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The present study was undertaken to assess the results of treatment in patients with pulmonary tuberculosis in the Arkhangelsk Region in 1999 and to analyze the results of treatment in relation to the infection with Mycobacterium tuberculosis with different profiles of sensitivity to antituberculous drugs. The outcomes of treatment were assessed in relation to the infection with Mycobacterium tuberculosis with different profiles of sensitivity to antituberculous drugs in 76 patients to whom the BACTEC test was applied. Beneficial effects of therapy were recorded in 150 (63.9%) of the 235 new cases. In 29 (12.3%) patients, it ended in death, ineffective treatment was recorded in 20 (8.5%) first detected patients; 29 (12.3%) new cases discontinued treatment; the result of therapy was unknown in 7 (3.0%). There was a low efficiency of chemotherapy (26.2%), its inefficiency in 24 (39.4%) patients; treatment was discontinued in 18 (29.5%) cases and its outcome was unknown in 1 (1.6%) patient. Resistance to one antituberculous agent timely used in the effective chemotherapy regimen did not affect the outcome of treatment. The spread of drug resistance in pulmonary tuberculosis in the Arkhagelsk Region directly affects the outcome of the disease.

In recent decades, the decline of tuberculosis has stopped in Western Europe, mainly due to increased immigration from high-prevalence countries. The objective of the current study was to identify risk factors for developing tuberculosis following recent infection, in order to better target interventions. Strains from 861 culture-positive cases, diagnosed in Norway in 1994-1999, were analysed by use of restriction fragment length polymorphism (RFLP). A cluster was defined as two or more isolates with identical RFLP patterns. Risk factors for being part of a cluster were identified by univariate and multivariate analysis. A total of 134 patients were part of a cluster. These constituted 5% Asian-born, 18% Norwegian-born, 24% European-born and 29% African-born patients. Four independent risk factors for being part of a cluster were identified: being born in Norway, being of young age, being infected with an isoniazid-resistant strain and being infected with a multidrug-resistant strain. Transmission of tuberculosis may be further reduced by improving case management, contact tracing, preventive treatment, screening of immigrants and access to health services for the foreign-born population.

In the first attempt to establish a quality assurance programme for susceptibility testing of Mycobacterium tuberculosis to fluoroquinolones, 20 strains with different fluoroquinolone susceptibility patterns were distributed by the Supranational Reference Laboratory in Stockholm to the other mycobacterial reference laboratories of the Nordic and Baltic countries. Susceptibility testing to fluoroquinolones was performed according to routine procedures in each laboratory. Results were compared to sequence analysis of the gyrA gene and minimal inhibitory concentration determination. Most laboratories found identical susceptibility patterns. The two resistant strains were correctly identified by all laboratories, but three laboratories each falsely reported one susceptible strain as resistant. These results indicate that the participating laboratories yield reliable results in detection of fluoroquinolone-resistant strains, although the need for a standardised quality assurance programme for drug susceptibility testing for fluoroquinolones is stressed by the strains falsely reported as resistant.

In this study, we determined the genetic diversity of Mycobacterium tuberculosis isolated in Norway from 1999 to 2001. The results were compared to those for strains isolated from 1994 to 1998. A total of 818 patients were diagnosed with tuberculosis (TB) during the last 3-year period. Of these cases, 576 (70%) were verified by culturing, and strains from 551 patients (96%) were analyzed by the IS6110 restriction fragment length polymorphism (RFLP) method. We excluded 13 strains (2.4%) from the analyses, since they were found to represent false-positive samples. A total of 67 strains (12%) that carried fewer than five copies of IS6110 were analyzed by spoligotyping. The strains were from 157 patients (29%) of Norwegian origin and 381 patients (71%) of foreign origin. The rate of diversity among all of the strains was 90%, while in 1994 to 1998 it was 87%. Clusters were assumed to have arisen from recent transmission; the degree of such transmission was 10% in 1999 to 2001, while for the whole 8-year period (1994 to 2001), it was 11%. Of the 109 patients diagnosed as being part of a cluster in 1999 to 2001, 89 were infected with a strain that carried more than four copies of IS6110. Among these 89 patients, 52 (58%) were infected with a strain that had already been identified in 1994 to 1998. The results indicated that most cases of TB in Norway were due to the import of new strains rather than to transmission within the country. This finding demonstrates that screening of immigrants for TB upon arrival in Norway needs to be improved. Outbreaks, however, were caused mainly by strains that have been circulating in Norway for many years.

A collection of 119 strains of Mycobacterium tuberculosis isolated from patients with pulmonary tuberculosis in the Archangel Oblast, Russia, in 1998 and 1999 were studied by using restriction fragment length polymorphism (RFLP) analysis with the IS6110 probe and spoligotyping. Resistance of the strains to antituberculosis drugs was analyzed by the BACTEC method, and mutations associated with rifampin resistance were detected by using the Inno-LiPA Rif. TB test. RFLP analysis and spoligotyping demonstrated that 53 (44.5%) of the strains belonged to the Beijing genotype. These strains showed a significantly higher rate of resistance than M. tuberculosis strains of other genotypes circulating in the region. In particular, 43.4% of the strains of the Beijing genotype were multidrug resistant; in contrast, only 10.6% of the other strains were. Of the strains of the Beijing genotype, 92.5% were part of a cluster, while only 33.3% of the remaining strains were clustered. Analysis of the medical records of the patients demonstrated that individuals infected with a strain of the Beijing genotype were significantly more likely to be alcohol abusers and to have chronic obstructive pulmonary disease prior to the tuberculosis diagnosis. Multivariate analysis showed that both variables were independently associated with infection by strains belonging to the Beijing genotype. Our study demonstrated that strains of the Beijing genotype are an important cause of tuberculosis in the Archangel Oblast and that dissemination of these strains is associated with the high incidence of drug resistance.

Setting: The Archangels oblast, Russia, 1998-2000., Objective: To study Mycobacterium tuberculosis resistance to anti-tuberculosis drugs in the Archangels oblast, and to reveal risk factors for the development of drug-resistant tuberculosis., Design: The drug susceptibility of strains isolated from 119 patients with pulmonary tuberculosis was studied using the BACTEC method. Medical records of the patients were reviewed, retrospectively, to identify factors associated with drug resistance., Results: Sixty-seven strains (56.3%) were resistant to at least one anti-tuberculosis drug. The highest rates of resistance were observed for streptomycin and isoniazid: respectively 40.4% and 66.7% of strains isolated from newly and previously treated patients were resistant to streptomycin, and respectively 37.1% and 73.3% of strains isolated from newly and previously treated patients were resistant to isoniazid. Thirty of the 119 strains (25.2%) were multidrug-resistant. Multidrug resistance was four times higher among previously treated patients than among new patients. A history of previous or interrupted treatment for tuberculosis and being female were significantly associated with drug resistance., Conclusion: Drug-resistant tuberculosis is an important problem in the Archangels oblast, Russia. The spread of drug resistance is attributed to several risk factors. Being female and evidence of previous treatment for tuberculosis are risk factors for the development of drug-resistant tuberculosis in the Archangels oblast. Patients with drug-resistant tuberculosis also showed a higher risk of interrupting their treatment.

The paper considers drug resistance in Mycobacterium tuberculosis (MBT) in the Barents region of Russia and Norway. Along with a rise in tuberculosis morbidity, there has been recently an increase in the number of patients isolating MBT that are resistant to antituberculous agents. The most dangerous trend is an increase in MDR of MBT strains. In the north-west of Russia there are high MBT drug resistance rated as compared to Norway. There are differences in the determination of drug resistance by the absolute concentration method and by the BACTEC method.

The incidence of tuberculosis in Norway is one of the lowest in the world, and approximately half of the cases occur in first- and second-generation immigrants. In the present study, the genetic diversity of 92% of all strains of Mycobacterium tuberculosis isolated in Norway in 1994 to 1998 was assessed using restriction fragment length polymorphism (RFLP) analysis, with the insertion sequence IS6110 and the repetitive element DR as probes, to determine the degree of active transmission between patients. The DR probe was used as a secondary molecular marker to support or rule out clustering of strains with fewer than five copies of IS6110. After exclusion of 20 cultures representing laboratory contamination, 573 different IS6110 patterns were found among the 698 strains analyzed. Of these 573 patterns, 542 were observed only once and 31 were shared by 2 to 14 isolates. Among 81 strains (11.5%) carrying fewer than five copies of IS6110, 56 RFLP patterns were found when the results of both the IS6110 and DR methods were combined. Among the 698 strains, 570 were considered to be independent cases. A total of 14.5% of the native Norwegians and 19.7% of the foreign patients were part of a cluster. Thus, the degree of recent transmission of tuberculosis in Norway is low and the great majority of the cases are due to reactivation of previous disease. Transmission between immigrants and native Norwegians is uncommon. Two outbreaks, one among native Norwegians and one mainly among immigrants, have been ongoing for several years, indicating that, even in a low-incidence country such as Norway, with a good national program for tuberculosis surveillance, certain transmission chains are difficult to break.

Rifampin resistance in respiratory isolates of Mycobacterium tuberculosis from Mozambique was detected by screening for point mutations using polymerase chain reaction (PCR) and DNA sequence analysis. The target template was a 350-bp fragment of rpoB encoding the beta-subunit of the RNA polymerase. Of the 66 strains studied, 38 were rifampin resistant by susceptibility testing with the radiometric method, 3 were intermediately resistant, and 25 were susceptible to rifampin. In 39 of the 41 rifampin-resistant strains, base-substitutions in the rpoB fragment were detected, and a total of 13 distinct mutations affecting 6 amino acids were observed. One of these mutations (His-->Thr in amino acid 526) was not previously described. The isolates were also investigated by restriction fragment length polymorphism (RFLP) analysis using the insertion element IS6110 as a hybridization probe. A total of 47 RFLP patterns were identified, with up to 9 isolates having the same RFLP pattern. Strains with the same RFLP pattern harbored different mutations in rpoB, suggesting that acquisition of rifampin resistance followed the spread of a rifampin-susceptible clone. The data showed that rifampin resistance can be detected with a high sensitivity by DNA sequence analysis of this fragment of rpoB. However, a few strains with rifampin resistance due to factors other than base substitutions in rpoB could be missed.