Search

The aim of this study was to analyze the course of the disease and efficacy of treatment of pulmonary multidrugresistant (MDR) cavitary tubercu losis in antituberculosis settings of Russian penitentiary system. Drug resistant was studied using the method of absolute concentrations. Among 190 males with MBTpositive cavitary pulmonary tuberculosis followedup in antituberculosis hospitals of Russian penitentiary system in Voronezh in 2003–2006, 79 patients (41.6 ± 3.4 %) were yielded MDR strains resistant to the firstline antimucobacterial drugs and 111 patients (58,4 ± 3,4 %) had strains resistant both to the firstline and the secondline drugs (isoniazid and rifampicin). Moreover, MBT strains resistant to cycloserine and quinolones were found in patients who have not been previously treated with these drugs. Both newly diagnosed patients with pulmonary tubercu losis and those with recurrent cavitary pulmonary tuberculosis had a high rate of primary and secondary MDR to the firstline and the secondline antimicobacterial drugs. Administration of I and IIA chemotherapeutic regimens in these patients resulted in occurrence of additional resistance to a wide spectrum of the firstline and the secondline antibiotics. Patients with chronic pulmonary tuberculosis are at high risk of MDR to combi nations of the firstline and the secondline drugs and need other treatment strategies including surgical interventions. Tuberculosis patients with MDR to combinations of the firstline and the secondline drugs were characterized by more severe chronic course of the disease with extended lesions and large cavities in the lungs. Adverse events to the secondline drugs were seen in 42.6 % of the patients with cavitary tuberculosis. Of them, serious adverse events requiring cancellation of the drug and change in chemotherapeutic regimen were noted in 17.9 % of cases.

The test-system "Sensititre MycoTB" was applied to analyze 159 cultures of M.tuberculosis isolated from patients with tuberculosis. According data of investigation in "Bactec 960" they are identified as cultures with multiple medicinal sensitivity. The detailed analysis of results of application of mentioned test-system (mycoTB) demonstrated that significant part of cultures with multiple medicinal sensitivity is sensitive to anti-tuberculosis pharmaceuticals. The significant part of cultures is characterized by "intermediate" sensitivity/resistance than can be established by mentioned test-system. This data permits enlarging possibilities of chemotherapy of tuberculosis.

Testing the direct nitrate reductase technique versus the absolute concentration test has indicated that the former may be successfully used for rapid determination of the sensitivity of Mycobacterium tuberculosis (MBT) to isoniazid and rifampicin and it can reduce the time of obtaining a result by 4-5 times in the cases that sputum bacterioscopy yielded a positive result that allows the modified method to be applied. The advantages of the TB-Biochip technique are the time of detection multidrug-resistant MBT (24 hours), a possibility of obtaining these data just when analyzing sputum-isolated MBT DNA, and characterization of the MBT genomic elements that are responsible for drug sensitivity to antituberculous agents, by determining mutations in the examined genes and this all by using one chip. The agreement of results of microbiological and molecular genetic studies study of drug MBT sensitivity was 98%. There were no differences in the results of those using isoniazid. As for rifampicin, there was a difference in two samples (3.8%). Analysis of a combination of mutations forming multidrug resistance indicated that 74.3% of multidrug-resistant MBT isolates had mutations in the codon Ser531Lue of the rpoB gene and in the codon Ser315Thr of the katG gene. 97.4% of strains with signs of multidrug resistance had mutations in the codon 315 of the katG gene. 20.5% of isoniazid-resistant strains were observed to have mutations in two genes (katG and inhA) and 28.2% of the strains exhibited double mutation in the katG gene - Ser315Thr and Ile335Val.

The paper presents the organizational aspects of antituberculous care delivered at penitentiary institutions of the Russian Federation. The priorities of development, including the interaction with civil public health care of Russia and the continuation of tuberculosis-controlling activities jointly with international organizations, are identified.

The authors propose to determine altered forms of Mycobacteria, including sputum and blood granular forms, and the level of tuberculosis antibodies and serum Mycobacterium antigens by enzyme immunoassay as additional criteria for diagnosis of active primary tuberculosis in children. The diagnostic value of these indices is accounted for by the fact that they are found significantly more frequently and their level is significantly higher than the similar indices in healthy, tuberculosis-infected children and tuberculin-negative, prior BCG-vaccinated ones. By taking into account an decrease in the detection rate of sputum and blood granular mycobacteria and a change in the level of tuberculosis antibodies during chemotherapy, which are observed along with positive clinical and X-ray changes of a process, these tests should be recommended for evaluation of the efficiency of primary a bacillary tuberculosis in children.

The results of determination of drug medium depend on both individual cultural properties of the strains tested and the type of the medium used. The composition of a medium is of significance for some strains: the latter grow in any medium and are characterized by the same spectrum of resistance. However, most drug-resistant strains have higher feeding demands which are not fully met on the lyophilized Löwenstein-Jensen medium. The strains in the lyophilized medium show an incomplete spectrum of resistance and less grow than do those in freshly prepared Löwenstein-Yersen medium.

The paper presents the results of long-term follow-ups of 107 patients with recurrent sarcoidosis registered as having Group VII-IB. In the patients, there was the greatest dissemination of the process in the lung, intrathoracic lymph nodes and other organs and MF MB in the blood, sputum, BAC? Group VIIIB patients need the greatest attention of physicians, treatment involving extracorporeal and physiotherapeutical methods to prevent respiratory failure and disability.

Antibodies to Mycobacterium tuberculosis antigens H37Rv and reverse strains previously isolated from patients with sarcoidosis with granular isolates were determined in 50 patients with sarcoidosis (including 16 patients isolating granular types) and 56 patients with tuberculosis, by using ELISA and immunoblotting. Serum antibodies from patients with sarcoidosis were ascertained to more commonly react in ELISA with the antigen (ultrasound disintegrant (USDs) obtained from reverse mycobacteria isolated (initially) from patients with sarcoidosis (AGS) than with the USD of the M. tuberculosis H37Rv (AGT) and, on the contrary, serum antibodies from patients with tuberculosis more frequently reacted with the M. tuberculosis H37Rv. The spectrum of serum antibodies from patients with sarcoidosis greatly differed at immunoblotting with AGS and AGT. There was most commonly a reaction with the antigenic determinants 79, 27, 30, and 50 kDa to AGS and that of the determinants 17, 35, 32 kDa to AGT.

In 80% of cases, antituberculosis antibodies from the sera of patients with tuberculosis were ascertained to react in enzyme immunoassay (EIA) with antigens (ultrasound disintegrants (USDs)) of reverse mycobacteria isolated (initially) from patients with sarcoidosis. The USDs of reverse mycobacteria isolated from patients with sarcoidosis reacted in EIA with monoclonal antibodies (MAb) against M. tuberculosis complex antigens (unique and crossover). Both common and distinctive (unique) antigenic determinants were detected via MAb against different mycobacterial types by immunoblotting in the antigenic complexes of M. tuberculosis H37Rv and reverse strains isolated from patients with sarcoidosis.

The paper describes guidelines for isolation of Mycobacterium tuberculosis by bacterioscopy. It shows high detection rates for Mycobacteria in patients included into the programme. The detection rates of patients by bacterioscopy are not different in two quarters.

Combined microbiological investigation of diagnostic material containing granular mycobacteria has revealed cultures-revertants both in tuberculous and sarcoidosis patients. Identification of the isolated cultures provided the conclusion on identity of granular mycobacterial structures discovered both in tuberculous and sarcoidosis patients.

Microbial spectrum in patients with disorders of the upper respiratory tract consisted mainly of streptococci, staphylococci and pneumococci in 1991-1993, 1994 and later, respectively. Most specific for detection of nontuberculous flora was brushing with protecting agar plugs in combination with transport medium and anaerobic culturing. Direct immunofluorescence allows detection of antigens M. chlamydia in 29.4%, M. pneumoniae in 18.5% of cases. In diagnosis of tuberculosis the following new technologies were introduced: bacterioscopy with previous culturing of the material on liquid culture media followed by biological test and polymerase-chain reaction; determination of drug resistance based on nitrate reductase activity of M. tuberculosis indicating resistance of M. tuberculosis on liquid media in 4-7 days, dense egg media in 8-12 days, usage of Popesku medium enables correction of tuberculosis chemotherapy one month after the test initiation; M. tuberculosis identification using Western blot with monoclonal antibodies in some cases for 7 days.

Biological properties of M. tuberculosis were investigated in 265 patients with tuberculosis of respiratory organs. Slow but more massive growth in culture medium is characteristic for drug-resistant M.tuberculosis. 32 patients discharging drug-resistant M.tuberculosis had unstable drug resistance to isoniazid, kanamycin, ethambutol and streptomycin. It is suggested that drug-resistant M.tuberculosis by virulence are similar to sensitive varieties.

The paper outlines difficulties in tuberculosis diagnosis and effectiveness of various methods of mycobacteria identification. The latter along with direct and indirect determination of mycobacterial drug resistance require perfection. There is a need in investigation of diagnostic samples from tuberculous and respiratory sarcoidosis patients for mycobacterial granular forms. A multimodality diagnostic approach to examination of clinical material from tuberculous patients is advocated.

The level and spectrum of antituberculous antibodies (AA) were assessed in mice and their hybrids sensitive or resistant to tuberculosis. The AA level in resistant animals (CBA) and hybrids (CBA x C57Bl/6) F1 surpassed that in the sensitive mice (C57Bl/6). The spectrum in resistant and hybrid mice appeared more varied than that in the sensitive animals. Resistant mice had bands in the range 15-20 kD.

Study of the protein spectra of the mycobacteria of a different taxonomic belonging and isoniazid, streptomycin- and rifampicin-resistant strains has shown typical differences of the protein complexes of the studied strains.

The activity of aspartate and alanine aminotransferases in mycobacteria of different specific affinity and the degree of resistance to antituberculous drugs were studied. Differences in alanine and aspartic acid transamination processes taking place in mycobacteria with different biological properties were demonstrated.