1.5.2. Preventive treatment of a latent tubercular infection (tuberculosis chemoprophylaxis) at children

Treatment of a latent tubercular infection is the important component in struggle against a tuberculosis. Though according to M.E. Villarino (2004 [130], prakticheyoskaja the importance of preventive chemotherapy of a latent tubercular infection (LTI) is represented doubtful in the countries with high and enlarged zayobolevaemostju a tuberculosis where priority value gets early vyyojavlenie and treatment sick of a tuberculosis.

In the USA the purpose of strategy of minimising of risk of transfer tuberkulezyonoj infections and case rate depressions is not only early revealing and

Treatment of patients with an active tuberculosis, but also revealings and treatments of persons with layotentnoj an infection, especially in the conditions of restriction of bacterination BTSZH [305].

CART recommended to spend treatment of a latent tubercular infection (preventive chemotherapy) to children aged till 5 years, living in a family with bakteriovydelitelem (as at early age danger of development miliarnogo a tuberculosis and a tubercular meningitis is great), to persons, infitsiyorovannym MBT against a HIV-infection as the risk of annual development akyotivnogo a tuberculosis at them increases.

In our country HP it is applied since 1962, and indications for its carrying out are much wider [64, 65, 66].

The leading place in preventive treatment, both in the world, and in Russia was occupied until recently with the scheme including Isoniazidum, the truth abroad throughout 6-12 months, in our country mainly - 3 months [66, 311]. Efficiency of preventive treatment in risk groups on a tuberculosis is proved by many domestic and foreign authors, probability razviyotija a tuberculosis as a result of the spent preventive treatment umenyoshilas on the average on 60 % [64, 100, 168].

The HIV-infection considerably enlarges risk of development of a tuberculosis at patsiyoentov with a latent infection. In the foreign literature more often profilaktiyocheskoe treatment is recommended to persons with positive tuberkulinovoj a Mantoux reaction (5мм and more) [300] though it is conventional, that at immunosupressii reakyotsija on a Mantoux reaction there is negative, and a risk of development of a tuberculosis poyovyshaetsja many times over. In these cases to the persons who are in contact with "zarazyonymi" with patients with a tuberculosis, recommend preventive treatment without dependence from results of the dermal test [279]. According to some authors the risk of development of an active tuberculosis at treatment latent tubercular inyofektsii decreases especially at persons with positive tuberkulinovoj assay and the lowered quantity of cells CD4 [266, 277].

The researches devoted to treatment of a latent tubercular infection at children with a HIV-infection, it was not spent, therefore references for this kategoyo
rii persons are based in world practice, including Russia, on rekomendayotsijah preventive treatment for the adults, sick HIV-infections, or for children from risk groups on disease by a tuberculosis in the general population.

Applied schemes of preventive treatment at adult sick HIV - an infection practically did not differ from those at adults without a HIV-infection.

The common opinion concerning duration of carrying out of preventive treatment is not present. In many countries prefer to run 9-month's courses proyofilakticheskoj chemotherapies Isoniazidum (H) [291] On opinion of the majority of authors and 6-mejachnye courses provide with Isoniazidum sufficient protection in prevention of disease by a tuberculosis, both at persons with a HIV-infection, and without a HIV-infection.

So by results of two meta-analyses [168,240,308] treatment by Isoniazidum within 6 months considerably reduces risk of development tuberkuyoleza (RR = 0,57-0,58; 95 % of Dee), however are noticed, that thus does not influence a mortality (RR = 0,93 0. 94; 95 % of Dee) sick HIV-infections. In many isyosledovanijah it becomes perceptible, that treatment of a latent tubercular infection was not effective among adult sick HIV-infections with negative tuberyokulinovymi assays and the normal immune status (the range of observations has made 4-33 months) [161, 164, 210, 211, 212, 257].

Considering practical complexities with the organisation long-term prevenyotivnoj therapies, bad adherence of patients to treatment at a long course, were studied short-term regimens of preventive treatment. So in neyoskolkih randomizirovannyh the researches spent in the beginning of 2000, efficiency of application of two antituberculous preparations - rifampicin (R) and Pyrazinamidum (Z) was estimated at treatment of a latent tubercular infection at sick HIV-infections of adults [239,307]. Comparative issleyodovanija 2 regimens more, than on 1500 persons with a HIV-infection and positive tuberkulinovoj breakdown, have shown, that at identical efficiency priveryozhennost than therapy was better in group which received ramfapitsin and pirazi - namid throughout 2 months, than in the group, receiving Isoniazidum and peridok - sin on an extent 12мес. (80 % in comparison with 69 % according to frequency zavershe -

48 nija treatments). In Zambia and Uganda tested regimens on a considerable quantity of patients with a HIV-infection (1053 and 2728 persons). Efficiency of the regimens including Isoniazidum throughout 6 months and ramfapitsina with pirazinami - the house throughout 3 months in relation to platsebo had identical about - tektivnyj effect throughout 3 years of observation [239,324]. Besides predyolagalsja a regimen from 3 antituberculous preparations: Isoniazidum with ramfapitsi - nomas and Pyrazinamidum throughout 3 months which efficiency was same, as well as the previous regimens. However all regimens of preventive treatment did not influence the general mortality of sick HIV-infections [208].

The researches devoted to safety of application of combination RZ, also are ambiguous. Despite convenience of a short-term regimen of preventive treatment with including of rifampicin and Pyrazinamidum during 2 or 3 mesjayotsev, many authors noted high toxicity of the offered combination of the preparations causing serious undesirable reactions from a liver, especially at persons of not infected HIV cases of a lethal outcome [276,277, 291] are described. According to other numerous researches of regimens, soyoderzhashchih ramfapitsin and Pyrazinamidum, the last did not cause serious pobochyonyh effects at treatment of a latent tubercular infection in persons, infitsiroyovannyh a HIV [164, 165, 208, 215, 239, 300, 307, 314]. Considering, that many issleyodovanija in the subsequent confirmed a treatment hepatotoxic rifampitsiyonom and Pyrazinamidum (frequency of undesirable reactions from a liver vstreyochalas from 6,9 % to 13,0 % of cases) in comparison with Isoniazidum, not challenging its efficiency [267, 268, 285], CDC did not recommend use ramfapi - tsina (rifabutina) in a combination to Pyrazinamidum at the persons who have been not infected with a HIV, and with care - at sick HIV-infections [296].

The scheme of preventive treatment of persons with polozhiyotelnoj tuberkulinovoj assay by rifampicin within 4 months has been besides, offered at ustojyochivosti to Isoniazidum [278, 279]. Last years, in connection with increase sick of a tuberculosis with plural medicinal fastness of the originator, pojavyoljajutsja reports on use with the preventive purpose ftorhinolonov

At persons from contacts with MLU MBT, however these researches individual and ispolzoyovanie ftorhinolonov for preventive treatment of persons with LTI it is surveyed as potential possibility [178].

Thus, the analysis of the foreign literature has shown, that for adult persons with a HIV-infection some schemes of preventive treatment layotentnoj are recommended to a tubercular infection, but the scheme, vkljuyochajushchaja Isoniazidum prescribed throughout 6-9 months is preferable.

Under the reference the CART with a HIV-infection is recommended to children appointment of preventive treatment, as well as the adult, with a positive Mantoux reaction or at contact to a sick tuberculosis, even if tuberkulinovaja assay at these children negative. References on treatment of a latent tubercular infection are reduced to Isoniazidum appointment daily within 6 months or two times a week throughout 9-12 months [291, 296]. Thus preparation reception should be supervised with the control of biochemical indicators of function of a liver.

At children with a HIV-infection a two-month course of daily reception rifamyopitsina and Pyrazinamidum with the preventive purpose it was not studied in force povyyoshennoj toxicity sochetannoj combinations of preparations, therefore naznayochat it it is not recommended to children [130]. In the Great Britain two schemes of treatment and children and adults with a latent tubercular infection are accepted: rifampicin and izoniayozid within 3 months or monotherapy by Isoniazidum within 6 months [258]. At fastness of the originator to Isoniazidum, it is recommended to prescribe rifampiyotsin to 6 months (in the absence of HIV-infection treatment nenukleozidnymi ingibiyotorami return transkriptazy and protease inhibitors).

Results of researches show, that preventive treatment concerning LTI Isoniazidum of children with a HIV-infection reduces a case rate tuyoberkulezom on 72 % and a mortality from all reasons on 64 % [209, 210, 211, 212, 216]. However according to some authors preventive treatment by Isoniazidum does not give advantages (under condition of absence of contact to a sick tuberculosis) if to children with a HIV-infection since a birth begin art and regularly survey on a tuberculosis [261].

Thus, to children with a HIV-infection for treatment latent tuberkuyoleznoj infections the scheme including Isoniazidum throughout 6-9 months is preferable.

In the Russian Federation recommend at early stages of a HIV-infection chemoprophylaxis of a tuberculosis by the adult to prescribe at revealing new sluyochaja a HIV-infection and at contact to a sick tuberculosis. At late stages - at depression CD4 to 200 mkl, occurrence of clinical implications of a HIV - of an infection (a stage 4Б, 4В, 5) and a current of a HIV-infection of 7 years and more. The regimen hi - mioprfilaktiki includes Isoniazidum and Pyrazinamidum (Ethambutolum) for 3 months or Isoniazidum for 6 months at early stages of a HIV-infection and at late stages before immunity restoration (CD4 should not be less than 200 mkl) [110, 134 142].

Now the unique document defining carrying out of preventive treatment to children from groups of risk, the new medical technology № ФС-2007/137 Treatment of children and teenagers with latent tuberkuyoleznoj an infection is. In the given document standard regimens proyovedenija HP with the duration indicating (from 3 till 6 months) and quantities PTP (from one to two) depending on risk factors of disease by a tuberculosis where a HIV-infection it is defined as a risk factor [68] are defined.

Alternative way of preventive maintenance of a tuberculosis at children from a HIV - an infection.

It is necessary to consider as an alternative method of preventive maintenance antiretrovirusyonuju therapy which the CART recommends to spend irrespective of level virusyonoj loads at children with a HIV-infection aged till 5 years; pregnant women and kormjayoshchih a breast from a HIV - an infection.

Earlier beginning of treatment of a HIV-infection can promote podyoderzhaniju health of patients, to reduction of quantity of a virus in blood, that sniyozhaet the risk of transfer of a HIV-infection, risk of a birth of the child from a HIV - the positive status and, accordingly, will allow to lower rates dalnejsheyogo diffusions of an infection [218].

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Scientific source KLEVNO HOPE IVANOVNA. TUBERCULOSIS At CHILDREN, SICK HIV-INFECTIONS (prevalence, features of clinical implications, diagnostics, treatment, preventive maintenance). The dissertation on competition of a scientific degree of the doctor of medical sciences. Moscow - 2015. 2015

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