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SETTING: Alcohol use increases the risk of multidrug-resistant tuberculosis (MDR-TB) and poses challenges for successful MDR-TB treatment, including the potential for additional adverse events. AIM: To investigate the association between alcohol consumption during MDR-TB treatment and adverse events and treatment outcomes in a cohort of patients in Tomsk, Russia. DESIGN: From 2000 to 2004, retrospective data were collected on 407 MDR-TB patients in Tomsk. Factors associated with treatment outcomes were assessed using logistic regression. RESULTS: Of the 407 patients, 253 (62.2%) consumed alcohol during treatment ('drinkers'), and 367 (90.2%) had at least one documented adverse advent. No significant differences were noted in frequency of adverse events in drinkers vs. non-drinkers. Drinkers had less favourable treatment outcomes (OR 0.28, 95%CI 0.18-0.45). Among drinkers, favourable treatment outcome was associated with adherence to at least 80% of prescribed doses (OR 2.89, 95%CI 1.30-6.43) and the occurrence of an adverse event requiring treatment interruption (OR 2.49, 95%CI 1.11-5.59). CONCLUSIONS: Alcohol use did not appear to increase the risk of adverse events during MDR-TB treatment; however, alcohol consumption was associated with poor outcome. Our findings suggest that individuals who drink alcohol should receive aggressive attention to optimise treatment adherence and manage adverse events.

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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.

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SETTING: A novel patient-centered tuberculosis (TB) treatment delivery program, 'Sputnik', was introduced for patients at high risk of treatment default in Tomsk City, Russian Federation. OBJECTIVE: To assess the effects of the Sputnik intervention on patient default rates. DESIGN: We analyzed the characteristics of patients referred to the program, treatment adherence of Sputnik program enrollees before and during the intervention, and final outcomes for all patients referred to the Sputnik program. RESULTS: For patients continuing their existing regimens after referral to the program (n = 46), mean adherence to treatment increased by 56% (from 52% of prescribed doses prior to enrolment to 81%). For patients initiating new regimens after referral ( n = 5), mean adherence was 83%. Mean adherence for patients with multidrug-resistant TB (MDR-TB; n = 38) was 79% and for all others (n = 13) it was 89%. The cure rate was 71.1% for patients with MDR-TB, 60% for all others and 68% in the program overall. CONCLUSION: The Sputnik intervention was successful in reducing rates of treatment default among patients at high risk for non-adherence.

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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.

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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.

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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.

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This paper was presented in place of one that was to have been given by the late Professor A.G. Khomenko, Director of the Central Tuberculosis Research Institute, Moscow. Professor Khomenko had a long and distinguished career and with his death Russia has lost one of its finest and most active workers in the fight against TB.

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