INTRODUCTION

Theme urgency

Now the World organisation of public health services and the United Nations Organization declared a tuberculosis and a HIV-infection the interconnected global problems of the destructive action demanding nezamedliyotelnogo an intervention [34,35].

By 2005 in the Russian Federation the fastest rate of diffusion of epidemic of a HIV-infection in the world [158] is fixed. M.I.Perelman with strayonits magazine «Problems of a tuberculosis and illnesses of lungs» (2005) has turned vnimayonie medical community (doctors of phthisiatricians, infektsionistov, others spe - tsialistov) on importance of studying of a problem sochetannoj pathologies of a tuberculosis and a HIV-infection, necessities to develop scientific and organizational asyopekty struggle against a tuberculosis and a HIV-infection as growth of number of sick HIV-infections and a case rate among them a tuberculosis have got ugrozhajuyoshchy character [96].

Even more often in epidemic process, both on a HIV-infection, and on tuberyokulezu, women, mainly young (genesial) age [153,158] are involved. Now in the world it is registered more than 30 million persons with a HIV-infection from which more than 40 % - women, and their share is constantly enlarged. From the beginning of development of epidemic of a HIV-infection it is registered boyolee 5 million children infected with a HIV owing to perinatalnoj of transfer. In Rosyosijsky Federation the quantity of children, born to the wife is annually enlarged
shchinami with a HIV-infection (in 2012 12402 children were born, that in 1,8 times bolyoshe, than in 2007).

The indicator of a case rate of a HIV-infection of children of 0-14 years on 100 thousand deyotej corresponding age was enlarged by 28 % - with 2,6 in 2005 до3,6 on 100 thousand in 2012г.

The unsuccessful situation as a whole on a tuberculosis and a HIV-infection in RosYOsii should be reflected in an epidemiological situation among children. According to the World organisation of public health services about 1 million ill with a tuberculosis are children aged till 15 years that makes 11 % from all new cases of disease. The risk of disease by a tuberculosis among children from a HIV - an infection, according to some authors, in 100-200 times above, than at children without a HIV-infection [306].v a case rate a tuberculosis deyotej (0-14лет) remains to the Russian Federation enough high. Annually are ill with a tuberculosis more than 3000 children from 0 till 14 years inclusive. The share of children sick tuberkuleyozom, sochetannym with a HIV-infection, makes 1,3 % - 1,5%случаев from all zaboyolevshih a tuberculosis of children of this age (among children of 15-17 years - 0,2 %). However the case rate a tuberculosis of children among sick HIV-infections is high: in 2012г.

The expected forecast the next 5 years on diffusion of a tuberculosis among sick HIV-infections in the Russian Federation adverse [141]. By 2020 among for the first time registered sick of a HIV-infection tuberculosis will have to 30 % sick (10 % now), on separate regions - to 40-50 % of patients [83]. Hence, the number of children with a tuberculosis among sick HIV-infections as they are in same social medium will accrue.

Features of a current, diagnostics, tuberculosis treatment, sochetannogo with a HIV-infection, at adults are in detail enough studied [10,11,15,24,46,136]. At children the tuberculosis problem, sochetannogo with a HIV-infection, to the present vreyomeni in a complex was not studied. In the domestic literature there are individual
Publications on sochetannoj pathologies at children born from women from a HIV - by an infection, and mainly, povoprosu bacterinations BTSZH of these children [21,47,128,154,155].

Studying influence of a HIV-infection on a tuberculosis current, will allow optiyomizirovat diagnostics and preventive maintenance of a tuberculosis at children, the sick HIV - an infection which are a priority direction of children's phthisiology.

Research objective: Scientifically to prove and develop a complex of measures on poyovysheniju efficiency of the antituberculous help to children sick of a HIV - by an infection, by studying of features of implication of a tuberculosis, sochetannogo with a HIV-infection.

Research problems

1. To carry out the analysis of prevalence of a tuberculosis, sochetannogo from a HIV - an infection, among children of 0-14 years in the Russian Federation on the basis of the given forms of the state statistical observation.

2. Vyjavitosobennosti implications of a tuberculosis at children, sick HIV - an infection.

3. To give the characteristic of a current of tubercular process depending on a clinical stage of a HIV-infection and maintenance CD4 ⁺-limfotsitov in periferiyocheskoj to blood sick of a tuberculosis, sochetannogo with a HIV-infection.

4. To study clinical implications of a HIV-infection at children of patients tuyoberkulezom, sochetannogo with a HIV-infection.

5. To analyse methods of revealing and diagnostics of a tuberculosis at deyotej, sick HIV-infections to estimate efficiency of application dermal imyomunologicheskih assays at different stages of a HIV-infection.

6. To estimate efficiency and safety preventive protivotu - berkuleznyhmeroprijaty at children born from women, sick HIV - an infection.

7. To study schemes of antituberculous treatment of children of patients tuberkuyolezom, sochetannogo with a HIV-infection, to define the most effective and bezoyopasnye chemotherapy regimens in a combination with antiretrovirusnymi preparations.

8. To develop tactics diagnostikii a technique himioprofilaktikituber - kuleza at children, sick HIV-infections, with uchetomklinicheskih and immunologicheyoskih stadijzabolevanija.

Scientific novelty

1. For the first time in the Russian Federation the problem tuberyokuleza, sochetannogo with a HIV-infection, at children at the age of 0-14 years is in a complex studied. It is spent anayoliz prevalence of a tuberculosis at children with a HIV-infection to Russia as a whole and on separate regions.

2. Features of implication of a tuberculosis at children, sick HIV - by an infection, ustanovlenazavisimost tjazhestituberkuleznogo process from a stage of a HIV-infection and immunodeficiency degree are taped.

3. Low diagnostic value of immunologic assays (Mantu with 2ТЕ and with allergen tubercular rekombinantnym) is established at revealing of a tubercular infection at children, sick HIV-infections, at depression koliyochestva Cd4-limfotsitov in peripheric blood less than 350 kl/mkl, less than 20 % on the basis of what the algorithm of diagnostics of a tuberculosis on late stayodijah a HIV-infection in the presence of an immunodeficiency is developed.

4. It is confirmed clinical and immunologic effektivnostproti - votuberkuleznoj bacterinations of children born from women, sick HIV - by an infection, but not infected HIV. It is proved low clinical and immunoyologicheskaja effektivnostprotivotuberkuleznoj to bacterination of children, infitsiroyovannyh a HIV. The positive role antiretrovirusnoj is shown therapy in preduyoprezhdenii serious forms of a tuberculosis, as alternative method profilaktiyoki.

5. Application in third of cases of individual schemes himioyoterapii in a combination with antiretrovirusnymi preparations is proved.

6. Prognostic value of depression of CD4-lymphocytes less than 350 kl/mkl, less than 20 % in development disseminirovannyh tubercular processes that allows to spend the differentiated approach to carrying out profilakyoticheskih actions is proved.

The practical importance of work

On the basis of studying of clinical implications of a tuberculosis at a combination to a HIV-infection:

- Criteria of risk of development disseminirovannyh forms tuberyokuleza at children with a HIV-infection are defined;

- The algorithm of diagnostics of a tuberculosis at children on late stayodijah a HIV-infection is developed;

- Indications are defined and reports of preventive treatment of a latent tubercular infection and chemoprophylaxis of a tuberculosis at children, sick HIV-infections are offered;

- Necessity of early bacterination against a tuberculosis of children born from sick HIV-infections of mothers, not infected HIV is proved;

- Low efficiency of bacterination against a tuberculosis of children infected with a HIV is proved;

- The importance in due time begun antiretrovirusnoj is shown therapy in the prevention disseminirovannyh forms of a tuberculosis and efficiency in the combined treatment of a tuberculosis;

- Improvement diagnostic and preventive protivotuyoberkuleznyh actions at children, sick HIV-infections, will be sposobstvoyovat to earlier revealing of a tuberculosis at children with a HIV-infection and preduyoprezhdeniju developments disseminirovannyh its forms, as a whole to rising effekyotivnosti the antituberculous help to children, sick HIV-infections.

The personal contribution of the author

The author independently develops the research plan; a definite purpose and research problems; the state-of-the-art review of the literature and the statutory acts regulating questions of the organisation of medical aid of patients with a combination of a tuberculosis and a HIV-infection is spent.

The author independently spent the collecting of a primary material, since 2005, requesting data under specially developed questionnaires on patients that -
berkulezom, sochetannym with a HIV-infection. At the initiative of the author hospitalisation sick of a tuberculosis and a HIV-infection from any region Russian Federation in children's unit of clinic of scientific research institute ftiziopulmonologii the First MGMU of I.M.Setchenov is organised

All material presented to the dissertations, is received, processed iproa - nalizirovan personally by the author.

Introduction of results of research

Dissertational work was a fragment of a complex theme «Kliniyoko-laboratory aspects of a tubercular infection at children and teenagers and orgayonizatsija the antituberculous help in the conditions of epidemiological neblayogopoluchija on a tuberculosis» (the principal managing department of a tuberculosis at deyotej and teenagers of scientific research institute FP, d.m.n., professor V.A.Aksenova).

Within the limits of the State contract № К-32-НИР/114-14от 31октября 2011 the project of order MZ the Russian Federation about modification is prepared and additions in Order MZ the Russian Federations from 31.01.2011 № 51н «About the statement of a national calendar of preventive inoculations and inoculations under epidemic indications» On the basis of children's unit of a university hospital of scientific research institute ftiziopul - monologii the First MGMU of I.M.Setchenov are provided chambers for gospiyotalizatsii children sick of a tuberculosis, sochetannym with a HIV-infection, in vozrasyote 3-14 years.

Dissertation materials have entered into working out of the following methodical reyokomendatsy:

Federal clinical references on diagnostics and treatment tuberyokuleza at sick HIV-infections (are confirmed by the Russian society ftiziatyorov, the report of session of Presidium of Board ROF from 14.10.2013. № 4);

Federal clinical references on diagnostics and treatment layotentnoj a tubercular infection at children with section including under reports of preventive treatment of children with a HIV-infection (are confirmed Russian obshcheyostvom phthisiatricians, the report of session of Presidium of Board ROF from 23.01.2014. № 1);

Federal clinical references on diagnostics and treatment tuberyokuleza organs of breath at children (are confirmed by the Russian society of phthisiatricians, the report of session of Presidium of Board ROF from 23.01.2014. № 1);

Federal clinical references on diagnostics and treatment tuberyokuleza organs of breath with plural and wide medicinal ustojchivoyostju the originator (are confirmed by the Russian society of phthisiatricians, the report zayosedanija Presidium of Board ROF from 14.10.2013. № 4);

The patent for the invention № 2473346 is received: «the Way of treatment lekarstvenno - the induced lesion of a liver at children sick of a pulmonary tuberculosis».

Publications. On a dissertation theme 65 printing works, including 19 articles in the editions recommended VAK are published.

Dissertation approbation. Dissertation materials dolozhenyi are discussed on scientifically-practical actions of various level, the cores from them: VIII Russian congress of phthisiatricians (Moscow, 5-7); scientifically-practical conference with the international participation «the Tuberculosis at children and teenagers» (Moscow, 17-18.12.2009); scientifically-practical conference «Actual problems of a tuberculosis, sochetannogo with a HIV-infection» (Moscow, 6-7); XX National Congress by illnesses of organs of breath (Moscow, 16-19.11, 2010); IX Russian congress of phthisiatricians (Moscow, 1-3); II Balkan interdisciplinary medical forum (Bulgaria, nesebr, 29, 2011); School-seminar «Problems of a tuberculosis at sick HIV-infections» (Moscow, 16-17.05.2011); the All-Russia scientifically-practical conference

«Medical aid perfection by a sick tuberculosis (Sankt - Petersburg, 20-22.10.2011); scientifically-practical conference« mezhdistsipliyonarnye aspects of differential diagnostics and treatment of patients tuberkuleyozom »(Moscow, 18-20.04.2012); Conferenceofte Union Europe Region (London 4­6.07.2012); 1st Congress of National Association of phthisiatricians (S-peterburg, 18­20.10.2012); IV scientifically-practical conference with the international participation« Actual problems of a tuberculosis at sick HIV-infections »(Moscow, 24.11.2012); General Assembly of Medical Association Balkan and
The Prichernomorsky countries «the Multidisciplinary approach to treatment zabolevayony: from diagnostics before development of the concept of treatment» (Bulgaria, nesebr, 21 22.09.2012); scientifically-practical conference «the Tuberculosis at children and teenagers» (Minsk, 12.12.2012); the All-Russia scientifically-practical conference with the international participation «Pressing questions of preventive maintenance, diagnostics and treatment of a tuberculosis at children and teenagers» (Moscow, 28­29.03.2013); XX Congress «the Person and a medicine» (Moscow, 17.04.2013); XXIII NaYOtsionalnyj the congress by illnesses of organs of breath (Kazan, 22-25.10.2013); the All-Russia scientifically-practical conference with the international participation (Moscow, 18-20.12.2013); II All-Russia scientifically-practical conference with the international participation «Pressing questions of preventive maintenance, diagnostics and treatment of a tuberculosis at children and teenagers (Moscow, 26-28.03.2014); Vserossijyosky scientifically-practical conference with the international participation «the Tuberculosis and a HIV-infection - threat of double epidemic. Pressing questions of preventive maintenance, diagnostics and treatment» (Moscow, 1-3); World Conferenceon Lung Healthof - theInternational Union Against Tuberculosisand Lung Disease (TheUnion), 45th (Bar - selona, Ispania, 2014); III Congress of National association of phthisiatricians (About Petersburg, 27-29.11.2014).

The substantive provisions which are taken out on protection:

1. The leading reason of a HIV-infection at children at the age of 0-14 years is perinatalnaja HIV transmission. A case rate a tuberculosis of children from a HIV - an infection in tens times above, than a case rate of children without a HIV-infection. The tuberculosis mainly at children aged till 7 years on pozdyonih HIV-infection stages is extended.

2. Clinical implications of tubercular process are more expressed at deyotej with a HIV-infection, than at children without a HIV-infection and are in a straight line zaviyosimosti from a clinical stage of a HIV-infection and quantity of Cd4yo-lymphocytes in peripheric blood.

3. The current of a HIV-infection at sick of a tuberculosis is accompanied naliyochiem secondary diseases and clinical syndromes that makes heavier a current
Specific process also limits application of antituberculous preparations in full.

4. The anergy (35,2 %) on allergens tubercular does not allow in bolshinstyove to tap cases a tuberculosis at children, sick HIV-infections, profilaktiyocheski. Sensitivity of dermal trouble-shooting tests decreases in process of depression CD4 ⁺-limfotsitov in peripheric blood.

Tactics of early revealing and diagnostics of a tuberculosis at children from a HIV - should be built by an infection depending on clinical and immunologiyocheskoj HIV-infection stages.

5. Bacterination BCG of children born by sick HIV-infections zhenshchiyonami, but not infected HIV, is safe and effective. Bacterination BCG deyotej, the infected HIV, is rather safe and ineffective. antiretyorovirusnaja therapy (art) reduces protective effect of vaccine BCG.

6. Complex treatment sick of a tuberculosis, sochetannogo from a HIV - an infection, in third of cases demands an individualization of regimens of chemotherapy. art is an effective component of complex treatment. Preventive therapy of a tubercular infection is an effective method of preventive maintenance of a tuberculosis at which appointment it is expedient to consider all factors risyoka tuberculosis developments, including degree immunosupressii.

Volume and dissertation structure. Dissertational work sostoitiz vveyodenija, the review of the literature, materials and methods, sobstvennyhrezultatov, obsuyozhdenija the received results, conclusions and prakticheskihrekomendatsy and the literature list. Work is stated on 349страницах, contains 88 tables, illjustriroyovana 50 drawings and 2 klinicheskimiprimerami. The literature list includes 160 domestic and 167зарубежных sources.