[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.

[Surgical treatment for pulmonary tuberculosis with Mycobacterium resistance to drugs].

The results of surgical treatment were analyzed in 481 patients who had been preoperatively found to have drug resistance. Patients with fibrocavernous, cirrhotic tuberculosis, chronic pleural empyema, and cavernous pneumonia constituted the vast majority (83.2%). Chemotherapy was performed by individual schemes, by taking into account MBT susceptibility. Glutoxim and pentaglobin were used as pathogenetic therapy for immunity correction. Resection-type operations [n = 368 (68.9%)], thorocoplastic interventions [n = 78 (14.6%)], thoracostomy or cavernostomy [n = 35 (6.5%)], pleurectomy [n = 26 (4.9%)], operation on the stump of the main bronchus [n = 15 (2.8%)], and mediastinal lymphadenectomy [n = 12 (2.2%)] were predominant. Postoperative complications occurred in 15.5% of cases; mortality was 1.7%. The mycobacterium resistance to drugs verified by laboratory studies exerted no evident impact on the number and pattern of postoperative complications. The results of treatment depended on the extent and presence of complications of a tuberculous process, comorbidity, suppressed immunity, and the scope of a surgical intervention.

[Tuberculosis of intrathoracic lymph nodes in children and adolescents: diagnosis and surgical treatment].

A hundred and seven children and adolescents with intrathoracic lymph node (LTLN) tuberculosis were operated on. Late diagnosis and long-term ineffective antituberculous therapy lead to the development of complicated forms of ITLN tuberculosis in 44% of children. Computed tomography significantly determines extent, localization, the state of the adjacent tissue, and the phase of a tuberculous process, evaluates the efficiency of antituberculosis therapy, and ascertains the optimum time of a surgical intervention. Surgical removal of the involved ITLN is a highly effective operation causing the minimum number of complications. Bilateral successive one-stage removal of the involved lymph nodes is possible in children with bilateral ITLN tuberculosis.

[A procedure for calculating needs for antituberculous drugs].

OBJECTIVE: to develop a procedure for calculating needs for antituberculous drugs (ATD). MATERIALS AND METHODS: A unified E-form (UEF) was developed as an "Excel" file with the underlying invariable formulas and coefficients for the computer-based calculation of ATD needs in any subject of the Russian Federation. The needs were estimated using the average number of tablets (capsules, vials) of each ATD required per man/course, by taking into account the conventional chemotherapy regimens, the duration of chemoprophylaxis, antirecurrent courses, ATD test therapy, a treatment regimen for complications due to BCG vaccination. Information on the inventory of ATDs at the end of the previous year and their estimated deliveries from various sources was additionally considered. Data to be filled in the UEF were obtained from the reporting documents: 1) TB Form No. 2 "Information on patients registered for treatment" approved by Order No. 50 "On Consummation of Recording and Reporting Documents as to Tuberculosis Monitoring" issued by the Ministry of Health of the Russian Federation on February 13, 2002; 2) Form No. 030-4/y "Tuberculosis Patient Follow-Up Schedule"; and 3) Form No. 33 "Information on Patients with Tuberculosis" approved by Regulation No. 80 issued by the Russian Statistics Agency on November 11, 2005. The filled-in UEFs were obtained from 82 subjects of the Russian Federation. RESULTS: among all the contingents of antituberculosis dispensaries, who were given ATDs, the absolute majority was the persons receiving chemoprophylaxis. Only 18.3% received chemotherapy for active tuberculosis. Of them, 56.8 and 15.3% were treated in accordance with chemotherapy regimens 1 and 3, respectively. The regimes (2B and 4) using second-line agents were given least frequently (7.1 and 7.1%, respectively). Comparing the data from Form No. 33 and those obtained on filling in UEF showed with a fair degree of assurance that the treatment of patients with a chronic tuberculous process had been incompletely registered. Personified registration of patients with multidrug Mycobacterium tuberculosis resistance should be performed in order to have objective information on the scope of required medical aid and the real calculation of needs for second-line ATDs. For unified calculation of needs for ATDs for chemotherapy, it is necessary to introduce a standardized approach to its performance at different dispensaries. By taking into account that ATDs are purchased and dispensed free of change, one should have a responsible attitude to consuming drugs, determining indications for their usage, and filling the UEF. TB Form No. 2 "Information on patients registered for treatment" and Register No, 03-TB/y "Register of patients with tuberculosis" should be improved, by adding data on the number of patients receiving chemoprophylaxis, antirecurrent courses, test therapy, and treatment of complications due to BCG vaccination.

[Video-assisted techniques in phthisiosurgery].

Ten years' experience in applying video-assisted techniques to surgery of pulmonary tuberculosis is generalized. For surgical diagnosis and treatment, a total of 465 patients underwent the following procedures: video-assisted thoracoscopy (n = 133), video-assisted open mini-invasive thoracotomies (n = 117), and mediastinoscopy (n = 215). The main indications for 250 video-assisted thoracoscopic operations were exudative pleuritis or pleural empyema, disseminated lesions to or round masses in the lung of unknown genesis, restrictive forms of pulmonary tuberculosis. After video-assisted thoracoscopic operations, complications were stated in 3.6% of cases; there were no deaths. The accumulated experience has shown that video-assisted thoracoscopy is of relatively limited utility. It is most effective in diagnosing pleuritis and disseminated lung lesions of unknown etiology. Video-assisted mini-invasive operations combine many advantages of open and endosurgical interventions. They may find more extensive use in the surgical treatment of different forms of pulmonary and pleural tuberculosis. In 215 patients, the indication for mediastinoscopy was intrathoracic lymph nodal abnormality of unknown genesis. Specimens for morphological studies were obtained in all cases, which promoted timely diagnosis and definition of treatment policy. Complications were observed in 1.4% of cases; no deaths were seen. Video-assisted mediasthinoscopy has been applied in the past 3 years. This endosurgical technique is technologically new, has a high resolution, and deserves wide use in thoracic surgery.

[Surgical treatment for tuberculosis of intrathoracic lymph nodes in children and adolescents].

Ninety-four children and adolescents with tuberculosis of intrathoracic lymph nodes (TITLN) were operated on. Late diagnosis and long-term ineffective antituberculous therapy (chemotherapy lasted 2-3 years in 29.8% and 4-5 years in 19.1%) lead to the occurrence of complicated forms of TITLN in 34% of children. Computed tomography (CT) reliably determines the extent, site, and phase of a tuberculous process, assesses the time course of changes in the efficiency of antituberculous therapy. CT aids in defining the optimal time of surgical interventions. Bilateral consecutive one-stage removal of affected lymph nodes is possible in children with bilateral TITLN.

[Optimization of tuberculosis complex chemotherapy with the use of moxifloxacin]. / Optimizatsiia komleksnoi chimioterapii tuberkuleza pri ispol'zovanii moksifloksatsina.

It was shown in vitro that moxifloxacin by its activity against Mycobacterium tuberculosis (susceptible and resistant to the main antituberculosis agents) was highly superior to lomefloxacin (by 2 to 4 times by the MIC and by 4 times by the MBC). In murine lung tissue culture the highest effect was observed with the use of moxifloxacin in combination with isoniazid and pirazinamide. The efficacy of the regimens with the use of moxifloxacin was estimated in the treatment of 152 patients with pulmonary tuberculosis diagnosticated for the first time. The use of moxifloxacin was shown to be most advantageous in complex therapy of patients with extended and progressive tuberculosis due to polyresistant Mycobacterium tuberculosis strains or patients with concomitant nonspecific inflammatory diseases of the respiratory tracts due to a great variety of grampositive and gramnegative organisms, acid fact bacteria, atypical bacteria and a great variety of anaerobes. The tolerance of the treatment regimens with the use of moxifloxacin was mainly satisfactory.

[The use of discrete characters in discriminant analysis for diagnosis of pulmonary tuberculosis and for classification of patients differing in treatment efficiency based on polymorphisms at nine codominant loci-HP, GC, TF, PI, PGM1, GLO1, C3, ACP1 and ESD]. / Ispol'zovanie diskretnykh priznakov v diskriminantnom analize pri diagnostike tuberkuleza legkikh i pri klassifikatsii bol'nykh s razlichnoi éffektivnost'iu lecheniia po raspredeleniiu polimorfizmov v deviati kodominantnykh lokusakh-HP, GC, TF, PI, PGM1, GLO1, C3, ACP1 i ESD.

Discriminant analysis was used to differentiate patients with pulmonary tuberculosis (N = 106) from healthy individuals (N = 328) and patients whose treatment was efficient (N = 71) from those whose treatment was inefficient (N = 35). The analysis involved the data on nine polymorphic codominant loci: HP, GC, TF, PI, PGM1, GLO1, C3, ACP1, and ESD. The loci were selected by significance of differences in genotype frequencies between tuberculosis patients and healthy controls (GC, TF, PI, C3, ACP1) or between the two groups of patients differing in treatment efficiency (HP, GC, PI, PGM1, C3, ESD). Discrimination was based on a graphic method of Bayes classification procedure with a single-variate nomograph allowing easy estimation of the a posteriori probabilities for an individual to be classified. The two groups of patients proved to be discriminated sufficiently well (probability of misclassification Perr = 0.24), whereas discrimination between tuberculosis patients and healthy individuals was less efficient (Perr = 0.33). The method was proposed as a means of predicting the efficiency of treatment in pulmonary tuberculosis. Along with clinical, roentgenological, and laboratory examination, discriminant analysis may be employed as an accessory test in diagnostics of pulmonary tuberculosis, especially when the diagnosis is questionable.

[Effect of glutoxim in the combination with antitubercular agents of the second choice on the growth of drug resistant Mycobacteria tuberculosis in the cultured murine lung tissue]. / Deistvie glutoksima na rost lekarstvennorezistentnykh mikobakterii tuberkuleza pri ego sochetanii s protivotuberkuleznymi preparatami vtorogo riada v kul'ture legochnoi tkani myshei.

It was demonstrated that glutoxim combination with second line drugs for tuberculosis treatment (cycloserine + rifabutine, cycloserine + protionamide) provided statistically significant decrease of intracellular mycobacteria growth in the murine lung tissue culture. The decrease rate when compared to the control group was 3-5 times. The investigated Mycobacterium tuberculosis strain was isolated from the patient and was multi-drug resistant (MDR). Glutoxim addition to the second line drugs combinations provided also decrease of the MDR bacteria microcolonies growth in the lung tissue culture. Glutoxim combination with second line antituberculosis drugs allowed to keep vitality and functional activity of lung tissue cells.