Social diseases tuberculosis hepatitis to hepatitis c. Provisions for defense
Violations of the function and structure of the liver in patients with tuberculosis may be a consequence of the influence of tuberculosis intoxication, hypoxemia, taking anti-tuberculosis drugs, concomitant diseases, tuberculosis lesions of the hepatobiliary system.
The influence of tuberculosis intoxication affects the enzymatic, protein-synthetic, coagulation, excretory functions liver, causes a decrease in volumetric blood flow in the organ and a slowdown in the rate of elimination of drugs. Common forms of tuberculosis may be accompanied by hepato- and splenomegaly. With general amyloidosis developing against the background of tuberculosis, liver damage is noted in 70-85% of cases.
At the cellular level, hypoxia leads to the switching of the respiratory chain to a shorter and more energetically favorable oxidation pathway. succinic acid, inhibition of the monooxidase system, which leads to damage to the structure of the endoplasmic reticulum and disruption of cellular transport.
The sequence of loss of liver function during hypoxia has been established: protein synthesis; the formation of pigments; the formation of prothrombin; synthesis of carbohydrates; excretion; urea formation; fibrinogen formation; esterification of cholesterol; enzymatic function. First of all, the excretory function suffers; absorption is broken only when respiratory failure III degree. There is also an inverse relationship: the addition of liver pathology to lung disease exacerbates the violation of ventilation and gas exchange, which is caused by damage to the cells of the reticuloendothelial, cardiovascular systems, dysfunction of hepatocytes.
Dissertation abstractin Medicine on Pulmonary Tuberculosis in Combination with Chronic Viral Hepatitis: Diagnosis, Treatment, Prognosis
As a manuscript
PETRENKO Tatiana Igorevna
PULMONARY TUBERCULOSIS IN COMBINATION WITH CHRONIC VIRAL HEPATITIS: DIAGNOSIS, TREATMENT, PROGNOSIS
14.00.26 - phthisiology 14.00.10 - infectious diseases
Novosibirsk - 2008
The work was carried out at the Novosibirsk Research Institute of Tuberculosis of the Federal Agency for Health and Social Development
Scientific consultants:
doctor of medical sciences, professor Krasnov Vladimir Aleksandrovich doctor of medical sciences, professor Tolokonskaya Natalya Petrovna
Official opponents:
doctor of medical sciences, professor Kononenko Vladimir Grigorievich
Doctor of Medical Sciences, Professor Chuikova Kira Igorevna Doctor of Medical Sciences, Professor Kopylova Inna Fedorovna
Lead organization: St. Petersburg Research Institute of Phthisiopulmonology of the Federal Agency for Health and Social Development
The defense will take place "years at /¿ ^ hours at a meeting of the Dissertation-
Council of the D 062^01 at the Novosibirsk State Medical University of the Federal Agency for Health and Social Development at the address: 630091, Novosibirsk, Krasny Prospekt, 52.
The dissertation can be found in the library of the Novosibirsk State medical university
Scientific Secretary of the Dissertation Council, ___
Candidate of Medical Sciences, Associate Professor N. G. Paturina
GENERAL DESCRIPTION OF WORK
The urgency of the problem. Pulmonary tuberculosis (TJI) is one of the most important modern medical and social problems due to the wide prevalence, the continuing trend of increasing the number of patients, their high disability and mortality, disabilities and toxicity of anti-tuberculosis therapy (Krasnov V. A. et al., 2003; Levashev Yu. N., 2003; Shilova M. V., 2005; Mishin V. Yu., 2007). In recent years, an increase in the incidence of co-infections involving various viruses. The development of an infectious disease is determined by a variety of factors: the impact of xenobiotics with the failure of detoxification mechanisms, disturbance of the internal environment of the body and the immune system, depletion of compensation reserves in persons with comorbidity (Tolokonskaya N.P. et al., 2007). Changes in homeostasis, the nature of metabolic and immune reactions in conditions of persistent viral infections give rise to new quality characteristics tuberculosis.
In the coming century, tuberculosis, viral hepatitis B and C are recognized as the leading pathology (WHO, 2002). The question of the mutual influence of two infections - TJI and chronic viral hepatitis(CG) is of great interest because of the high frequency of their combination (Elkin A. V. et al., 2005) and in connection with the leading role of the liver in the immune response, in detoxification and metabolism of anti-tuberculosis drugs (Mishin V. Yu., 2007 ).
Inhibition of the liver monooxygenase system (MOS) leads to an increase in the frequency of toxic reactions to drugs, the inactivation of which is carried out by the liver (Mayansky D.N., Ursov I.G., 1997; Pospelova T.I., Nechunaeva I.N., 2004) . One of the most informative indicators of MOS activity is the antipyrine test, which is considered as reflecting the "oxidative metabolism of liver drugs" (Gurley B. J. et al., 1997), and as a "general metabolic test" (Matzke G. R. et al., 2000) . Despite a significant number of works devoted to the metabolism of antipyrine during various diseases, only a few evaluate the activity of MOS in patients with TJI (Hamide A. et al., 1990), the dependence of the state of MOS on the methods and frequency of taking anti-tuberculosis drugs has not been determined.
Traditional multi-month daily bacteriostatic therapy of tuberculosis often causes side (especially hepatotoxic) reactions in patients, a drug disease, and can cause the patient's death (Kolpakova T. A., 2002; Decocq G. et al., 1996; Ungo J. R. et al. ., 1998). Due to the growth of drug-resistant forms of TJI, WHO experts recommend prescribing 6-8 anti-tuberculosis drugs (ATPs) daily without taking into account concomitant pathology and MOS activity. Such treatment causes the appearance of adverse reactions to the main anti-TB drugs in 17% of cases (Mishin V. Yu. et al., 2003), and to 2nd line drugs - in 73% (Chukanov V. I. et al., 2004). The development of adverse reactions is limited
improves the possibilities of chemotherapy and reduces the effectiveness of the treatment of patients with TJI according to such criteria as the timing of the cessation of bacterial excretion and closure of caverns (Mishin V. Yu., 2007).
Since the 1970s, the Novosibirsk Research Institute of Tuberculosis has been developing and implementing bactericidal intravenous chemotherapy for patients with TJI in an intermittent mode from the first days of treatment (Ursov I. G. et al., 1979). The experiment showed that intravenous treatment 2 and 3 times a week, compared with daily oral or intravenous administration of anti-TB drugs, significantly reduces the severity of structural and metabolic disorders in the liver (Kurunov Yu. N. et al., 1982). In a clinic setting intravenous treatment 2 or 3 times a week is highly effective, significantly reduces the number of adverse reactions (Borovinskaya T. A., 1983, Kononenko V. G., 1998). However, the introduction of this chemotherapy technique into the widespread practice of anti-tuberculosis institutions is difficult due to order No. 109 of the Ministry of Health of the Russian Federation of March 21, 2003, which regulates the appointment of 4 or more anti-TB drugs orally daily for 2 or more months. The rationale is the generally accepted opinion that the discontinuity of anti-TB therapy leads to the development of secondary drug resistance (SDR) of the pathogen. But this has not been proven in the case of prescribing intravenous anti-TB drugs 2 or 3 times a week, when the concentrations of drugs in the blood are several times higher than their minimum inhibitory concentration, and the treatment is controlled.
Etiotropic chemotherapy alone, without affecting the mechanisms of the pathological process, often does not allow achieving good results treatment. Accumulated convincing evidence of immunosuppression in patients with destructive forms TJI (Vasilyeva G. Yu., 2004), chronic hepatitis B and C (Zmyzgova A. V., 2002). Negative changes in immunity in both tuberculosis and hepatitis are manifested in a decrease in the number of T-cells, a change in their subpopulation structure, in the proliferative nature of the response of T-lymphocytes to mitogens, in violation of the functional activity of monocytes, and an imbalance in the cytokine system (Royt A. and et al., 2000; Voronkova O. V. et al., 2007; Lai S. K. et al., 1997). The presence of immunosuppression and the contingency of its severity with the severity of concomitant infectious pathology (pulmonary tuberculosis and viral hepatitis) dictates the need to search for effective means immunocorrection as important component therapy. Currently one of promising directions biological therapy V clinical medicine is the use of cytokines such as interferon-a. Its action as an initiator of a balanced production of pro-inflammatory and anti-inflammatory cytokines has been shown earlier in various types infectious pathology (Rakhmanova A. G. et al., 1998; Malinovskaya V. V., 1999; Varfolomeeva S. R. et al., 2003; Zein N. N., 1998). It is required to develop a universal therapy aimed at self-regulation of the body, which has a signal character, which is achieved by choosing doses.
drugs, as reduced as possible, and methods of administration (Kolpakov M.A., 2001; Tolokonskaya N.P. et al., 2007). These arguments served to plan the purpose and objectives of this study, which is devoted to important issues of diagnosis, treatment and prognosis in comorbid infectious pathology.
Goal of the work. Based on the study of diagnostic features, patterns of course, comparison of anti-tuberculosis treatment regimens and determination of factors affecting the prognosis, develop a therapeutic approach for managing patients with concomitant infectious pathology- pulmonary tuberculosis and chronic hepatitis B and / or C.
Research objectives:
1. To determine the frequency of detection and the range of diagnostic markers of HBV and HCV infection in patients of TB hospitals with different terms course of pulmonary tuberculosis.
2. To identify medical and social factors associated with an unfavorable course of pulmonary tuberculosis (in patients with chronic viral hepatitis compared with patients without hepatitis).
3. Determine the relationship between the morphological activity of pathological processes in the liver and immunological characteristics and response to anti-tuberculosis therapy in patients with combined infectious pathology.
4. To assess the state of the liver monooxygenase system in patients with newly diagnosed pulmonary tuberculosis during intravenous intermittent treatment in comparison with daily traditional anti-tuberculosis therapy.
5. To study the frequency, timing of development and spectrum of secondary drug resistance of Mycobacterium tuberculosis in newly diagnosed patients with pulmonary tuberculosis who received intravenous intermittent chemotherapy.
6. To analyze the results of treatment of pulmonary tuberculosis in patients with mono- and mixed infections, taking into account different regimens of therapy (intravenous intermittent and daily traditional).
7. To develop an effective therapeutic tactic for inpatient management of patients with pulmonary tuberculosis in combination with chronic viral hepatitis with the inclusion of reaferon in anti-tuberculosis therapy.
8. To evaluate the effect of interferon therapy on the characteristics of tissue reactions in patients with pulmonary tuberculosis with concomitant chronic hepatitis B and C.
Scientific novelty. For the first time, the patterns of the patient's response to the simultaneous damage of several systems of the macroorganism by various infectious agents were studied, the influence of pathological processes of different etiologies on each other and on the success of treatment was studied.
each of them.
For the first time, a marker profile of chronic blood-borne hepatitis was determined in patients with tuberculosis hospitals with different periods of the course of LT. It has been shown that newly diagnosed pulmonary tuberculosis is associated with an increased relative risk of HBV infection, and long-term current, including chronic TB - HCV - and HCV + HBV infection.
Factors associated with the detection of chronic viral hepatitis in patients with TL have been established. The clinical features of the course of mixed infection, as well as immunological, morphological, biochemical parameters that adversely affect the prognosis of pulmonary tuberculosis, were revealed. It is shown that the presence of combined infectious pathology negatively affects the results of treatment of patients with newly diagnosed pulmonary tuberculosis.
It has been established that for forecasting and monitoring toxic complications chemotherapy, to determine the rate of metabolic processes in the liver of a patient with pulmonary tuberculosis, the optimal research method is an antipyrine test that is easy to interpret, simple to perform, atraumatic for the patient (Patent for the invention "Method for determining antipyrine in saliva" No. 2004127706/15 dated 16.09.2004).
It has been shown for the first time that the activity of the monooxygenase system of the liver in patients with pulmonary tuberculosis during daily treatment with anti-tuberculosis drugs decreases in comparison with patients who received intravenous intermittent chemotherapy, which indicates a more aggressive nature of daily chemotherapy for LT in relation to metabolic function liver.
It has been established that for patients with pulmonary tuberculosis with concomitant chronic hepatitis B and C, a highly effective method of treatment that prevents the occurrence of toxic reactions is preferable - intravenous intermittent chemotherapy 2 times a week.
For the first time, the incidence of secondary drug resistance in patients treated with intravenous intermittent chemotherapy was studied in comparison with the daily oral treatment group. It was found that the incidence of secondary LU in the groups of patients was the same, and multiple LU with intermittent treatment developed less frequently. During intravenous intermittent chemotherapy, secondary LU appeared more slowly than with intravenous intermittent chemotherapy. daily intake chemotherapy drugs, on average 3 months after the start of chemotherapy.
An indicator of the "dose density" of anti-tuberculosis drugs was developed and applied in order to objectively divide patients into groups of daily and intermittent treatment and impartially evaluate the results of TB treatment in them. This indicator made it possible to identify an intermediate group of "problem" patients, the regularity of the drug regimen in which, for various reasons, is impaired, and to analyze
they have unfavorable prognostic factors for the course of pulmonary tuberculosis.
For the first time for the treatment of patients with pulmonary tuberculosis with concomitant chronic hepatitis B and C, reaferon (interferon) was used, administered at a dose of 3 million IU rectally drip on the days of intravenous intermittent anti-tuberculosis therapy (Patent for invention No. 2002131208/14 dated November 20, 2002). It was shown that in the group of patients receiving reaferon, there were more patients who achieved the cessation of bacterial excretion and closure of the cavity(s) of decay into therapeutic stage, and in more early dates than in the comparison group. It was established that combined treatment with reaferon in combination with intravenous intermittent chemotherapy 2 times a week led to a decrease in the recovery time for hemogram parameters, an increase in the number of blood lymphocytes and their subclasses, and a decrease in the manifestations of cytolysis and cholestasis.
For the first time, morphological signs of the anti-inflammatory action of reaferon were obtained (when it was included in the therapy of patients with TL) both directly in the area of specific inflammation and in the surrounding lung tissues.
Theoretical and practical significance. The results of the study allow us to expand the existing ideas about the interaction of mixed infection (TL + CG) in the patient's body, about the effect of hepatotropic viruses on the course, treatment and prognosis of pulmonary tuberculosis.
A system for examining patients with pulmonary tuberculosis has been developed, which makes it possible to identify chronic viral hepatitis in them depending on their etiology, biochemical and morphological activity, and, taking this into account, to plan therapeutic measures.
The revealed features of the clinical course of a combined infection, characterized by a weak severity of the symptoms of each of the diseases separately, indicating insufficient activity of the metabolic and immune reactions of the macroorganism, determine the search for additional diagnostic and therapeutic measures aimed at the complete clinical cure of the patient from pulmonary tuberculosis in the conditions of persistence of viruses.
To predict the course and outcomes of pulmonary tuberculosis and chronic hepatitis B and C, as well as adverse reactions in patients with TB, a very simple, non-invasive, easy-to-interpret antipyrine test is proposed, which is carried out in dynamics during anti-tuberculosis therapy.
In order to objectively divide patients into groups according to the treatment regimen and evaluate the effectiveness of chemotherapy, an indicator of the "dose density" of anti-tuberculosis drugs has been proposed.
The use of the antipyrine test and the “dose density” indicator, along with traditional clinical and laboratory research methods, made it possible to demonstrate that intravenous intermittent
Chemotherapy is preferred in TL patients with concomitant CG as an effective treatment method that prevents toxic reactions in conditions of a liver compromised by the virus.
The obtained clinical, biochemical, immunological and morphological data indicate the high therapeutic efficacy of reaferon in patients with TL with concomitant CG and allow us to recommend it for practical use.
The developed tactics of managing patients with mixed infection can improve the verification of the diagnosis of chronic viral hepatitis during TB practice by 89%, to increase the effectiveness of the treatment of pulmonary tuberculosis: to reduce the time for the cessation of bacterial excretion by 1.8 months, the closure of cavities - by 1.4 months.
Provisions for defense:
1. A comprehensive immuno-biochemical examination of patients in TB hospitals in Novosibirsk makes it possible to identify diagnostic markers of HBV and HCV infection in 32-48% of cases. In patients with long-term pulmonary tuberculosis, the relative risks of HCV- and HCV + HBV infection are increased, and in patients with newly diagnosed tuberculosis - HBV infection.
2. In socially maladjusted patients with pulmonary tuberculosis, the relative risk of detecting chronic viral hepatitis is increased. The combination of pulmonary tuberculosis and chronic hepatitis B and C is characterized by: predominantly mild symptoms of tuberculosis intoxication with no temperature reaction; low-symptom course of hepatitis with elevated levels of ALT, AST and GGTP; a 2-fold decrease in the probability of early (up to 3 months) cessation of bacterial excretion with a relative risk of developing drug resistance to ethambutol and kanamycin; a 2.3-fold decrease in the probability of a favorable x-ray picture upon discharge from the hospital. In the absence of obvious clinical signs of comorbidity (TL + CG), the role of additional methods examinations (laboratory, morphological), which are important to take into account in the aggregate to develop optimal approaches to treatment and prognosis.
3. Factors of an unfavorable course of pulmonary tuberculosis in patients with comorbidities are: a) the presence of CHC or CHC in comparison with CHB; b) mild liver fibrosis compared to moderate or severe; V) low degree morphological activity of hepatitis in comparison with moderate or high; d) normal levels of ALT and ACT compared with elevated; e) severe neutrophilia in the sinusoids and lipofuscinosis of hepatocytes in comparison with the absence or mild severity of these parameters; f) the level of all lymphocytes is less than 1000 per µl and the level of CD4+ is less than 400 cells per µl in comparison with their high level.
4. Intravenous intermittent chemotherapy has a number of advantages over daily chemotherapy: a) more frequent closure of decay cavities, b) the absence of suppression of the monooxygenase system of the liver and the rare development of toxic complications, c) the absence of an increase in the frequency of secondary LU, and in cases of its occurrence, development into later ones. terms.
5. The results of the immunomodulatory action of reaferon in combination with intravenous intermittent (2 times a week) chemotherapy in patients with tuberculosis with concomitant chronic viral hepatitis are: a) shortening the time for cessation of bacterio-excretion and closing of decay cavities, b) a decrease in signs of cytolysis and cholestasis, c ) decrease morphological manifestations specific and nonspecific inflammation in lung tissue.
Approbation of work. Thesis materials were reported and discussed at: 7th Russian Congress of TB Physicians "Tuberculosis Today" (Moscow, 2003), at the International Congress of the European Respiratory Society (Glasgow, 2004), at the international conference "Development international cooperation in the field of study infectious diseases» (Novosibirsk, 2004), on the internal scientific and practical conference NNIIT (Novosibirsk, 2005), at the meeting of the Scientific Council of NNIIT (June 24, 2005), at the international congress of the European Respiratory Society (Copenhagen, 2005), at the regional society of phthisiatricians (Novosibirsk, May 31, 2006), at the international congress of the European Respiratory Society (Munich, 2006), at the II Russian-German conference "Tuberculosis, AIDS, viral hepatitis" (Tomsk, 2007), at the anniversary interregional scientific and practical conference "Modern healthcare: problems and prospects" (Novosibirsk, 2007) .
Implementation of the research results. The dissertation materials, its conclusions and recommendations are used in educational process the Department of Tuberculosis of the Faculty of Advanced Studies and the Department of Pathological Anatomy of the Novosibirsk State Medical University. The developed tactics for managing patients with mixed infection is implemented in clinical practice clinics Novosibirsk Research Institute tuberculosis, St. Petersburg Research Institute of Phthisiopulmonology, Ekaterinburg Research Institute of Phthisiopulmonology, Specialized Tuberculosis Hospital No. 3 (Novosibirsk).
The volume and structure of the dissertation. The work consists of an introduction, 4 chapters, including an analytical review of the literature, a description of research methods and characteristics of patients, the results of their own research and a discussion of the results, conclusions, practical
Author's personal contribution. The work was performed on the basis of the clinic of the Novosibirsk Research Institute of Tuberculosis (Director - Professor V.A. Krasnov), at the Department of Pathological Anatomy of the Novosibirsk State Medical University (Head of the Department - Academician of the Russian Academy of Medical Sciences, Professor V.A. Shkurupiy), at the Institute of Clinical Immunology of the Siberian Branch of the Russian Academy of Medical Sciences (Director - Academician of the Russian Academy of Medical Sciences, Professor V.A. Kozlov), Children's Clinical Hospital No. 3 in Novosibirsk (Chief Physician - Candidate of Medical Sciences N.A. Nikiforova), Tuberculosis Hospital No. 3 in Novosibirsk (Chief Physician - E.I. Vitenkov ).
The author independently collected, statistically processed and analyzed all the data obtained. Conducted clinical trial approved by the local ethics committee of the Novosibirsk Research Institute of Tuberculosis of Rosmedtekhnologii.
The author expresses his sincere gratitude to his colleagues in joint research: Associate Professor of the Department of Pathological Anatomy, NSMU, MD. P.N. Filimonov, head Laboratory of Clinical Immunology, IKI SB RAMS, MD, prof. B.C. Kozhevnikov, Researcher, Laboratory of Immunology, NNIIT, Ph.D. V.V. Romanov, doctors of the clinical and biochemical laboratory of NNIIT, Ph.D. Yu.M. Kharlamova and N.S. Kizilova, head otd. DIKB No. 3 Ph.D. A.C. Pozdnyakov, employees of NNIIT and Tuberculosis Hospital No. 3 in Novosibirsk. Special thanks-
Kurunov) and scientific consultants - d.m.s., prof. V.A. Krasnov, Doctor of Medical Sciences, Professor N.P. Tolokonskaya.
MATERIALS AND RESEARCH METHODS
Characteristics of patients included in the study, the concept of the "dose density" indicator.
A total of 566 patients with various forms of pulmonary tuberculosis were examined in the NNIIT clinic and in the tuberculosis hospital No. 3 in Novosibirsk in 2000-2007.
Figure 1 schematically shows the stages of the study.
Research structure. At the 1st stage of the study, the solution of the problem of coinfection caused by the causative agents of tuberculosis and viral hepatitis B and / or C. The frequency of detection and the spectrum of diagnostic markers of NVU- and NCV-infection were determined in 188 patients who were consecutively admitted to NNIIT in 2002-2003 . and in 154 patients hospitalized in the Tuberculosis Hospital No. 3 in Novosibirsk in 2003-2004. with different periods of the course of pulmonary tuberculosis. Long-term ill TB included patients whose follow-up period in the TB service was 1 year or more.
Frequency of detection and with Varieties of CG markers l*342
Morphological and immunological characteristics of TP ♦ CG n=84
Effect of different treatment regimens on VLU
Therapeutic and diagnostic tactics of managing patients with TL+CHG
Optimal therapeutic n=134 tactics
Effectiveness of various treatment regimens
Figure 1. Scheme of the study
We studied the medical and social factors that cause an unfavorable course of pulmonary tuberculosis (in patients with chronic viral hepatitis compared with patients without hepatitis). 224 patients were examined and prospectively observed in the clinic of NNIIG, of which 95 patients did not have hepatitis (group 1), 129 patients had chronic hepatitis B and C (group 2): B (CHB) - in 58 patients , C (CHC) - in 29, B + C (CHC) - in 42. Patients with CHB were older (36.3 ± 12.2 years) than those with CHC (26.6 ± 5.6 years, p = 0.0003) and CHCV (29.7 ± 8.7 years, p = 0.005). ). The mean age of patients without hepatitis was 30.9 ± 11.2 years. Patients in group 1 were selected by random numbers. Exclusion criteria: focal and fibrous-cavernous tuberculosis, caseous pneumonia, primary forms of tuberculosis, generalized tuberculosis, age of patients less than 17 and more than 70 years.
At the 2nd stage of the study, in patients with combined infectious pathology, the relationship between the morphological activity of pathological processes in the liver and immunological characteristics and response to anti-tuberculosis therapy was assessed. During the first 2 weeks of hospitalization, 84 patients with pulmonary tuberculosis with concomitant chronic hepatitis B and C underwent a puncture liver biopsy. In these patients, relationships between clinical, biochemical, morphological and immunological parameters were determined. In addition, we compared the results of immunological examination and inpatient treatment of these patients and 49 patients with TJI who did not have hepatitis. The groups did not differ in sex, age, forms of the tuberculosis process.
At the 3rd stage of the study - the study of the reaction of a macro- and microorganism to various regimens of anti-tuberculosis therapy. The state of the monooxygenase system of the liver of patients with newly diagnosed LT during intravenous intermittent therapy was assessed in comparison with the daily traditional intake of anti-tuberculosis drugs. The antipyrine test was studied during the first 2 weeks
the stay in the clinic of the Research Institute of Tuberculosis and after 6 months in 47 patients of the intermittent treatment group (against the background of intravenous therapy 2 times a week) and in 52 newly diagnosed patients of the daily treatment group.
We determined the frequency and timing of development, the spectrum of secondary drug resistance (SDR) of Mycobacterium tuberculosis (MBT) in newly diagnosed patients with TJI (including those with concomitant chronic hepatitis) receiving intravenous intermittent chemotherapy. We analyzed the data of the drug sensitivity test of mycobacteria in 76 patients - bacterial excretors with newly diagnosed TJT, who were admitted for treatment at the clinic of the Novosibirsk Research Institute of Tuberculosis in 2004-2005. All these patients did not receive anti-tuberculosis therapy before admission to the hospital. The selection of patients in the groups of daily and intermittent treatment was carried out randomly. The follow-up period for patients was 5-14 months. Intravenous intermittent chemotherapy was prescribed from the first days of treatment to 38 patients (main group); daily intake of anti-TB drugs - 38 patients who made up the comparison group. There were 11 patients with CHB and/or CHC concomitant with tuberculosis in the main group, and 8 in the comparison group. The terms of observation of patients ranged from 5 to 14 months (during the entire time of stay in the hospital).
At the 4th stage of the study - analysis of the results of treatment of pulmonary tuberculosis in patients with mono- and mixed infection, taking into account different chemotherapy regimens (intravenous intermittent and daily traditional) and the development of optimal therapeutic tactics. Information about the clinical, biochemical, radiological, bacteriological, serological, biochemical, immunological, morphological dynamic examination of 224 patients in dynamics during the course of inpatient treatment was entered into the SPSS statistical table. Upon subsequent analysis of the applied treatment regimens, it turned out that not all patients were able to complete the anti-tuberculosis therapy regimen in the form in which it was prescribed. Thus, in some patients, the development of irreversible or severe adverse reactions to treatment was observed, which forced the abolition of anti-TB drugs for some time, followed by a gradual selection of drugs and doses. In a number of other patients, MBT drug resistance was detected during treatment, accompanied by clinical and radiological signs of disease progression, which forced the revision of treatment regimens and regimens. We divided the number of days each patient was treated with anti-TB drugs (number of doses) by the number of bed-days they spent in the clinic, and came up with a measure that we called “dose density”. This made it possible to single out a group of patients (X) from 224 patients who could not be attributed to either the intermittent group (2 times a week) or the daily treatment group.
Patients with a "dose density" of 0.22 to 0.3 were assigned to group A: 128 people (during the entire period of stay in the hospital they followed the treatment regimen 2 times a week); less than 0.22 and from 0.31 to 0.6 - to group X: 45 patients (the treatment regimen was changed for the reasons listed above); from 0.61 and more - to group B: 51 patients (taking drugs 5-7 times a week). Patients who did not complete the course of inpatient treatment (discharged early for violation of the regimen; their bed-day was from 8 days to 3 months) were excluded from the analysis of the results of anti-TB therapy.
To develop effective therapeutic tactics for inpatient management of patients with pulmonary tuberculosis with concomitant chronic hepatitis B and C, we evaluated the results of treatment with reaferon-EC as part of complex intravenous intermittent chemotherapy in 134 patients with TB, in 92 (68.7%) of them - in in combination with CG B and/or C. The selection of patients in the comparison groups was carried out according to the criteria of a prospective cohort study: 67 people received reaferon and made up group I, and 67 patients of group II did not receive reaferon. The course of treatment with reaferon was 6 months or more.
To identify signs of the influence of interferon therapy on the characteristics of tissue reactions in pulmonary tuberculosis, 34 patients with infiltrative LT in the decay phase were selected, who had previously undergone a preliminary 5-6-month course of PTP therapy in combination with reaferon, after which surgical resection treatment was performed. At the time of the operation, in 25 patients of this group, the pulmonary process was represented by tuberculomas, in 9 - by fibrous-cavernous tuberculosis. The comparison group consisted of 35 operated patients with similar changes in the lungs (tuberculomas - in 25 people, fibrous caverns - in 10 people), who were treated under the same conditions, but without reaferon. When selecting patients in the comparison group, we tried to match all parameters: gender, age, nature of the tuberculosis process at the time of surgical intervention etiology of chronic viral hepatitis.
The object of the study was the surgical material of the lungs. Pieces of tissue from the walls of caverns, capsules of foci and tuberculomas, macroscopically unchanged areas, were subjected to microscopic examination, the bronchus was examined at the place of its intersection along the edge of the resection. We used staining with hematoxylin and eosin, picrofuchsin according to Van Gieson in combination with fuchselin, staining according to Zshpo-Nelsen on MBT.
To objectify the morphological characteristics lung tissue in patients of the compared groups, histological preparations were studied without any information about the patient at that time. The main structural compartments of the lungs were assessed using the developed by us together with MD. P. N. Filimonov schemes of semi-quantitative morphometry:
¡.Encapsulated zones caseous necrosis(foci and tuberculomas)
a. Capsule maturity: mature - 0 (fibrocytes predominate, dense arrangement of collagen bundles without lymphocytic infiltration, lymphocytes only around the capsule in the form of rare small clusters), immature - 1 (fibroblasts predominate, collagen bundles are loose, edematous, the capsule is diffusely infiltrated with mononuclear cells)
b. Signs of a specific lesion of the capsule: no - 0, yes - 1 (areas of caseosis of the structures of the capsule)
c. Inflammatory tissue infiltration around the capsule: minimal productive - 0, pronounced productive - 1, exudative - 2
2. Lung tissue at a distance from the foci of specific inflammation
a. Signs of chronic bronchitis: none - 0, remission - 1 (focal mononuclear infiltration of the peribronchial tissue without signs of epitheliotropism), exacerbation - 2 (diffuse, often muff-like nature of the peribronchial infiltration, a significant admixture of plasma cells and neutrophilic granulocytes among the cells of the infiltrate, signs of damage to the bronchial epithelium, edema stroma)
b. Obstructive nature of bronchitis: no - 0, yes - 1 (presence of mucous and/or purulent exudate, desquamated epithelial cells)
c. Focal pneumonia: no - 0, yes - 1 (airless areas, exudate in the lumen of the alveoli, neutrophilic infiltration of the interalveolar septa)
(1. Interstitial-desquamative pneumonia (focal or diffuse thickening of the interalveolar septa due to infiltration by mononuclear cells, hyperplasia and desquamation of alveolar macrophages and type 2 alveolocytes into the lumen of the alveoli): no - 0, minimal - 1, moderate / severe - 2
3. Bronchial tuberculosis: no - 0, yes - 1 (any signs of caseification of the bronchial wall with damage to its epithelium)
4. Pneumofibrosis (excessive deposition of masses of collagen, proliferation of fibroblasts of varying degrees of maturity)
a. Perivascular and peribronchial: no or minimal - 0, moderate - 1, severe - 2
b. Interstitial (out of visible connection with vessels and bronchi): no - 0, minimal - 1, moderate / severe - 2.
Examination of patients with pulmonary tuberculosis. Information about all patients included in the study was entered into a special table. They covered passport data, anamnesis, complaints and objective signs of the disease, comorbidities, complications of the tuberculosis process, the results of laboratory and other research methods, the nature of the treatment and its results. dynamics clinical symptoms diseases were assessed on the basis of anamnesis data and the results of daily clinical examinations of the examined patients.
X-ray examination included a panoramic radiography of the chest in two projections, targeted tomography of the zone inflammatory response lung tissue, according to the indications, digital tomography and computed tomography of the chest organs were performed. X-ray control of the dynamics of the tuberculosis process was carried out monthly. Tuberculous process, covering 3 or more segments of the lungs, was considered “common”.
Bacteriological examination included sputum cultures for MBT and fluorescent microscopy, which were performed three times on admission and twice monthly during anti-tuberculosis therapy. In patients with bacterial excretion, the MBT drug sensitivity test was determined for all anti-tuberculosis drugs (1st and 2nd row) and this study was repeated every 2 months if bacterial excretion persisted during chemotherapy.
Such careful monitoring made it possible to identify primary drug resistance and ascertain the appearance of secondary drug resistance of MBT, to establish the moment of cessation of bacterial excretion, the persistence of sputum negativity, to judge the time of closing the decay cavities and radiological dynamics in the compared groups.
The scope of examination for the diagnosis of viral hepatitis.
Hepatitis in patients was detected during special survey which included anamnesis, complaints, physical examination, research biochemical analysis blood, ultrasonography bodies abdominal cavity, an enzyme immunoassay method that made it possible to detect markers of hepatitis B (HBsAg, aHBs, aHBcIgG, aHBcIgM, HBeAg, aHBelgG), hepatitis C (aHCV total, aHCVIgM, aHCVcorelgG, aHCVNS3IgG, aHCVNS4, aHCVNS5), hepatitis D (aHDV total), polymerases a chain reaction of blood and liver tissue taken during a puncture biopsy, a morphological study of liver biopsy specimens.
The frequent use of alcohol during the collection of anamnesis included indications for taking hard liquor once a week or more often.
Biochemical studies were carried out on a system automated analyzer Konelab 20, with a capacity of 200 photometric studies per hour. We used Konelab biochemical kits and control materials from Thermo Clinical Labsystems, Finland.
Dynamics of key indicators functional state liver was carried out according to the biochemical blood test, which was performed upon admission to the hospital, and then monthly. The levels of total, conjugated and free bilirubin, activity of liver marker enzymes (AJIT, ACT, GGTP, ALP), prothrombin index -PTI, fibrinogen, thymol test were assessed.
Patients with markers of hepatitis B and/or C underwent puncture liver biopsy, inflammation and sclerosis in histological preparations
evaluated according to R.G. Knodell (1981), V.V. Serov, L.O. Severgina (1996).
Percutaneous puncture biopsy of the liver was performed with a Menghini needle under anesthesia in the operating room. The puncture material was sent to the pathomorphological laboratory. Tissue fragments were fixed in 10% neutral formalin, dehydrated in ascending alcohols, and embedded in paraffin. In sections stained with hematoxylin and eosin and according to van Gieson, the activity of necroinflammatory changes was determined according to the principles of semi-quantitative assessment of R.G. Rnodell et al., according to the scheme of V.V. Serova, L.O. Severgina with the addition of such parameters as fatty degeneration of hepatocytes (0-3 points), the presence of neutrophilic granulocytes in sinusoids (0-3 points), pericellular (0-3 points), and pericentral fibrosis (0-3 points), apoptotic bodies are perisinusoidal (0-2 points), plasmacytic infiltration of the portal tracts (0-3 points).
We used an improved antipyrine test based on the method of V.V. Brodie et al. (1949) as modified by D. Davidsson, J. Mac Intyre (1956) (Invention Patent No. 2004127706/15 dated September 16, 2004).
Immunological research methods.
The immunological examination included the quantitative assessment of lymphocytes and their subclasses carrying CD3+, CD4+, CD8+, CD16+, CD19+ molecules using monoclonal antibodies labeled with fluorochromes (FITC, phycoerythrin, peridide-chlorophyll protein) produced by Sorbent, MedBioSpectr (Russia). ) and Becton Dickinson (USA). The functional activity of the monocyte-macrophage link was assessed by determining the granulocytes and monocytes that absorbed latex labeled with FITC, the expression of HLA-DR molecules (Sorbent, Russia) on monocytes; activated and spontaneous lucigenin-dependent chemiluminescence of neutrophils, the content of TNF-producing cells.
Cytometry was performed using the CellQuest program (Becton Dickinson, USA) on a FACSCallibur instrument (Becton Dickinson, USA). These methods were performed as described in the antibody manufacturer's instructions.
regimens of anti-tuberculosis therapy.
A group of patients with an intermittent treatment regimen received four anti-tuberculosis drugs (ATDs) twice a week: oral ethambutol at a rate of 20 mg/kg or pyrazinamide 25 mg/kg, after 1 hour - intramuscularly streptomycin or kanamycin at a dose of 16 mg/kg, and more after 1 hour - isoniazid 12 mg/kg intravenously, and then rifampicin 7.5 mg/kg. Followed a strict order medicines, taking into account the rate of creation of the maximum concentration of drugs in the lungs at different ways their introductions.
Daily chemotherapy was carried out in accordance with the regulations set forth in Order No. 109 dated March 21, 2003.
Against the background of chemotherapy for six or more months, the dynamics of the tuberculosis process was studied using the following criteria: the rate of cessation of bacterial excretion and closure of decay cavities.
Methodology complex treatment patients with pulmonary tuberculosis with concomitant chronic hepatitis, including intermittent therapy with anti-tuberculosis drugs and reaferon.
In order to increase the effectiveness of therapeutic management of patients with pulmonary tuberculosis with concomitant chronic hepatitis B and C, recombinant interferon-a - reaferon-EC (Vector-Medica, Novosibirsk, Russia) was used at a dose of 3 million IU of dry matter dissolved in 50 ml physiological saline rectally drip for 30 minutes after 15-20 minutes after intravenous administration chemotherapy drugs 2 times a week, on the days of anti-tuberculosis therapy.
On average, patients received reaferon for 6 months in parallel with intermittent anti-tuberculosis therapy (Patent for invention No. 2002131208/14 dated November 20, 2002).
Statistical research methods.
Statistical processing of the study results was carried out according to standard methods using Microsoft Excel 2000, Statistica 6.0 and SPSS 12.0 software. At the same time, such statistical indicators as the arithmetic mean, standard deviation, the standard error of the mean. Under the conditions of normal distribution (Kolmogorov-Smirnov test), the statistical significance of differences (p) was determined using Student's t test, %2 Pearson, Mann-Whitney u-test, Wilcoxon paired test. If in the 2x2 table at least one of the compared frequencies was less than 5, Fisher's exact test was used to obtain the value of the achieved significance level p.
Relative risk was calculated as the ratio of incidence among individuals exposed to and not exposed to risk factors. The odds ratio (OR) was defined as the ratio of the odds of an event in one group to the odds of an event in the other group. The statistical accuracy of the estimate of the observed effect size was expressed using 95% confidence interval(95% CI).
The probability of outcome (cessation of bacterioexcretion or closure of cavities) was assessed by the Kaplan-Meier (K-M) method and pairwise comparison using a logarithmic rank test. The data in the tables are presented as the arithmetic mean ± standard error of the mean. Differences were considered statistically significant at p< 0,05.
RESULTS AND DISCUSSION
The combination of pulmonary tuberculosis and chronic viral hepatitis B and/or C is topical issue medicine due to the frequent occurrence, the lack of developed tactics for the management and treatment of such patients, the lack of knowledge of the prognosis of the course and outcomes of pulmonary tuberculosis in patients with concomitant chronic hepatitis.
Studies by individual authors and their own observations indicate a high incidence of NVU- and HCV-infection among patients with pulmonary tuberculosis. The numbers of this detectable ™ vary significantly, which can be explained by differences in the epidemic situation (depending on the territory and time interval), the volume of methods used for diagnosing CG, as well as differences in the contingents of the examined patients.
So, Zaretsky B.V. (1997) and Kamelzhanova B.T. (2003) provide information about patients with newly diagnosed pulmonary tuberculosis. Leading them was NVU-infection.
When examining 188 patients with newly diagnosed pulmonary tuberculosis who were successively admitted to the NIIT in 2002-2003 ( infiltrative tuberculosis lungs - 165 people, disseminated pulmonary tuberculosis - 19, tuberculous pleurisy - 4) it was found that 60 people (31.9%) had positive result for one or more ELISA markers for HVD and HCV infections. They were much more likely to have NVU- and NVU + NVU infection than in the above studies (Table 1).
Table 1. The frequency of occurrence of various ELISA markers of HVU and HCV infection in patients with pulmonary tuberculosis according to different authors (in %)
Indicator Our results n=188 Data from Zaretsky B.V. (1997) n = 266 Data from Kamelzhanova B.T. (2003) n = 252
Markers of HBV infection 14.9% 43% 47.5%
Including only HBvA^ 4.2% 12.1% 5.1%
HCV infection markers 6.9% 2.0% 4.8%
Markers NVU + NSU 10.1% 5.4% no data
In 2003 - 2004 154 patients who were consecutively admitted to the Tuberculosis Hospital No. 3 of Novosibirsk were examined for markers of NVU- and NCV-infection. Of these, 74 patients (48%) were found to have markers
ry. Men were predominantly infected (65 patients - 87.8%) with exacerbation of chronic forms of TB, who were ill for a long time. Thus, exacerbation of the tuberculosis process in the form of disseminated tuberculosis was observed in 7 people (9.5%), infiltrative - in 15 (20.3%), fibrous-cavernous TB - in 19 (25.7%) , caseous pneumonia (as an outcome of fibrous-cavernous tuberculosis) - in 3 (4%), i.e. in total, there were 44 (59.5%) such long-term ill patients. For the first time identified patients with disseminated tuberculosis were 7 (9.5%), with infiltrative - 23 (31%). Proportion of patients with various options hepatitis were approximately the same (Figure 2).
Figure 2. Spectrum of detected markers of NVU- and NCV-infection in patients of tuberculosis hospital No. 3 in Novosibirsk (n = 74)
The following markers were identified: aHBcog1gM - in 1 (1.35%), HBsAg - in 8 (10.8%), aHBcog^O - in 48 (64.9%), HBeAg - in 1 (1.35%) %). - ty patients with aHCV-NV (44%) were found to have aHCV-NV, which indicates the possible reproductive activity of the HCV virus.
In the group of patients with long-term TB disease (n = 44), the proportion of patients with NVU infection (43.2%) and NVU + NVU (43.2%) turned out to be large, and the proportion of patients with NVU infection was 13.6% . In the group of patients with newly diagnosed TL (n = 30), the proportion of persons with NVU-infection prevailed (63.3%) than those with NVU (20%) and NVU + NVU (16.7%) (compared with long-term ill r = 0.0001, x2) - Thus, in virus-infected patients with long-term tuberculosis, in comparison with those newly diagnosed, the relative risks of having HCV infection are higher (2.2 times, 95% CI 1.8-2.5) , HCV + HVD (by 2.6 times, 95% CI 2.1-3), while the relative risk of HVD infection, on the contrary, decreases (by 4.6 times, 95% CI 3.7-5.6). This can be explained by the fact that patients with long-term TB are 4.3 times more likely to indicate having been in prison in the past (p = 0.006, %2). Also define
A significant role in this process may be played by the high frequency of integrative forms of HBV infection, which are difficult to diagnose.
Identification of factors indicating social exclusion of patients with pulmonary tuberculosis is associated with the presence of increased relative risks of detecting chronic viral hepatitis B and C:
no permanent job (p = 0.03);
Alcohol abuse (p = 0.009), smoking (p = 0.047), drug use (p = 0.0005);
Stay in places of deprivation of liberty in the past (p = 0.0003);
Weak adherence to anti-tuberculosis therapy (p = 0.01).
The absence of clinical symptoms of pulmonary tuberculosis was revealed in
33 (34.7%) of 95 patients of group 1 (with pulmonary tuberculosis) and 53 (41.1%) of 129 patients of group 2 (with chronic hepatitis B and C concomitant with tuberculosis) (p > 0.05, y2). That is, 38.4% of patients indicated the absence of any complaints. Pulmonary tuberculosis was detected when they underwent a fluorographic examination, most often when applying for a job.
Most often, patients of groups 1 and 2 with complaints were cough (62.9%) with sputum production - (50.4%), weakness (45.1%), sweating (41.1%), weight loss, subfebrile condition, shortness of breath during physical exertion. Less common were complaints of fever to febrile numbers, chest pain during breathing and coughing, loss of appetite. One of the most frequently reported complaints by patients was fever, an increase in body temperature from subfebrile to febrile numbers (50.9%), which prompted patients to seek medical attention. medical assistance. This complaint was significantly less common in patients with hepatitis: 58 out of 129 compared with 56 out of 95 (p = 0.04, %2).
Patients of groups 1 and 2 equally rarely presented gastrointestinal complaints at admission: 6 out of 95 in group 1 and 11 out of 129 patients in group 2 (p = 0.7, x2) - The most frequent complaints were nausea, heaviness and pain in the right hypochondrium, lack of appetite.
Assessment of physical data (dullness of percussion sound, altered breathing, wheezing over the lungs) at admission did not reveal significant differences in patients of the compared groups. No differences were found either general analysis blood in the compared groups, as well as the frequency of bacterial excretion, which was detected in group 1 in 74 (77.9%) of 95, and in the group of patients with TL combined with chronic hepatitis B and C - in 105 (81, 4%) of 129 patients (p = 0.4, %2).
Noteworthy is the fact of a 2.2 times higher risk of drug resistance to ethambutol (p< 0,05) и в 2,9 раза - к кана-мицину (р < 0,05) у пациентов с микст-инфекцией. Оказалось неприемлемым использовать эти весьма активные противотуберкулёзные препараты с наименьшим гепатотоксическим действием у больных с компрометированной вирусом печенью.
The presence of hepatitis 3 times increased the chances of elevated levels
ALT (p< 0,01), в 3,3 раза - ACT (р < 0,001) и в 4,6 раза - ГГТП (р < 0,0001) в начале противотуберкулёзной терапии. Морфологическая активность гепатита (по шкале Knodell R. G., 1981) прямо коррелировала с уровнями АЛТ (г = 0,49, р = 0,000003), ACT (г = 0,45, р = 0,00002) и ГГТП (г = 0,4, р = 0,00033).
Thus, in TL patients with concomitant CG, asymptomatic forms of chronic hepatitis B and/or C were more common (91.5%), which are characterized by the absence of any gastrointestinal symptoms, the absence or mild increase in ALT and ACT activity (in 1.25 -2.45 times). They did not observe jaundice during the entire stay in the hospital.
The latent course of chronic hepatitis often leads to underdiagnosis and underestimation of the role of liver damage in tuberculosis. It turned out that chronic hepatitis adversely affects the pulmonary process: the presence of viral hepatitis in patients with pulmonary tuberculosis 2 times reduced the likelihood of an early (up to 3 months) cessation of bacterial excretion and 2.3 times reduced the likelihood of a favorable x-ray picture upon discharge from the hospital.
Puncture liver biopsy was performed in 84 patients with newly diagnosed LT, who, upon admission to the NNIIT clinic, were found to have: chronic hepatitis B - 36 (42.9%), C - 23 (27.4%), B + C - 25 ( 29.8%. In the comparison group, there were 49 patients with TL without signs of hepatitis.
Discovered morphological features hepatitis in patients with pulmonary tuberculosis: more frequent detection of the reactive component of inflammation - polymorphonuclear leukocytes among the cells of the inflammatory infiltrate of the portal tracts and lobular parenchyma; lipofuscinosis, mainly pericentral parts of the lobules; centro-pericentral plethora, sometimes accompanied by atrophy of hepatocytic trabeculae of the central parts of the lobules; pericentral fibrosis. All these features indicate, apparently, the presence of a long-term impairment in patients. venous outflow from the liver and are also a morphological reflection of changes associated with more frequent use of alcohol and drugs by patients of the groups under consideration (half of the patients with CL with chronic hepatitis indicated frequent alcohol use, 1/5 patients indicated intravenous drug use).
In all parameters of the semi-quantitative assessment of histological changes in the liver, the indicators for CHC and CHCV exceeded those for CHB. It is of interest to compare morphological changes, which are among the so-called "morphological markers" of the etiology of CG. The triad of signs characteristic of CHC (fatty degeneration of hepatocytes, lymphoid follicles, damage to bile ducts), was significantly less common in patients with CHB. The presence of two viruses (B + C) led to increased damage in the liver (table 2). Our data also indicate a more pronounced stage of chronicity (fibrosis) at the time of the study in patients with CHC and CHCV, which allows us to consider this group of patients with anti-tuberculosis
institutions as a group increased risk development of hepatotoxic reactions during anti-tuberculosis therapy.
Table 2. Results of semi-quantitative evaluation* of pathomorphological parameters of liver biopsy specimens in patients with viral hepatitis
Parameters (scores) Type of hepatitis p**
CHF I (n = 36) CHC II (n = 23) CHC (n = 25) 1-P 1-Sh
Periportal necrosis 0.4±0.6 2.2±1.5 2.1±1.6 0.001" 0.001"
Lobular necrosis 0.5±0.9 1.8±1.3 1.5±1.4 0.001" 0.005"
Fatty degeneration 1.3±1 2.1±1 2.1±1.1 0.02" 0.02"
Lymphoid follicles 0.1±0.3 0.9±1.1 1.3±1.3 0.01" 0.001"
Damage to the epithelium of the bile ducts 0.2±0.5 0.9±0.9 1±1 0.01" 0.003"
Portal fibrosis, stage 1.5±0.5 2±0.7 2.1±0.6 0.03" 0.001"
Activity, degree 1.1±0.3 1.8±0.4 1.7±0.7 0.001" 0.001"
Pericellular fibrosis 0.3±0.6 0.6±0.7 0.8±0.8 - 0.05"
Lipofuscinosis 1.9±0.7 0.8±1 1±1.1 0.001" 0.01"
Note: * - according to Serov V. V. and Severgina L. O (1996, with add.);
** - Mania-Whitney test;" - statistically significant differences (p< 0,05)
Often, the severity of the identified morphological changes did not correspond to a favorable biochemical and clinical picture, but it made it possible to establish the activity of inflammation and the stage of liver fibrosis, to clarify the diagnosis of CG in patients with TL.
At the time of performing a puncture liver biopsy in patients with all types of hepatitis, the minimum - in 49 people (58.3%) and moderate - in 35 (41.7%), the degree of morphological activity of inflammation prevailed (according to V.V. Serov , L. O. Severgina, 1996). At the same time, the distribution of activity levels among hepatitis was unequal (Figure 3), with CHB activity is statistically significantly lower than with CHC and CHCV (p = 0.0001, x2) -
It turned out that an increase in the degree of morphological activity of hepatitis (CHC + CHCV in total) leads to a decrease in the average term for cessation of bacterial excretion: with activity of 2-3 points according to V.V. Serov - 3.4 months (95% CI 2.5-4.3 ), and with an activity of 1 point - 7.4 months (95% CI 4-10.8, p = 0.014, Kaplan-Meier analysis).
9 TiTii HPuWiffi"
Number of patients
♦HGW AHGS 1HGWS
Figure 3. Distribution of hepatitis according to the degree of morphological activity (according to V. V. Serov)
With CHC + CHCV and the presence of severe fibrosis (3-4 points according to Ishak), bacterial excretion stopped in all 14 patients, and with mild (1-2 points) fibrosis, only 1 B out of 25 (p = 0) .08, x2) -
A relationship was established between markers of liver cytolysis and the effectiveness of tuberculosis treatment: bacterial excretion stopped with an increased level of AJIT in 23 out of 24 patients (TJI + CG), and with normal - in 9 out of 15 (p = 0.016, x2 ); the cavities were closed (therapeutically) with an elevated level of ALT in 23 out of 24 patients (TL + CG), and with a normal level - in 11 out of 20 (p = 0.0045, x2) - For ACT, a similar same trend. Thus, with initially higher rates of biochemical activity of hepatitis, the response to the treatment of the tuberculosis process was higher.
The absence or weak severity of morphological and biochemical manifestations of CG, that is, the hyporegenerative type of response of the macroorganism to a viral infection, indicates the failure of the mechanisms of adaptation and immunity, which does not allow the patient to achieve a full clinical cure pulmonary tuberculosis.
With mild sinus neutrophilia, only 2 patients out of 44 did not have cavities closed, and with significant - in 10 out of 34 (p = 0.007, x2). Sinusoid neutrophilia reflects both the total level of blood neutrophils and the severity of the reactive component of hepatitis, and can be largely associated with alcoholic disease liver. The data indicate that with a more pronounced reactive component of hepatitis, lung regeneration is impaired: the decay cavities close more often in the presence of a minimal level of sinusoidal neutrophilia compared to a significant one (OR 8.8; 95% CI 1.8-43.5).
Using the example of patients with pulmonary tuberculosis with concomitant CHC and CHCV, it was found that in the presence of severe lipofuscinosis of hepatocytes, the cavities did not close in 3 out of 5 patients, while in the case of mild lipofuscinosis or its absence - only in 5 of them. 41st (p = 0.042, x2) - Pronounced lipofuscinosis of hepatocytes can also become a marker of an increased risk of retaining bacilli excretion: in the presence of this parameter, bacterial excretion ceased in 1 patient out of 4, and in the absence - in 31 out of 35 ( p = 0.015, x0> i.e. pronounced sinusoid neutrophilia and hepatocyte lipofuscinosis are negative factors that negatively affect the prognosis of pulmonary tuberculosis.
In persons without hepatitis, no significant differences were found in the probability of achieving the TJI outcome (closure of cavities) between the two groups with different levels of CD4+ blood lymphocytes, while in patients with concomitant chronic hepatitis (the term for closure of cavities in terms of no more than 6 months, closure by therapeutic means) there were such differences: at a CD4+ level (at admission) of less than 400 cells, the average period for closing the cavities was 5.4 months (95% CI 4.7-6.1), and at a level of more than 400 cells
3.6 months (95% CI 3-4.1, p = 0.013, K-M). The same pattern was found for a total lymphocyte count of less than 1000/mcL in patients with concomitant chronic hepatitis: the median closure time was 5.6 months (95% CI 4.9–6.3), while in individuals with higher lymphocyte counts, the time was 3.6 months (95% CI 3-4.1, p = 0.01, K-M). When calculating the terms of closing the cavities in the lungs by therapeutic means in all patients (including those without CG), it was also found that with a total lymphocyte level of less than 1000 per µl, the terms for closing the cavities were prolonged by almost 2 months in comparison with patients in whom the level of lymphocytes exceeded 1000 per µl (6.9 months, 95% CI 5.6-8.1, and 5.1 months, 95% CI 4.3-5.9, p = 0.036, K-M). The results obtained indicate that in persons with absolute and CD4+ lymphopenia (associated, as can be assumed, with the presence of hepatotropic and other viral infections, underweight, drug use, etc.), lung repair processes are clearly slowed down.
It has been shown that in patients with TJI in combination with CG, an unfavorable course of tuberculosis is observed with:
The presence of CHC or CHV compared with the presence of CHB;
Low degree of morphological activity of hepatitis in comparison with moderate or high;
Mild liver fibrosis compared to moderate or severe;
Normal levels of AJ1T and ACT compared to elevated;
Pronounced neutrophilia in the sinusoids of the liver in comparison with a small one;
Severe lipofuscinosis of hepatocytes compared with mild or absent;
The level of the total number of lymphocytes is less than 1000 per μl and the level of CD4+ is less than 400 cells per μl in comparison with their high level.
The signs listed above should be taken into account when choosing the tactics of managing and treating patients with LT with concomitant chronic hepatitis. These issues are acute for practical phthisiologists, because they are not studied and require special discussion. It is known that anti-tuberculosis drugs cause adverse reactions, of which the most serious in terms of severity and possible consequences include neuro- and hepatotoxic. According to Mishin M. Yu. et al. (2004) in the course of combined chemotherapy there is a violation of the general metabolic background (homeostasis) of the body, the work of the main organs of the detoxification system - the liver and kidneys. Impaired liver function during the treatment of anti-TB drugs is due to the fact that many drugs are metabolized in it, and this causes their hepatotoxicity. toxic effects, characterized by a violation of the antitoxic, protein-synthetic functions of the liver, a reversible increase in indicator enzymes - ALT, ACT, GGTP, alkaline phosphatase, general and direct bilirubin. It turned out that a very simple, non-invasive, easy-to-interpret antipyrine test, carried out in dynamics during anti-tuberculosis therapy, makes it possible to predict the development of adverse reactions in TB patients.
According to the data of the antipyrine test, there was a statistically significant decrease in liver MOC activity (an increase in the half-life of antipyrine (p = 0.001), a decrease in the elimination constant (p = 0.001)) in LT patients during daily anti-TB therapy (n = 52) in comparison with the group of patients intermittent treatment (n = 47). The incidence of adverse reactions in the daily treatment group was also significantly higher, with toxic reactions predominating, requiring the abolition of chemotherapy drugs and long-term (from 2 weeks to 3 months) pathogenetic therapy (OR 4.3, 95% CI 1.8-10.5) (table 3).
Table 3. Characteristics of adverse reactions in patients of the compared groups against the background of anti-tuberculosis therapy
Symptom Patients Allergic reactions Toxic reactions allergic reactions
Neurotoxic Hepatotoxic
Moderate severity Extremely severe
Daily treatment group (n = 52) 0 7 4 13 4
Intermittent treatment group (n = 47) 5 0 1 2 2
In the intermittent treatment group, allergic reactions were predominantly observed, which were quickly stopped by the appointment of desensitizing drugs (1-2 days).
Table 4 shows data indicating an increase in the level of biochemical markers of cytolysis and cholestasis in patients on the background of daily chemotherapy, in contrast to the intermittent treatment group.
Table 4 Biochemical indicators blood in patients of the compared groups upon admission to the hospital and after 3 months of anti-tuberculosis therapy ______
Patients Biochemical ^h. parameters Daily treatment group (n = 52) М±m Р* Intermittent group. treatment (n = 47) M±w R* Range of normal values
Total bilirubin (µmol/l) Initially 8.8±0.5 0.1 8.3±0.6 0.15 3.417.0
Dynamic 10.7±0.6 9.1±0.5
ALT (U/l) Initially 39.5±9.0 0.008# 43.1±7.8 0.001# 0-40
Dynamic 74.6±13.2 27.9±7.2
ACT (U/l) Initially 39.9±8.9 0.005# 39.8±4.5 0.06 0-40
Dynamic 64.8±8.6 33.2±5.1
GGTP (U/l) Initially 38.1±4.1 0.002# 38.3±7.7 0.8 0-80
Dynamic 68.1±6.9 30.8±3.2
Notes. * - comparison of differences was carried out using a paired Wilcoxon test; # - statistically significant differences compared to baseline values (p< 0,05)
All these facts indicate the most important advantage of the technique of intermittent intravenous chemotherapy - its better tolerance due to the reduced drug load on the patient's body. This approach to the treatment of TL is the most harmless of the currently existing ones, since it does not affect the activity of the monooxygenase system of the liver and does not cause manifestations of cytolysis and cholestasis in the patient. The method of intravenous intermittent chemotherapy should be recommended in the treatment of patients with pulmonary tuberculosis in combination with chronic hepatitis as sparing and preventing toxic effects in a compromised liver.
In TL patients with concomitant CG with "normal" levels
ALT and ACT rate of antipyrine inactivation was higher than in patients with high levels of cytolysis markers, and did not change during anti-tuberculosis therapy. Perhaps one of the reasons for the "normal" levels of ALT and AST in patients with chronic hepatitis is the genetically determined ability to quickly inactivate xenobiotics, including these biochemical markers. The high metabolic rate in these patients appears to be the cause of normal (low) levels of ALT and ACT. Special attention should be paid to such patients, since they have the same frequency of adverse reactions to chemotherapy as in patients with CG who have elevated ALT and AST levels (adverse reactions occurred in 3 out of 11 patients with normal ALT levels). and ACT and in 3 out of 12 patients with elevated values of these biochemical markers (p = 1.0, TTP)), and high speed inactivation of chemotherapy drugs can lead to failures in the treatment of TL, to the development of VLU of mycobacteria.
In recent years, researchers have pointed out that the serum ALT value does not correlate with the severity of liver disease and in itself has a small predictive value(Kaplan M. M., 2002). Although high level ALT is usually associated with significant hepatocyte damage, and a low ALT value does not always indicate mild liver disease. Studies have shown that in 1-29% of patients with HCV infection and normal level ALT has stage 3-4 fibrosis according to biopsy data (Bacon B. R., 2002). M.L.Shiffman et al. (2000) revealed advanced liver damage (bridging fibrosis/cirrhosis) in 11.4% of patients with normal ALT activity, and inflammatory changes in the portal tracts in another 25.7%. One of the explanations for this phenomenon, in our opinion, may be the accelerated inactivation of ALT and ACT by the system of “fast metabolizers” monooxygenases.
Thus, it is difficult to overestimate the importance of the antipyrine test, which makes it possible to determine the metabolic rate in a patient with a combination of LT and CG during treatment with toxic anti-TB drugs, when serious liver damage can be hidden behind the normal value of ALT and ACT.
In patients with moderate activity of chronic hepatitis, in comparison with patients with minimal inflammation activity (according to the results of liver biopsy), in the course of anti-tuberculosis therapy, a tendency to inhibition of the rate of antipyrine inactivation, to a decrease in liver MOS activity was revealed (Table 5). This did not affect the incidence of adverse reactions in these patients, since most of them (7 out of 9) were treated according to the method of intermittent therapy. Adverse reactions met in 3 patients with minimal activity CG and in 3 patients with its moderate activity (p = 0.9, TTF).
Adverse reactions were diagnosed in 32 out of 76 (42.1%) LT patients without hepatitis and in 6 out of 23 (26.1%) patients with concomitant chronic hepatitis (p = 0.26, x2)■
Table 5. The main pharmacokinetic parameters of the antipyrine test in patients with pulmonary tuberculosis with minimal and moderate hepatitis activity at baseline and during anti-tuberculosis therapy
X^ Patients Min. active- Moderate, active- R* Min. active- Moderate, active- P*
N.
indicators. initially (n = 14) initially (n = 9) dynamics (n = 14) dynamics (n = 9)
Т1/2 (hour) 6.5±0.7 6.9±1.2 0.3 7.9±1.4 12.9±3.1 0.09
Clearance (ml/hour/kg) 11.3±2.1 19.1±5.0 0.4 7.2±1.1 7.5±1.2 0.8
Constant 0.1±0.01 0.1±0.02 0.9 0.1±0.01 0.08±0.01 0.08
elimination (hour "1)
Note: * - Mann-Whitney U-test
Intermittent regimens (intermittent) administration of anti-tuberculosis drugs are believed to lead to the development of secondary drug resistance (SDR) in Mycobacterium tuberculosis. However, this issue is not closed: there are studies on short courses of intermittent chemotherapy that refute the above opinion. In order to study the frequency of development and the spectrum of VLU of mycobacterium tuberculosis in newly diagnosed patients with TL receiving intravenous intermittent chemotherapy in comparison with similar patients in the daily treatment group, a bacteriological study was carried out in 76 patients-bacterio-excretors, 38 of whom received anti-TB drugs in an intermittent mode (main group) and 38 - daily (comparison group).
As a result of chemotherapy, bacterial excretion stopped in 36 (94.7%) patients of the main group and in 34 (89.5%) of the comparison group after an average of 3.17 ± 0.4 and 2.7 ± 0.5 months, respectively (p = 0.17, Mann-Whitney U test). Bacterial excretion at the time of discharge from the hospital remained in 2 patients of the main group and in 4 patients of the comparison group.
In the course of intravenous intermittent chemotherapy, VLU occurred in 5 (13.2%) patients, of which one had multidrug resistance. In the daily treatment group, VLU developed in 4 people (10.5%), of which 3 had multidrug resistance. Average term the onset of VLU was 3 ± 0.3 and 2 ± 0 months, respectively (p = 0.03, Mann-Whitney U test).
Thus, the incidence of VLU with intravenous intermittent chemotherapy is the same as with daily oral anti-TB drugs, but secondary multiple
drug resistance develops less frequently. During intravenous intermittent chemotherapy, VLU appears more slowly than with daily chemotherapy.
We positively assessed the fact that in the intermittent treatment group, no VLU to rifampicin was detected in any case (except for one patient with secondary multidrug resistance), since it is known that drug resistance to this drug leads to a significant increase in the number of treatment failures and relapses of the process, even with standard chemotherapy regimens with 3 or 4 drugs (Espinal M.A., 2000). WHO experts emphasize that rifampicin is a key component of modern tuberculosis chemotherapy and the single most important drug with a short-term treatment regimen (T. Frieden, M. Espinal, 2004). In the daily treatment group, secondary multidrug resistance was observed in 3 patients and in 1 patient - drug resistance to rifampicin, rifabutin and prothionamide. Based on these results, it was concluded that intravenous administration of rifampicin avoids the development of VLU to this drug providing a sterilizing effect of chemotherapy in patients with tuberculosis.
With the help of the “dose density” indicator of anti-tuberculosis drugs, an objective division of patients into groups of intermittent (A) and daily (B) treatment was carried out in order to assess the results of TB treatment in them. This indicator made it possible to identify an intermediate group of patients with a variable regimen of therapy (group X) and analyze their unfavorable prognostic factors for the course of pulmonary tuberculosis.
Thus, in group X there were more patients with disseminated bilateral lung disease (p = 0.02, TTF), with clinical manifestations of tuberculosis: acute onset of the disease (p = 0.036, x2) > lack of appetite (p = 0.08, TTF) , auscultatory - wet and dry rales over the lungs (p = 0.069, x2), almost half of the patients isolated MBT with multidrug resistance (p = 0.07, TTF). When analyzing the indicators of the effectiveness of chemotherapy, they noted a decrease in the rate of cessation of bacterial excretion (p = 0.005, K-M) and closure of decay cavities (p = 0.047, K-M) compared with patients in the intermittent and daily treatment groups.
Patients of the other two groups (A and B) had a similar clinical picture of pulmonary tuberculosis and approximately the same rate of cessation of bacterial excretion and closure of decay cavities. However, there were more patients in the intermittent treatment group who had complete closure of the cavities than in the daily treatment group (p = 0.012, x2) (Table 6).
Table 6 Closure of cavities in patients various groups
Closing the split- Group A Group X Group B
yes (n=101) (n=37) (n=36)
Abs. % abs. % abs. %
Complete 94 93.1 31 83.8 29 80.6
Partial 2 2.0 2 5.4 6 16.7
Not closing 5 5.0 4 10.8 1 2.8
With an increase in the "dose density", an increase in the frequency of development and severity of toxic reactions was noted (p = 0.0001, TTF) (Table 7).
Table 7. Tolerability of anti-tuberculosis therapy in patients of _ different groups __
Tolerability of anti-tuberculosis therapy Group A (n=113) Group X (n=42) Group B (n=49) P*
Abs. % Abs % Abs. %
Satisfactory 88 77.9 26 61.9 24 49.0 0.001#
Unsatisfactory, - including: 25 22.1 16 38.1 25 51.0
Allergic reactions 9 8.0 5 P.9 0 0 0.064
Toxic reactions 9 8.0 10 23.8 21 42.9 0.0001"
Toxic-allergic reactions 7 6.2 1 2.4 4 8.2 0.5
Note: *-%2 Pearson; * - statistically significant differences (p< 0,05)
There was no correlation between the development of toxic reactions and the presence of concomitant chronic hepatitis (p = 0.78, %2). In patients with toxic reactions, the effectiveness of anti-tuberculosis therapy was worse compared to patients without toxic reactions: an increase in the time for closing the decay cavities in patients of group B and group X was found in comparison with group A (p = 0.059, K-M) and an increase in the time for cessation of bacterial excretion in patients of group X compared with groups A and B (p = 0.04, K-M). This was not observed in patients without toxic reactions in the compared groups. Due to the fact that in most patients toxic reactions developed during the first 10-14 days of hospitalization (32 patients out of 40), best method Prevention of the development of toxic reactions turned out to be an intermittent method of administering anti-TB drugs from the first days of treatment.
In order to develop effective management tactics for TB patients with concomitant hepatitis B and C, a comprehensive examination was carried out.
evaluation and evaluation of the effectiveness of their treatment with reaferon-EC (interferon-a), administered at a dose of 3 million IU rectally drip on the days of intravenous intermittent anti-tuberculosis therapy (2 times a week).
55 patients of group I and 64 patients of group II were bacterial excretors. During the stay and treatment in the clinic, 52 patients of group I stopped bacterial excretion in a therapeutic way, on average, after 3.02 ± 0.36 months, while in group II, bacterial excretion at the therapeutic stage disappeared in 50 people, on average, after 4.8 ± 0.6 month. That is, in the group of patients treated with reaferon (group I), there were more patients who reached the cessation of bacterioexcretion at the therapeutic stage, and at an earlier time compared to group II (earlier by 1.8 months, p = 0.02, K -M). When analyzing the rate of termination of bacterial excretion by therapeutic means among patients with concomitant chronic hepatitis, the differences between the groups also turned out to be statistically significant. In group I of 46 patients with pulmonary tuberculosis, MBT+, with concomitant CG B and/or C, bacterial excretion stopped during their stay in the hospital in 43 (93.5%) on average after 4.0 ± 0.6 month. In group II, out of 37 patients with TL, MBT+, with concomitant CG B and/or C, bacterial excretion stopped during the hospital stay in 27 (73.0%) patients on average after 6.0 ± 1.1 months ( p = 0.05, K-M). Bacterial excretion did not stop in 3 (6.5%) and 10 (27.0%) patients with concomitant CG, respectively (p = 0.01, TTF).
53 patients of group I and 59 patients of group II had decay cavities. During the stay and treatment at the NNIIT clinic, the decay cavities closed therapeutically in 47 patients of group I on average after 5.2 ± 0.4 months, while in group II - in 42 patients on average after 6.6 ± 0.5 months. That is, for patients treated with reaferon, earlier closure of the decay cavity(s) is characteristic in comparison with the group of patients not treated with reaferon (earlier by 1.4 months, p = 0.045, K-M). In group I, out of 44 patients with LT with concomitant CG B and/or C, complete closure of decay occurred during their stay in the hospital in 38 (86.4%) patients on average after 7.0 ± 0.8 months. In group II, out of 35 patients with TL with concomitant CG B and/or C, the decay cavities completely closed during their stay in the hospital in 24 (68.6%) patients on average after 8.0 ± 0.1 months (p = 0.1, K-M). The cavities did not close in 6 (13.6%) and 11 (31.4%) patients, respectively (p = 0.05, TTF).
During treatment with reaferon, a decrease in markers of cytolysis and cholestasis was noted (Figure 4), which was not observed in the comparison group (Figure 5).
ALT p=0.08 AST p=0.01 GGTP p=0.08
Figure 4. Biochemical parameters of blood in patients of group I
Note: * - statistically significant differences (p< 0,05)
60 50 40 30 20 10 0
ALT p=0.08 AST p=0.4 GGTP p=0.5
On admission to the hospital
W after 4 months
Figure 5. Biochemical parameters of blood in patients of group II
Therapy with reaferon in patients contributed to an earlier normalization of hemogram parameters in comparison with patients of group II (p = 0.048, K-M).
In 45 patients of group I and in 37 patients of group II with mixed infection, an immunological examination was performed at baseline and after 4 months of treatment, which included a quantitative assessment of lymphocytes and their
subclasses carrying SB3+, SB4+, SB8\SE16+, SB19+ molecules (table
Table 8. The content of the main subpopulations of lymphocytes in the blood of patients of groups I and II at baseline and after 4 months of therapy
Cells (thousands per µl) Donors (n = 68) Group I (n = 45) P* Group II (n = 37) p**
Initially After 4 months Initially After 4 months
Lymphocytes 1882±80 2052±125 2438±141 0.04" 2191±138 2259±106 0.5
SBZ+ 1183±46 1352±97 1591±110 0.07 1465±109 1439±76 0.8
SB4+ 730±58.3 822±64.6 980±70.4 0.08 900±74.4 859±45.8 0.9
SB8+ 465±53.6 563±57.5 721±53.5 0.007* 645±51.1 734±50.6 0.03*
SB16+ 354±33.3 378±43.4 458±40.7 0.1 379±35.7 428±33.8 0.15
SB19+ 211±24.5 251±28.1 302±26.7 0.01# 276±28.1 296±22.9 0.2
Note: * - pair test Wilcoxon for group I; ** - paired Wilcoxon test for group II; * - statistically significant differences compared to baseline values (p< 0,05)
In patients of group I, on the background of treatment with reaferon, an increase in the content of lymphocytes and their subclasses POP+, CD4+, CD8+, CD19+ was noted. In the comparison group (group II), no significant changes in the number of lymphocytes and their subclasses were found during anti-tuberculosis therapy, except for an increase in the content of CD8 + lymphocytes. That is, the clinical and biochemical improvement correlated with an increase in the content of immunocompetent blood cells in patients during treatment with reaferon.
Part of the patients of the reaferon group (n = 34) and the comparison group (n = 35) after 5-6 months of anti-tuberculosis therapy underwent resection operations. The surgical material of the lungs was subjected to histological examination, preliminary coding, so that the pathologist did not have any information about the patient at the time of microscopy. The results of morphometry were presented as scores and contingency tables were used to evaluate them with the calculation of the criterion %2 (or accurate test Fisher). The results obtained are shown in tables 9 and 10.
In patients of the reaferon group, a mature capsule of the tuberculosis focus was more often found, less severity of inflammation around the capsule was observed, and manifestations of chronic bronchitis, bronchial obstruction and bronchial tuberculosis from the cut-off site were less common in the surrounding lung tissue than in the comparison group. The obtained morphological results indicate that the use of reaferon along with intravenous intermittent chemotherapy in patients with tuberculosis is accompanied by a decrease in inflammatory manifestations both directly in the focus of infection and at a distance.
Table 9. Assessment microscopic examination of the resected lung tissue in the area of the specific lesion in patients of the compared groups
Patients Sign Reaferon group (n = 34) Control group (n = 35) P
Capsule maturity Mature 12 5 0.04**#
Immature 22 30
Specific damage to the capsule None 22 19 0.38*
Available 12 16
Inflammation around the capsule Minimal productive 13 6 0.08*
Expressed productive 11 11
Exudative 10 18
Note: * - x2 Pearson; ** - TTF; * - statistically significant differences (p< 0,05)
Table 10. Assessment of microscopic examination of the resected
lung tissue outside the site of a specific lesion in patients of _comparable groups_
" Patients Sign ~~- Reaferon group (n = 34) Control group (n = 35) R
Chronic bronchitis Remission 12 5 0.04**#
Aggravation 22 30
Bronchial obstruction None 10 1 0.003**"
Available 24 34
Focal pneumonia Absent 25 20 0.2**
Available 9 15
Interstitial desquamative pneumonia None 3 0 0.18*
Minimum 11 14
Expressed 20 21
Tuberculosis of the bronchus Absent 22 14 0.035**"
Available 12 21
Fibrotic changes along the vessels and bronchi Minimal 3 10 0.07*
Moderate 23 21
Pronounced 8 4
Interstitial fibrosis None 5 0 0.047**
Minimum 13 19
Pronounced 16 16
Note: * - X2 Pearson; ** - TTF; * - statistically significant differences (p<
Conducted clinical, biochemical, immunological and morphological data demonstrate high therapeutic efficacy and good tolerability of reaferon in patients with pulmonary tuberculosis with concomitant chronic viral hepatitis and allow us to recommend it for practical use.
1. The proportion of patients in anti-tuberculosis hospitals in whom markers of viral hepatitis B and C were detected varies from 32 to 48%. Newly detected pulmonary tuberculosis is associated with an increased relative risk of HBV infection, and long-term -HCV- and HCV + HBV infection.
2. Medical and social factors associated with the unfavorable course of pulmonary tuberculosis were identified:
2.1. Patients with pulmonary tuberculosis and signs of social maladjustment (lack of a permanent job; alcohol abuse, smoking, drug use; past imprisonment; poor adherence to anti-tuberculosis therapy) have increased relative risks of chronic viral hepatitis.
2.2. The combination of pulmonary tuberculosis and chronic hepatitis B and C is characterized by predominantly mild symptoms of tuberculosis intoxication with no temperature response, a high frequency of bacterial excretion with a relative risk of developing drug resistance to ethambutol and kanamycin, an asymptomatic clinical course of hepatitis with elevated levels of AJIT, ACT and GGTP.
2.3. The presence of viral hepatitis in patients with pulmonary tuberculosis 2 times reduces the likelihood of early (up to 3 months) cessation of bacterial excretion and 2.3 times the likelihood of a favorable x-ray picture at the end of the inpatient stage of treatment.
3. In patients with pulmonary tuberculosis in combination with chronic hepatitis, an unfavorable course of tuberculosis is observed in: the presence of CHC or CHCV in comparison with CHB; mild liver fibrosis compared to moderate or severe; low degree of morphological activity of hepatitis in comparison with moderate or high; "normal" levels of AJIT and ACT compared to elevated; severe neutrophilia in the sinusoids of the liver in comparison with a small one; pronounced lipofuscinosis of hepatocytes in comparison with weak or its absence; the level of the total number of lymphocytes is less than 1000 per μl and the level of CD4+ is less than 400 cells per μl in comparison with their high level.
4. Intravenous intermittent anti-tuberculosis therapy does not inhibit the activity of the liver monooxygenase system in comparison with daily traditional treatment, which is clinically associated with a decrease in the number of toxic drug complications (OR
4.3; 95% CI 1.8-10.5).
5. The frequency of development of secondary drug resistance was comparable in different regimens of therapy (intravenous intermittent and daily traditional). With intravenous intermittent chemotherapy, the risk of secondary multidrug resistance is reduced, VLU appears more slowly than with daily chemotherapy, on average after 3 months from the start of chemotherapy, which coincides with the time of cessation of bacterial excretion in patients of both groups.
6. Identification of groups of patients according to the dosing regimen of anti-tuberculosis drugs is important in determining the effectiveness of treatment and prognosis.
6.1. The proportion of patients with closure of decay cavities with intravenous intermittent chemotherapy was 12.5% higher than with daily treatment. With an increase in the "dose density" of anti-tuberculosis drugs, the frequency and severity of adverse toxic reactions increased, which negatively affected the effectiveness of anti-tuberculosis therapy. There was no quantitative dependence of toxic reactions on the presence of concomitant chronic hepatitis.
6.2. In patients with a “dose density” of less than 0.22 and from 0.31 to 0.6, factors significantly associated with an unfavorable prognosis of tuberculosis were identified: disseminated bilateral lung disease, acute onset of the disease, lack of appetite, moist and dry rales over the lungs, excretion multidrug-resistant mycobacteria, an increase in the incidence and severity of toxic reactions.
7. The combination of intravenous intermittent chemotherapy with rectal drip of reaferon 2 times a week for pulmonary tuberculosis with concomitant chronic hepatitis B and C increases the effectiveness of treatment, which is expressed in shortening the time for cessation of bacterial excretion and closure of decay cavities, normalization of hemogram parameters, reduction in the manifestations of cytolysis and cholestasis , restoring the content of immunocompetent cells in the blood of patients.
8. Complex intravenous intermittent chemotherapy in combination with reaferon leads to a decrease in the morphological manifestations of specific and nonspecific inflammation in the lung tissue.
1. In order to assess the functional disorders of the regulatory systems that determine the nature of the course of concomitant infections (pulmonary tuberculosis and chronic hepatitis B and / or C), it is necessary to use a number of indicators: a biochemical blood test (bilirubin and its fractions, ALT, ACT, alkaline phosphatase, GGTP, thymol sample), HBsAg, aHBcIgG, aHBcIgM,
aNSU-total by enzyme-linked immunosorbent assay, morphological study of liver biopsy specimens, indicators of immune status.
2. To predict the course, outcomes of pulmonary tuberculosis and adverse reactions of anti-tuberculosis therapy, at the beginning and during chemotherapy in patients with mixed infection, it is necessary to evaluate the pharmacokinetic parameters of antipyrine metabolism, pay attention to the increase in the half-life and the decrease in clearance and elimination constant.
3. For an unbiased comparison of the results of treatment of patients receiving intermittent and daily chemotherapy drugs, we recommend using the “dose density” indicator, which is equal to the number of days of treatment with anti-TB drugs (number of doses) divided by the total number of bed-days spent by the patient in the hospital. This approach to the study allows us to identify a group of "problem" patients who, for various reasons, cannot complete their prescribed chemotherapy regimens and require an individualized assessment of the effectiveness of therapeutic measures.
4. Since in most patients toxic reactions developed during the first 2 weeks of taking anti-tuberculosis drugs, to prevent them in patients with pulmonary tuberculosis with concomitant chronic hepatitis B and C (including patients with "normal" AJIT and ACT values) it is advisable to carry out intravenous intermittent chemotherapy from the first days of treatment.
5. In order to increase the therapeutic efficacy of treatment of patients with pulmonary tuberculosis with concomitant chronic hepatitis B and C, it is necessary from the first days of treatment to prescribe reaferon-EC at a dose of 3 million IU, dissolved in 50 ml of saline, rectally drip 15-20 minutes after intravenous administration of chemotherapy drugs 2 times a week, on the days of anti-tuberculosis therapy. The course of treatment with reaferon should be 6 months or more, taking into account clinical, biochemical, radiological data.
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41. Petrenko T. I. Comparative clinical and morphological characteristics of the course and outcomes of the pulmonary process in patients with tuberculosis in combination with chronic hepatitis / T. I. Petrenko, P. N. Filimonov, N. S. Kizilova, T. A. Khudyakova / / Siberian Council. - 2006. - No. 3. -S. 25-31.
42. Petrenko T. I. Chronic viral hepatitis in a patient with pulmonary tuberculosis / T. I. Petrenko, P. N. Filimonov // Proceedings of the VIII Russian Congress of Phthisiologists “Tuberculosis in Russia. Year 2007". - Moscow. -2007.-S. 412.
43. Petrenko T. I. Secondary drug resistance in patients receiving intravenous intermittent chemotherapy / T. I. Petrenko, A. G. Cherednichenko, V. A. Krasnov, JI. V. Muzyko // Proceedings of the VIII Russian Congress of Phthisiologists “Tuberculosis in Russia. Year 2007". -Moscow. - 2007. - S. 443.
44. Petrenko T. I. Chronic hepatitis B and C in patients with tuberculosis
lung disease / T. I. Petrenko, P. N. Filimonov // II Russian-German Conference of the Koch-Mechnikov Forum "Tuberculosis, AIDS, viral hepatitis ...". - Tomsk. -2007. - S. 104-105.
45. Petrenko T. I. Marker profile of hepatitis B and C in patients with newly diagnosed and chronic pulmonary tuberculosis / T. I. Petrenko, P. N. Filimonov, V. V. Romanov, E. I. Vitenkov, T. R. Amitina, I. K. Pasazhennikova, E. E. Lipkina // Siberian Council. - 2007. - No. 8. -S. 70-72.
ALT-alanine aminotransferase
ACT - aspartate aminotransferase
VG - hepatitis viruses
SDR - secondary drug resistance
11 "111 - gamma-glutamyl transpeptidase
CI - confidence interval
ELISA - enzyme immunoassay
K-M - Kaplan-Meier method
MBT - mycobacterium tuberculosis
MOS - monooxygenase system
NNIIT - Novosibirsk Research Institute of Tuberculosis
OSH - odds ratio
PTP - anti-tuberculosis drugs
TL - pulmonary tuberculosis
TTF - Fisher's Exact Test
CG - chronic hepatitis
CHB - chronic viral hepatitis B
CHC - chronic viral hepatitis C
CHV - chronic viral hepatitis B + C
AP - alkaline phosphatase
HBV - hepatitis B virus
HCV - hepatitis C virus
LIST OF ABBREVIATIONS
Applicant
T.Iletrenko
Signed for publication on 17.09.08. Format 60x84 1/16 Headset Time Offset paper Cond. oven l. 2.0 Circulation 100 copies. Order No. 64 Printing on the Shg-ZOO ER risograph
Printed at the Federal State Institution Novosibirsk Research Institute of Tuberculosis 630040, Novosibirsk, st. Okhotskaya 81a
Social diseases are diseases of people, the occurrence and spread of which is associated with unpleasant socio-economic conditions (venereal diseases, tuberculosis, etc.).
Natural and social hazards include:
1. Epidemics of infectious diseases:
Viral infection - influenza;
Botkin's disease, viral hepatitis;
Tuberculosis;
Foodborne diseases (food infections, food
poisoning).
2. Venereal diseases:
Syphilis;
Gonorrhea.
3. Oncological diseases
In Ukraine, 9 million cases of infectious diseases were recorded per year.
Consider some of the most important infectious diseases caused by viruses.
Viruses
The most common viral infection is - flu, that emerges like an epidemic annually. In developed countries, influenza, depending on the season, takes 1 - 2 place in the statistics of death from infectious diseases, and in terms of social significance, the first position among all diseases that affect the human body.
In Ukraine, from 10 to 126 million people get sick from influenza and acute respiratory infections during the year. This is approximately 95% of all infectious diseases.
The first influenza epidemic in history occurred in 1889.
Another covered the whole of Europe in 1918 - 1920, while 20 million people.
Influenza virus is very unstable, has type A, B, C, D, as well as many other subtypes.
The most common viruses are A (Nacon flu, Chinese flu). It is transmitted through contact with sick people through small droplets that enter the air when the patient coughs and sneezes. The incubation period is 1 - 2 days.
Flu symptoms:
The patient freezes;
The temperature rises;
There is severe pain;
Muscle pain.
There is a danger of getting a secondary infection (for example, pneumonia, inflammation of the middle ear, pleurisy, etc.), which can lead to death.
In some cases, the flu causes a complication in the form of:
Damage to the heart, kidneys, joints, brain and meninges.
Every year in the world, 5 to 15% of the population gets sick from influenza, about 2 million people die from influenza.
Everyone knows that the disease is easier to prevent than to cure. The best form of flu prevention is to activate the body's defenses.
Complex homeopathic remedies such as aflubin and immunal, can help with this.
One of the most effective ways to prevent influenza in the world is to immunization influenza vaccines. When using vaccines, protection against the disease reaches 90 - 98%.
Botkin's disease, or viral hepatitis
This disease is associated with the spread of a viral infection. known at least seven sources of disease- A, B, C, D, E, G and TTV of different specifics and severity of consequences.
The most common and less dangerous is
hepatitis A. This is a disease of "dirty hands", that is, associated with non-compliance with the rules of personal hygiene. Sources hepatitis A also enter the human body from contaminated water and food. As a rule, hepatitis A does not give severe and chronic forms. The disease is cured within 2 weeks.
Very dangerous and widespread Hepatitis B, 350 million inhabitants of the planet are infected with it. It is characterized by a long incubation period and severe consequences (cirrhosis and liver cancer). Suffice it to say that liver cancer in 9 out of 10 cases are a consequence of previous hepatitis.
The virus is transmitted through most body fluids (blood, saliva). The risk arises when these fluids from infectious people get to healthy people when:
Sexual contacts;
Infectious drug use;
Transfusion of blood and their components;
From an infectious mother to a child;
When applying tattoos, and other procedures when the skin and mucous membranes are damaged.
One hundred percent result of infection is given by blood transfusions and sexual contacts. Young people aged 125-29 are very often infected through injecting drugs.
The hepatitis B virus is capable of not showing its presence for a long time, waiting for the moment of weakening the body's defense reaction.
Activation of the virus is caused by colds, flu, unjustified intake of antibiotics.
Virus C which experts call "gentle killer" very dangerous. For a very long time, the disease passes without symptoms, but in most cases it ends with severe liver damage. Hepatitis C carriers are 150 million people. Infection with the hepatitis C virus is carried out in the same way as hepatitis B, but more often this form of hepatitis is infected during medical procedures, especially during blood transfusion.
Hepatitis is one of the most common infections in the world. Every third person on the planet suffers from it; about 2 billion people. A lot of people are chronically ill. The main rule for the prevention of these diseases is:
Washing hands before eating;
Boil water for drinking;
Wash vegetables and fruits before eating;
Use condoms during sexual intercourse.
A reliable way to protect against hepatitis B is vaccination.
With tuberculosis, there is a high risk of developing viral hepatitis B, D and C. This process is manifested in the high frequency of detection of markers of viral infection by each type of disease. This indicator varies from 10% to 36.5%, which is significantly higher than in healthy patients. Hepatitis B, C, and D develops against the background of tuberculosis due to:
- A significant number of asymptomatic carriers of the infection
- Prolonged stay in hospital, characterized by increased parenteral loading
- Progression of the immunosuppressive state, which is due to the course of tuberculosis or ongoing medical therapy.
The combination of tuberculosis and hepatitis cannot be detected at first, since the disease proceeds in an anicteric and subclinical form compared to patients in whom hepatitis is not complicated by other ailments.
A characteristic sign of the development of hepatitis B-type in patients with symptoms of tuberculosis is a long icteric period and prolonged detection of HBsAg. In such patients, the transition of the disease to a chronic form occurs more often, the carriage of the virus is determined.
For more information about tuberculosis, please visit
Pathogenesis
The causative agent of hepatitis B is resistant to low temperatures, as well as various disinfectant solutions.
The disease is transmitted percutaneously, perinatally, and also sexually. Susceptibility to this virus in humans is quite high. It enters the body through the skin and mucous membranes, after which it is introduced into hepatocytes. Pathological changes in the B-form occur inside the bile ducts. With an active process, there is a high risk of developing cirrhosis of the liver.
Hepatitis C carriers are patients suffering from acute or chronic liver diseases, whose blood test determines the presence of anti-HCV. Hepatitis C is usually transmitted through blood contact. Infection occurs through blood transfusion or the use of contaminated medical instruments. It is not excluded perinatal, domestic, as well as sexual infection.
It is worth noting that HCV can be present inside cells and tissues for several years without causing an appropriate immune response. With prolonged inflammation, the disease progresses sharply, cirrhosis develops, and hepatocarcinomas form. Clinical and laboratory diagnostic methods distinguish between acute and chronic forms of the course of the C-form of the disease.
It is worth noting that chronic hepatitis, as well as cirrhosis of the liver, can manifest themselves in almost the same way. It is possible to detect the disease with a liver biopsy with further histological examination of biopsy specimens.
It is also worth considering extrahepatic signs that indicate hepatitis C:
- Anemia of aplastic type
- Periarthritis nodular
- Thrombocytopenia
- Deterioration of the thyroid gland
- Dermatomyositis
- macroglobulinemia
- Cardiomyopathy.
Quite often, hepatitis D develops against the background of the B-type. The disease is characterized by the severity of the course, usually has an unfavorable prognosis for the patient.
D-form carriers are patients suffering from acute or chronic HDV.
With parenteral intervention, blood can be a source of infection in almost any phase of HDV development. During recovery, a gradual release of the virus from liver cells is observed, anti-HDV IgM disappears, and anti-HDV IgG decreases.
Diagnostics
If hepatitis occurs against the background of respiratory tuberculosis, there is a high probability that the disease will be detected late. Usually diagnosed by chance - as a result of laboratory tests. The progression of the disease and its development into a chronic form has a negative impact on the course of such a disease as tuberculosis, complicating its treatment.
Difficulties are manifested in the impossibility of continuous anti-tuberculosis therapy. Treatment of the underlying disease may not be as effective as expected.
Treatment
Pathogenetic treatment of hepatitis in acute or chronic form against the background of the course of tuberculosis requires the implementation of a number of rules of the protective regime, adherence to a special diet, the use of various drugs for functional pathological disorders of the liver.
Viral replication can be suppressed by interferon gamma. Its use is indicated for a course of up to six months at a dosage of 3,000,000 IU three times a week (subcutaneous and intramuscular administration is provided).
Such treatment cannot be carried out with pronounced cirrhosis of the liver, as well as severe concomitant ailments, mental disorders, leukopenia, excessive drinking, thrombocytopenia.
If the previous treatment did not give the expected effect, it is recommended to repeat the course of therapy. Combination treatment with interferon gamma and ribavirin may be more effective. Interferon-gamma is prescribed in the same dosage, and ribavirin is recommended to be used in a daily dose of 1000-1200 mg. Treatment of a chronic disease against the background of tuberculosis must be agreed with an infectious disease specialist.
Comprehensive treatment will reduce the risk of death.
Prevention
Viral hepatitis against the background of the course of tuberculosis is quite difficult to cure, but it can be prevented. Measures of prevention in tuberculosis departments of honey. institutions imply the implementation of sterilization of honey. instruments, the use of disposable syringes, increased control over the process of blood transfusion, as well as its other components.
Prevention of the disease is also carried out through vaccination. Passive immunization is carried out with the use of donor hyperimmune immunoglobulin. Such prophylactic treatment will be effective only if it begins no later than 2 days from the moment of infection.
Compliance with the rules of prevention will protect yourself and your family from such intractable diseases as hepatitis and tuberculosis.
Social diseases and their danger to society
Introduction
Human immunodeficiency virus (HIV) disease
Tuberculosis
Viral hepatitis
Anthrax
Helminthiases
Conclusion
List of used literature
Introduction
Socially significant diseases - diseases caused mainly by socio-economic conditions, causing damage to society and requiring social protection of a person.
Social diseases are human diseases, the occurrence and spread of which to a certain extent depend on the influence of unfavorable conditions of the socio-economic system. To S. b. include: tuberculosis, venereal diseases, alcoholism, drug addiction, rickets, beriberi, and other diseases of malnutrition, some occupational diseases. The spread of social diseases is facilitated by conditions that give rise to class antagonism and exploitation of the working people. The elimination of exploitation and social inequality is a necessary prerequisite for a successful fight against social diseases. However, socio-economic conditions have a direct or indirect impact on the emergence and development of many other human diseases; it is also impossible to underestimate the role of the biological characteristics of the pathogen or the human body when using the term "social diseases". Therefore, since the 1960s and 70s the term is becoming more and more limited.
In connection with the aggravated problem of socially significant diseases, the Government of the Russian Federation issued Decree of December 1, 2004 N 715 Moscow "On approval of the list of socially significant diseases and the list of diseases that pose a danger to others"
The Resolution includes:
1. List of socially significant diseases:
1. tuberculosis.
2. infections transmitted mainly through sexual contact.
3. hepatitis B.
4. hepatitis C.
5. disease caused by the human immunodeficiency virus (HIV).
6. malignant neoplasms.
7. diabetes.
8. mental and behavioral disorders.
9. diseases characterized by high blood pressure.
2. List of diseases that pose a danger to others:
1. disease caused by the human immunodeficiency virus (HIV).
2. viral fevers transmitted by arthropods and viral hemorrhagic fevers.
3. helminthiases.
4. hepatitis B.
5. hepatitis C.
6. diphtheria.
7. sexually transmitted infections.
9. malaria.
10. pediculosis, acariasis and others.
11. glanders and melioidosis.
12. anthrax.
13. tuberculosis.
14. cholera.
Consider some of the most common and dangerous diseases from the above list, included in the 1st and 2nd group.
1. Human immunodeficiency virus (HIV) disease
HIV infection, like a wildfire, has now engulfed almost all continents. In an unusually short time, it has become the number one concern for the World Health Organization and the United Nations, pushing cancer and cardiovascular disease into second place. Perhaps no disease has given scientists such serious riddles in such a short period of time. The war against the AIDS virus is being waged on the planet with increasing efforts. New information about HIV infection and its causative agent is published monthly in the world scientific press, which often force a radical change in the point of view on the pathology of this disease. As long as there are more mysteries. First of all, the unexpected appearance and speed of the spread of HIV. Until now, the question of the causes of its occurrence has not been resolved. The average and maximum duration of its latent period is still unknown. It has been established that there are several varieties of the causative agent of AIDS. Its variability is unique, so there is every reason to expect that the next variants of the pathogen will be found in different regions of the world, and this can dramatically complicate the diagnosis. More mysteries: what is the relationship of AIDS in humans with AIDS - similar diseases in animals (monkeys, cats, sheep, cattle) and what is the possibility of embedding the genes of the causative agent of AIDS in the hereditary apparatus of germ cells? Further. Is the name itself correct? AIDS stands for Acquired Immune Deficiency Syndrome. In other words, the main symptom of the disease is the defeat of the immune system. But every year more and more data is accumulating, proving that the causative agent of AIDS affects not only the immune system, but also the nervous system. Completely unforeseen difficulties are encountered in the development of a vaccine against the AIDS virus. The peculiarities of AIDS include the fact that it is, apparently, the first acquired immunodeficiency in the history of medicine, associated with a specific pathogen and characterized by epidemic spread. Its second feature is an almost “targeted” defeat of T-helpers. The third feature is the first epidemic human disease caused by retroviruses. Fourth, AIDS, in terms of clinical and laboratory features, is unlike any other acquired immunodeficiency.
Treatment and prevention: Effective treatments for HIV infection have not yet been found. At present, at best, it is only possible to delay the fatal denouement. Particular efforts should be focused on infection prevention. Modern drugs and measures used for HIV infection can be divided into etiological, affecting the immunodeficiency virus, pathogenetic, correcting immune disorders and symptomatic, aimed at eliminating opportunistic infections and neoplastic processes. Of the representatives of the first group, preference, of course, should be given to azidothymidine: thanks to it, it is possible to weaken clinical manifestations, improve the general condition of patients and prolong their life. However, recently, judging by some publications, a number of patients have developed refractoriness to this drug. The second group includes immunomodulators (levamisole, isopripozin, thymosin, thymopentin, impreg, indomethacin, cyclosporin A, interferon and its inducers, taktivin, etc.) and immunosubstitutes (mature thymocytes, bone marrow, thymus fragments). The result of their use is rather doubtful, and a number of authors generally deny the expediency of any stimulation of the immune system in patients with HIV infection. They believe that immunotherapy may promote unwanted reproduction of HIV. Symptomatic therapy is carried out according to nosological principles and often brings noticeable relief to patients. As an illustration, we can refer to the result of electron beam irradiation of the main focus of Kaposi's sarcoma.
Prevention of its spread should form the basis of the modern fight against HIV infection. Here, special attention should be directed to health education in order to change behavioral and hygiene habits. In sanitary and educational work, it is necessary to reveal the ways of transmission of the disease, emphasizing that the main one is sexual; show the perniciousness of promiscuity and the need to use condoms, especially with casual contacts. Persons at risk are advised not to participate in donation, and infected women - to refrain from pregnancy; it is important to warn against sharing toothbrushes, razors and other personal hygiene items that may be contaminated with the blood and other body fluids of those infected.
However, infection is impossible by airborne droplets, through household contacts and through food. An important role in the fight against the spread of HIV infection belongs to the active identification of those infected through the use of test systems for the determination of antiviral antibodies. Such a definition is subject to donors of blood, plasma, sperm, organs and tissues, as well as homosexuals, prostitutes, drug addicts, sexual partners of patients with HIV infection and infected, patients with venereal diseases, primarily syphilis. Serological testing for HIV should be carried out by Russian citizens after a long stay abroad and foreign students living in Russia, especially those who come from regions endemic for HIV infection. The urgent measure to prevent HIV infection remains the replacement of all single-use syringes, or at least strict adherence to the rules of sterilization and the use of conventional syringes.
AIDS is one of the most important and tragic problems facing all mankind at the end of the 20th century. And it's not just that many millions of people infected with HIV have already been registered in the world and more than 200 thousand have already died, that one person is infected every five minutes on the globe. AIDS is a complex scientific problem. Until now, even theoretical approaches to solving such a problem as cleaning the genetic apparatus of cells from alien (in particular, viral) information are unknown. Without a solution to this problem, there will be no complete victory over AIDS. And this disease has raised many such scientific questions ...
AIDS is a major economic problem. The maintenance and treatment of the sick and infected, the development and production of diagnostic and therapeutic drugs, the conduct of basic scientific research, etc. are already worth billions of dollars. The problem of protecting the rights of AIDS patients and those infected, their children, relatives and friends is also a very difficult one. It is also difficult to address the psychosocial issues that have arisen in connection with this disease.
AIDS is not only a problem for physicians and health workers, but also for scientists in many fields, statesmen and economists, lawyers and sociologists.
2. Tuberculosis
Tuberculosis occupies a special place among diseases related to social diseases. The social nature of tuberculosis has long been known. Even at the very beginning of the 20th century, this disease was called the "sister of poverty", the "proletarian disease". In old St. Petersburg on the Vyborg side, mortality from tuberculosis was 5.5 times higher than in the central regions, and in modern conditions the material well-being of people plays an important role in the emergence of tuberculosis. As shown by a study conducted at the Department of Public Health and Healthcare of St. acad. IP Pavlov, and at the end of the 20th century, 60.7% of tuberculosis patients were defined as unsatisfactory financial and material situation.
Currently, the incidence of tuberculosis in developing countries is much higher than in economically developed countries. Despite the great achievements of medicine in the treatment of patients with tuberculosis, this problem continues to be very relevant in many countries. It should be noted that in a certain period our country has made significant progress in reducing the incidence of tuberculosis. However, in the last decade of the 20th century, our positions on this issue have noticeably weakened. Since 1991, after many years of decline, the incidence of tuberculosis in our country began to grow. Moreover, the situation is rapidly deteriorating. In 1998, the number of newly diagnosed patients with tuberculosis in the Russian Federation more than doubled compared to 1991. In St. Petersburg, the incidence of active tuberculosis (per 100,000 population) increased from 18.9 in 1990 to 42.5 in 1996. A number of epidemiological indicators are used to characterize the effectiveness of tuberculosis control.
Morbidity. As noted above, the number of patients newly diagnosed with active tuberculosis in recent years tends to increase.
Of the total number of patients with a first diagnosis, 213 were men, and almost half of them are in persons 20-40 years old. More than 40% of those identified isolated VC, more than 1/3 were first diagnosed with advanced forms of tuberculosis. Firstly, all this indicates an unfavorable epidemiological situation for tuberculosis, and secondly, that the asocial part of society (homeless people, alcoholics, people deprived of liberty for crimes) makes up a significant part of the contingent of newly ill tuberculosis. When accounting for the first time cases, they do not include:
a) patients registered in another district;
b) cases of recurrence of the disease.
Soreness. Indices of morbidity, in connection with the success of the treatment of patients with tuberculosis, and in the period when there was a decrease in the incidence by 5 times, decreased only by 2 times. That is, this indicator, with successful work to reduce tuberculosis, changes at a slower pace than the incidence.
Mortality. Thanks to advances in the treatment of tuberculosis over a 20-year period, the death rate from tuberculosis has decreased by 7 times. Unfortunately, in recent years, positive shifts in reducing the prevalence of tuberculosis as a social phenomenon have stopped and, on the contrary, there are negative trends. The mortality rate from tuberculosis in the Russian Federation more than doubled, amounting in 1998 to 16.7 per 100,000 population.
World experience, as well as the experience of our country, has shown that the most effective treatment and preventive institution for working with tuberculosis patients is an anti-tuberculosis dispensary. Depending on the service area, the dispensary can be district, city, regional. The TB dispensary operates on a territorial-district basis. The entire service area is divided into sections, and a TB doctor is attached to each site. Depending on local conditions (the number of registered persons and foci of tuberculosis infection, the presence of large industrial enterprises, etc.), the population in one phthisiatric site can range from 20-30 thousand to 60 thousand. It is important that the border of several therapeutic sites polyclinics and one phthisiatric site coincided so that the district phthisiatrician worked in close contact with certain general practitioners, pediatricians, and general practitioners.
In the structure of the TB dispensary, the main part is the outpatient link. In addition to the usual offices (doctors' offices, a treatment room, a functional diagnostics office, it is highly desirable to have a dental office. Naturally, an integral part is a bacteriological laboratory and an X-ray room. Some dispensaries have fluorography stations. In addition, there may be hospitals.
The dispensary carries out all the work to combat tuberculosis in the area of operation on the basis of a comprehensive alan. Participation in the implementation of such a plan is very important not only for medical institutions, but also for other departments. Real progress in reducing the incidence of tuberculosis can only be achieved through the implementation of the interdepartmental program "Tuberculosis", which was also developed in St. Petersburg. The main part of the comprehensive plan is sanitary and preventive measures:
Organization of timely detection of patients and revaccination of uninfected;
Organization of timely detection of patients and mass targeted preventive examinations;
Improvement of foci of tuberculosis infection, housing of bacillus carriers;
Labor arrangement of patients;
Sanitary and educational work.
A significant place in the comprehensive plan is occupied by new methods of diagnosing and treating patients, inpatient and sanatorium treatment, and the training of doctors in phthisiology.
There are several ways to identify patients with tuberculosis. The main place is occupied (80% of all identified patients) by identification when patients seek medical help. The role of polyclinic doctors is very important here; as a rule, the sick person goes there first of all. Targeted preventive medical examinations play a certain role. An insignificant place is occupied by the observation of contacts and the data of pathoanatomical studies. The latter method testifies to shortcomings in the work of tuberculosis treatment and prevention institutions.
The TB dispensary is a closed institution, i.e. the patient is sent there by a doctor who detects such a disease. When tuberculosis is detected in any medical institution, a “Notice of a patient with an established diagnosis of active tuberculosis for the first time in his life” is sent to the anti-tuberculosis dispensary at the patient’s place of residence.
The doctor of the TB dispensary organizes a thorough examination and, when clarifying the diagnosis, puts the patient on a dispensary record.
In our country, tuberculosis prevention is carried out in two directions:
1. Sanitary prevention.
2. Specific prevention.
The means of sanitary prophylaxis include measures aimed at preventing infection of healthy people with tuberculosis, at improving the epidemiological situation (including current and final disinfection, education of hygienic skills of tuberculosis patients).
Specific prophylaxis is vaccination and revaccination, chemoprophylaxis.
For successful work to reduce the incidence of tuberculosis, significant state allocations are needed for the provision of housing for bacillus carriers, for the sanatorium treatment of patients, for the provision of free medicines for outpatients, etc.
The WHO's leading TB control strategy is currently the DOTS (Directly observed treatment, short-course) program. It includes such sections as the identification of contagious TB patients seeking medical care by analyzing the clinical manifestations of pulmonary diseases and microscopic analysis of sputum for the presence of acid-fast microbacteria; appointment of identified patients with two-stage chemotherapy.
As the main specific goal of the fight against tuberculosis, WHO puts forward the requirement to achieve recovery of at least 85% of new patients with infectious forms of pulmonary tuberculosis. National programs that succeed in doing this have the following impact on the epidemic; the incidence of tuberculosis and the intensity of the spread of the infectious agent immediately decrease, the incidence of tuberculosis gradually decreases, drug resistance develops less often, which facilitates the further treatment of patients and makes it more accessible.
By early 1995, some 80 countries had adopted the DOTS strategy or were beginning to adapt it to their own circumstances; With about 22% of the world's population living in areas where the DOTS program is being applied, many countries have achieved high TB cure rates.
The adoption of the law of the Russian Federation "On the protection of the population from tuberculosis" (1998) suggests the development of new conceptual, methodological and organizational approaches to the formation of a system of outpatient and inpatient TB care. To stop the aggravation of the problem of tuberculosis in the changed socio-economic conditions in Russia is possible only with the strengthening of the role of the state in the prevention of this infection, the creation of a new concept for the conduct and management of anti-tuberculosis activities.
Preventive measures are taken in all foci, but first of all, in the most dangerous ones. The first step is hospitalization of the patient. After inpatient treatment, patients are sent to a sanatorium (free of charge).
Persons who were in contact with patients are observed in the TB dispensary according to the 4th group of dispensary registration. They are given chemoprophylaxis, if necessary, vaccination or BCG revaccination.
Organization of anti-tuberculosis work.
If the first principle of the fight against tuberculosis in our country is its state nature, then the second principle can be called treatment and prevention, the third principle is the organization of anti-tuberculosis work by specialized institutions, the broad participation of all medical institutions in this work.
The Comprehensive TB Control Plan includes the following sections: strengthening the material and technical base, incl. equipping medical facilities, providing the necessary personnel and improving their skills, taking measures aimed at reducing the reservoir of tuberculosis infection and preventing its spread among the healthy population, identifying patients and treating them.
It must be remembered that tuberculosis is classified as controlled, i.e. controllable, infectious diseases and the implementation of clear and timely measures for the prevention of tuberculosis can achieve a significant reduction in the prevalence of this dangerous disease.
3. Syphilis
Social and economic transformations in Russia in the 1990s were accompanied by a number of negative consequences. Among them is the syphilis epidemic that has engulfed most of the territories of the Russian Federation. In 1997, the incidence of this infection increased by a total of 50 times compared with 1990, and the incidence of children increased by 97.3 times.
The population of all territories of the North-West region of Russia was involved in the epidemic. The highest rates of syphilis incidence occurred in the Kaliningrad region. It should be noted that this area turned out to be the first territory where the HIV epidemic began. The incidence of syphilis in children in 1997 (the year of maximum increase) in the territories of the North-West was characterized by different indicators.
They were the highest in Novgorod, Pskov, Leningrad and Kaliningrad regions. Such areas are called areas of risk. In recent years, the incidence of syphilis has begun to gradually decline, but it is still at a high level. In 2000, more than 230,000 patients with all forms of syphilis were diagnosed in the Russian Federation as a whole, including more than 2,000 cases registered among children under 14 years of age (in 1997-1998, more than 3,000 diseases were diagnosed annually, of which 700 800 cases among children under 1 year of age). According to the dermatovenerological dispensary, in the Leningrad region in 1990-1991. about 90 patients with syphilis were revealed. In 2000, more than 2,000 new cases of the disease were diagnosed. At the same time, it should be noted that among the sick, 34% were rural residents, that is, this problem is not only in big cities. A study of the age structure of those with syphilis in 2000 showed that the bulk (42.8%) were young people aged 20-29 (Fig. 4).
More than 20% in the structure were occupied by men and women of the age group of 30-39 years. However, the group of the highest risk of the disease are persons 18-19 years old. This group, which includes only two age categories, occupied about 10% in the structure of those with syphilis, while other groups include 10 or more age categories of the population. 133 cases of syphilis were also detected among children and adolescents.
To the above, it must be added that in recent years syphilis has taken first place among the causes of abortion for medical reasons. Unfulfilled life, along with the low birth rate in the last decade as a whole, also characterizes the incidence of syphilis as a serious social problem. The high incidence of syphilis, which confirms the changes in the sexual behavior of the population, gives grounds to predict an increase in the incidence of other sexually transmitted infections, including HIV infection.
The epidemiological situation associated with the epidemic growth of sexually transmitted diseases, including syphilis, became so serious that it served as the subject of a special discussion at the Security Council of the Russian Federation, where a corresponding decision was made (Yu. K. Skripkin et al., 1967) . Since syphilis during an epidemic outbreak has significant features that contribute to the activation of the process, attention is paid to improving the effectiveness of treatment, rehabilitation and prevention measures. Attention is drawn to the presence of many factors that provoke and contribute to the increase in the incidence of syphilis.
1st factor - social conditions: extremely low level of information about venereal diseases among the population of the country; a catastrophic increase in drug use; progressive increase in alcoholism; active, immoral propaganda of sex by all types and media; economic trouble of the country; progressive increase in the number of unemployed; no legalized prostitution.
2nd factor: the general medical situation of the country; a pronounced decrease in immunity in a significant part of the population due to impoverishment; an increase in the number of manifest forms of syphilis and malignant, atypical manifestations; it is difficult to diagnose secondary fresh and recurrent syphilis due to the atypicality and small number of rashes, rare accessibility to medical institutions; an increase in the number of patients with latent and unknown syphilis; tendency to self-treatment of a significant contingent of persons.
Serious attention is drawn to the fact that antibiotics are widely used in the country for intercurrent diseases that contribute to immunosuppression and change the clinic and course of the syphilitic process. Syphilitic infection has undergone significant pathomorphism over the past decades. So, V.P. Adaskevich (1997) emphasizes the milder course of syphilis without the severe consequences observed several decades ago. In recent years, tuberculous and gummous syphilis have become rare, as have severe lesions of the central nervous system (acute syphilitic meningitis, tabic pain and crises, tabetic atrophy of the optic nerves, manic and agitated forms of progressive paralysis, arthropathy), gummas of the bones of the skull and internal organs. Severe syphilitic lesions of the liver, aortic aneurysm, aortic valve insufficiency, etc. are much less common. However, diseases of a combined nature - tuberculosis and syphilis, syphilis and HIV infection - have become more frequent.
For the purpose of more detailed information about the features of the modern syphilis clinic, V.P. Adaskevich (1997) summarized the clinical peculiarity of the symptoms of the primary and secondary periods of syphilis, which are characteristic of the present.
Clinical features of the primary period are: the formation of multiple chancres in 50-60% of patients, an increase in the number of cases of ulcerative chancres; herpetic giant chancres are recorded; atypical forms of chancres became more frequent; more often there are complicated forms of chancres with pyoderma, viral infections with the formation of phimosis, paraphimosis, balanoposthitis.
The number of patients with extragenital chancres has increased: in women - mainly on the mucous membranes of the oral cavity, pharynx, in men - in the anus; draws attention to the absence of regional scleradenitis in 7-12% of patients.
Clinical features of the secondary period: roseolous and roseolous-papular elements are more often recorded; rashes of roseolous rash on the face, palms, soles are stated. Atypical roseolous elements are possible in a significant number of patients: elevating, urticarial, granular, confluent, scaly. The combination of palmar-plantar syphilides with leukoderma and alopecia has become more frequent in patients with secondary fresh syphilis.
In secondary recurrent syphilis, a papular rash predominates in patients, less often a roseolous rash. Often there are low-symptom isolated lesions of the palms and soles; in a significant number of patients, erosive papules and wide condylomas of the anogenital region are often recorded. Pustular secondary syphilides are less common, and if they occur, then superficial impetiginous ones.
Attention is drawn to the predominance of cases of secondary recurrent syphilis among the treated contingent of patients, which is a consequence of late negotiability and late detection of fresh forms.
V.P. Adaskevich (1997) and a number of authors note certain difficulties in detecting pale treponomas in the discharge of syphilides. The frequency of detection of pale treponomas in the discharge of chancre in primary syphilis does not exceed 85.6-94% and 57-66% in the discharge of papular elements during repeated studies.
Manifestations of the tertiary period of syphilis are currently rarely recorded and are characterized by the scarcity of clinical symptoms, a tendency to manifestations of a systemic nature from the internal organs, with a mild course. There are almost no cases of tertiary syphilis with abundant tuberculous rashes, gummas, significant bone deformities.
Over the past decades, there has been a pronounced increase in latent forms of syphilis, which, according to some data, account for from 16 to 28% of all cases of the disease detected per year, which can be complicated by significant epidemiological distress.
To successfully reduce the incidence of syphilis, the need for a set of measures has been established. Timely diagnosis with the identification of sources and contacts is combined with the active prescription of modern treatment in accordance with the characteristics of the patient's body and the originality of the symptomatology of the process. The work carried out by many research institutes, departments of skin and venereal diseases of medical institutes, aimed at improving the methods of treating syphilis, has been repeatedly discussed at congresses and international symposiums of dermatovenereologists. At the same time, recommendations and instructions were developed for the use of methods and schemes that were theoretically substantiated and practically verified by many years of clinical observations, providing a full-fledged therapeutic effect.
Principles and methods of treatment. Drugs for the treatment of patients with syphilis are called antisyphilitic drugs. They are prescribed after the diagnosis is established with the obligatory confirmation of its laboratory data. It is recommended to start treatment as early as possible (with early active syphilis firms - in the first 24 hours), since the earlier treatment is started, the more favorable the prognosis and the more effective its results.
Reducing the incidence of syphilis and its prevention is not only a medical task, but the state and society as a whole.
4. Viral hepatitis
Viral hepatitis is a group of nosological forms of diseases that differ in etiological, epidemiological and clinical nature, occurring with a predominant lesion of the liver. According to their medical and socio-economic characteristics, they are among the ten most common infectious diseases of the population of modern Russia.
Currently, the following are subject to official registration in accordance with Form No. 2 of the Federal State Statistical Observation in accordance with ICD-X:
Acute viral hepatitis, including acute hepatitis A, acute hepatitis B and acute hepatitis C;
Chronic viral hepatitis (for the first time established), including chronic hepatitis B and chronic hepatitis C;
Carriage of the causative agent of viral hepatitis B;
Carriage of the causative agent of viral hepatitis C
The last five years have been marked by a significant increase in the prevalence of all nosological forms of viral hepatitis, which is associated both with the next cyclic rise and with a wide range of social conditions of the population that contribute to the implementation of infection transmission routes. In 2000, compared with 1998, the incidence of hepatitis A increased by 40.7%, hepatitis B - by 15.6% and hepatitis C by 45.1%. The rates of latent parenteral hepatitis B also increased by 4.1% and hepatitis C by 20.6%. Started only in 1999, the official registration of newly diagnosed cases of chronic viral hepatitis (B and C) revealed that the figure for the year increased by 38.9%. As a result, in 2000, 183,000 cases of acute viral hepatitis were detected and recorded by the country's medical institutions (including: A - 84, B - 62, C - 31, others - 6 thousand cases); 296 thousand cases of carriage of the causative agent of viral hepatitis B and C (140 and 156 thousand cases, respectively); 56 thousand cases of newly diagnosed chronic viral hepatitis B and C (21 and 32 thousand cases, respectively).
Thus, the number of all cases of viral hepatitis in 2000 exceeded 500 thousand, including the number of acute cases of hepatitis (A, B, C), occurring in manifest and latent form - 479 thousand (of which B and C - 390 thousand cases). The ratio of registered manifest forms to non-manifest ones was 1:2.2 for hepatitis B and 1:5.0 for hepatitis C.
The total prevalence of all forms of hepatitis B and hepatitis C per 100,000 population is practically the same - 152.4 and 150.8. With the exclusion of the number of newly diagnosed cases of chronic viral hepatitis from the indicators, the values will decrease to 138.2 and 129.6, respectively. As for the prevalence of hepatitis A, it is more than 3 times less than each of the considered parenteral hepatitis.
Differences in the frequency and proportion of the incidence of children with various forms of viral hepatitis are clearly visible, which boil down to a significant spread of hepatitis A in children. Among parenteral hepatitis, children are 2 times more likely to have hepatitis B than hepatitis C (both acute and chronic forms). ).
Assessing the significance of hepatitis for public health, let us also cite mortality statistics: in 2000, 377 people died from viral hepatitis in Russia, including hepatitis A - 4, acute hepatitis B - 170, acute hepatitis C - 15 and chronic viral hepatitis 188 people (mortality was 0.005%, 0.27%, 0.04% and 0.33%, respectively).
The analysis of official statistical information outlined the social, medical and demographic contours of the problem of viral hepatitis. At the same time, it is of no small importance to characterize the economic parameters of these infections, which allows using numbers to judge the damage caused to the economy, and ultimately make the only right choice regarding the strategy and tactics of combating them.
Comparison of economic losses associated with one case of hepatitis of various etiologies indicates that the greatest damage is caused by hepatitis B and C, which is associated both with the duration of the course (treatment) of these diseases, and with the possibility of chronicity of the process.
The given damage values (for 1 case), calculated for the Russian Federation, can be used to determine the total economic losses both for the country as a whole and for its individual regions. In the latter case, the size of the error in the obtained significance values will mainly depend on how much the basic parameters of damage per 1 case of the disease differ (the ratio of sick children and adults, the duration of inpatient treatment, the cost of a hospital day, the wages of workers, etc.) in the region and in average for the country.
The greatest economic losses from morbidity in 2000 are associated with hepatitis B - 2.3 billion rubles. Somewhat less damage from hepatitis C - 1.6 billion rubles. and even less from hepatitis A - 1.2 billion rubles.
In 2000, the economic damage from all viral hepatitis in the country exceeded 5 billion rubles, which in the structure of the total damage from the most common infectious diseases (25 nosological forms without influenza and SARS) was 63% (Fig. 2). These data make it possible to characterize viral hepatitis not only in general, but also to compare the economic significance of individual nosological forms.
Thus, the results of the analysis of the incidence and economic parameters of viral hepatitis allow us to consider these diseases as one of the most priority problems of infectious pathology in modern Russia.
5. Anthrax
Anthrax is an acute infectious zoonotic disease caused by Bacillus anthracis and occurs mainly in the form of a cutaneous form, inhalation and gastrointestinal forms are less common.
From 2000 to 20000 cases of anthrax are registered annually in the world. This infection acquired particular relevance after the use of Bacillus anthracis spores as a bacteriological weapon in the USA in the fall of 2001.
Bacillus anthracis belongs to the family Bacilaceae and is a Gram-positive, non-motile, spore-forming and capsule-like bacillus that grows well on simple nutrient media; vegetative forms quickly die under anaerobic conditions, when heated, and under the action of disinfectants. Spores are highly resistant to environmental factors. The main reservoir for the pathogen is the soil. The source of infection is cattle, sheep, goats, pigs, camels. entrance gate
The causative agent of hepatitis B is DNA containing the hepatitis B virus (aka HBV and HVB), also called the Dane particle.
What is syphilis? How can you get syphilis? What is the probability of infection during a single sexual contact without a condom with a patient with syphilis?
The general clinical picture of the immunodeficiency virus, its first symptoms and the order of detection. Possible ways of human infection with AIDS, measures for its prevention and prevention. Conservative treatment of the disease and its effectiveness. AIDS tests.
