Diaskintestj in diagnostics of a tubercular infection

Successes of modern medicine have allowed to synthesise rekombinantnyj fiber ESAT6 - CFP10 (Renshaw P.S., Panagiotidou P., Whelan A., 2002; Ravn P Waters W.R., Nonnecke B.J., Palmer M.V., 2004; Andersen P., Munk M.E., 2005).

Last years, according to the order of Ministry of Health of the Russian Federation № 855 from 29.10.09"About modification of the appendix 4 to the order of Ministry of Health of Russia from March, 21st, 2003 №109», it is applied ^Diaskintestj, representing tubercular rekombinantnyj fiber. Fiber is produced by genetically modified culture Escherichia coli BL21 (DE3)/pCFP-ESAT. This fiber is dissolved in a sterile isotonic phosphatic buffered solution with preservative (Phenolum). It contains two antigens which are available in virulent strains MBT and absent in BTSZH. Preparation structure: in one dose (0,1 ml) 0,2 mkg of fiber rekombinantnogo, sodium fosfornokislogo two-replaced 2-water, sodium of Sodium chloridum, a monosubstituted potassium fosfornokislogo, polisorbata 80, Phenolum (0,25мг), waters for injections - to 0,1 ml (Litvinov V. I, Slogotsky L contain. V, Seltsovsky Item P, 2009).

The technics of statement and the account of results is spent, as at a Mantoux reaction (Order MZ the Russian Federation from 29.10.09 № 855).

^Diaskintestj causes specific reaction in persons with a tubercular infection, thus at vaccinated BTSZH reaction on ^Diaskintestj is absent. The test allows to differentiate reactions at the infected
M.tuberculosis. It is applied at diagnostics of activity of tubercular process at children and teenagers (Aksyonova V. A, Klevno N.I., etc., 2009).

The finding of markers specific to a tubercular infection (or antigens) has allowed to overcome the basic disadvantages of a tuberculin - a difficult admixture of fibers and peptides of a bacteriemic cell and products of their degradation. The structure of a tuberculin with the high maintenance of "a ballast material» also has defined its low sensitivity and specificity at patients with the weakened immunity, at persons, sensibilizirovannyh atypical micobacteria or BTSZH (Huebner R.E., Schein M.F., Bass J.B., 1993, Menzies R.I., 2000).

In 2008г. Safety of application of a new preparation for diagnostics of a tubercular infection at people in vivo (Arend S.M has been described., Franken W.P.J., Aggerbek H., 2008).

The preparation has been framed on a basis rekombinantnogo dimera ESAT6 (early secreted antigenic target, early specific antigen M. Tuberculosis) also has successfully passed a phase of clinical tests. It has been established, that early secretory fibers CFP10 (culture filtered protein) and EAST6 (early secreted antigenic target) deletsionnogo region 1 (RD1) M. Tuberculosis play a key role in development of a tubercular infection in vivo. The proof of it, the work spent on mice (Majlessi L is., Brodin P., Brosch R., 2005). These given steels a basis for working out of preparation ^Diaskintestj M. Tuberculosis - CFP10 and EAST6. Preparation Industrial production ^{"Diaskintestj"} has been organised on the basis of Joint-Stock Company «Pharmaceutical firm" ЛЕККО "(the Vladimir region).

^Diaskintestj has passed doklinicheskoe research which has shown, that the preparation is nontoxical and specific (Reece S.T., Stride N., Ovendale P., 2005).

Rekombinantnyj allergen tubercular ^Diaskintestj possesses the expressed biological activity concerning the porpoises infected with virulent strain M. Tuberculosis H 37Rv also does not cause the answer at vaccinated BTSZH porpoises. The preparation is effective for becoming infected diagnostics by virulent strains M. Tuberculosis also is more sensitive in comparison with a standard tuberculin, now in use.

Clinical researches are carried out. ^Diaskintestj at sick of an active tuberculosis causes the expressed dermal reaction that proves its application at tuberculosis diagnostics (Kiselyov V. I, Baranovsky P. M, Pupyshev S.A., 2008, Kozlova A.V., Shuravina M. G, 1995, Litvinov V. I, Slogotskaja L.V., Seltsovsky Item P, 2009).

Data tuberkulinovogo the PPD-L and assay ^Diaskintestj test at a tuberculosis in an advance phase do not differ at for the first time taped tuberculosis in a phase beginning kaltsinatsii, that confirms high activity of tubercular process, despite "visible" self-healing with formation kaltsinatov in a pulmonary tissue and (or) lymph nodes (Dovgaljuk I.F., Pavlova M. V, Skvortsova L.A., Starshova A.A., 2007).

In 2008-2009гг. On the basis of scientific research institute ftiziopulmonologii MMA of I.M.Setchenov, the Samara regional antituberculous dispensary, the Ryazan regional antituberculous dispensary the method of continuous single-step selection carries out research with preparation ^Diaskintestj - persons from risk groups on disease by a tuberculosis in which result advantages of early revealing of implications of a tubercular infection are proved at use of the developed technique with use
Dermal assay with preparation ^Diaskintestj and to the subsequent observation in the conditions of an antituberculous dispensary (Aksenova V. A, Klevno N.I., 2010, the Instruction on application ^{"Diaskintestj"} 2008, Order MZ the Russian Federation about 21.03.2003 №109, Order Minzdravsotsrazvitija of Russia from 29.10.2009, Glantz S.A., 2001).

According to Slogotskoj L.V., Litvinova V. I, Filippova A.V. and soavtr. 2009, researches of specificity and sensitivity of the dermal test with application of preparation ^Diaskintestj which results have shown high sensitivity at an active tuberculosis are carried out, and at hidden - latentoj a tubercular infection: at the persons treated concerning local forms of a tuberculosis, not finished treatment, the high percent (83,8 %) positive reactions on ^Diaskintestj, at children who have finished treatment becomes perceptible, positive reactions are noted in 78,3 % of cases, the highest sensitivity ^Diaskintestj is noted at children in the presence of family contact with bakteriovydeliteljami (91,7 %).

Frequency of negative results ^Diaskintestj at healthy infected MBT patients has made 56 % - specificity of a method. Frequency of positive takes at 87,9 % sick of a tuberculosis - sensitivity of a method. In the presence of positive take ^Diaskintestj frequency of disease by a tuberculosis in 4,95 above, than at negative ^Diaskintestj (Kasimtseva O. V, Demihova O. V, Karpin N.L., 2011)

In the literature experience of application ^Diaskintestj at children and teenagers is presented at various variants of a tubercular infection to Chuvashiya (Vozjakova T.R., Masterova A.V., Gavrilova G. H, etc., 2011).

It is studied informativnost ^Diaskintestj at children and teenagers with various activity of tubercular process of organs of breath and vnelegochnoj
Localisations, specificity of the test in groups of the dispensary account at persons with a latent tubercular infection and contact, dynamics of change of reaction against chemoprophylaxis and chemotherapy is estimated. Sensitivity to ^Diaskintestj has made 93,3 % among all forms of a tuberculosis and 92 % among forms with a lesion of organs of breath, and larger value took place at patients with active process in breath organs. Reaction to a tuberculin and the size of papule ^Diaskintestj has a relationship of cause and effect: reaction to a tuberculin is especially expressed, the it is more and reaction on ^Diaskintestj (factor Pirsona 0,48) communication a straight line, average degree of expression. Only at persons with positive Mantoux reactions positive takes ^Diaskintestj took place, parodoksalnyh reactions were not, i.e. there is no positive assay on ^Diaskintestj without corresponding reaction to a Mantoux reaction. Persons with a postvaccinal allergy did not have positive takes on ^Diaskintestj. At children of group of the risk, having accurately come into contact to a sick tuberculosis, positive reaction on ^Diaskintestj in 3 times more often, than at not having it. Contact presence was accompanied by augmentation of quantity positive and even giperergicheskih results on ^Diaskintestj. It is shown, that from risk groups children with positive ^Diaskintestj which on the average make 49 % are subject to carrying out HT. Against chemotherapy within 3 months, reaction on ^Diaskintestj changes slightly. As a result of chemotherapy the size ^Diaskintestj decreases only in the end of course of treatment (Vozjakova T.R., Masterova A.V., Gavrilova G. H, etc., 2011).

In work of employees TSNIIT of Gubkinoj M. F, Ovsjankinoj E.S., Ershovoj N.G., Hohlovoj J.J., under the guidance of director TSNIIT Yerokhin V.V. (2011г), sensitivity ^Diaskintestj in group of patients with is minimum active changes taped only at carrying out is studied
KT ogranov a thoracal cavity which has made 100 % that allows to recommend ^Diaskintestj for the differentiated approach to carrying out KT to children observed in groups of risk on a tuberculosis. Authors do a conclusion, that most this algorithm is shown children with high and accruing in dynamics and giperergicheskoj sensitivity on a Mantoux reaction and from the centres of a tubercular infection. Also it is taped, that at negative result ^Diaskintestj at infected MBT persons (6 group of the account), but in the presence of additional risk factors and remaining high sensitivity on a Mantoux reaction with 2ТЕ, carrying out KT also is shown. In these cases there is a probability of revealing of tubercular changes in a phase of an involution without activity signs prootsessa (Gubkin M. F, Ovsjankina E.S., Ershova N.G., Hohlova J.J., Yerokhin V.V., 2011).

Diagnostics vnelegochnyh forms at early stages is one of phthisiology challenges (Gurjev O. I, Oshchepkova N.M., 2011). Have applied dermal assay with ^Diaskintestj to identification of a tuberculosis of peripheric lymph nodes at children and teenagers. By comparison of dermal assay ^Diaskintestj and Mantoux reactions with 2ТЕ it is authentic more significant for differential diagnostics of a tubercular and nonspecific lymphadenitis is ^Diaskintestj (Gurjev O. I, Oshchepkova N.M., 2011).

Often there are problems at diagnostics of a tuberculosis at persons with the expressed accompanying pathology (Zaharova A.V., Makovej J.V., Majstar R. V, Kladova E.T., etc., 2011). It is studied ^Diaskintestj in an estimation of activity of a tuberculosis at patients with accompanying mental diseases. It is shown, that informativnost ^Diaskintestj in an estimation of activity of a tuberculosis at patients with mental diseases makes more than 70 %. The greatest quantity of positive assays became perceptible at
bakteriovydelitelej with MLU - 89 %. At for the first time taped patients the number of positive assays on 24 % exceeded a similar indicator at is long ill patients. Informativnost ^Diaskintestj allows to use it for screening in psychiatric hospitals, and also in inspection programs on a tuberculosis of nontransportable persons.

Tuberculosis revealing at use of assay with ^Diaskintestj in quality skriningovogo a method of inspection of children at the age from 1 till 7 years has made 0,07 % from number of the surveyed and 2,0 % from number of the persons reacting on ^Diaskintestj. The Intracutaneous test with ^Diaskintestj can be used at skriningovom inspection of children with a tubercular infection (Aksenova V. A, Klevno N.I., Baryshnikova L.A., 2011).

Application of an intracutaneous test with DST as screening on a tubercular infection promotes: to reduction of number of children of the preschool age requiring interpreting of reactions more than in 15 times; to augmentation of the contingents observed in VI group of the account at the phthisiatrician more than in 2 times. The indicator of risk of a primary becoming infected is comparable to an indicator of number of children positively reacting to assay with DST (Baryshnikova L.A., Iljasova E.V., Lebedeva N.O., Aksenova V. A, 2011).

The analysis of results of complex inspection has shown, that reactions on DST were positive, including giperergicheskimi, at active tubercular process. Negative reaction on dstregistrirovalas at healthy children and children with inactive tubercular process, thus reactions to a tuberculin at these children were positive and giperergicheskimi. At sick of active tubercular process and infected MBT children from contact with sick of a tuberculosis reaction on DST more expressed (giperergicheskie reactions, including with a lymphangitis, vezikulo - necrotic reactions) in comparison with reaction to a tuberculin.

Application KT of organs of a thorax has larger value in comparison with traditional rentgenotomograficheskimi methods in revealing of "small" forms of a tuberculosis at children and teenagers. Hence, application of assay with DST in a complex with KT thorax organs can raise efficiency of diagnostics of a tuberculosis (Belova E.V., Stakhanov V. A, 2011).

^Diaskintestj has shown high sensitivity and at the latent, so-called latent tubercular infection (Valiev R. SH, Fatyhova R. H, Teplov Etc., Bikkenina G. K, 2011).

The comparative analysis of results tuberkudinodiagnostiki and ^Diaskintestj in the Voronezh area indications for appointment himioprofilakticheskogo allow to narrow treatments to children with a latent tubercular infection taking into account risk factors. The computer tomography is a necessary method of inspection of children and teenagers at expressed and giperergicheskom DST. It is expedient to include the given method in the medical standard of inspection at an exception of diseases of a tubercular aetiology, especially among children from tubkontakta and with risk social factors (Ikonina I. V, Odnolko O. V, Skovzgird I.N., 2011).

The accompanying pathology influences expression of positive reaction on DST towards its rising (Lozovsky M. E, Belushkov V.V., Novik G. A, Gurin O. P, SHibakova N In, 2011)

^Diaskintestj can be used both for the purpose of early revealing of a tuberculosis, and for the purpose of differential diagnostics for the first time taped infiltrativnyh changes in lungs at children and teenagers (Ovsjankina E.S., Gubkin M. F, Ershova N.G., Kobulashvili M. G, 2011) the Divergence of results of laboratory and dermal tests at 3 from 40 patients can speak that there are no exact criteria positive
Reactions QF while the papule of any size DST is regarded as positive reaction (Slogotskaja L.V., Kochetkov J.A., Ivanova D.A., Senchihina O. JU, Aleshchenkova O. I, Kulikovskaja N.V., Vaneeva T.V., 2011).

Assay with preparation ^Diaskintestj raises efficiency of revealing of a tuberculosis at children and teenagers with chronic nonspecific diseases in the conditions of the general medical network (Sokolsky E.A, Klevno N.I., Aksenova V. A, Baryshnikova L.A., 2011).

Screening of children on a tuberculosis should be spent more specific preparation ^Diaskintestj, having excluded parallel application of assay with a tuberculin. At a reaction estimation on ^Diaskintestj it is expedient to apply 2 terms: "positive" - at an infiltrate of 5 mm and more in diameter; "negative" - at absence or presence of an infiltrate to 5 mm in diameter. The erroneous term «doubtful reaction» has no demonstrative base and value in clinic. Hyperergichesky reactions are observed in single instances and studying of specifications on performance of assay (Stavitskaja N.V., Doroshenkova A.E., Molchanova N.V., 2011) demand.

In 61,7 % of cases it is defined normergicheskaja sensitivity to a tuberculin at ill children that does not allow to estimate activity of a tubercular infection. Sensitivity DST in diagnostics TVGLU in comparison with a tuberculinodiagnosis has made 74,5 % against 38,3 %, specificity - 71,9 %, against 46,4 %, diagnostic efficiency of 73,2 % (DST) against 42,4 % (tuberculinodiagnosis) (Starshinova A.A., Korneva N.V., Dovgaljuk I.F., 2011).

Use of diagnostic assay with preparation ^Diaskintestj at children of younger age of Stavropol Territory gives the chance to avoid "bend" hyperdiagnostics tuberkulinovyh assays. The received results at inspection of children from IV group of a dispensary observation show
Larger risk of development in them of a tuberculosis, than at children from VI group (Terehina T.V., Baronova O. D, Moiseeva N.N., 2011). Contact to the sick tuberculosis allocating steady against antituberculous preparations MBT, is a risk factor of occurrence of a lekarstvenno-steady tuberculosis at children and teenagers. More often it is long the existing not separated closely related (family) contacts (Kavtarashvili S.M., Klevno N.I., Madasova V. G, Aksenova V. A, 2011).

Thus, experience of carrying out DST within 5 years, shows ambiguity of results, high efficiency of diagnostics to 80 %. The comparative characteristic of results of assay with preparation Diaskintestj with earlier known tuberkulinovymi assays at children with active forms of a tuberculosis is in a studying stage. This theme is actual now. The special problem is made by data about presence of negative result ^Diaskintestj at an active tuberculosis, imeeno and dissertational research is devoted this problem.