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.

Hepatotoxicity during treatment for multidrug-resistant tuberculosis: occurrence, management and outcome.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) treatment program in Tomsk, Russia. OBJECTIVE: To describe the incidence and management of hepatotoxicity during treatment of MDR-TB, and to assess risk factors associated with its development and impact on treatment outcomes. DESIGN: A retrospective case series performed among 608 patients. RESULTS: Hepatotoxicity, using American Thoracic Society (2006) definitions, was observed in 91/568 patients (16.5%). The median time to the first hepatotoxic event was 196 days post treatment commencement. Baseline factors associated with hepatotoxicity included elevated alanine aminotransferase/aspartate aminotransferase/bilirubin (OR 53.9, 95%CI 6.30-438.7), and renal insufficiency (OR 19.6, 95%CI 2.71-141.6). High treatment adherence (OR 3.25, 95%CI 2.07-5.09) and starting treatment in prison (OR 1.77, 95%CI 1.04-3.01) were associated with treatment success. Smoking (OR 0.44, 95%CI 0.21-0.92) and bilateral cavitary disease (OR 0.51, 95%CI 0.34-0.77) were associated with worse outcomes. For alcohol users, developing hepatotoxicity was associated with better outcomes (OR 4.40, 95%CI 1.79-10.81) than not (OR 0.42, 95%CI 0.25-0.68). One or more medications were permanently stopped in 10/91 patients, but in no case was treatment entirely discontinued. CONCLUSION: MDR-TB treatment in the face of hepatotoxicity during therapy did not result in a statistically significant increase in poor outcomes.

Treating multidrug-resistant tuberculosis in Tomsk, Russia: developing programs that address the linkage between poverty and disease.

Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) are diseases of poverty. Because Mycobacterium tuberculosis exists predominantly in a social space often defined by poverty and its comorbidities--overcrowded or congregate living conditions, substance dependence or abuse, and lack of access to proper health services, to name a few--the biology of this organism and of TB drug resistance is intimately linked to the social world in which patients live. This association is demonstrated in Russia, where political changes in the 1990s resulted in increased socioeconomic inequality and a breakdown in health services. The effect on TB and MDR-TB is reflected both in terms of a rise in TB and MDR-TB incidence and increased morbidity and mortality associated with the disease. We present the case example of Tomsk Oblast to delineate how poverty contributed to a growing MDR-TB epidemic and increasing socioeconomic barriers to successful care, even when available. The MDR-TB pilot project implemented in Tomsk addressed both programmatic and socioeconomic factors associated with unfavorable outcomes. The result has been a strengthening of the overall TB control program in the region and improved case-holding for the most vulnerable patients. The model of MDR-TB care in Tomsk is applicable for other resource-poor settings facing challenges to TB and MDR-TB control.

Adverse reactions among patients being treated for MDR-TB in Tomsk, Russia.

BACKGROUND AND SIGNIFICANCE: Treatment of multidrug-resistant tuberculosis (MDR-TB) is challenging because of the toxicity of second-line medications. Little is known about whether adverse events impact treatment outcome. METHODS: We conducted a retrospective case series of 244 MDR-TB patients enrolled in Tomsk between 10 September 2000 and 10 September 2002. Adverse reactions were determined by laboratory data and/or clinical criteria. A multiple logistic regression model was performed to determine whether the occurrence of adverse reactions was associated with poor treatment outcome. RESULTS: In this cohort, 76.0% were cured, 6.6% failed, 4.9% died and 11.5% defaulted. Adverse events were observed in 73.3% of patients, occurring in 74.8% of patients who were adherent (taking at least 80% of prescribed doses) and 59.1% of non-adherent individuals (P = 0.11). The impact of adverse events on outcome was modified by non-adherence; among adherent patients, the occurrence of any adverse reaction was associated with treatment cure (adjusted odds ratio 3.24, 95% confidence interval 1.56-6.70). CONCLUSION: Adverse reactions occurred frequently in MDR-TB patients in Tomsk, Russia, but did not negatively impact treatment outcome. The occurrence of adverse reactions among adherent patients was associated with treatment cure.

Treatment outcomes in an integrated civilian and prison MDR-TB treatment program in Russia.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) is a major problem in countries of the former Soviet Union in both the civilian and prison sectors. OBJECTIVE: To evaluate outcomes of the MDR-TB treatment program (DOTS-Plus) in Tomsk, Russia. DESIGN: Retrospective case series of all patients enrolled in this program between 10 September 2000 and 10 September 2002. The program involves both the civilian and penitentiary TB services in Tomsk. Poor treatment outcome was defined as death, default and treatment failure. RESULTS: Among the 244 patients who received treatment, 77% were cured, 5% died, 7% failed, and 12% defaulted. In a multivariable analysis, alcohol consumption during treatment and the presence of both cavitary and bilateral disease were found to be the strongest predictors of poor treatment outcome. CONCLUSIONS: The integration of civilian and penitentiary TB services in the Tomsk MDR-TB treatment program has resulted in high cure rates and low rates of default. However, alcohol use among patients with MDR-TB is associated with poor treatment outcomes. Better understanding and programmatic alcohol interventions are needed if large-scale treatment of MDR-TB is to be successful in areas with high rates of alcohol use disorders.

Ionic conductivity in crystalline polymer electrolytes.

Polymer electrolytes are the subject of intensive study, in part because of their potential use as the electrolyte in all-solid-state rechargeable lithium batteries. These materials are formed by dissolving a salt (for example LiI) in a solid host polymer such as poly(ethylene oxide) (refs 2, 3, 4, 5, 6), and may be prepared as both crystalline and amorphous phases. Conductivity in polymer electrolytes has long been viewed as confined to the amorphous phase above the glass transition temperature, Tg, where polymer chain motion creates a dynamic, disordered environment that plays a critical role in facilitating ion transport. Here we show that, in contrast to this prevailing view, ionic conductivity in the static, ordered environment of the crystalline phase can be greater than that in the equivalent amorphous material above Tg. Moreover, we demonstrate that ion transport in crystalline polymer electrolytes can be dominated by the cations, whereas both ions are generally mobile in the amorphous phase. Restriction of mobility to the lithium cation is advantageous for battery applications. The realization that order can promote ion transport in polymers is interesting in the context of electronically conducting polymers, where crystallinity favours electron transport.