Anti-tuberculosis drug resistance in community and prison patients, Orel Oblast, Russian Federation.

SETTING: Orel Oblast, Russian Federation. OBJECTIVES: To determine baseline levels of anti-tuberculosis drug resistance in Orel Oblast. DESIGN: Drug susceptibility testing (DST) records from 1 July 1999 to 30 June 2000 for patients with sputum acid-fast bacilli smear-positive pulmonary tuberculosis were reviewed. Treatment and incarceration status were obtained from the tuberculosis register. Patients with 1 month or less of prior treatment were defined as new cases; those previously treated for more than 1 month were defined as retreatment cases. RESULTS: Of 246 smear-positive isolates, 212 (86%) had DST performed. Of these, 190 (90%) were from new and 22 (10%) from retreatment cases; 171 (81%) were from community and 41 (19%) were from prison patients. Any drug resistance was more common among prison than community patients (44% vs. 30%, P = 0.05). MDR-TB was found in 14 (6.6%) of 212 isolates, and was more prevalent in prison compared with community patients (12% vs. 5%, P = 0.05). Retreatment cases were more likely than new cases to have MDR-TB (prevalence ratio [PR] = 8.5, 95%CI = 3.3-22.3), although the PR was higher for prison than for community retreatment cases (10.0 vs. 5.8). CONCLUSIONS: New cases with MDR-TB were less prevalent in Orel Oblast compared with other survey sites in Russia. Any drug resistance and MDR-TB were associated with prior treatment, especially in the prison population. Continued monitoring of trends in drug resistance following DOTS implementation is needed.

Encouraging outcomes in the first year of a TB control demonstration program: Orel Oblast, Russia.

SETTING: Orel, Russia. OBJECTIVE: To evaluate outcomes of tuberculosis (TB) patients treated in the first year of a TB control demonstration project using a revised strategy of directly observed treatment, short-course (DOTS). Standard methods recommended by World Health Organization (WHO) were adapted to include mycobacterial cultures. DESIGN: Retrospective cohort analysis of TB patients diagnosed between October 1999 and September 2000. RESULTS: Among 749 TB patients, 65% had bacteriologic confirmation of pulmonary TB, 31% were diagnosed clinically, and 4% had extra-pulmonary TB. Most (92%) had no previous TB treatment, but 8% were identified as retreatment cases. Of all patients, 41% had new sputum smear-positive TB. No patients were HIV-infected. Multidrug-resistant (MDR) TB levels were 3% among new and 17% among retreatment patients. Among new smear-positive patients, treatment success was 79% (72% cure, 7% completion); remaining outcomes were 8% failure, 3% default, 8% death, and 1% transfer. Success rates for new culture-positive and clinically diagnosed patients were 81% and 91%, respectively. CONCLUSION: Despite historical differences, successful implementation of the revised TB strategy in Russia is possible. Treatment success rates were high, suggesting WHO targets of 85% cure for smear-positive patients is attainable. Obstacles include drug resistance and elevated death rates among smear-positive patients.

Results of the external quality assessment of Mycobacterium tuberculosis drug susceptibility testing in Russia, 2005-2007.

SETTING: External quality assessment (EQA) of Mycobacterium tuberculosis drug susceptibility testing (DST) in bacteriological tuberculosis (TB) laboratories in the Russian Federation. OBJECTIVE: To improve the EQA of DST of first-line anti-tuberculosis drugs using proficiency testing in the Russian Federation. METHOD: Three rounds of DST proficiency testing using Mycobacterium tuberculosis isolates provided by the Swedish Institute for Infectious Disease Control, a World Health Organization Supranational Reference Laboratory (SRL). In total, 42 TB laboratories in the Russian civilian and prison sectors participated in at least one round of proficiency testing, and 17 laboratories participated in all three rounds. RESULTS: Ninety-seven per cent (87/89) of reports were received for the three rounds: 67% of laboratories in the first round and 86% of laboratories in the second round demonstrated >or=95% accuracy for isoniazid, and respectively 72% and 80% of laboratories in the first and second rounds reported >or=95% accuracy for rifampicin. CONCLUSION: Coordination with the SRL network resulted in the introduction of 90 well-characterised strains for EQA in the Russian Federation. Successive rounds of DST proficiency testing have helped to identify highly proficient laboratories that will be used as expert laboratories for proficiency testing in the future.

Low-molecular-weight trypsin inhibitors of microbial origin.

Three hundred actinomyces cultures newly isolated from the soil of different regions of the Soviet Union were tested for their ability to produce inhibitors of trypsin-like proteases. Seven previously not known to produce trypsin inhibitors (Streptomyces bikiniensis 17-5, S. sporoclivatus 28-1, S. filamentosus 32-11, S. diastatochromogenes 20-4, S. lavendulae 29-4, S. violacens 52-8, and Streptoverticillium cinnamoneum 36-8) were found to possess high antitrypsin activity. The morphological and cultural properties of the strains and the dynamics of inhibitor production were investigated. S. bikiniensis 17-5 was studied in greatest detail. Its culture filtrate contained several inhibitors for trypsin and one for chymotrypsin. A mixture of oligopeptides with Mr of 300-500 was obtained by the described procedure which included the adsorption of the culture fluid filtrate on charcoal followed by ion-exchange chromatography on CM-cellulose. Four trypsin inhibitors (Sb-IT1, Sb-IT2, Sb-IT3, and Sb-IT4) were isolated from the mixture in a highly purified state by reversed-phase high-performance liquid chromatography. Sb-IT2 has been recognized as formylhistidylvaline with an Mr of 282. No trypsin inhibitor of this structure has been described previously.

Glucose effect in tgl mutant of Escherichia col K12 defective in methyl-alpha-D-glucoside transport.

1. The dependence of the rate of accumulation of methyl-alpha-D-glucoside on its extracellular concentration was studied in the tgl mutant of Escherichia coli K12, isolated earlier. It has been shown that the kinetics of methyl-alpha-D-glucoside transport differ sharply from those in wild-type bacteria. 2. The beta-galactosidase synthesis in tgl strain is much less sensitive both to permanent and transient glucose catabolite repression. The level of cyclic AMP in mutant cells under the conditions of glucose catabolite repression is several times higher than in the parent strain. 3. The tgl mutation does not affect the manifestation of catabolite inhibition and inducer exclusion with glucose. 4. The data obtained are discussed in the light of a hypothesis concerning the existence of two sites, binding and pecific enzyme II of the phosphoenolpyruvate-dependent phosphotransferase system. The tgl mutation alters the first site, and the second one is damaged by the pgt mutation. 5. It is suggested that the products of the tgl and gpt genes are necessary for the manifestation of the phenomena of glucose permanent and transient repression. The effects of catabolite inhibition and inducer exclusion are realized irrespective of the existence or absence of the tgl product.

TNF alpha-induced aerobic synthesis of ATP on plasma membranes of target cells. The relation to the expression of the nuclear oncogene c-myc.

The accumulation of ATP by preparations of plasma membranes enriched particles (PMEP) isolated from rat hepatocytes, murine splenocytes and human T-lymphocytes has been investigated after the binding of human and murine tumour necrosis factors (TNF alpha) to their specific receptors. The TNF alpha-induced expression of the nuclear oncogene c-myc in intact hepatocytes has been also studied. TNF alpha induced the marked biosynthesis of ATP on PMEP of hepatocytes and splenocytes within the first minute of incubation. The biosynthesis of ATP was independent of the activity of adenylate kinase and only occurred in the presence of all the components of aerobic phosphorylation and the electron acceptor, cytochrome C or diferric transferrin. The level of ATP on PM correlated with the degree of expression of the nuclear oncogene c-myc in the same target cells. Adriamycin totally suppressed the biosynthesis of ATP on PM and simultaneously inhibited the expression of c-myc. The ATP synthesized on PM is suggested to be involved in transduction of the proliferative or growth signal to the cell nucleus.