Low rates of recurrence after successful treatment of multidrug-resistant tuberculosis in Tomsk, Russia.

SETTING: Tomsk, Russia, where multidrug-resistant tuberculosis (MDR-TB) is prevalent. OBJECTIVES: To report rates of recurrence following successful treatment of MDR-TB in a program providing individualized treatment regimens designed according to the current global standard of care. DESIGN: A retrospective cohort study of 408 adults successfully treated for pulmonary MDR-TB from 10 September 2000 to 1 November 2004, and followed for up to 6 years post-treatment. We used Poisson regression with generalized estimating equations to assess whether recurrence rates changed significantly with time. RESULTS: We analyzed 399 (97.5%) patients with at least one follow-up visit (15 850 person-months of observation [PMO]). Baseline resistance to second-line drugs was common (65.2%); 398 patients (99.7%) were human immunodeficiency virus (HIV) negative. In the first year of post-treatment follow-up, there were six episodes of recurrence (1.4/1000 PMO, 95%CI 0.5-3.0). After the first post-treatment year, there were 21 episodes of recurrence (1.8/1000 PMO, 95%CI 1.1-2.8). The rate did not change significantly with time. CONCLUSION: Individualized regimens designed according to the current global standard of care achieved low rates of MDR-TB recurrence among non-HIV-infected persons treated in a programmatic setting.

Note: ε(T) dependence behavior in GaP diodes at high temperatures.

Temperature behavior of static dielectric constant ε in a base area of GaP diode has been studied by processing its capacity-voltage characteristics in the temperature range 300-575 K. The ε(T) function has been determined to be a monotonic function of temperature with a maximum in high temperature region. The temperature behavior of ε could be explained by the effect of mixed electron-ion mechanism of polarization in wide bandgap III-V semiconductor compounds. Temperature dependences ε(T) and Δε(T) obtained within this work would be useful for developers of high-temperature electronics and thermometry.

Note: Determination of temperature dependence of GaP bandgap energy from diode temperature response characteristics.

A simple method of E(g)(T) dependence determination for active areas of semiconductor devices based on wide bandgap semiconductors has been proposed and developed. Verification of the method has been carried out while determining E(g)(T) dependence in a base area of p(+)-n-type GaP diodes in the temperature range 77-523 K. The method is based on U-T characterization of the diodes and calculation of E(g)(T) dependence according to the expression obtained within present study. Satisfactory agreement between experimental and theoretical results has been achieved including references available on gallium phosphide. The method proposed could be applied to experimental data processing in high-temperature thermometry.

Relationship between CYP2E1 polymorphism and increase of ALT activity during therapy of patients with pulmonary tuberculosis.

Association of CYP2E1 polymorphism with ALT activity increase was studied in patients with pulmonary tuberculosis receiving therapy by intermittent and daily protocols. The greatest increment of ALT activity in the group receiving therapy by intermittent protocol was seen in the patients with CYP2E1*7632TA genotype. In patients with wild homozygotic 1C/1C (6/6) genotype, ALT activity significantly increased, but remained within the normal range (p=0.048). In the group on daily regimen, activity of ALT increased significantly in patients with all genotypes identified. A more pronounced elevation surpassing the median of the upper threshold of ALT norm was observed in patients with 7632TA genotype (p=0.0051) and in patients with 7632TA or -71GT or 1C/1D genotypes in combinations with wild type alleles by other detected polymorphisms (p=0.0277). Detection of the CYP2E1 gene 7632T

[Rifapex, a new antituberculosis agent].

Clinico-roentgenologic and bacteriologic efficacy and safety of rifapex (rifapentin) were investigated in the complex therapy of 90 patients with newly recorded drug-susceptible tuberculosis. Pifapex was shown to be effective in the treatment of the patients during the acute phase of the disease, during the treatment completeness and during the short preoperative period.

[Interferon alpha-2b in the complex therapy of patients with pulmonary tuberculosis concurrent with bronchoobstructive syndrome].

Interferon alpha-2b was tested for its effect on therapeutic effectiveness in pulmonary tuberculosis patients with bronchoobstructive syndrome and signs of secondary immunodeficiency. The patients were randomized to 2 groups. The study group (n=35) received rectal interferon alpha-2b, 3 million IU, on chemotherapy days (twice weekly). The total duration of a course of immunochemothery was 4 months or more. The control group (n=35) did not take the immunomodulator. The use of interferon contributed to the normalization of T-cell immunological parameters in 60.6% of the patients and functional parameters in 35.7% and could achieve closure of decay cavities (the only cavity or one of the cavities) in 90.6% of cases (in the control group, these were in 33.3, 20, and 64.3%, respectively).

Tuberculosis in North Siberian and Far East inhabitants.

Novosibirsk TB Research Institute is a center of the pursuance and coordination of scientific investigations and the providing of an antituberculosis cure in Siberian and Far East federal regions. Northern territories are included in the zone of Institute supervision. We have chosen two territories (Taimyr and Koryakia) to study peculiarities of the TB problem on the North. We have estimated social, demography, ethnic, ecological, political, economical, epidemic, technology factors, and quality of TB control work in considering the situation on TB. We have marked out problem areas in the sphere of TB control in Northern territories. Novosibirsk TB Research Institute, in cooperation with other Scientific Centers, provides actions on improving the system of support to TB control facilities of the Northern territories, taking into account peculiarities in the situation with TB in the following directions: organizational activities on interaction with authorities and general health care; prediction of clinical course and treatment outcome based on study of the clinical, immunogenetic, and morphological peculiarities of TB; study of bacteriological and immunogenetic peculiarities of Mycobacterium tuberculosis to improve TB diagnostics, to use TB drugs in accordance to the data on drug-resistance and to provide timely correction of treatment course.

[The clinicobiological status of patients with pulmonary tuberculosis concurrent with chronic hepatitis B and/or C].

Examination was made in 155 patients, including 60 patients were diagnosed as having hepatitis, hepatic lesion being first detected by a screening survey for markers of hepatitis. The antipyrine test was carried out. Patients with slow and rapid hydroxylation were identified. No changes were found in the biotransformation functions of the liver in patients with pulmonary tuberculosis 6 months after intravenous intermittent chemotherapy twice a week from the beginning of therapy; however, there was inhibition of the activity of monooxygenases and a two-fold increase in the number of patients with slow hydroxylation among patients with concomitant chronic hepatitis B and/or C. The best results of chemotherapy were found in tuberculous patients with slow hydroxylation: they less frequently underwent surgical interventions since decay cavities were therapeutically closed.

Novel conjugate of moxifloxacin and carboxymethylated glucan with enhanced activity against Mycobacterium tuberculosis.

Mycobacterium tuberculosis is an intracellular pathogen that persists within macrophages of the human host. One approach to improving the treatment of tuberculosis (TB) is the targeted delivery of antibiotics to macrophages using ligands to macrophage receptors. The moxifloxacin-conjugated dansylated carboxymethylglucan (M-DCMG) conjugate was prepared by chemically linking dansylcadaverine (D) and moxifloxacin (M) to carboxymethylglucan (CMG), a known ligand of macrophage scavenger receptors. The targeted delivery to macrophages and the antituberculosis activity of the conjugate M-DCMG were studied in vitro and in vivo. Using fluorescence microscopy, fluorimetry, and the J774 macrophage cell line, M-DCMG was shown to accumulate in macrophages through scavenger receptors in a dose-dependent (1 to 50 microg/ml) manner. After intravenous administration of M-DCMG into C57BL/6 mice, the fluorescent conjugate was concentrated in the macrophages of the lungs and spleen. Analyses of the pharmacokinetics of the conjugate demonstrated that M-DCMG was more rapidly accumulated and more persistent in tissues than free moxifloxacin. Importantly, therapeutic studies of mycobacterial growth in C57BL/6 mice showed that the M-DCMG conjugate was significantly more potent than free moxifloxacin.

[Molecular and genetic characterization of rifampicin- and/or izoniazid-resistent strains of M. tuberculosis, isolated in Novosibirsk and Tomsk regions].

The purpose of the work was to study rifampicin- and izoniazid-resistent strains of M. tuberculosis, circulating in Western Siberia, by VNTR and IS6110 typing. The authors also studied genetic causes of resistance to these antibiotics and undertook a search of new VNTR loci, displaying polymorphism in genomes of closely related clonally-disseminated variants of Mycobacterium tuberculosis in W-Beijing family model analysis.

[The forced oscillation techniques in the detection of bronchial obstruction in patients with pulmonary tuberculosis].

Clinical trials of the forced oscillation (FO) technique could identify criteria for bronchial obstruction: viscosity airway resistance (VAR) (R(fo), R(in), R(ex)), and its frequency dependence. VAR studies promoted detection of bronchial patency in further 21.9% of the patients who had no bronchial obstruction, as evidenced by spirography (SG) and F-FEV curve recording. To improve the diagnosis of impaired bronchial patency, it is expedient to explore VAR by the FO technique along with the routine methods (SG and F-FEV curve recording).

[KatG Ser3 15Thr mutation as the main reason of isoniazid resistance in Mycobacterium tuberculosis isolated in the Novosibirsk and Kemerovo Regions]. / Mutatsiia Ser315Thr gena katG--osnovnaia prichina ustoichivosti k izoniazidu u izoliatov Mycobacterium tuberculosis, rasprostranennykh v Novosibirskoi i Kemerovskoi oblastiakh.

KatG Ser3 15Thr mutation is one of the main reasons of resistance to isoniazid in Mycobacterium tuberculosis isolates. The frequency rate of the above mutation among isoniazid-resistant isolates made 94% in Novosibirsk Region and 93% in Kemerovo Region. The use of PCR-restriction fragment length polymorphism (PCR-RFLP) can be regarded as an adequate method for rapid screening of isoniazid resistance in Mycobacterium tuberculosis isolated in the West-Siberian Region.

[The genetic diversity of Mycobacterium tuberculosis and an assessment of risk factors of tuberculosis spread in Russia's Siberian region by molecular epidemiological methods]. / Geneticheskoe raznoobrazie Mycobacterium tuberculosis i otsenka faktorov riska rasprostraneniia zabolevaniia tuberkulezom v Sibirskom regione Rossii metodami molekuliarnoi épidemiologii.

Molecular epidemiology approaches provided for a new interpretation of the TB infection transmission dynamics, contributed to changing the focuses of attention and updated the monitoring practice. On the basis of 101 cases of isolates of Mycobacterium tuberculosis (MBT) complex sampled from 84 patients with pulmonary tuberculosis in the Siberian region, we proved that the independent methods of IS6110 RFLP genetic typing and VNTR-typing by five accurate repeat tandems of ETR A, B, C, D, and E bring about similar results and can be used in studying the MTB clonal structure population in the Siberian region for the purpose of defining the TB infection transmission dynamics. The most widespread genetic types were detected, i.e. Beeijing family strains, the S42 spoligotype, and the 31323 VNTR type, which account for 52.3% of all samples. The general parameters describing the epidemic process intensity were evaluated, i.e. those characterizing the strains (91.6%) and the transmission activity factor (72%). Consequently, each three of the four analyzed TB cases resulted from a recent transmission. However, there is a trend, within the analyzed samples, towards a higher percentage of clusterization in the age group ranging from 40 to 60. Such trend is typical of a prevalence of TB reactivation cases caused by MBT complex strains spread intensively in the discussed territory. As for the clusterized isolates, which are endemic for the territory, such data should be interpreted as a recent transmission only cautiously. 28.5% of the studied isolates are resistant to anti-TB drugs used in medical practice; and 35.7% of them are resistant to izoniazide and rifampicin, therefore, according to the WHO classification they are considered to be poly-antibiotics-resistant (PAR). No strict associations were found between the spectrum of antibiotics-resistance and any of genotypes, however, 30% of PAR strains are 32525 and 42525 types VNTR (spoligotype S1 or Beejing type).

[Outlooks for promoting antituberculosis care for the Siberian population]. / Perspektivy razvitiia protivotuberkuleznoi pomoshchi naseleniiu Sibiri.

An analysis of the TB situation in three Siberian territories, i.e. the Kemerovo, Omsk and Tomsk Regions, is presented. Conclusions pertaining to the key specific features were made and a correlation between an epidemic level tension, on the one hand, and an efficiency of the anti-TB activity management, on the other hand, was established. The conclusions were considered as a precondition for setting up a management structure in the sphere of the anti-TB activity that would accumulate the achievements of home phthisiology and of modern methodological and methodical management approaches. Results of elaborations of Novosibirsk Research Institute of TB Issues, which are related with establishing an anti-TB management system in Siberia, are presented; such system would comprise aims, functions, a structure and the key management components. Supposedly, the described approach is expected to optimize the efficiency and good results in the anti-TB management activity at all levels with the resources being distributed and used on the rational basis.

[On early transfer of new cases of pulmonary tuberculosis to outpatient treatment]. / O rannem perevode na ambulatornoe lechenie vpervye vyiavlennykh bol'nykh tuberkulezom legkikh.

Based on 228 clinical cases, the authors propose procedures for complex two-stage (inpatient and outpatient) treatments of new cases of pulmonary tuberculosis by using intermittent intravenous chemotherapy that makes it possible to have a high therapeutic effect in a short space of time, to reduce the duration of hospital treatment substantially, to on the average 2-4 months, and to ensure controlled chemotherapy at the outpatient stage.

[Modalities of complex therapy in different categories of patients with pulmonary tuberculosis]. / Varianty kompleksnoi terapii razlichnykh kategorii bol'nykh tuberkulezom legkikh.

The paper proposes the standards of combined treatment involving intermittent intravenous bactericidal chemotherapy for different groups of patients. It describes treatment regimens at the inpatient stage, defines the scope and time of control examination and correction of a treatment protocol by taking into account the pattern, phase, and dissemination of a process and the duration of the disease.

[Role of surgical treatments in patients with fibrocavernous pulmonary tuberculosis]. / Rol' khirurgicheskikh metodov v lechenii bol'nykh fibrozno-kavernoznym tuberkulezom legkikh.

Three hundred and seventy patients operated on at the Institute Surgical Clinic underwent 638 surgical interventions: 356 and 282 in Groups 1 and 2 patients, respectively. Intraoperative complications occurred in 24 (3.8%) cases, in 6.5% of the patients operated on. Twenty-two complications were successfully eliminated, 2 patients died. Postoperative complications were established in 25 (14.8%) of the 169 patients of Group 1 and in 12 (6.0%) of the 201 patients of Group 2. The incidence of complications largely depended on the type of an operation. Complications were observed in 8 (36.4%) of the 22 patients undergone pulmonectomy. The active phase of a specific process as a surgical risk factor is prime consideration. In patients operated for emergency indications in the phase of an non-arrested exacerbation of tuberculosis, pleuropulmonary complications occur 2.5 times as frequently as those in patients with relative process stabilization.