RU2368372C1 - Treatment method of pulmonary tuberculoisis with hiv-infected patients - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine and namely to phthisiology. Method involves antituberculous therapy performed according to standard conditions. In addition, starting from the first day of treatment there injected every day are 3 pills of Wobenzym, thrice a day, 30 minutes prior to the meal during the whole treatment course. Endermic electroneurostimulation of points GI4, TR5, J19, R27, T14, V13, V17, V18, and T7 is performed every day. Frequency of 77 Hz is applied to each point during 30 days, 2 minutes per each point, and total time is 30 minutes.

EFFECT: method increases treatment efficiency of pulmonary tuberculosis of HIV-infected patients owing to decreasing abacillation periods, closing degradation cavities, resolution of infiltration changes in lungs, and improving immune properties.

2 ex, 3 tbl

Description

The invention relates to medicine, namely to phthisiology, and can be used in the complex treatment of pulmonary tuberculosis in patients with HIV infection.

Tuberculosis and HIV infection have become global problems of modern medicine requiring immediate action. These diseases are largely interconnected. HIV infection is an important factor contributing to the development of the tuberculosis epidemic. The prevalence of tuberculosis in the general population correlates with the prevalence and increase in tuberculosis incidence among HIV-infected patients.

Of particular relevance at the present stage is the problem of combined pathology - HIV infection and tuberculosis. Both diseases affect mainly the young, able-bodied population of our country and, as a result, are socially significant, leading to a decrease in labor potential. Over the past 3 years in our country, there has been a significant increase in the number of patients with combined pathology. Cumulative indicator of the number of registered cases of tuberculosis associated with HIV infection for the period 2005-2007. doubled from 9713 in 2005 to 19782 people in 2007

The leading method in the treatment of tuberculosis is antibiotic therapy with anti-TB drugs (order of the Ministry of Health of the Russian Federation dated March 21, 2003 No. 109). In many cases, anti-tuberculosis therapy is ineffective. Especially low is the effectiveness of treatment for HIV-associated tuberculosis. Persons living with HIV infection experience immunosuppression with impaired cellular immunity, in particular, the function of CD4 lymphocytes, namely those cells that are of great importance for the fight against mycobacterium tuberculosis, suffers. In this regard, the search continues for various methods of pathogenetic effects that increase the effectiveness of anti-tuberculosis therapy in patients with HIV infection. The question of increasing the effectiveness of treatment of pulmonary tuberculosis in HIV-infected patients is relevant, since long-term maintenance of bacterial excretion leads to an increase in the number of epidemiologically dangerous foci of tuberculosis infection.

Conducted research of medical, scientific and patent literature identified various methods of treatment of pulmonary tuberculosis.

So, in the work of L.A. Ivanov and P.M. Chuzhova “New aspects in the treatment of progressive pulmonary tuberculosis” (Materials of the scientific-practical conference “Modern pharmacotherapy: cytokines”, Minsk, 2000), a method for treating pulmonary tuberculosis with inclusion in the complex therapy of roncoleukin®.

In the work of S.S. Arshinova and B.V. Pinegin, “Immunomodulators in the treatment of patients with active pulmonary tuberculosis” (Journal of the Treating Doctor, October 2002, No. 10, pp. 36-37), a method for treating pulmonary tuberculosis is described, which provides inclusion in the complex chemotherapy of patients with polyoxidonium.

In the work of A.K. Ivanov “Dynamics of humoral immunity and biochemical parameters in patients with pulmonary tuberculosis against the background of complex treatment using acupuncture” (Immunological and biochemical fundamentals of reactivity in tuberculosis: collection of scientific papers / Leningrad Research Institute of Phthisiopulmonology / M., 1988, pg. 92-95) describes a method for the treatment of pulmonary tuberculosis using acupuncture.

Patent of the Russian Federation No. 2299438 (BIMP No. 14, 2007) protected the "Method of choosing pathogenetic treatment of patients with acute progressive pulmonary tuberculosis", which consists in the fact that stress-limiting drugs include GHB, glycine, dalargin and tocopherol acetate.

RF patent No. 2242222 (BIMP No. 35, 2004) protected the "Method for the treatment of focal and infiltrative pulmonary tuberculosis", which provides for the additional introduction of 0.125 g of amixin into the course of treatment for 36 days.

The closest in essence and taken as a prototype is the method of treatment of tuberculosis, provided for by the order of the Ministry of Health of the Russian Federation No. 109 dated 03/21/03, “On the improvement of anti-TB measures in the Russian Federation”, which defines standard chemotherapy regimens for tuberculosis patients, consisting of 2 phases with different tasks:

1. The intensive care phase is aimed at eliminating the clinical manifestations of the disease, maximizing the effect on the mycobacterium tuberculosis population in order to stop bacterial excretion and prevent the development of drug resistance, and to reduce infiltrative and destructive changes in organs;

2. The phase of continued therapy is aimed at suppressing the persisting mycobacterial population. It provides a further reduction in inflammatory changes and involution of the tuberculosis process, as well as restoration of the patient’s functional capabilities.

The disadvantage of this method of treating pulmonary tuberculosis in patients with HIV infection is its low efficiency in relation to closing the decay and abacillation cavities, the duration of the course of therapy, which leads to the formation of drug resistance of mycobacteria to anti-TB drugs.

The aim of the invention is to increase the effectiveness of treatment of pulmonary tuberculosis in patients with HIV infection by reducing the terms of abacillation and closing of the decay cavities, as well as the disappearance of the clinical manifestations of the disease and the reduction in the duration of inpatient treatment.

This goal is achieved by prescribing anti-tuberculosis therapy according to standard regimes with the additional inclusion of Wobenzym 3 tablets 3 times a day 30 minutes before meals daily, for the entire course of treatment and daily percutaneous electroneurostimulation of points GI 4, TR 5, J 19, R 27, T 14, V 13, V 17, V 18, T 7, 2 minutes each, for a total duration of 30 minutes, in a comfortable energy mode with a frequency of 77 Hz, for 30 days.

The method is as follows: the patient, after examination and diagnosis, is prescribed anti-tuberculosis therapy according to standard modes. At the same time, from the first day, 3 tablets are included in the treatment of pulmonary tuberculosis 3 tablets 3 times a day 30 minutes before meals daily, for the entire course of treatment. Percutaneous electroneurostimulation is performed daily, for example, with the Dia-DENS-DT apparatus of points GI 4, TR 5, J 19, R 27, T 14, V 13, V 17, V 18, T 7, 2 minutes each, for a total duration of 30 minutes, in a comfortable energy mode with a frequency of 77 Hz, for 30 days.

The ability of Wobenzym to increase the concentration of antibiotics in the lesion enables us to use it in the pathogenetic therapy of pulmonary tuberculosis and to accelerate the resorption of infiltrative changes. The ability of wobenzym to improve microcirculation and the supply of oxygen and nutrients to tissues is used in destructive processes to accelerate repair. Given the development of an immunodeficiency state with common tuberculous lesions due to HIV infection, we use wobenzym to enhance the effect on the immunological reactivity of the body, increase the functional activity of macrophages and phagocytic activity of cells.

Electrical stimulation of skin receptors is advisable, first of all, because of the ability to influence information regulatory processes in the body, which are mediated by the nervous system, since electric current can be considered as a physiologically adequate irritant of nerve structures. The more pronounced effect of electrostimulation of acupuncture points compared to acupuncture is due primarily to the fact that by passing an electric current a more effective effect on receptor formations is possible even if the location of the point is not completely determined. Under the influence of electropuncture, the functional state of thoracic structures changes, significant changes in blood composition and phagocytic activity occur, which indicates the active involvement of immune processes in the general reaction of the body to reflex effects. Electropuncture effects lead to pronounced changes in the content of serotonin, catecholamines, acetylcholine and an increase in the production of endogenous opiates, which play an important role in the regulation of immune processes. The change in the number of catecholamines that have a stimulating effect on immunogenesis is part of the general reactions of the body, which are realized by the hypothalamic-pituitary-adrenal system.

The use of electroneurostimulation through reflex and neurochemical reactions triggers the body's own adaptive mechanisms, which improves the effectiveness of treatment of pulmonary tuberculosis in HIV-infected patients.

Unlike other methods of physiotherapy, electroneurostimulation can be used from the first day of treatment of the patient; not contraindicated in hemoptysis; gives a quick response of the body. Electroneurostimulation improves microcirculation in organs and tissues; It has anti-inflammatory and analgesic effects; increases immunity and resistance to infections; normalizes the ratio and enhances the formation of certain types of neurohumoral substances (endorphins, cortisone, dopamine, etc.); It has an antispastic and decongestant effect.

The choice of acupuncture points for electroneurostimulation was based on the main clinical symptoms of pulmonary tuberculosis in patients with HIV infection. So, the effect on the T 7 point is shown with a decrease in appetite and fever, which is often found with pulmonary tuberculosis in patients with HIV infection. The impact on points J 19, R 27, V 18 is indicated for weakness, coughing, hemoptysis, shortness of breath, which are characteristic symptoms of pulmonary tuberculosis in patients with HIV infection. Point V 13 is the "point of the lungs", the effect on it is indicated for pulmonary tuberculosis, bronchitis, pneumonia. Given the decrease in the immune status in patients with HIV infection, to normalize the immune parameters, we applied the effect on points T 14, GI 4, TR 5. To reduce the side effects from the action of anti-TB drugs, we acted on the “liver point” - V 18.

The practical feasibility of the claimed method is illustrated by examples from clinical practice.

Example 1: patient Sh., 42 years old, was admitted for inpatient treatment to the Rostov branch of the State Health Institution “Tuberculosis Clinical Dispensary” in the Rostov Region for infiltrative tuberculosis of the upper lobe of the right lung in the phase of decay and contamination, MBT (Mycobacterium tuberculosis) +. From the anamnesis it is known that the patient was diagnosed with HIV infection, at the time of admission to the department, the 4B stage was established. The patient's condition upon admission is moderate, the manifestations of tuberculous intoxication are expressed, the skin is pale, the nutrition is low. Auscultatory in the lungs, vesicular breathing is heard, on the right in the upper lobe there are single wet and dry rales. NPV - 23-24 in 1 minute. HELL - 100/60 mm Hg PE - 84 in 1 minute.

Survey data at admission:

R-grams and T-grams - in the upper lobe of the right lung, uneven infiltration of the lung tissue of the focal structure, with a decay cavity up to 3.5 cm in diameter, with polymorphic foci around and in S6 of the right lung, with a wide broncho-vascular "path" to the root of the lung.

Blood test - HB - 130 g / l, Er - 4.3 × 10 ¹² / l, L - 4.8 × 10 ⁹ / l, E - 2, P - 15, C - 52, L - 27, M - 4, ESR - 31 mm / hour.

Sputum smear analysis by direct bacterioscopy - CMC (acid-resistant mycobacteria) were found (4-6 in the field of view). Sputum culture gave rise to 2 colonies of the Office (Mycobacterium tuberculosis). Mantoux test with 2 TE - 4 mm.

Immunogram - CD4 - 12.9% (176 cells / ml), CD8 - 65.5% (927 cells / ml), IRI (immunoregulatory index) - 0.18. Viral load - 506902 copies / ml.

The patient was prescribed treatment according to the claimed method: anti-tuberculosis therapy according to the intensive phase 1 of the standard treatment regimen - streptomycin 1 g, isoniazid 0.6 g, rifampicin 0.6 g, pyrazinamide 1.5 g, multivitamins, vitamin B6 and, at the same time, to treatment Wobenzym was added 3 tablets 3 times a day 30 minutes before meals daily, for the entire course of treatment and daily percutaneous electroneurostimulation of points GI 4, TR 5, J 19, R 27, T 14, V 13, V 17, V 18, T 7, 2 minutes each, for a total duration of 30 minutes, in a comfortable energy mode of frequencies oh 77 Hz, for 30 days.

Data of control examination after 4 months:

R-grams and T-grams - in the upper lobe of the right lung pneumofibrosis, scattered medium density, small foci with clear contours, in S6 - pneumosclerosis.

Blood test - HB - 149 g / l. Er - 3.9 × 10 ¹² / l, L - 5.0 × l0 ⁹ / l, E - 3, P - 5, C - 63, L - 25, M - 4, ESR - 7 mm.

Sputum smear analysis by bacterioscopy - no CMC found. Inoculation of sputum at the office gave a negative result. Immunogram - CD4 - 26.2% (408 cells / ml), CD8 - 57.7% (899 cells / ml), IRI - 0.45. Viral load - 667 copies / ml.

As a result of treatment according to the claimed method, a positive trend was achieved. The patient's condition improved, the infiltration resolved, the decay cavity was closed, abacillation was achieved, during the treatment he gained 4.5 kg in weight, catarrhal phenomena were not heard. Immune indicators improved - the level of CD4 lymphocytes increased and the level of CD8 lymphocytes decreased, as a result of which the IRI increased. An improvement in cellular immunity has led to a decrease in viral load. In satisfactory condition, the patient was discharged for outpatient treatment. The duration of inpatient treatment was 142 bed days.

Example 2: patient M., 35 years old, was admitted for inpatient treatment to the Rostov branch of the State Health Institution “Tuberculosis Clinical Dispensary” in the Rostov Region for infiltrative tuberculosis of the lower lobe of the right lung in the phase of decay and seeding, MBT (Mycobacterium tuberculosis) +. From the anamnesis it is known that the patient was diagnosed with HIV infection, at the time of admission to the department, the 4B stage was established. The patient's condition at admission is relatively satisfactory, the food is somewhat moderate. Auscultatory in the lungs, vesicular breathing was heard, without catarrhal phenomena. NPV - 22 in 1 minute. HELL - 125/75 mm Hg State of emergency - 80 in 1 minute.

Survey data at admission:

R-grams and T-grams - in the lower lobe of the right lung, intense heterogeneous, focal lung tissue infiltration of about 7.5 × 8.0 cm in size with a decay cavity up to 4.5 × 2.5 cm, with a wide broncho-vascular "path "to the root of the lung.

Blood test - HB - 103 g / l, Er - 3.6 × 10 ¹² / l, L - 7.9 × 10 ⁹ / l, E - 10, P - 10, C - 51, L - 22, M - 7, ESR - 20 mm / hour.

Sputum smear analysis by direct bacterioscopy - CMC found (2-4 in the field of view).

Sputum culture gave rise to 5 colonies of the Office.

Mantoux test with 2 TE - 4 mm.

Immunogram - CD4 - 19.5% (182 cells / ml), CD8 - 41.9% (376 cells / ml), IRI - 0.5. Viral load - 13300 copies / ml.

The patient was prescribed treatment according to the claimed method: anti-tuberculosis therapy according to the intensive phase 1 of the standard therapy regimen - streptomycin 1 g, isoniazid 0.6 g, rifampicin 0.6 g, pyrazinamide 1.5 g, multivitamins, vitamin B6 and, at the same time, to treatment Wobenzym was added 3 tablets 3 times a day 30 minutes before meals daily, for the entire course of treatment and daily percutaneous electroneurostimulation of points GI 4, TR 5, J 19, R 27, T 14, V 13, V 17, V 18, T 7, 2 minutes each, for a total duration of 30 minutes, in a comfortable energy mode, the frequency th 77 Hz, for 30 days.

Data of control examination after 4 months:

R-grams and T-grams - in the lower lobe of the right lung pneumofibrosis, foci of medium size with clear contours, medium density. Blood test - HB - 141 g / l, Er - 4.6 × 10 ¹² / l, L - 5.9 × 10 ⁹ / l, E - 1, P - 6, C - 62, L - 24, M - 7, ESR - 14 mm.

Sputum smear analysis by bacterioscopy - no CMC found. Inoculation of sputum at the office gave a negative result. Immunogram - CD4 - 40.2% (514 cells / ml), CD8 - 39.0% (515 cells / ml), IRI - 1.0. Viral load - less than 400 copies / ml.

As a result of treatment according to the claimed method, a positive trend was achieved. The patient's condition improved, the infiltration resolved, the decay cavity was closed, abacillation was achieved. Immune indicators improved - the level of CD4 lymphocytes increased and the level of CD8 lymphocytes decreased, as a result of which the IRI increased. An improvement in cellular immunity has led to a decrease in viral load. In satisfactory condition, the patient was discharged for outpatient treatment. The duration of inpatient treatment was 148 bed days.

Under our supervision there were 30 patients with pulmonary tuberculosis with HIV infection. Of these, 15 people received anti-tuberculosis therapy according to standard regimens (control group). The second group consisted of 15 people (main group). In this group of patients, wobenzym 3 tablets 3 times a day 30 minutes before meals was included in the course of treatment of tuberculosis together with anti-tuberculosis therapy from the first day, for the entire course of treatment and daily percutaneous electroneurostimulation of points GI 4, TR 5, J 19, R 27, T 14, V 13, V 17, V 18, T 7, 2 minutes each, for a total duration of 30 minutes, in a comfortable energy mode with a frequency of 77 Hz, for 30 days. Comparative treatment results are presented in tables 1-3.

Table 1 The dynamics of the clinical manifestations of pulmonary tuberculosis in HIV-infected patients when Wobenzym and percutaneous electroneurostimulation are included in the standard therapy regimen Clinical manifestations The main group (n = 15) abs. /% Comparison group (n = 15) abs. /% before treatment after treatment before treatment after treatment Weakness 13 people / 86.7% 1 people / 6.7% 12 people / 80.0% 7 people / 46.7% Rise t ° 11 people / 73.3% 1 people / 6.7% 10 people / 66.7% 6 people / 40.0% Mass deficit 11 people / 73.3% 3 people / 20.0% 11 people / 73.3% 7 people / 46.7% Cough 10 people / 66.7% 2 people / 13.3% 9 people / 60.0% 6 people / 40.0% Sputum 9 people / 60.0% 1 people / 6.7% 8 people / 53.3% 4 people / 26.7% Dyspnea 9 people / 60.0% 2 people / 13.3% 9 people / 60.0% 4 people / 26.7%

As can be seen from table 1, in most of the patients of the main group, after 4 months of treatment carried out in accordance with the claimed method, the clinical manifestations of pulmonary tuberculosis disappeared, while in the majority of patients in the comparison group, the clinical symptoms of tuberculosis persisted.

table 2 The effectiveness of treatment of tuberculosis in HIV-infected patients when Wobenzym and percutaneous electroneurostimulation are included in the standard therapy regimen Indicators The main group (n = 15) abs. /% Control group (n = 15) abs. /% Decay cavity closure 7 pax - 46.7% 3 pax - 20.0% Abacillation 8 pax - 53.3% 4 pax - 26.7% Resorption of infiltration 7 pax - 46.7% 4 pax - 26.7% Average bed day 146 198

As can be seen from table 2, as a result of treatment carried out in accordance with the claimed method, in the main group revealed an increase in the effectiveness of treatment: closing of cavities higher by 2.3 times, abacillation by 2 times, resorption of lung tissue infiltration by 2.3 times, reduction the terms of inpatient treatment is 1.35 times.

Table 3 Dynamics of immune parameters in patients with pulmonary tuberculosis of HIV-infected patients when wobenzym and percutaneous electroneurostimulation are included in the standard therapy regimen Indicators The main group (n = 15) abs. /% Comparison group (n = 15) abs. /% before treatment after treatment before treatment after treatment CD4 (abs.) 354.2 ± 26.4 481.1 ± 21.4 356.8 ± 23.7 354.7 ± 22.9 CD4 (%) 21.9 ± 0.6 31.1 ± 0.4 22.7 ± 0.8 22.7 ± 0.9 CD8 (abs.) 836.1 ± 37.2 628.4 ± 29.8 834.7 ± 38.1 836.8 ± 32.6 CD8 (%) 57.6 ± 1.3 44.7 ± 1.7 56.9 ± 1.2 57.1 ± 1.4 IRI 0.38 ± 0.6 0.70 ± 0.4 0.41 ± 0.8 0.40 ± 0.5 CD20 (%) 5.1 ± 0.9 7.8 ± 0.8 5.4 ± 0.7 5.6 ± 0.4 IgA (g / l) 5.98 ± 0.13 4.87 ± 0.16 6.01 ± 0.14 5.98 ± 0.17 IgM (g / l) 2.67 ± 0.17 2.12 ± 0.18 2.74 ± 0.18 2.71 ± 0.17 IgG (g / l) 30.1 ± 0.16 23.4 ± 0.12 31.0 ± 0.17 30.8 ± 0.15 CEC (%) 129.4 ± 2.1 112.0 ± 1.9 128.8 ± 1.9 126.7 ± 1.6

As can be seen from table 3, the immune group improved in patients of the main group - the level of CD4 lymphocytes increased and the level of CD8 lymphocytes decreased, as a result of which increased IRI, in addition, the indicators of humoral immunity improved, the number of circulating immune complexes decreased. In patients of the comparison group, there were no significant changes in the indicators of cellular and humoral immunity.

Thus, in comparison with anti-tuberculosis therapy according to standard regimes, the proposed method for the treatment of pulmonary tuberculosis in HIV-infected patients can improve the effectiveness of treatment by improving the closure of decay cavities, resorption of infiltrative changes in the lungs, and abacillation; accelerates the disappearance of the clinical manifestations of the disease, improves the general condition of patients and makes it possible to shorten the length of their stay in the hospital, and also improves immune parameters.

Claims (1)

A method of treating pulmonary tuberculosis in patients with HIV infection, which provides for anti-tuberculosis therapy according to standard regimes, characterized in that in addition to the treatment, from the first day of treatment, they include wobenzym 3 tablets 3 times a day 30 minutes before meals daily for the entire course of treatment and daily percutaneous electroneurostimulation of points GI4, TR5, J19, R27, T14, V13, V17, V18, T7, 2 minutes each, for a total duration of 30 minutes, in a comfortable energy mode with a frequency of 77 Hz, for 30 days.