Barriers to successful tuberculosis treatment in Tomsk, Russian Federation: non-adherence, default and the acquisition of multidrug resistance

OBJECTIVE: To identify barriers to successful tuberculosis (TB) treatment in Tomsk, Siberia, by analysing individual and programmatic risk factors for non-adherence, default and the acquisition of multidrug resistance in a TB treatment cohort in the Russian Federation. METHODS: We conducted a retrospective cohort study of consecutively enrolled, newly detected, smear and/or culture-positive adult TB patients initiating therapy in a DOTS programme in Tomsk between 1 January and 31 December 2001. FINDINGS: Substance abuse was strongly associated with non-adherence [adjusted odds ratio (OR): 7.3; 95% confidence interval (CI): 2.89-18.46] and with default (adjusted OR: 11.2; 95% CI: 2.55-49.17). Although non-adherence was associated with poor treatment outcomes (OR: 2.4; 95% CI: 1.1-5.5), it was not associated with the acquisition of multi-drug resistance during the course of therapy. Patients who began treatment in the hospital setting or who were hospitalized later during their treatment course had a substantially higher risk of developing multidrug-resistant TB than those who were treated as outpatients (adjusted HRs: 6.34; 95% CI: 1.35-29.72 and 6.26; 95% CI: 1.02-38.35 respectively). CONCLUSION: In this cohort of Russian TB patients, substance abuse was a strong predictor of non-adherence and default. DOTS programmes may benefit from incorporating measures to diagnose and treat alcohol misuse within the medical management of patients undergoing TB therapy. Multidrug-resistant TB occurred among adherent patients who had been hospitalized in the course of their therapy. This raises the possibility that treatment for drug-sensitive disease unmasked a pre-existing population of drug-resistant organisms, or that these patients were reinfected with a drug-resistant strain of TB.     

Impact of Cytokine Expression in the Pre‐Implanted Donor Lung on the Development of Chronic Lung Allograft Dysfunction Subtypes

The long‐term success of lung transplantation continues to be challenged by the development of chronic lung allograft dysfunction (CLAD). The purpose of this study was to investigate the relationship between cytokine expression levels in pre‐implanted donor lungs and the posttransplant development of CLAD and its subtypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Of 109 patients who underwent bilateral lung or heart–lung transplantation and survived for more than 3 months, 50 BOS, 21 RAS and 38 patients with No CLAD were identified by pulmonary function test results. Using donor lung tissue biopsies sampled from each patient, expression levels of IL‐6, IL‐1β, IL‐8, IL‐10, interferon‐γ and tumor necrosis factor‐α mRNA were measured. IL‐6 expression levels were significantly higher in pre‐implanted lungs of patients that ultimately developed BOS compared to RAS and No CLAD (p = 0.025 and 0.011, respectively). Cox regression analysis demonstrated an association between high IL‐6 expression levels and BOS development (hazard ratio = 4.98; 95% confidence interval = 2.42–10.2, p < 0.001). In conclusion, high IL‐6 mRNA expression levels in pre‐implanted donor lungs were associated with the development of BOS, not RAS. This association further supports the contention that early graft injury impacts on both late graft function and early graft function.