[Effectiveness of new diagnostic drug Diaskintest in children for tuberculosis diagnostic].

DST was ascertained to have a high sensitivity in virtually all patients with tuberculosis and a positive reaction was first noted in the infected. With stabilization and regression, the response to DST was much less pronounced than that in clinical and primary infection (that to the Mantoux test being more evident). DST showed its use as a marker of active tuberculosis not only in its local forms, but also in latent tuberculous infection. This makes it possible to apply DST when preventive treatment is performed. The agent may be used to monitor the progress of treatment. DST has a high specificity--healthy individuals had a negative response to DST while the Mantoux test was positive in many cases. The high specificity of DST was suggested by the fact that the persons vaccinated with (this caused BCG ostitis) had a negative reaction to DST while the Mantoux test was positive in all cases BCG-vaccinated BCG. The findings warrant the use of DST for the differential diagnosis of tuberculosis and BCG-associated complications and the possibility of differentiating postvaccinal and infection allergy in children and adolescents.

[Clinical trials of the new skin test Diaskintest for the diagnosis of tuberculosis].

A new reagent for a skin test given the name Diaskintest has been designed for the screening diagnosis of tuberculosis and preclinical and clinical trials conducted. Preclinical trials were carried out on 315 laboratory animals (guinea-pigs, albino mice). The reagent Diaskintest was ascertained to be nontoxic, to have no sensitizing properties, to be safe and specific, and to induce no positive reactions in BCG-vaccinated animals and healthy guinea-pigs. Its specific activity was comparable with that of the national reference--purified tuberculin PPD-L-2. With progression of tuberculous lesions, the guinea-pigs showed higher responses to Diaskintest dilution and the BCG-vaccinated animals lacked responses to Diaskintest with increased delayed type hypersensitivity. The clinical trial was permitted by the Federal Service for Surveillance in Health Care and Social Development of the Russian Federation. Clinical trials were conducted in 150 persons. The safety, specificity, sensitivity of Diaskintest were first examined in the clinical studies and its action was compared with the results of tuberculin skin test (Mantoux test) with 2 TE of PPD L-2. Diaskintest was ascertained to be highly sensitive when given in a dose of 0.2 microg in 0.1 ml. In patients with active tuberculosis and new cases of Mycobacterium tuberculosis infection, the agent induced a positive skin reaction (a papule of more than 10 mm) in 98-100% of cases (p < 0.05). The agent caused no reaction associated with BCG vaccination. The specificity of the test was 93-100% with 95% significance. The rate of overexuberant reactions (vesicular necrotic changes, lymphangitis, and lymphadenitis) was 4-14% with 95% significance. Tuberculosis patients with significant immunopathological disorders might have no skin sensitivity to Diaskintest, as to PPD L-2 (a negative test). The findings substantiate the use of Diaskintest for mass epidemiological surveys for the differential diagnosis of tuberculosis and BCG vaccination-associated complications. The agent may be also used to evaluate the activity of the process in patients with tuberculosis and the efficiency of treatment in combination with other methods and to make a differential diagnosis of tuberculosis.

[Vaccine prophylaxis of tuberculosis: implication and problems].

The paper presents data on vaccine prophylaxis in Russia. A sophisticated analysis of the data available in the literature on approaches to vaccination against tuberculosis in different countries of the world is provided. The results of the studies made by Russian investigators to develop different regimes of BCG re-administrations an their frequencies are given. The fact that it is necessary to change a tuberculosis prophylaxis calendar under the present conditions, by keeping in mind the age of a child and the epidemic situation in the country's region, has been established. A particular section is dedicated to the problem associated with the occurrence of complications in response to tuberculosis vaccine. Based on the Federal Center data on complications due to BCG/ BCG-M, the authors provide information on the incidence and pattern of complications occurring in Russia. As compared with 1995, the incidence of postvaccination complications slightly changed (21.1 in 100,000 in 1995 versus 20.3 in 2002-2003). In the children inoculated at a maternity hospital, postvaccination lymphadenitis was observed 2 times more frequently than in those vaccinated at a polyclini (77.1 and 37% of cases, respectively) and cold abscesses were 3.3 times less frequently than those inoculated at the polyclinic (19.1 and 63% of cases, respectively). The study has ascertained main reasons for the higher incidence of severe complications as BCG ostitis.

[The quality of bacteriological detection and determination of drug sensitivity of Mycobacterium tuberculosis by the participants of the External Clinical Laboratory Study Quality Assessment made by the Federal System in 2002-2003].

The paper presents the results of the assessment of the quality of cultural detection and determination of Mycobacterium tuberculosis (MBT) sensitivity at Russia's public health laboratories, which has been made by the Federal System for External Assessment of the Quality of Clinical Laboratory Studies in 2002-2003. The "Bacteriological Detection" Section involved 102 laboratories, of them 57 laboratories also participated in the section "Detection of Drug Resistance". Sixty-three laboratories operated as part of specialized tuberculosis-controlling service facilities and 39 laboratories worked as part of general medical care therapeutic-and-prophylactic institutions. A set of 5 lyophilized samples containing 2.5 x 10(6) M. tuberculosis H37Rv (n = 1); 2.5 x 10(4) M. tuberculosis H37Rv (n = 2); M. fortuitum (n = 1); E. coli in the mixture with autoclaving-killed M. tuberculosis H37Rv (n = 1). 77% of the laboratories could detect in the cultural sample with a high content of M. tuberculosis, by obtaining a correct result; 85% revealed MBT if only in every three MBT-containing samples; 15% of the laboratories could not find MBT in none of the three positive samples. 12% of the laboratories took the growth of microorganisms in the M. fortuitum-containing sample for that of M. tuberculosis. 58% of the laboratories obtained correct results if only in one sample containing M. tuberculosis H37Rv; 42% reported the detection of resistance to one or several antituberculous drugs in the samples containing the drug-sensitive strain H37Rv (a false drug resistance). All the results of determination of drug resistance (DR) in the M. fortium-containing sample were correct. The findings suggest that it is necessary to increase the professional competence of laboratory personnel to the level that ensures the adequate of fulfillment of the standard protocols for detecting MTB and determining DR, which have been introduced by the Ministry of Health of the Russian Federation through its order No. 109 on March 21, 2003.

[Antituberculosis antibodies in patients with tuberculosis during chemotherapy]. / Protivotuberkuleznye antitela u bol'nykh tuberkulezom legkikh v protsesse khimioterapii.

Enzyme immunoassay of the titer of antituberculosis antibodies (ATAb) from patients with pulmonary tuberculosis has indicated that their levels depend on the different characteristics of a specific process: the form of active tuberculosis, the extent of changes in the lung tissue, the presence of destruction and bacterial isolation, the type of specific inflammatory reaction, and the duration of the treatment performed. Whether there was a correlation of ATAb titers with skin tuberculin sensitivity the level was studied by the Mantoux test using 2 TE PPD-L. The time course of changes in ATAb titers in patients with pulmonary tuberculosis during the routine chemotherapy was analyzed.

[BCG vaccination: characteristics of drugs and causes of vaccinal complications]. / Vaktsinatsiia BTsZh: kharakteristika preparatov i prichiny postvaktsinal'nykh oslozhnenii.

Series of BCG and BCG-M vaccines causing complications in children vaccinated in Russia's areas in 1995 were checked up. All the series met the Russian and international specifications for BCG and BCG-M vaccines. The incidence of postvaccinal lymphadenitis was 5 times less than the limit laid down by an official article. The properties of the agents produced no significant effect on the number and type of postvaccinal complications. The risk for complications was much less when BCG-M was used. The risk factors were defects of intradermal vaccine administration and contaminant abnormalities prior to vaccination and at the moment of local vaccinal response.

[The detection of mycobacteria in children and adolescents by using the polymerase chain reaction]. / Vyiavlenie mikobakterii s pomoshch'iu polimerazno-tsepnoi reaktsii u detei i podrostkov.

A polymerase chain reaction (PCR) was used for determination of mycobacterial DNA in clinical samples from children and adolescents. The results were positive in 23 and 53% of cases, respectively, while standard microbiological methods failed to show presence of any bacteria in the samples. Case histories contained information on high incidence of positive Mantoux test. Microbiologically the diagnosis was confirmed only in 7 adolescents. In children mycobacteria were not found.

[The level and spectrum of antituberculosis antibodies in BCG-vaccinated mice and in mice and rabbits infected with a virulent mycobacterial culture]. / Uroven' i spektr protivotuberkuleznykh antitel u vaktsnirovannykh BTsZh myshei i zarazhennykh virulentnoi kul'turoi mikobakterii myshei i krolikov.

The authors examined CBA mice infected with a virulent culture (H37 Rv), BCG-vaccinated mice and intact mice and rabbits infected with a virulent culture Bovinus-8 after preliminary sensitization. It was established that the level of antituberculous antibodies in the enzyme-linked immunoassay was higher in H37 Rv infected mice than in BCG-vaccinated animals (regardless of the used antigen, the ultrasonic disintegrator BCG or H37 Rv). The spectrum of antituberculous antibodies was different in the infected and vaccinated mice, the infected mice showed additional bands in the 20 kD area. The level of antituberculous antibodies was higher in rabbits with a limited process than in those with a disseminated process. With the latter, antibodies to antigenic determinants that had lower molecular weight (25-35 kD) were detectable.

[BCG revaccination of school children in circumstances of low incidence of tuberculosis]. / Revaktsinatsiia BTsZh u shkol'nikov v usloviiakh nizkoi zaboloevaemosti tuberkulezom.

The results of study of a tuberculosis infection course in different conditions and its association with BCG revaccination are presented. The Moscow region was tentatively divided into 3 groups of regions. Children of Group 1 were not given revaccination at 7 and 12 years, those of Group 2 at 12 years and those of group 3 received revaccination according to the routine techniques at 7, 12 and 17 years. BCG revaccination withdrawal caused no increase in tuberculosis morbidity and tuberculin sensitivity. Tuberculosis detections were unassociated with the frequency of previous BCG revaccination.

[Comparative evaluation of the effectiveness of vaccination of newborn infants with BCG and BCG-M vaccines]. / Sravnitel'naia otsenka éffektivnosti vaktsinatsii novorozhdennykh vaktsinami BTsZh i BTsZh-M.

A comparative effectiveness of the newborn BCG- and BCG-M vaccination was analysed as to the indices of primary infection, morbidity and its structure. The rate of postvaccination complications in 1,645,360 children, aged under 3 years, and living in the areas with different epidemiological situations for tuberculosis was studied too. 2,142,292 and 799486 healthy newborns were BCG- and BCG-M-vaccinated, respectively. The studies were carried out in Moscow, Kiev, Vilnius++ and Tashkent. The obtained results indicate that the number of complications in the form of regional lymphadenitis induced by BCG-M vaccine is 5 times less frequent than those caused by BCG. Under favourable epidemiological conditions, the primary infection and morbidity are alike, while under unfavourable ones the former is higher, particularly in infants in their first year as compared to the BCG-vaccinated. On the basis of the available data BCG-M can be recommended for the vaccination of all the newborns living in the areas with a favourable epidemiological situation for tuberculosis, thus increasing the newborn vaccination coverage and bringing the morbidity down.

[Method for immunization against tuberculosis using BCG-M vaccine--a preparation with a reduced antigenic load]. / Metod immunizatsii protiv tuberkuleza vaktsinoi BTsZh-M--preparat s umen'shennoi antigennoi nagruzkoi.

Experimental and clinical investigations on the possibility of reducing the antigenic content of the vaccine intended for the immunization of newborn infants have been made. Experiments on guinea pigs and white mice have demonstrated that the reduced dose of the preparation, twice as low by weight (0.025 mg), produces the same level of protection against tuberculosis as the full dose (0.5 mg). A new preparation with reduced antigenic content, vaccine BCG-M, has been developed, the technical specifications for this preparation have been approved, and its serial production has been allowed. Clinical tests have revealed that the use of the new preparation makes it possible to decrease the occurrence of unusual postvaccinal reactions and complications (lymphadenitis, ulceration) 3-fold and at the same time to increase the coverage of infants by primary immunization against tuberculosis by 7-8% annually. Since January 1986 this vaccine has been introduced into medical practice.

[A new method of applying a tuberculin ointment for cutaneous use compared to the Mantoux test]. / Izuchenie novogo metoda applikatsii tuberkulinovoi mazi dlia nakozhnogo primeneniia v sravnenii s proboi Mantu.

The method for the applications of tuberculin ointment for the skin test by means of special aluminum chambers (Finn Chambers, obtained from Epitest Ltd. OY, Finland) was approved after trial. For control, the Mantoux test (intracutaneous tuberculin test) was used. The results of these two tests, made in parallel, were found to coincide in children with clinical symptoms of tuberculosis, or infected with Mycobacterium tuberculosis, in 84% of cases. The tuberculin skin test with the use of Finn Chambers proved to be more sparing, painless and safe. At the present stage of investigation, the new skin test may be recommended for children of preschool age.

[Biologic effect of atypical mycobacteria against a background of BCG vaccination]. / Eksperimental'noe izuchenie biologicheskogo deistviia atipichnykh mikobakterii na fone vaktsinatsii BTsZh

A study was made of the specific sensitivity to tuberculin in the animals vaccinated with BCG in case of their additional sensitization with various atypical mycobacteria. The mentioned experimental study appeared to be necessary for the purpose of a more proper treatment of the epidemiological date referred to the sensitivity of man to tuberculin and sensitins against the background of mass BCG vaccination. Preliminary BCG vaccination of the animals with their subsequent infection with atypical mycobacteria altered the allergic response to the antigens from the mycobacteria increasing the response reactions not only to tuberculin, but also to sensitins from mycobacteria of the I--III groups by Runyon's classification, closely connected in antigenic respect with mycobacteria tuberculosis. Skin reactions to sensitins from the saprophytic mycobacteria which had in their composition much less common antigens with mycobacteria tuberculosis, remained at the low level. Sensitization with atypical mycobacteria of animals preliminarily vaccinated with BCG failed to cause significant influence on the production of immunity to the subsequent virulent infection with tuberculosis.