diagnostics of a tuberculosis at children with a HIV-infection

The approach to diagnostics of a tuberculosis in the presence of a HIV-infection basically the same, that idlja diagnostics of this disease without a HIV-infection. OdnaYOko at persons with a HIV-infection timely diagnostics of a tuberculosis can be complicated with often enough meeting at them atypical clinical karyotinoj diseases and low, up to negative, sensitivities to tuberyokulinu.

Diagnostics of a tuberculosis at children, sick HIV-infections, in the absence of bacteriological acknowledgement of the diagnosis, is based on clinical priyoznakah, contact to a sick tuberculosis in the anamnesis, results tuberkulinoyovoj dermal assay and radiological methods of research of organs of a thorax [126,162,167,170].

Clinical signs of a tuberculosis prospektivno have been investigated in koyogorte from 596 South African children with bakteriologicheski confirmed diyoagnozom a tuberculosis in the presence of a HIV-infection or without it. At disease by a tuberculosis such symptoms, as tussis, prodolzhajuyoshchijsja more than two weeks (57,7 %), loss of mass of a body (53,4 %) or impossibility to type weight, rise in temperature (47,7 %) [198] more often were observed. In India at 49 % of children with kulyoturalno the confirmed pulmonary tuberculosis, the augmentation periyofericheskih lymph nodes [174] was observed.

However these symptoms are not specific to a tuberculosis and moyogut to be bound to other HIV-assotsiirovannymi conditions as at 25 % of children similar chronic symptoms became perceptible at absence tuberkuyoleza [162].

It is necessary to notice, that methods of revealing and tuberculosis diagnostics in razyonyh world regions, including in Russia (taking into account availability high tehnoyology), therefore researches in Southern Africa hardly reflect all projavleyonija a tuberculosis at children, including with a HIV-infection.

Timely and early revealing of a tubercular infection is vazhyonym the factor of the prevention of the widespread and complicated forms tuberkuyo
leza at children as clinical signs of disease or are absent, liyobo appear at advance of tubercular process [7]. Early vyjavyolenie a tubercular infection it is based on revealing of hypersensitivity of the slowed down type in sensibilizirovannom MBT an organism. First of all, it is dermal tuberkulinovye the tests offered in the beginning of the last century [245, 283].nesmotrja that tuberkulinovym to assays (Mantu) more than 100 years, tuberyokulinovaja dermal assay is still rather informative for statement diyoagnoza a tuberculosis at children [198], including at children with a HIV-infection though it is less sensitive at the infected HIV in comparison with neinfitsiroyovannymi a HIV [226, 234, 249, 266]. In the general population approximately at 10 % of children with normal immunity at an active tuberculosis reaction to a Mantoux reaction appears negative [287, 292, 316].pri it as authors note, the share negative tuberkulinovyh assays depends on the disease form: At sohranyonom immunity tuberkulinovye assays appear negative in 17 % of cases miliarnogo a tuberculosis and only in 3 % of cases of a pulmonary tuberculosis.

At a HIV-infection tuberkulinovye assays have limited diagnoyosticheskuju the importance as the HIV, causing disturbances in the immune status, in larger degree bound with T-limfotsitami, can lead to depression of response to a tuberculin.

The researches spent to Romania (1997-2005гг.), have shown zavisiyomost expressions of reaction to a tuberculin (10 THOSE) from quantity With І) 4T - lymphocytes: the infiltrate more than 5 mm was registered at children with maintenance CD4 of cells more 500в mkl in 88,0 % of cases, at number CD4 of cells less than 400 in mkl - this share was considerably smaller [60].

Summary data about frequency of registration negative tuberkulinovyh assays at children, sick HIV-infections and a tuberculosis, we have found in the accessible literature. However researches of small groups of children with a HIV-infection and tuyoberkulezom, show, that among them a share of negative reactions on tuberkuyolin it is ready above, than at a tuberculosis at children without a HIV-infection [186, 199, 253, 254, 269, 290, 303, 304].

Since 2000, there were researches on diagnostics tuberkulezyonoj infections by means of test system on the maintenance of interferon at in integral blood in vitro Quanti FeRoNj-tuberculosis (company Cellestis Limited manufactures, Sent-Kilda, Australia). Test of the given test has shown, that as a whole it will well be compounded with results tuberkulinovoj assays, but more spetsifiyochen as does not depend on bacterination BTSZH, allows to distinguish true becoming infected M. Tuberculosis. Therefore interpreting of results of this test is less subjective, than interpreting of results tuberkulinovoj assays [191]. In November, 2001 CDC has officially approved application of this test system for diagnostics of a tuberculosis at adults with normal immunity, however it yet has not received a wide circulation at children and sick HIV-infections.

The research spent among zambijskih sick tuberculosis with poyolozhitelnym by a smear of a sputum, has allowed to establish statistically significant depression of sensitivity of test Quanti FERON-TB among persons with a HIV-infection (63 %), in comparison with not infected HIV patients (84 %) [201].

The immunoenzymatic method (ELISPOT) for tuberculosis diagnostics opreyodeljaet quantity of the T-cages cosecreting interferon scale, after stimuljayotsii two antigens - fiber of a filtrate of crops (CFP-10) and early sekretoryonym antigenic fiber (ESAT-6) is considered more perspective for revealing of a tubercular infection at persons with a HIV-infection for the purpose of risk definition razyovitija diseases [282, 313].

In prospektivnom research of 293 African children sensitivity ELISPOT (Т-Spot) was considerably above in comparison with tuberkulinovym kozhyonym the test (83 % against 63 %), including at children with a HIV-infection: at low tuberkulinovoj sensitivities (36 %), sensitivity ELISPOT remained high (73 %) [204].

Authors assume, 4TOELISPOT for diagnostics active and latentnoyogo a tuberculosis at the persons infected with a HIV, it can appear more informativyonym, than tuberkulinovyj the dermal test, though sensitivity of the test also sniyozhaetsja in process of reduction of number CD4 of cells [284].

However the volume of researches in children's practice is still limited, it is not enough data for global conclusions and references [259].

In the Russian Federation the tuberculinodiagnosis to today's momenyota is the basic mass method of revealing of a tubercular infection and a tuberculosis at children. Unfortunately, this method of early diagnostics of a tuberculosis has smaller value at a HIV-infection.

At research tuberkulinovoj to sensitivity at adult sick by a tuberculosis and a HIV-infection it is shown, that the number of positive takes of a Mantoux reaction decreases in process of advance of a HIV-infection and depression of CD4-lymphocytes: at maintenance CD4 in blood less than 200 cages/mkl - frequency of negative results on a Mantoux reaction with 2ТЕ makes 80 %, at soderzhayonii CD4 100 cages/mkl frequency of registration of positive takes not preyovyshaet 10 %, though at patients without an immunodeficiency (CD4 cells more than 500 in mkl) frequency makes them 90-95 % [48,51,131].

Probably at introduction of the big doses of a tuberculin (5ТЕ) efficiency of revealing of a latent tubercular infection at this category of patients can be raised [28].

In children's practice while there are no researches on sensitivity to tuberkuyolinu depending on HIV-infection and degree stages immunosupressii. In individual publications data on frequency positive and otritsayotelnyh reactions to a Mantoux reaction with 2 THOSE (are cited including at a tuberculosis), poluchenyonye at inspection of children born from women, sick HIV-infections. Expressed and giperergicheskie reactions to a tuberculin in this case are taped in 15-33 %, negative - within 15 % of cases [22,47,79,89,128].

Since 2009, dermal trouble-shooting test on analoyogii with tuberkulinovym the test, allergen tubercular rekombinantnyj in stanyodartnom delution of 0,2 mkg in 0,1 ml (Diaskintest) is applied. The given test is based on vyyojavlenii the cellular immune answer (development of reaction of hypersensitivity of the slowed down type) to stimulation by specific antigens M. tuberculosis (ESAT-6 and CFP-10) at persons with a tubercular infection, excepting the vaccine

Strain BTSZH [85]. The expression and secretion of fibers ESAT-6 and CFP-10 are closely bound to process of reproduction MBT that has been shown on models infected tuyoberkulezom animals. This fact has found reflexion with a view of and problems of application of allergen tubercular rekombinantnogo in clinical practice, especially among children [196].

Now the test is widely applied to diagnostics of a tuberculosis among the adult and children's contingents observed in antituberculous establishments as its sensitivity at an active tuberculosis is very high and makes 85-96 % [26, 41, 116].

In children's practice, besides, the test is widely applied to diagnostics of an "active" tubercular infection. According to many authors, allergen tuyoberkuleznyj rekombinantnyj possesses larger specificity, than tuberkuyolin, that pozvoljaetvyjavljat high risk of transition latent tubercular inyofektsii in an active tuberculosis and in due time to spend preventive leyochenie [31, 69, 85, 90, 113], to form groups of high risk on disease by a tuberculosis [13, 24,118, 119].poslednie years tubercular rekombiyonantnyj offer allergen as screening of revealing by true tubercular inyofektsii among the general population of the children's population [2, 31, 189].

Researches on application and efficiency of allergen tubercular rekombinantnogo at persons with a HIV-infection not numerous, but they show comparability of results to results of a Mantoux reaction.

L.V.Slogotsky's researches and co-workers. (2011 [106], executed on priyomeneniju the test at 88 patients with a tuberculosis combination (various localisation) and HIV-infections, have shown: sensitivity of the test has made 30-40 % (at 95 % of Dee), that much more low, than at persons with a tuberculosis without a HIV-infection. CHastoYOta positive takes on allergen tubercular rekombinantnyj zaviyosit from quantity Cd4-limfotsitovi it is comparable to sensitivity to tuber - kulinu [24,26,48, 106]. Probability of negative results on allergen tuyoberkuleznyj rekombinantnyj above, than on a tuberculin (69,8 % and 77,9 %), but akyo
tivnyj the tuberculosis authentically was more often taped at persons with the positive test for allergen tubercular rekombinantnyj, than on a tuberculin (3,9 % and 7,1 %) [27].

Data on application of assay with allergen tubercular rekombiyonantnym at children with a HIV-infection individual on an example of 5-10 children [47, 89].

Thus, the literature analysis has shown, that at children, sick HIV - an infection, sensitivity to a tuberculin in dependence otraspro - stranennosti process, a HIV-infection and degree stage immunosupressii is not studied.

The tuberculinodiagnosis defines a circle of persons (risk group), which neyoobhodimo a X-ray inspection for the purpose of revealing local tuyoberkuleza. Besides radiological inspection is shown all persons with symptoms suspicious on a tuberculosis and to children from the infection centres, poyoskolku they are most vulnerable on disease by a tuberculosis.

On the conclusion of many authors, the X-ray pattern at issledoyovanii thorax organs is characterised by similar signs at infitsiyorovannyh and not infected HIV of children with the confirmed diagnosis tuberyokuleza [198, 242, 290, 297]. However interpreting of results of roentgenography of organs of a thorax becomes complicated in connection with similar symptoms, vyzvanyonymi other HIV-assotsiirovannymi conditions and diseases [221]. BoYOlee that, the roentgenogram of organs of a thorax can be in norm even at the active form of a tuberculosis as it was observed in India at 56 % from 148 children by which the diagnosis has been confirmed bakteriologicheski [174].

The picture of radiological changes in leyogochnoj tissues at adult sick of a tuberculosis and a HIV-infection, which razyolichajutsja depending on HIV-infection stages is widely enough studied. At early stages of a HIV - of an infection the radiological semeiology of tubercular process is similar with takoyovoj at persons without a HIV-infection [10,129,133].

At late stages of a HIV-infection at a serious immunodeficiency rentgeyonologicheskaja the picture is atypical: infiltrates bilaterial, are localised more often in the bottom departments, in most cases there are no caverns, uvelichivayo
etsja frequency of an intrathoracic adenopathy, appears focal or focal dis - the seven-nation, a lesion of serous covers [10, 15, 55, 143, 178].

As at children more often in pathological process at a tuberculosis intrathoracic lymph nodes (75 %) traditional rentgenoyologicheskoe inspection are involved (the survey roentgenogram and the linear tomogram) oryoganov a thorax often enough does not allow to tap process in limfatiyocheskih mediastinum knots, or the doctor exposes the tuberculosis diagnosis at otsutyostvii direct signs of the last. The error of such radiological method of inspection submitted various authors fluctuates in limits of 43,0 % 60,0 % [33, 53, 63, 107].naibolshej informativnostju the computer tomography of organs of a thorax which gives the chance to tap neznayochitelnee changes in a pulmonary tissue and in VGLU [32, 37, 59, 119, 197, 246] possesses.

Possibly, computer tomography should become a choice method diagnoyostiki a tuberculosis at children with a HIV-infection, especially at negative tuberyokulinovyh assays and presence of clinical symptoms of respiratory character when late diagnostics can lead to generalisation tubercular inyofektsii. Though interpreting of data and decision-making in favour of certain disease depend on qualification of the doctor and the roentgenologist, and the phthisiatrician.

In L.F.Shamuratovoj's research and co-workers. (2011 [58] from 13 children, sick HIV-infektsieji a tuberculosis 7 bolnymdiagnoz established during from 1 till 5 months from the disease beginning, that at 2 children has led to development generaliyozovannogo a tuberculosis.

As a whole, radiological implications of a tuberculosis at children from a HIV - an infection in aggregate with various implications of a HIV-infection not izucheyony.

The bacteriological method of diagnostics of a tuberculosis at children does not possess tayokoj the importance as at adults as children, owing to features tuberkuyoleznogo process, are not in the majority bakteriovydeliteljami. CHasYOtota detection M. tuberculosis by means of microscopy and bacteriological methods at children it is insignificant. According to some foreign researches hour
tota originator allocation kulturalnym a method makes less than 50 %, and diyoagnosticheskaja value of microscopy of the smears painted on Tsilju-Nilsenu, it appeared even more low [213, 297]. Many authors assume, frequency obnaruyozhenija the originator should be above at children, sick HIV-infections [186, 199, 253, 269, 303, 316].

Thus, the literature analysis has shown, that at children with a HIV-infection, especially at its late stages, tuberculosis diagnostics in larger degree should be based on the anamnesis (contact to a sick tuberculosis), klinicheyoskoj a picture of disease and radiological methods of diagnostics, a predpochyotitelno-computer tomography.

For early revealing and diagnostics of a tubercular infection very much vayozhen the fact of early diagnostics of a HIV-infection as last is znayochimym a risk factor of transition of a latent tubercular infection in zabolevayonie. Acknowledgement of the diagnosis of a HIV-infection on the first year of a life is possible at reception of two positive takes of inspection on a genetic material of a HIV. After 1,5 years acknowledgement of the diagnosis of a HIV-infection at children is carried out as at adults [23, 35, 62, 81].

1.4.