was admitted with acute symptoms of intoxication, changes in hematological and biochemical parameters, erythrocyte sedimentation rate reached 25 ml/h, stab SDW>4- 150, CD8- 325; we have decreased proliferative response rbtl to TTD to zero, the activity of T-lymphocytes rbtl for PHA to 30%, serological reactions with tuberculous antigen were: RPK with PPD - 52,0.E., RGL with PPD - 33,0.E., ELISA with PPD - 0,71. E. On radiographs and tomograms of the patient's lungs was determined expressed exudative-productive changes in the upper lobes of both lungs with multiple cavities and pockets of contamination exudative-necrotic type in all lung fields. Bacteriological study found that office-resistant S (streptomycin), for low and medium concentrations of H (isoniazid), the combination of S and H, S+H+R (rifadin), (kanamycin), R and E (ethambutol). Thus, the patient was admitted to the hospital with progressive specific process, called LU strains of Mycobacterium tuberculosis. The patient was assigned to intensive chemotherapy: N - vnutrivnutrivenno drip 900 mg/day, Z (pyrazinamide) - per os 200 mg/day, ciprofloxcin - per os 1000 mg/day. Roncoleukin was injected intravenously at a dose of 500 thousand ME through day 3. In the treatment of symptoms of intoxication were eliminated after 2 weeks, normal hematological, biochemical and immunological the several increased proliferative response rbtl to TTD. The patient was bazillion 2 months, and after 3 radiographically closed cavity decay. Was discharged in good condition after 3 months.

Example 2. Patient P., 1975, p., I. B. 390. Was admitted to the hospital on September 28, 1999, the Patient was diagnosed with disseminated tuberculosis in both lungs in the phase of infiltration and degradation of MBT(+). Tuberculosis of peripheral lymph nodes, active form. Specific process was first identified in April 1999 : it was noted the peripheral lymph nodes and lung tissue limited to the patient before admission to a Department conducted local treatment and chemotherapy sensitivity of the office. Sticks Koch were resistant to S, and a low concentration N, the combination of S and H, S+H+R, K, R, Z and E. Thus, the patient was admitted to the Department of therapy with generalized tuberculosis defeat as lung tissue and peripheral lymph nodes. The patient was observed symptoms of intoxication, changes in hematological and biochemical parameters, erythrocyte sedimentation rate reached 32 ml/h, stab shift of neutrophilic leukocytes of 13%, the number of lymphocytes was 8.5 percent, immunological indicators: CD3- 659, CD4- 241, CD8- 3 the s on rbtl for PHA to 24%, serological reactions with tuberculous antigen were: RPK with PPD - 42,0.E. , RGL with PPD - 42,0.E., ELISA with PPD - 0,358.E. On radiographs and tomograms of the lungs was determined WITH1-2WITH3WITH4and C6large exudative - necrotic infiltrates pnevmokolesnymi cavities collapse. The patient was assigned to intensive chemotherapy: intravenous infusion of 900 mg/day, intramuscular injection of 1000 mg/day ciprofloxacin - per os 1000 mg/day, Pb (rifabutin) - per os 450 mg/day. Roncoleukin was injected intravenously at a dose of 500 thousand ME through day 3. On the background of the treatment showed a significant clinical rentgenologicsky positive dynamics: reduction of body temperature, appetite improved, the x-ray light fixed resorption significant amount of infiltration and focal changes, reducing destruction cavities; improvement of biochemical, hematological and immunological parameters, the number of CD3grew up 1725,8, CD4- 604,0, CD8- 527,0, was slightly increased and the proliferative response rbtl to TTD.

Authors in the clinic with the use of Roncoleukin treated 25 patients with destructive and progressive tuberculosis of the lungs, called LU shtam the decrease in intensity or smear conversion, reducing the number and size of the cavities collapse, the stabilization of the specific process, the surgical treatment more favourable background, the improvement of immunological parameters. Complications with the drug were observed.

Sources of information

1. Vasiliev A. C., Galkin Century B. Dynamics of the spread of tuberculosis in the North of Russia //New technologies in the diagnosis and treatment of tuberculosis of various organs and systems. T. II.-SPb.-1998.-C. 10.

2. Ivanov, L. A. Modern methods of correction etiopathogenetic treatment of destructive forms of tuberculosis: author. Diss. D. M. N., St. Petersburg. 1995.

3. Shabasheva N. In. Lectures on clinical immunology. -SPb., 1998.

4. Ivanov, L. A. Immunoactive drugs thymus in the treatment of patients with infiltrative destructive pulmonary tuberculosis: author. Diss. K. M. N.-L., 1986.

5. Changes in immunological parameters in cardiac surgery patients during therapy with the drug Roncoleukin* //N. A. Asenov, N. B. Silver, I., Khubulava etc.// III scientific conference with international participation "the Days of immunology at St. Petersburg 99: conference Materials. -SPb., 1999, -Volume 1,- 3-4-S. 114.

6. The impact of therapy is om C. //M. Smirnov, A. I. Gorkin, S. L. Firsov, etc.// III scientific conference with international participation "the Days of immunology at St. Petersburg 99: conference proceedings.-SPb., 1999.-Volume 1, a - 3-4.-S. 134.

7. Snoring B. E., Simbirtsev A. C. cytokine Production in various forms of pulmonary tuberculosis.// Probl.the tubes.-1998 - 3.-S. 67-71.

8. Freidlin, I. S. Immune system and its defects. -SPb., 1998.

9. The use of recombinant IL-2 in the treatment of experimental tuberculosis / Zabolotny N. In., Alexandrov A. E., Antonenkova E. C., Khromov-Borisov N. N. // Molecular basis of pathogenesis and diagnosis of tuberculosis and other pulmonary pathology: collection summary. -M., 1995.-C. 16-17.

A method of treating destructive and progressive forms of tuberculosis caused by drug-resistant strains of Mycobacterium tuberculosis, by conducting etiopathogenetic therapy, characterized in that the injected Roncoleukin at a dose of 500 thousand ME through a day, treatment 3 procedures.

 

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