28 results on '"Kliiman K"'
Search Results
2. Resistance to second-line injectables and treatment outcomes in multidrug-resistant and extensively drug-resistant tuberculosis cases
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Migliori, G. B., Lange, C., Centis, R., Sotgiu, G., Mutterlein, R., Hoffmann, H., Kliiman, K., De Iaco, G., Lauria, F. N., Richardson, M. D., Spanevello, A., Cirillo, D. M., Ortmann, J., Kirsten, D., Ruesch Gerdes, S., Piana, F., Gori, A., Codecasa, L. R., Ferrarese, M., Toungoussova, O. S., Ferrara, Giovanni, Matteelli, A., De Lorenzo, S., Troupioti, P., Besozzi, G., Fattorini, L., Iona, E., Gualano, A., De Mori, P., Bevilacqua, N., Girardi, E., Danilovits, M., Hollo, V., and Mariandyshev, A.
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Estonia ,Pulmonary and Respiratory Medicine ,Drug ,medicine.medical_specialty ,Tuberculosis ,Settore MED/17 - Malattie Infettive ,Capreomycin ,FLUOROQUINOLONES ,Extensively Drug-Resistant Tuberculosis ,media_common.quotation_subject ,Drug Resistance ,Antitubercular Agents ,Drug resistance ,Injections ,Russia ,Mycobacterium tuberculosis ,Multidrug-resistant tuberculosis ,Drug Resistance, Multiple, Bacterial ,Germany ,Internal medicine ,tuberculosis MYCOBACTERIUM-TUBERCULOSIS ,Humans ,Medicine ,Registries ,Treatment Failure ,XDR-TB ,media_common ,biology ,business.industry ,Bacterial ,Extensively drug-resistant tuberculosis ,Odds ratio ,biology.organism_classification ,medicine.disease ,Survival Analysis ,Injectable second-line drugs ,Injections, Intravenous ,Italy ,Surgery ,Multiple drug resistance ,drug resistance, extensively drug-resistant tuberculosis, injectable second-line drugs, multidrug-resistant tuberculosis, tuberculosis MYCOBACTERIUM-TUBERCULOSIS, XDR-TB, FLUOROQUINOLONES ,Intravenous ,business ,Multiple ,medicine.drug - Abstract
No information is currently available on the influence of injectable second-line drugs on treatment outcomes of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) patients. To investigate this issue, a large series of MDR- and XDR-TB cases diagnosed in Estonia, Germany, Italy and the Russian Federation (Archangels Oblast) between 1999 and 2006 were analysed. All study sites performed drug susceptibility testing for first- and second-line anti-TB drugs, laboratory quality assurance and treatment delivery according to World Health Organization recommendations. Out of 4,583 culture-confirmed cases, 240 MDR- and 48 XDR-TB cases had a definitive outcome recorded (treatment success, death, failure). Among MDR- and XDR-TB cases, capreomycin resistance yielded a higher proportion of failure and death than capreomycin-susceptible cases. Resistance to capreomycin was independently associated with unfavourable outcome (logistic regression analysis: odds ratio 3.51). In the treatment of patients with multidrug-resistant and extensively drug-resistant tuberculosis, resistance to the injectable drug capreomycin was an independent predictor for therapy failure in this cohort. As Mycobacterium tuberculosis drug resistance is increasing worldwide, there is an urgent need for novel interventions in the fight against tuberculosis.
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- 2008
3. Extensively drug-resistant tuberculosis is worse than multidrug-resistant tuberculosis: different methodology and settings, same results
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Migliori, G. B., Lange, C., Girardi, E., Centis, R., Besozzi, G., Kliiman, K., Ortmann, J., Matteelli, A., Spanevello, A., Cirillo, D. M., Kirsten, D., Codecasa, L. R., Gori, A., De Lorenzo, S., Troupioti, P., De Iaco, G., Gualano, G., De Mori, P., Fattorini, L., Iona, E., Ferrara, G., Sotgiu, G., Danilovits, M., Hollo, V., Mariandyshev, A., and Toungoussova, O.
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Microbiology (medical) ,medicine.medical_specialty ,Tuberculosis ,Extensively Drug-Resistant Tuberculosis ,Treatment outcome ,MEDLINE ,Antitubercular Agents ,Drug Resistance ,Drug resistance ,Microbial Sensitivity Tests ,Treatment failure ,Mycobacterium tuberculosis ,Internal medicine ,medicine ,Humans ,Treatment Failure ,biology ,business.industry ,Bacterial ,Extensively drug-resistant tuberculosis ,Multidrug-Resistant ,medicine.disease ,biology.organism_classification ,Multiple drug resistance ,Infectious Diseases ,Treatment Outcome ,Regression Analysis ,Drug Resistance, Multiple, Bacterial ,Tuberculosis, Multidrug-Resistant ,business ,Multiple - Published
- 2008
4. Clinical and operational value of the XDR-TB definition
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Migliori, G., Besozzi, G., Kliiman, K., Lange, C., Toungoussova, O., Ferrara, Giovanni, Cirillo, D., Gori, A., Matteelli, A., Spanevello, A., Codecasa, L., and Raviglione, M.
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- 2007
5. Clinical and operational value of the extensively drug-resistant tuberculosis definition
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Migliori, G. B., Besozzi, G., Girardi, E., Kliiman, K., Lange, C., Toungoussova, O. S., Ferrara, G., Cirillo, D. M., Gori, A., Matteelli, A., Spanevello, A., Codecasa, L. R., Raviglione, M. C., Ortmann, J., Kirsten, D., Ruesch-Gerdes, S., Piana, F., Ferrarese, M., De Iaco, G., De Lorenzo, S., Troupioti, P., Fattorini, L., Iona, E., Gualano, A., De Mori, P., Centis, R., Danilovits, M., Hollo, V., and Mariandyshev, A.
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Pulmonary and Respiratory Medicine ,Risk ,medicine.medical_specialty ,Tuberculosis ,Time Factors ,medicine.medical_treatment ,Extensively Drug-Resistant Tuberculosis ,Antitubercular Agents ,Drug Resistance ,Drug resistance ,Global Health ,Communicable Diseases ,Russia ,Multidrug-resistant tuberculosis ,Isoniazid ,Medicine ,tuberculosis MYCOBACTERIUM-TUBERCULOSIS ,Humans ,Clinical value ,Extensively drug-resistant tuberculosis ,Drug Resistance, Multiple ,Population Surveillance ,Public Health ,Rifampin ,Treatment Outcome ,Intensive care medicine ,Ethambutol ,business.industry ,Pyrazinamide ,medicine.disease ,Surgery ,clinical value, drug resistance, extensively drug-resistant tuberculosis, multidrug-resistant tuberculosis, tuberculosis MYCOBACTERIUM-TUBERCULOSIS ,Tuberculosis management ,business ,Multiple ,Rifampicin ,medicine.drug - Abstract
Currently, no information is available on the effect of resistance/susceptibility to first-line drugs different from isoniazid and rifampicin in determining the outcome of extensively drug-resistant tuberculosis (XDR-TB) patients, and whether being XDR-TB is a more accurate indicator of poor clinical outcome than being resistant to all first-line anti-tuberculosis (TB) drugs. To investigate this issue, a large series of multidrug-resistant TB (MDR-TB) and XDR-TB cases diagnosed in Estonia, Germany, Italy and the Russian Federation during the period 1999-2006 were analysed. Drug-susceptibility testing for first- and second-line anti-TB drugs, quality assurance and treatment delivery was performed according to World Health Organization recommendations in all study sites. Out of 4,583 culture-positive TB cases analysed, 361 (7.9%) were MDR and 64 (1.4%) were XDR. XDR-TB cases had a relative risk (RR) of 1.58 to have an unfavourable outcome compared with MDR-TB cases resistant to all first-line drugs (isoniazid, rifampicin ethambutol, streptomycin and, when tested, pyrazinamide), and an RR of 2.61 compared with "other" MDR-TB cases (those susceptible to at least one first-line anti-TB drug among ethambutol, pyrazinamide and streptomycin, regardless of resistance to the second-line drugs not defining XDR-TB). The emergence of extensively drug-resistant tuberculosis confirms that problems in tuberculosis management are still present in Europe. While waiting for new tools which will facilitate management of extensively drug-resistant tuberculosis, accessibility to quality diagnostic and treatment services should be urgently ensured and adequate public health policies should be rapidly implemented to prevent further development of drug resistance.
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- 2007
6. European Union Standards for Tuberculosis Care
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Migliori, G.B., primary, Zellweger, J.P., additional, Abubakar, I., additional, Ibraim, E., additional, Caminero, J.A., additional, De Vries, G., additional, D'Ambrosio, L., additional, Centis, R., additional, Sotgiu, G., additional, Menegale, O., additional, Kliiman, K., additional, Aksamit, T., additional, Cirillo, D.M., additional, Danilovits, M., additional, Dara, M., additional, Dheda, K., additional, Dinh-Xuan, A.T., additional, Kluge, H., additional, Lange, C., additional, Leimane, V., additional, Loddenkemper, R., additional, Nicod, L.P., additional, Raviglione, M.C., additional, Spanevello, A., additional, Thomsen, V.Ø., additional, Villar, M., additional, Wanlin, M., additional, Wedzicha, J.A., additional, Zumla, A., additional, Blasi, F., additional, Huitric, E., additional, Sandgren, A., additional, and Manissero, D., additional
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- 2012
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7. TB and MDR/XDR-TB in European Union and European Economic Area countries: managed or mismanaged?
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Migliori, G. B., primary, Sotgiu, G., additional, D'Ambrosio, L., additional, Centis, R., additional, Lange, C., additional, Bothamley, G., additional, Cirillo, D. M., additional, De Lorenzo, S., additional, Guenther, G., additional, Kliiman, K., additional, Muetterlein, R., additional, Spinu, V., additional, Villar, M., additional, Zellweger, J. P., additional, Sandgren, A., additional, Huitric, E., additional, and Manissero, D., additional
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- 2012
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8. TB and M/XDR-TB infection control in European TB reference centres: the Achilles' heel?
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Sotgiu, G., primary, D'Ambrosio, L., additional, Centis, R., additional, Bothamley, G., additional, Cirillo, D. M., additional, De Lorenzo, S., additional, Guenther, G., additional, Kliiman, K., additional, Muetterlein, R., additional, Spinu, V., additional, Villar, M., additional, Zellweger, J. P., additional, Sandgren, A., additional, Huitric, E., additional, Lange, C., additional, Manissero, D., additional, and Migliori, G. B., additional
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- 2011
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9. Predictors of poor treatment outcome in multi- and extensively drug-resistant pulmonary TB
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Kliiman, K., primary and Altraja, A., additional
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- 2009
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10. Rezistenşa la medicamente injectabile de linia a II-a şi rezultatele tratamentului în cazurile de tuberculoză multidrog-rezistentă şi cu rezistenşă extinsă.
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Migliori, G. B., Lange, C., Centis, R., Sotgiu, G., Mutterlein, R., Hoffmann, H., Kliiman, K., De Iaco, G., Lauria, F. N., Richardson, M. D., Spanevello, A., and Cirillo, D. M.
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- 2008
11. Enhanced tuberculosis case detection among substitution treatment patients: a randomized controlled trial
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McNutt Louise-Anne, Kliiman Kai, Sepp Tiiu, Loit Helle-Mai, Rüütel Kristi, and Uusküla Anneli
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Medicine ,Biology (General) ,QH301-705.5 ,Science (General) ,Q1-390 - Abstract
Abstract Background Historically, HIV, TB (tuberculosis) and illegal drug treatment services in Estonia have been developed as vertical structures. Related health care services are often provided by different health care institutions and in different locations. This may present obstacles for vulnerable groups, such as injecting drug users (IDU), to access the needed services. We conducted a small scale randomized controlled trial to evaluate a case management intervention aimed at increasing TB screening and treatment entry among IDUs referred from a methadone drug treatment program in Jõhvi, North-Eastern Estonia. Findings Of the 189 potential subjects, 112 (59%) participated. HIV prevalence was 86% (n = 96) and 7.4% (n = 8) of participants were interferon gamma release assay (IGRA) positive (6.5% were both HIV and IGRA-positive, n = 7). Overall, 44% of participants (n = 49) attended TB clinic, 17 (30%) from control group and 32 (57%) from case management group (p = 0.004). None of the participants were diagnosed with TB. In a multivariate model, those randomized to case management group were more likely to access TB screening services. Conclusions These findings demonstrate the urgent need for scaling up TB screening among IDUs and the value of more active approach in referring substitution treatment patients to TB services. Trial registration ClinicalTrials.gov: NCT01290081
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- 2011
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12. Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study.
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Sharma A, Hill A, Kurbatova E, van der Walt M, Kvasnovsky C, Tupasi TE, Caoili JC, Gler MT, Volchenkov GV, Kazennyy BY, Demikhova OV, Bayona J, Contreras C, Yagui M, Leimane V, Cho SN, Kim HJ, Kliiman K, Akksilp S, Jou R, Ershova J, Dalton T, and Cegielski P
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- Asia, Humans, Mycobacterium tuberculosis drug effects, Risk Factors, Russia, South Africa, Antitubercular Agents therapeutic use, Extensively Drug-Resistant Tuberculosis drug therapy, Models, Theoretical
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Background: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa., Methods: We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa., Findings: The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12·4% (95% prediction interval 9·4-16·2) in India, 8·9% (4·5-11·7) in the Philippines, 32·5% (27·0-35·8) in Russia, and 5·7% (3·0-7·6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8·9% (95% prediction interval 5·1-12·9) in India, 9·0% (4·0-14·7) in the Philippines, 9·0% (4·8-14·2) in Russia, and 8·5% (2·5-14·7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040., Interpretation: MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR tuberculosis., Funding: US Agency for International Development and US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
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- 2017
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13. Factors signifying gender differences in clinical presentation of sarcoidosis among Estonian population.
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Lill H, Kliiman K, and Altraja A
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- Adult, Carbon Monoxide metabolism, Estonia epidemiology, Female, Humans, Lung chemistry, Male, Middle Aged, Regression Analysis, Sex Factors, Sarcoidosis, Pulmonary epidemiology, Sarcoidosis, Pulmonary pathology
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Introduction: Sarcoidosis is endemically prevalent in Northern Europe, but gender differences among the sarcoidosis population have not yet been compositely addressed., Objectives: To reveal independent factors that formulate gender differences in the presentation of sarcoidosis., Methods: All Caucasian patients with confirmed sarcoidosis were recruited from the outpatient department of the Lung Clinic of the Tartu University Hospital, Estonia, between February 2009 and April 2011. Data on demographics, complaints, symptoms, clinical presentation, extrapulmonary manifestations, radiographic stage, lung function parameters and sarcoidosis-related laboratory indices were all drawn from patients' clinical records at presentation. Factors characteristic of female gender were estimated using multivariate logistic regression analysis., Results: Of 230 cases included, there were significantly more females (56.5%, P = 0.005). After adjustment for age, females appeared distinguishable from males by older age [adjusted odds ratio (OR) 1.04, 95% confidence interval (CI) 1.02-1.07], less frequent smoking (OR 0.25, 95% CI 0.13-0.49), higher probability of extrapulmonary complaints (OR 2.06, 95% CI 1.16-3.65) and musculoskeletal sarcoidosis (OR 3.22, 95% CI 1.65-6.29), and after adjustment for both age and smoking status lower forced expiratory volume in 1 s and lung carbon monoxide diffusing coefficient % predicted (OR 0.89, 95% CI 0.82-0.97 and OR 0.98, 95% CI 0.96-0.995, respectively), but by higher forced vital capacity % predicted (OR 1.12, 95% CI 1.03-1.22)., Conclusion: Women with sarcoidosis are independently characterized by greater airflow obstruction, lower lung diffusing coefficient, older age, less smoking, and more frequent extrapulmonary complaints and musculoskeletal involvement. This may urge special attention when addressing female patients in both differential diagnostic and management settings., (© 2014 John Wiley & Sons Ltd.)
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- 2016
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14. Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance.
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Cegielski JP, Kurbatova E, van der Walt M, Brand J, Ershova J, Tupasi T, Caoili JC, Dalton T, Contreras C, Yagui M, Bayona J, Kvasnovsky C, Leimane V, Kuksa L, Chen MP, Via LE, Hwang SH, Wolfgang M, Volchenkov GV, Somova T, Smith SE, Akksilp S, Wattanaamornkiet W, Kim HJ, Kim CK, Kazennyy BY, Khorosheva T, Kliiman K, Viiklepp P, Jou R, Huang AS, Vasilyeva IA, Demikhova OV, Lancaster J, Odendaal R, Diem L, Perez TC, Gler T, Tan K, Bonilla C, Jave O, Asencios L, Yale G, Suarez C, Walker AT, Norvaisha I, Skenders G, Sture I, Riekstina V, Cirule A, Sigman E, Cho SN, Cai Y, Eum S, Lee J, Park S, Jeon D, Shamputa IC, Metchock B, Kuznetsova T, Akksilp R, Sitti W, Inyapong J, Kiryanova EV, Degtyareva I, Nemtsova ES, Levina K, Danilovits M, Kummik T, Lei YC, Huang WL, Erokhin VV, Chernousova LN, Andreevskaya SN, Larionova EE, and Smirnova TG
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- Adolescent, Adult, Aged, Drug Resistance, Multiple, Bacterial, Female, Humans, Male, Middle Aged, Mycobacterium tuberculosis isolation & purification, Prospective Studies, Sputum microbiology, Treatment Outcome, Young Adult, Antitubercular Agents therapeutic use, Mycobacterium tuberculosis drug effects, Tuberculosis, Multidrug-Resistant drug therapy
- Abstract
Background: Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined., Methods: Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens., Results: Of 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P < .001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ≤1 to ≥5 (P < .001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P < .001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval, .56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome., Conclusions: Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance., (Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)
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- 2016
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15. Association between Regimen Composition and Treatment Response in Patients with Multidrug-Resistant Tuberculosis: A Prospective Cohort Study.
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Yuen CM, Kurbatova EV, Tupasi T, Caoili JC, Van Der Walt M, Kvasnovsky C, Yagui M, Bayona J, Contreras C, Leimane V, Ershova J, Via LE, Kim H, Akksilp S, Kazennyy BY, Volchenkov GV, Jou R, Kliiman K, Demikhova OV, Vasilyeva IA, Dalton T, and Cegielski JP
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- Adolescent, Adult, Aged, Aged, 80 and over, Clinical Protocols, Cohort Studies, Drug Therapy, Combination statistics & numerical data, Global Health, Humans, Microbial Sensitivity Tests, Middle Aged, Proportional Hazards Models, Prospective Studies, Sputum microbiology, Young Adult, Antitubercular Agents pharmacology, Antitubercular Agents therapeutic use, Mycobacterium drug effects, Tuberculosis, Multidrug-Resistant drug therapy
- Abstract
Background: For treating multidrug-resistant tuberculosis (MDR TB), the World Health Organization (WHO) recommends a regimen of at least four second-line drugs that are likely to be effective as well as pyrazinamide. WHO guidelines indicate only marginal benefit for regimens based directly on drug susceptibility testing (DST) results. Recent evidence from isolated cohorts suggests that regimens containing more drugs may be beneficial, and that DST results are predictive of regimen effectiveness. The objective of our study was to gain insight into how regimen design affects treatment response by analyzing the association between time to sputum culture conversion and both the number of potentially effective drugs included in a regimen and the DST results of the drugs in the regimen., Methods and Findings: We analyzed data from the Preserving Effective Tuberculosis Treatment Study (PETTS), a prospective observational study of 1,659 adults treated for MDR TB during 2005-2010 in nine countries: Estonia, Latvia, Peru, Philippines, Russian Federation, South Africa, South Korea, Thailand, and Taiwan. For all patients, monthly sputum samples were collected, and DST was performed on baseline isolates at the US Centers for Disease Control and Prevention. We included 1,137 patients in our analysis based on their having known baseline DST results for at least fluoroquinolones and second-line injectable drugs, and not having extensively drug-resistant TB. These patients were followed for a median of 20 mo (interquartile range 16-23 mo) after MDR TB treatment initiation. The primary outcome of interest was initial sputum culture conversion. We used Cox proportional hazards regression, stratifying by country to control for setting-associated confounders, and adjusting for the number of drugs to which patients' baseline isolates were resistant, baseline resistance pattern, previous treatment history, sputum smear result, and extent of disease on chest radiograph. In multivariable analysis, receiving an average of at least six potentially effective drugs (defined as drugs without a DST result indicating resistance) per day was associated with a 36% greater likelihood of sputum culture conversion than receiving an average of at least five but fewer than six potentially effective drugs per day (adjusted hazard ratio [aHR] 1.36, 95% CI 1.09-1.69). Inclusion of pyrazinamide (aHR 2.00, 95% CI 1.65-2.41) or more drugs to which baseline DST indicated susceptibility (aHR 1.65, 95% CI 1.48-1.84, per drug) in regimens was associated with greater increases in the likelihood of sputum culture conversion than including more drugs to which baseline DST indicated resistance (aHR 1.33, 95% CI 1.18-1.51, per drug). Including in the regimen more drugs for which DST was not performed was beneficial only if a minimum of three effective drugs was present in the regimen (aHR 1.39, 95% CI 1.09-1.76, per drug when three effective drugs present in regimen). The main limitation of this analysis is that it is based on observational data, not a randomized trial, and drug regimens varied across sites. However, PETTS was a uniquely large and rigorous observational study in terms of both the number of patients enrolled and the standardization of laboratory testing. Other limitations include the assumption of equivalent efficacy across drugs in a category, incomplete data on adherence, and the fact that the analysis considers only initial sputum culture conversion, not reversion or long-term relapse., Conclusions: MDR TB regimens including more potentially effective drugs than the minimum of five currently recommended by WHO may encourage improved response to treatment in patients with MDR TB. Rapid access to high-quality DST results could facilitate the design of more effective individualized regimens. Randomized controlled trials are necessary to confirm whether individualized regimens with more than five drugs can indeed achieve better cure rates than current recommended regimens.
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- 2015
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16. Additional drug resistance of multidrug-resistant tuberculosis in patients in 9 countries.
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Kurbatova EV, Dalton T, Ershova J, Tupasi T, Caoili JC, Van Der Walt M, Kvasnovsky C, Yagui M, Bayona J, Contreras C, Leimane V, Via LE, Kim H, Akksilp S, Kazennyy BY, Volchenkov GV, Jou R, Kliiman K, Demikhova OV, and Cegielski JP
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- Antitubercular Agents therapeutic use, Extensively Drug-Resistant Tuberculosis drug therapy, Humans, Microbial Sensitivity Tests, Antitubercular Agents pharmacology, Drug Resistance, Multiple, Bacterial, Extensively Drug-Resistant Tuberculosis epidemiology, Extensively Drug-Resistant Tuberculosis microbiology, Mycobacterium tuberculosis drug effects
- Abstract
Data from a large multicenter observational study of patients with multidrug-resistant tuberculosis (MDR TB) were analyzed to simulate the possible use of 2 new approaches to treatment of MDR TB: a short (9-month) regimen and a bedaquiline-containing regimen. Of 1,254 patients, 952 (75.9%) had no resistance to fluoroquinolones and second-line injectable drugs and thus would qualify as candidates for the 9-month regimen; 302 (24.1%) patients with resistance to a fluoroquinolone or second-line injectable drug would qualify as candidates for a bedaquiline-containing regimen in accordance with published guidelines. Among candidates for the 9-month regimen, standardized drug-susceptibility tests demonstrated susceptibility to a median of 5 (interquartile range 5-6) drugs. Among candidates for bedaquiline, drug-susceptibility tests demonstrated susceptibility to a median of 3 (interquartile range 2-4) drugs; 26% retained susceptibility to <2 drugs. These data may assist national TB programs in planning to implement new drugs and drug regimens.
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- 2015
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17. Sputum culture conversion as a prognostic marker for end-of-treatment outcome in patients with multidrug-resistant tuberculosis: a secondary analysis of data from two observational cohort studies.
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Kurbatova EV, Cegielski JP, Lienhardt C, Akksilp R, Bayona J, Becerra MC, Caoili J, Contreras C, Dalton T, Danilovits M, Demikhova OV, Ershova J, Gammino VM, Gelmanova I, Heilig CM, Jou R, Kazennyy B, Keshavjee S, Kim HJ, Kliiman K, Kvasnovsky C, Leimane V, Mitnick CD, Quelapio I, Riekstina V, Smith SE, Tupasi T, van der Walt M, Vasilyeva IA, Via LE, Viiklepp P, Volchenkov G, Walker AT, Wolfgang M, Yagui M, and Zignol M
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- Adolescent, Adult, Aged, Humans, Middle Aged, Mycobacterium tuberculosis isolation & purification, Prospective Studies, Treatment Outcome, Young Adult, Sputum microbiology, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Pulmonary drug therapy
- Abstract
Background: Sputum culture conversion is often used as an early microbiological endpoint in phase 2 clinical trials of tuberculosis treatment on the basis of its assumed predictive value for end-of-treatment outcome, particularly in patients with drug-susceptible tuberculosis. We aimed to assess the validity of sputum culture conversion on solid media at varying timepoints, and the time to conversion, as prognostic markers for end-of-treatment outcome in patients with multidrug-resistant (MDR) tuberculosis., Methods: We analysed data from two large cohort studies of patients with MDR tuberculosis. We defined sputum culture conversion as two or more consecutive negative cultures from sputum samples obtained at least 30 days apart. To estimate the association of 2 month and 6 month conversion with successful treatment outcome, we calculated odds ratios (ORs) and 95% CIs with random-effects multivariable logistic regression. We calculated predictive values with bivariate random-effects generalised linear mixed modelling., Findings: We assessed data for 1712 patients who had treatment success, treatment failure, or who died. Among patients with treatment success, median time to sputum culture conversion was significantly shorter than in those who had poor outcomes (2 months [IQR 1-3] vs 7 months [3 to ≥24]; log-rank p<0·0001). Furthermore, conversion status at 6 months (adjusted OR 14·07 [95% CI 10·05-19·71]) was significantly associated with treatment success compared with failure or death. Sputum culture conversion status at 2 months was significantly associated with treatment success only in patients who were HIV negative (adjusted OR 4·12 [95% CI 2·25-7·54]) or who had unknown HIV infection (3·59 [1·96-6·58]), but not in those who were HIV positive (0·38 [0·12-1·18]). Thus, the overall association of sputum culture conversion with a successful outcome was substantially greater at 6 months than at 2 months. 2 month conversion had low sensitivity (27·3% [95% confidence limit 16·6-41·4]) and high specificity (89·8% [82·3-94·4]) for prediction of treatment success. Conversely, 6 month sputum culture conversion status had high sensitivity (91·8% [85·9-95·4]), but moderate specificity (57·8% [42·5-71·6]). The maximum combined sensitivity and specificity for sputum culture conversion was reached between month 6 and month 10 of treatment., Interpretation: Time to sputum culture conversion, conversion status at 6 months, and conversion status at 2 months in patients without known HIV infection can be considered as proxy markers of end-of-treatment outcome in patients with MDR tuberculosis, although the overall association with treatment success is substantially stronger for 6 month than for 2 month conversion status. Investigators should consider these results regarding the validity of sputum culture conversion at various timepoints as an early predictor of treatment efficacy when designing phase 2 studies before investing substantial resources in large, long-term, phase 3 trials of new treatments for MDR tuberculosis., Funding: US Agency for International Development, US Centers for Disease Control and Prevention, Division of Intramural Research of the US National Institute of Allergy and Infectious Diseases, Korea Centers for Disease Control and Prevention., (Copyright © 2015 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2015
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18. Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis.
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Cegielski JP, Dalton T, Yagui M, Wattanaamornkiet W, Volchenkov GV, Via LE, Van Der Walt M, Tupasi T, Smith SE, Odendaal R, Leimane V, Kvasnovsky C, Kuznetsova T, Kurbatova E, Kummik T, Kuksa L, Kliiman K, Kiryanova EV, Kim H, Kim CK, Kazennyy BY, Jou R, Huang WL, Ershova J, Erokhin VV, Diem L, Contreras C, Cho SN, Chernousova LN, Chen MP, Caoili JC, Bayona J, and Akksilp S
- Subjects
- Adolescent, Adult, Aged, Cohort Studies, Female, Genotyping Techniques, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Mycobacterium tuberculosis isolation & purification, Prospective Studies, Selection, Genetic, Sputum microbiology, Young Adult, Antitubercular Agents therapeutic use, Drug Resistance, Multiple, Bacterial, Mycobacterium tuberculosis drug effects, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant microbiology, Tuberculosis, Pulmonary drug therapy, Tuberculosis, Pulmonary microbiology
- Abstract
Background: Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance., Methods: To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC., Results: In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16-.47) for XDR tuberculosis, 0.28 (.17-.45) for FQ, and 0.15 (.06-.39) to 0.60 (.34-1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07-.62) for acquired XDR tuberculosis and 0.23 (.09-.59) for acquired FQ resistance., Conclusions: Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)
- Published
- 2014
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19. Prevalence of IGRA-positivity and risk factors for tuberculosis among injecting drug users in Estonia and Latvia.
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Rüütel K, Karnite A, Talu A, Abel-Ollo K, Kirvelaite G, Kliiman K, Loit HM, and Uusküla A
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- Adolescent, Adult, Cross-Sectional Studies, Estonia epidemiology, Female, Humans, Interferon-gamma blood, Latvia epidemiology, Male, Middle Aged, Prevalence, Risk Factors, Substance Abuse, Intravenous blood, Substance Abuse, Intravenous complications, Substance Abuse, Intravenous immunology, Tuberculosis blood, Tuberculosis complications, Tuberculosis immunology, Young Adult, HIV Seroprevalence, Interferon-gamma immunology, Substance Abuse, Intravenous epidemiology, Tuberculosis epidemiology
- Abstract
Background: Illegal drug use and HIV are independent risk factors for tuberculosis (TB) among injecting drug users (IDU). Estonia and Latvia have experienced high rates of TB as well as IDU and HIV outbreaks. There is a lack of knowledge about TB among IDUs in these countries. The purpose of the current study was to estimate the prevalence and risk factors of Mycobacterium tuberculosis (MTB) infection among IDUs in Estonia and Latvia., Methods: Participants for this cross-sectional study were recruited from syringe exchange programmes using respondent-driven sampling. For assessing infection with MTB interferon-gamma release assay (IGRA) was used., Results: The study included 375 participants from Estonia and 313 from Latvia. The prevalence of IGRA-positivity among IDUs was 7.7% in Estonia and 25.6% in Latvia. HIV-prevalence was 62% in Estonia and 23% in Latvia. In both countries, IGRA-positivity rates did not differ between HIV-positive and HIV-negative participants. IGRA-positivity was independently associated with a prior diagnosis of TB in Estonia and with imprisonment (ever within a lifetime) and preceding contact with a TB patient in Latvia., Conclusion: Our findings indicate there is an urgent need for a more vigorous approach in providing IDUs with TB screening services., (Copyright © 2013 Elsevier B.V. All rights reserved.)
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- 2014
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20. Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study.
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Dalton T, Cegielski P, Akksilp S, Asencios L, Campos Caoili J, Cho SN, Erokhin VV, Ershova J, Gler MT, Kazennyy BY, Kim HJ, Kliiman K, Kurbatova E, Kvasnovsky C, Leimane V, van der Walt M, Via LE, Volchenkov GV, Yagui MA, Kang H, Akksilp R, Sitti W, Wattanaamornkiet W, Andreevskaya SN, Chernousova LN, Demikhova OV, Larionova EE, Smirnova TG, Vasilieva IA, Vorobyeva AV, Barry CE 3rd, Cai Y, Shamputa IC, Bayona J, Contreras C, Bonilla C, Jave O, Brand J, Lancaster J, Odendaal R, Chen MP, Diem L, Metchock B, Tan K, Taylor A, Wolfgang M, Cho E, Eum SY, Kwak HK, Lee J, Lee J, Min S, Degtyareva I, Nemtsova ES, Khorosheva T, Kyryanova EV, Egos G, Perez MT, Tupasi T, Hwang SH, Kim CK, Kim SY, Lee HJ, Kuksa L, Norvaisha I, Skenders G, Sture I, Kummik T, Kuznetsova T, Somova T, Levina K, Pariona G, Yale G, Suarez C, Valencia E, and Viiklepp P
- Subjects
- Adolescent, Adult, Aged, Extensively Drug-Resistant Tuberculosis drug therapy, Extensively Drug-Resistant Tuberculosis epidemiology, Female, Humans, Male, Middle Aged, Prevalence, Risk Factors, Socioeconomic Factors, Tuberculosis, Multidrug-Resistant epidemiology, Young Adult, Antitubercular Agents therapeutic use, Tuberculosis, Multidrug-Resistant drug therapy
- Abstract
Background: The prevalence of extensively drug-resistant (XDR) tuberculosis is increasing due to the expanded use of second-line drugs in people with multidrug-resistant (MDR) disease. We prospectively assessed resistance to second-line antituberculosis drugs in eight countries., Methods: From Jan 1, 2005, to Dec 31, 2008, we enrolled consecutive adults with locally confirmed pulmonary MDR tuberculosis at the start of second-line treatment in Estonia, Latvia, Peru, Philippines, Russia, South Africa, South Korea, and Thailand. Drug-susceptibility testing for study purposes was done centrally at the Centers for Disease Control and Prevention for 11 first-line and second-line drugs. We compared the results with clinical and epidemiological data to identify risk factors for resistance to second-line drugs and XDR tuberculosis., Findings: Among 1278 patients, 43·7% showed resistance to at least one second-line drug, 20·0% to at least one second-line injectable drug, and 12·9% to at least one fluoroquinolone. 6·7% of patients had XDR tuberculosis (range across study sites 0·8-15·2%). Previous treatment with second-line drugs was consistently the strongest risk factor for resistance to these drugs, which increased the risk of XDR tuberculosis by more than four times. Fluoroquinolone resistance and XDR tuberculosis were more frequent in women than in men. Unemployment, alcohol abuse, and smoking were associated with resistance to second-line injectable drugs across countries. Other risk factors differed between drugs and countries., Interpretation: Previous treatment with second-line drugs is a strong, consistent risk factor for resistance to these drugs, including XDR tuberculosis. Representative drug-susceptibility results could guide in-country policies for laboratory capacity and diagnostic strategies., Funding: US Agency for International Development, Centers for Disease Control and Prevention, National Institutes of Health/National Institute of Allergy and Infectious Diseases, and Korean Ministry of Health and Welfare., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
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- 2012
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21. Cost and cost-effectiveness of multidrug-resistant tuberculosis treatment in Estonia and Russia.
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Floyd K, Hutubessy R, Kliiman K, Centis R, Khurieva N, Jakobowiak W, Danilovits M, Peremitin G, Keshavjee S, and Migliori GB
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- Adolescent, Adult, Antitubercular Agents therapeutic use, Cohort Studies, Cost-Benefit Analysis, Estonia, Female, Humans, Male, Middle Aged, Quality-Adjusted Life Years, Russia, Treatment Outcome, Tuberculosis, Multidrug-Resistant drug therapy, World Health Organization, Young Adult, Antitubercular Agents economics, Health Care Costs, Tuberculosis, Multidrug-Resistant economics
- Abstract
Evidence on the cost and cost-effectiveness of treatment of multidrug-resistant tuberculosis (MDR-TB) is limited, and no published data are available from former Soviet Union countries, where rates of MDR-TB are highest globally. We evaluated the cost and cost-effectiveness of MDR-TB treatment in Estonia and Russia (Tomsk Oblast), comparing cohorts enrolled on treatment according to World Health Organization (WHO) guidelines in 2001 and 2002 with cohorts treated in previous years. Costs were assessed from a health system perspective in 2003 US$; effects were measured as cures, deaths averted and disability-adjusted life-years (DALYs) averted. Cure rates when WHO guidelines were followed were 61% (90 out of 149) in Estonia and 76% (76 out of 100) in Tomsk Oblast, with a cost per patient treated of US$8,974 and US$10,088, respectively. Before WHO guidelines were followed, cure rates were 52% in Estonia and 15% in Tomsk Oblast; the cost per patient treated was US$4,729 and US$2,282, respectively. Drugs and hospitalisation accounted for 69-90% of total costs. The cost per DALY averted by treatment following WHO guidelines was US$579 (range US$297-US$902) in Estonia and US$429 (range US$302-US$546) in Tomsk Oblast. Treatment of patients with MDR-TB can be cost-effective, but requires substantial additional investment in tuberculosis control in priority countries.
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- 2012
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22. Enhanced tuberculosis case detection among substitution treatment patients: a randomized controlled trial.
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Rüütel K, Loit HM, Sepp T, Kliiman K, McNutt LA, and Uusküla A
- Abstract
Background: Historically, HIV, TB (tuberculosis) and illegal drug treatment services in Estonia have been developed as vertical structures. Related health care services are often provided by different health care institutions and in different locations. This may present obstacles for vulnerable groups, such as injecting drug users (IDU), to access the needed services. We conducted a small scale randomized controlled trial to evaluate a case management intervention aimed at increasing TB screening and treatment entry among IDUs referred from a methadone drug treatment program in Jõhvi, North-Eastern Estonia., Findings: Of the 189 potential subjects, 112 (59%) participated. HIV prevalence was 86% (n = 96) and 7.4% (n = 8) of participants were interferon gamma release assay (IGRA) positive (6.5% were both HIV and IGRA-positive, n = 7). Overall, 44% of participants (n = 49) attended TB clinic, 17 (30%) from control group and 32 (57%) from case management group (p = 0.004). None of the participants were diagnosed with TB. In a multivariate model, those randomized to case management group were more likely to access TB screening services., Conclusions: These findings demonstrate the urgent need for scaling up TB screening among IDUs and the value of more active approach in referring substitution treatment patients to TB services., Trial Registration: ClinicalTrials.gov: NCT01290081.
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- 2011
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23. Predictors and mortality associated with treatment default in pulmonary tuberculosis.
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Kliiman K and Altraja A
- Subjects
- Adult, Aged, Alcoholism mortality, Chi-Square Distribution, Estonia epidemiology, Female, HIV Infections mortality, Humans, Logistic Models, Male, Middle Aged, Mycobacterium tuberculosis isolation & purification, Odds Ratio, Prisoners statistics & numerical data, Proportional Hazards Models, Recurrence, Residence Characteristics statistics & numerical data, Retrospective Studies, Risk Assessment, Risk Factors, Sputum microbiology, Time Factors, Treatment Outcome, Tuberculosis, Multidrug-Resistant diagnosis, Tuberculosis, Multidrug-Resistant microbiology, Tuberculosis, Pulmonary diagnosis, Tuberculosis, Pulmonary microbiology, Unemployment statistics & numerical data, Urban Population statistics & numerical data, Young Adult, Antitubercular Agents therapeutic use, Medication Adherence, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant mortality, Tuberculosis, Pulmonary drug therapy, Tuberculosis, Pulmonary mortality
- Abstract
Objective: To identify risk factors for default from pulmonary tuberculosis (TB) treatment and to assess mortality associated with default in Estonia., Design: All patients with culture-confirmed pulmonary TB who started treatment during 2003-2005 were included in a retrospective cohort study., Results: In 1107 eligible patients, the treatment success rate was 81.5% and the default rate 9.4% (respectively 60.4% and 17.0% in multidrug-resistant TB [MDR-TB]). Independent predictors of treatment default were alcohol abuse (OR 3.22, 95%CI 1.93-5.38), unemployment (OR 3.05, 95%CI 1.84-5.03), MDR-TB (OR 2.17, 95%CI 1.35-3.50), urban residence (OR 1.85, 95%CI 1.00-3.42) and previous incarceration (OR 1.78, 95%CI 1.05-3.03). Of the defaulters, 29.4% died during follow-up (median survival 342.0 days). Cox regression analysis revealed that unemployment was associated with all-cause and TB-related mortality among defaulters (respectively HR 4.58, 95%CI 1.05-20.1 and HR 11.2, 95%CI 1.58-80.2). HIV infection (HR 51.2, 95%CI 6.06-432), sputum smear positivity (HR 9.59, 95%CI 1.79-51.4), MDR-TB (HR 8.56, 95%CI 1.81-40.4) and previous TB (HR 5.15, 95%CI 1.64-16.2) were predictors of TB-related mortality., Conclusion: The main risk factors for treatment default can be influenced. Interventions to reduce default should therefore concentrate on socially disadvantaged patients and prevention of alcohol abuse, with special attention given to MDR-TB patients.
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- 2010
24. Consensus not yet reached on key drugs for extensively drug-resistant tuberculosis treatment.
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Migliori GB, Sotgiu G, D'Arcy Richardson M, Centis R, Guenther G, Hoffmann H, Cirillo DM, Toungossova O, Kliiman K, De Lorenzo S, Spanevello A, and Lange C
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- Adult, Consensus, Female, Humans, Male, Middle Aged, Treatment Outcome, Antitubercular Agents therapeutic use, Extensively Drug-Resistant Tuberculosis drug therapy
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- 2009
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25. Predictors of extensively drug-resistant pulmonary tuberculosis.
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Kliiman K and Altraja A
- Subjects
- Adult, Alcoholism complications, Antitubercular Agents therapeutic use, Cross-Sectional Studies, Estonia epidemiology, Extensively Drug-Resistant Tuberculosis drug therapy, Female, HIV Infections complications, Ill-Housed Persons, Humans, Male, Middle Aged, Mycobacterium tuberculosis drug effects, Odds Ratio, Prevalence, Retrospective Studies, Risk Factors, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant epidemiology, Tuberculosis, Pulmonary drug therapy, Young Adult, Extensively Drug-Resistant Tuberculosis epidemiology, Tuberculosis, Pulmonary epidemiology
- Abstract
Background: About 40 000 cases of extensively drug-resistant tuberculosis emerge worldwide annually, but the predictors of extensive drug resistance are unclear., Objective: To identify risk factors for extensively drug-resistant tuberculosis and multidrug-resistant but non-extensively drug-resistant tuberculosis in patients with culture-confirmed pulmonary tuberculosis., Design: Cross-sectional, countrywide study., Setting: Estonia, a country with 1 of the world's highest rates of extensively drug-resistant and multidrug-resistant tuberculosis., Patients: All patients with culture-confirmed pulmonary tuberculosis with clinical or radiologic evidence of active disease detected from January 2003 to December 2005., Measurements: Risk determinants from patients' demographic characteristics, socioeconomic variables, and tuberculosis-related data or HIV status., Results: Of 1163 patients, 60 (5.2%) had extensively drug-resistant tuberculosis and 196 (16.9%) had multidrug-resistant but non-extensively drug-resistant tuberculosis. Previous antituberculosis treatment (adjusted odds ratio [OR], 10.54 [95% CI, 5.97 to 18.62]), HIV infection (OR, 3.12 [CI, 1.31 to 7.41]), homelessness (OR, 2.73 [CI, 1.15 to 6.48]), and alcohol abuse (OR, 1.98 [CI, 1.08 to 3.64]) increased risk for extensive drug resistance. Previous treatment (OR, 4.11 [CI, 2.77 to 6.08]) and age 24 years or younger (OR, 2.57 [CI, 1.09 to 6.06]), 25 to 44 years (OR, 2.64 [CI, 1.35 to 5.16]), and 45 to 64 years (OR, 2.06 [CI, 1.06 to 3.99]) were determinants of multidrug resistance. In patients age 24 years or younger, female sex (OR, 6.23 [CI, 1.02 to 37.99]) and birth outside of Estonia (OR, 82.04 [CI, 3.46 to 1945.47]) increased risk for multidrug resistance., Limitation: Patients' comorbid conditions and drug abuse history were not incorporated into analyses because of inconsistent source data., Conclusion: Previous treatment is a common risk factor for extensively drug-resistant and multidrug-resistant tuberculosis. Reducing relapses; screening persons younger than 65 years and immigrants; and combating against HIV infection, alcoholism, and homelessness are key issues for decreasing the spread of highly drug-resistant tuberculosis.
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- 2009
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26. Fluoroquinolones: are they essential to treat multidrug-resistant tuberculosis?
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Migliori GB, Lange C, Girardi E, Centis R, Besozzi G, Kliiman K, Codecasa LR, Spanevello A, and Cirillo DM
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- Anti-Bacterial Agents pharmacology, Estonia epidemiology, Fluoroquinolones pharmacology, Germany epidemiology, Humans, Italy epidemiology, Risk Factors, Russia epidemiology, Tuberculosis, Multidrug-Resistant mortality, Anti-Bacterial Agents therapeutic use, Fluoroquinolones therapeutic use, Tuberculosis, Multidrug-Resistant drug therapy
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- 2008
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27. Extensively drug-resistant tuberculosis is worse than multidrug-resistant tuberculosis: different methodology and settings, same results.
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Migliori GB, Lange C, Girardi E, Centis R, Besozzi G, Kliiman K, Ortmann J, Matteelli A, Spanevello A, and Cirillo DM
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- Antitubercular Agents therapeutic use, Drug Resistance, Multiple, Bacterial, Humans, Microbial Sensitivity Tests, Mycobacterium tuberculosis pathogenicity, Regression Analysis, Treatment Failure, Treatment Outcome, Antitubercular Agents pharmacology, Extensively Drug-Resistant Tuberculosis drug therapy, Extensively Drug-Resistant Tuberculosis microbiology, Extensively Drug-Resistant Tuberculosis mortality, Mycobacterium tuberculosis drug effects, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant microbiology, Tuberculosis, Multidrug-Resistant mortality
- Published
- 2008
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28. Clinical and operational value of the extensively drug-resistant tuberculosis definition.
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Migliori GB, Besozzi G, Girardi E, Kliiman K, Lange C, Toungoussova OS, Ferrara G, Cirillo DM, Gori A, Matteelli A, Spanevello A, Codecasa LR, and Raviglione MC
- Subjects
- Communicable Diseases therapy, Drug Resistance, Multiple, Global Health, Humans, Population Surveillance, Public Health, Risk, Russia, Time Factors, Treatment Outcome, Antitubercular Agents pharmacology, Extensively Drug-Resistant Tuberculosis classification, Extensively Drug-Resistant Tuberculosis diagnosis, Extensively Drug-Resistant Tuberculosis epidemiology, Isoniazid pharmacology, Rifampin pharmacology
- Abstract
Currently, no information is available on the effect of resistance/susceptibility to first-line drugs different from isoniazid and rifampicin in determining the outcome of extensively drug-resistant tuberculosis (XDR-TB) patients, and whether being XDR-TB is a more accurate indicator of poor clinical outcome than being resistant to all first-line anti-tuberculosis (TB) drugs. To investigate this issue, a large series of multidrug-resistant TB (MDR-TB) and XDR-TB cases diagnosed in Estonia, Germany, Italy and the Russian Federation during the period 1999-2006 were analysed. Drug-susceptibility testing for first- and second-line anti-TB drugs, quality assurance and treatment delivery was performed according to World Health Organization recommendations in all study sites. Out of 4,583 culture-positive TB cases analysed, 361 (7.9%) were MDR and 64 (1.4%) were XDR. XDR-TB cases had a relative risk (RR) of 1.58 to have an unfavourable outcome compared with MDR-TB cases resistant to all first-line drugs (isoniazid, rifampicin ethambutol, streptomycin and, when tested, pyrazinamide), and an RR of 2.61 compared with "other" MDR-TB cases (those susceptible to at least one first-line anti-TB drug among ethambutol, pyrazinamide and streptomycin, regardless of resistance to the second-line drugs not defining XDR-TB). The emergence of extensively drug-resistant tuberculosis confirms that problems in tuberculosis management are still present in Europe. While waiting for new tools which will facilitate management of extensively drug-resistant tuberculosis, accessibility to quality diagnostic and treatment services should be urgently ensured and adequate public health policies should be rapidly implemented to prevent further development of drug resistance.
- Published
- 2007
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