[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.

[Detection of tuberculosis in Moscow adolescents].

Retrospective analysis of the data available in the reporting form 0-89/y-[cyrillic letter: see text] and information analytical tables for Moscow tuberculosis monitoring) over 7 years on all notified new cases of tuberculosis among 15-17-year-old children has indicated that it is necessary to change the procedure for detecting tuberculosis for this age group of children in order to improve the early diagnosis of the disease. The Mantoux test is likely to be rather effective in examining adolescent schoolchildren and students from secondary specialized establishments and ineffective among unorganized young people and in migrants' families. Planned fluorography is of rather informative value in all the groups under study if there is a timely referral for examination. The authors consider whether it is worth making a tuberculosis 2 TE PPD-L in organized collective bodies (schools, colleges, etc.). Other groups of children may undergo only digital small-dose fluorography. Unorganized children above 10 years of age who lack annual Mantoux test results must be referred for digital small-dose fluorography. Refusal to undergo fluorography is justifiable only if there is no tuberculin sensitivity or evident symptoms of intoxication. In the megapolis, due to uncontrolled migration, a lawmaker must consolidate the statute on that mandatory control should be exercised over 15-17-year-old adolescents who must undergo fluorography during their each visit to a health care facility, on entering an educational establishment, or on employment. On consulting a physician, the adolescent who has undergone fluorography 6 months before must have it again.

[Tuberculin diagnosis in children with a family history of allergy].

Two hundred and eighteen Mycobacterium tuberculosis-infected children and adolescents aged 4 to 18 years were examined. Whether the patients and their relatives had a history of allergic reactions was ascertained. A complex of diagnostic studies is of great value in verifying the presence of concomitant allergic diseases. The rate of allergic reactions in the child's history does not itself determine the likelihood of development of allergic states. The Mantoux (tuberculin) test in allergic children does not lead to an exacerbation of the underlying disease at remission. The remission manifestations of paraallergy are noted in 15.8% of the patients with allergic diseases and in 42.9% of the children having allergic reactions in the history. This supports the quality of a follow-up and treatment by an allergist, as well as an adequate response to a Mantoux test with 2 TE of PPD-L in the bulk of allergic children. The use of antihistamines as preparation for the test allows an inference about true infection and the sensitivity to tuberculin in both the most of allergic patients and persons with a history of allergic manifestations.

[Tuberculin diagnosis in children. Latent tuberculosis?].

The 2000-2006 results of tuberculin diagnosis made in a city numbering 10.5 million people were retrospectively analyzed on the basis of an epidemiological tuberculosis survey among children. The higher cut-offs are not helpful in interpreting the tuberculin test. With more than 5 mm, it is necessary to have criteria for clear differences between the active tuberculous process, inactive tuberculous changes, and recent or previous Mycobacterium tuberculosis infection. With the low prevalence of tuberculosis among children in a megapolis, the sensitivity of the method was 97.4%. Its specificity was 41.7%; out of these children, a risk group forms in 1% of cases and the children who had been referred by a pediatrician and had failed to be examined by a specialist at a tuberculosis dispensary. With positive and negative tests, the likelihood of the disease in a child is 0.01 and 99.9%, respectively. At the same time, morbidity in risk group children formed by the results of tuberculin tests is high and indicative of a need for searching for objective indicators (except for tuberculin diagnosis and history data) to identify the disease just before registration as a risk group. The practical value of chemotherapy for latent tuberculosis infection in the megapolis requires studies and evidence-based results. Preventive chemotherapy is currently the priority in preventing tuberculosis for individual risk groups (among the HIV-infected and those who are from tuberculosis infection foci).

[Comparative analysis of tuberculosis morbidity in children and adolescents from Moscow and the Penza Region].

Tuberculosis morbidity was comparatively analyzed in the children and adolescents of Moscow and the Penza Region. The epidemiology of tuberculosis in the children and adolescents was established to be universal in the compared regions in the study period. This manifested itself as a stable tendency for higher morbidity rates (MR), increased incidence of destructive tuberculosis, inadequate use of the existing methods for active detection of tuberculosis in these age groups, and, among those who had fallen ill with this disease, an increase in the number of persons from the foci of tuberculous infection and persons with established contact with patients with tuberculosis. Along with a steady MR growth for tuberculosis among the children and adolescents, there has been a quantitative modification to the proportion of all epidemiologically hazardous forms of tuberculosis, such as the bacillary and destructive forms of pulmonary tuberculosis complicated by extrapulmonary tuberculosis. Hypodiagnosis of tuberculous pleurisy and extrapulmonary tuberculosis has been recently noted in the general health care network. The analysis also leads to the conclusion that the quality of mass tuberculin diagnosis remains poor. In both regions, general pediatricians are not adequately alert to tuberculosis, extrapulmonary tuberculosis in particular. With a rise in tuberculosis endemic, the incidence of tuberculosis in 18-21-year-old persons is 2-3 times greater than that in adolescents, which is associated with the greater activity of this population group and with the underdetection of the asymptomatic forms of tuberculosis in adolescents.

[A systemic inflammatory response in teenagers with new-onset tuberculosis].

Fifty-eight adolescents aged 13-17 years who had new-onset pulmonary tuberculosis were examined. The serum levels of C-reactive protein (CRP), alpha-antitrypsin (alpha1-AT), haptoglobin (Hp), serum protein fractions, medium-weight molecules (MWM), and malonic dialdehyde (MDA) were assayed in the patients on admission, 2 weeks, and 1, 2, 3, and 6 months after treatment. The parameters of a systemic inflammatory response were ascertained to naturally vary in the adolescents with new-onset tuberculosis, by reflecting as both a defense reaction (increases in the levels of CRP, a,-AT, Hp) and as metabolic decompensation manifestations (increases in the concentrations of MWM and MDA and a reduction in the almubin/globulin (A/G) ratio. The magnitude of these changes makes it possible to judge the severity of a process to a certain extent and it is unassociated with the genesis of the disease. The levels of acute-phase reagents and MDA undergo positive changes just 2 weeks of effective specific chemotherapy whereas there are no changes after ineffective treatment. After correction of chemotherapy and achieving a clinical effect, there was a complete normalization in the levels of CRP, Hp, and A/G ratio, but a slight increase in alpha1-AT and MDA in all the children by month 6 of therapy. In all the adolescents, the baseline increased concentration of MWM increased at the early stage of chemotherapy and returned to the original value after 6-month therapy, by remaining significantly higher than the normal values.

[Adolescence tuberculosis in Moscow: epidemiological situation and problems].

The paper provides the data of analysis of antituberculous care to teenagers in Moscow and characterizes its problems. Emphasis is placed on the tense and unstable situation associated with the detection of the disease in this age group. In the bulk of adolescents, the disease is identifies when they come to see a doctor, including at somatic hospitals. Active tuberculosis detection techniques (tuberculin diagnosis and fluorography) fail to produce adequate effect mainly due to organizational problems (the bulk of teenagers are outside the organized collective bodies or the latter are frequently changed; the detection of tuberculosis in Moscow nonresidents or in whose who enter secondary specialized colleges claims attention). Age-related sociomedical risk factors, such as hormonal rearrangement, comorbidity, a negative attitude towards preventive medical measures, deviant behavior, social family, and dysadaption, are of importance for the development of tuberculosis. A sociomedical portrait of an adolescent with tuberculosis is given. Attention is drawn to the fact that on implementing antituberculous measures, it is a need for an interaction of a tuberculosis-controlling service with general care health network facilities, including those that deal with the problems of social diseases and educational establishments.

[Principles in the performance of chemotherapy in dispensary group VI children and adolescents].

Based on the annual reports of Moscow tuberculosis dispensaries, the analysis of their follow-up of dispensary registration group VI patients, the authors have developed preventive chemotherapy regimens in relation to the specific features of tuberculin sensitivity, the presence or absence of additional risk factors (concomitant somatic diseases, social risk factors). Regimen I (1 antituberculous drug (isoniazid) for 3 months) may be used in dispensary registration groups VIA and VIB patients without additional risk factors. Regimen II (2 antituberculous drugs (isoniazid + pyrazinamide/ethambutol) for 3 months) may be employed in dispensary registration groups VIA and VIB patients with additional risk factors, as well as in children from dispensary registration group VIB, whether additional risk factors are present or absent. A repeated course of preventive chemotherapy regimen II is indicated when tuberculin sensitivity is increased or a hyperergic reaction is retained after termination of treatment in patients having additional risk factors.

[Role of specific immunoglobulins of classes G, E and subclasses G1, G4 in the diagnosis of tuberculosis in children with hyperergic tuberculin sensitivity].

The study covered 56 patients (aged 6-14 years) having hyperergic tuberculin sensitivity, including 28 patients with pulmonary tuberculosis (Group 1) and 28 patients infected with Mycobacterium tuberculosis (MBT) (Group 2). All tuberculous processes were asymptomatic and limited. Minor forms of tuberculosis, diagnosed by computed tomography, were found in 71.4% of cases. The signs of incomplete calcification were detectable in 93% of cases. In the past year, tuberculin sensitivity has progressed to hyperergic one in 75% of Group 2 patients. The patients with tuberculosis were treated with 3 drugs; those infected with M BT received 2 agents. In the patients with minor forms of tuberculosis, the level of specific IgG antibodies was equal to those in healthy MBT-infected individuals with hyperergic tuberculin sensitivity, the levels of immunoglobulins of subclasses G1 and G4 were lower, that of IgE antibodies were higher than in the MTB-infected. These data may suggest the stability of the immune system in patients with minor forms of tuberculosis, detected in the phase of calcification, and its instability in the MBT-infected with tuberculin sensitivity increasing up to hyperergic one.

[Tuberculin sensitivity in children and adolescents with tuberculosis].

The specific features of tuberculin sensitivity were studied in 210 children and adolescents aged 4-17 years who had active pulmonary tuberculosis. There were more common significant and hyperergic tuberculin sensitivities, conversion of tubercular tests, and an increase in tuberculin sensitivity. Timely phthisiological examination of patients with these values of tuberculin sensitivity could promote early detection of local forms of tuberculosis in 71.1% of the patients detected on their visit to a doctor. There was a correlation of the hyperergic tuberculin sensitivity with the phase of incomplete calcification in patients with tuberculosis of the intrathoracic lymph nodes, which may suggest that the macroorganism is hypersensitized in patients with slow reparative processes. There is evidence that the Mantoux test with 2 TE of PPD-L preserves its diagnostic value in patients with clinical and X-ray changes in the differential diagnosis of tuberculosis and nonspecific diseases of the lung.

[Treatment and outcomes of tuberculosis with multidrug resistance of MBT in children and adolescents].

Eighteen patients with multidrug resistant Mycobacterium tuberculosis (MBT), including 4 (22.2%) children aged 12-14 years and 14 (77.8%) adolescents, were followed up. In 89% of cases, 5 drugs were included into the intensive phase of the chemotherapy regimen. The commonest causes limiting the use of the sixth drug were MBT resistance to essential and reserve drugs (41.2%), uncorrectable adverse reactions to the drugs to which sensitivity was retained (30.7%). The intensive phase lasted 5 months; the mean continuation phase was 5.5 months. The reduction in the latter is attributable to the surgical treatment in 38.9% of the patients with sustained decay cavities and bacterial isolation. Treatment should be complex, by applying different treatment options, such as chemotherapy, collapdotherapy, and surgical treatment. After complex treatment, bacterial isolation ceased in 94.4% of cases, decay cavities closed in 83.3%. There were pronounced residual changes in 66.6%.

[Clinical and X-ray characteristics of first detected intrathoracic lymph node tuberculosis in children].

Sixty-two case histories of Moscow children aged 4-12 years, treated at the Central Research Institute of Tuberculosis, Russian Academy of Medical Sciences, for first detected intrathoracic lymph node tuberculosis (ITLNT), were studied. Planned and prophylactic studies revealed the disease in 95.1% (including 66.1% after mass tuberculin diagnosis and 29% on examination for their contact). The disease was more commonly asymptomatic. Mild or moderate signs of the total disorder syndrome were prevalent in the clinical picture. In 56.5% of cases, a tuberculous process was detected in the phase of consolidation and calcinations. Among the patients with intrathoracic lymph nodal changes in the infiltration phase, the children with minor forms of ITLNT whose diagnosis was verified by computed tomography were 72.7%. The use of computed tomography in the diagnosis of ITLNT allowed one to make the fullest evaluation of changes in intrathoracic lymph nodes, including the groups of the anterior and posterior mediastinum.

[Chemotherapy for tuberculosis in children and adolescents: problems and ways of their solution].

Treatment of 329 patients aged 4-17 years who had first detected tuberculosis was analyzed. The clinical pattern is mainly represented by infiltrative, focal tuberculosis and tuberculosis of intrathoracic lymph nodes (94.5%) and, in single cases, by other forms of tuberculosis. Treatment was performed according to regimens I and III. The time of abacillation is 1-2 months shorter than positive X-ray changes. In this connection, the results of X-ray monitoring may be regarded as the leading criterion for completion of intensive care. Microbiological monitoring methods should be primarily used to evaluate the initial combination of chemotherapy. The active application of pathogenetic treatment modalities that promote the acceleration of reparative processes (physiotherapy in particular) generated the necessity of using 3 antituberculous agents in the phase of treatment continuation.

[Efficiency of preventive chemotherapy in children and adolescents from the bacterial isolation foci of tuberculous infection].

A follow-up of 558 children and adolescents contacting the patients with tuberculosis who isolated bacteria was analyzed. In 46.5% of cases, the children and adolescents contacting the patients with tuberculosis were in the foci of drug-resistant Mycobacterium tuberculosis (MBT) in the source of infection. The patients from these foci fell ill with tuberculosis 3.4 times more frequently than those from the foci where the sources of infection isolated MBT susceptible to antituberculous drugs. Processes with bacterial isolation were detected in 47.7% of the ill children and adolescents, primary MBT resistance to antituberculous drugs being noted in 68.8% of cases. Preventive chemotherapy reduces the risk for children and adolescents contacting the patients with tuberculosis to fall ill by 7.6 times. Ineffective preventive chemotherapy performed in those contacting the patients was due to the use of MBT-resistant antituberculous drugs in the source of infection. The administration of the MBT-resistant drugs in the source of infection led to the same high incidence of tuberculosis in children and adolescents from the bacterial foci of tuberculous infection as in its absence.

[Methodological approaches to organizing nonspecific prevention of tuberculosis].

The paper presents the basic sections of the nonspecific prevention of tuberculosis. The main objective, tasks, and methods for solving the latter are formulated for each section. Emphasis is placed on the social and age groups of the population while doing sanitary and educational work. Attention is given to that it is necessary to evaluate the efficiency of implementation of educational programs, which is important for making amendments when the epidemic situation and the population's sanitary education change.

[The reserve drugs: their safety for children and adolescents].

For the treatment of children and adolescents with tuberculosis, the needs for reserve drugs are 24.0 and 48.6%, respectively. The main reason of the use of reserve drugs is intolerability of essential antituberculous drugs in children (16.4%), and resistance to these drugs in adolescents (40%). Overall, different types of intolerability events (allergic, toxic, toxicoallergic reactions) were observed in 27 (34%) of 79 children and in 46 (65%) of 70 adolescents. Adverse reactions to essential drugs were significantly more frequently observed than those to reserve drugs in both the children and the adolescents: in 96.3 and 3.7% (p < 0.001) and in 89.1 and 10.9% (p < 0.001) cases, respectively.