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      Tuberculosis treatment outcomes in Ethiopia from 2003 to 2016, and impact of HIV co-infection and prior drug exposure: A systematic review and meta-analysis

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          Abstract

          Background

          Knowledge of tuberculosis (TB) treatment outcomes is substantially needed to assess the performance of national TB controls programs (NTPs). To date, the overall estimates of treatment outcomes have not been determined in Ethiopia. Therefore, this meta-analysis was undertaken to produce pooled estimates of TB treatment outcomes and to analyze the impact of prior anti-TB drug exposure and HIV co-infection.

          Methods

          Potentially relevant studies were retrieved from PubMed, EMBASE, and MEDLINE online databases. The unpublished studies have been retrieved from the grey literature through Google and Google Scholar. The pooled estimates were calculated using random effect model. The summary estimates were also presented using Forest plots and Tables. The outcome measures were successful and unsuccessful treatment outcomes. Patients who were cured or with completed treatment defined as successful treatment outcome and patients meeting the definition of death, defaulting and failure are considered as unsuccessfully treated cases.

          Results

          A total of 34 studies are included for meta-analysis. The pooled estimate of successful TB treatment outcomes amounts to 83.7% (95% CI 81.1%–86.3%). Of successfully treated cases, 33.9% were cured and the remaining completed cases. Besides, among patients with unsuccessful treatment outcome, nearly 50% were dead and the rest were treatment failures and defaulters. Sub-group analysis shows that high treatment success rate was estimated in Afar; 88.9% (95% CI 83.8%–94.2%), followed by Oromia; 88.5% (95% CI 82.6%–94.5%) and Gambella; 86.1% (95% CI 84.4%–87.9%), whereas relatively poor treatment outcome was noted in Tigray; 20.0% (95% CI 2.1%–37.9%) and Amhara; 19.0% (95% CI 12.6%–25.5%). The unsuccessful TB treatment outcome was found to be higher among HIV/TB co-infected cases with an odds ratio of 1.98 (95%CI, 1.56–2.52) and re-treated cases with an odds ratio of 2.17 (95%CI, 1.55–3.03). The time trend was assessed from 2003 to 2016, but it shows insignificant variation with treatment outcome (P = 0.108).

          Conclusion

          The rate of successful treatment outcome in Ethiopia appears generally high, only slightly below the threshold suggested by the World Health Organization. History of tuberculosis treatment and HIV/TB co-infection were inversely associated with favorable treatment outcomes.

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          Most cited references47

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          Controlling the seedbeds of tuberculosis: diagnosis and treatment of tuberculosis infection

          The billions of people with latent tuberculosis infection serve as the seedbeds for future cases of active tuberculosis. Virtually all episodes of tuberculosis disease are preceded by a period of asymptomatic Mycobacterium tuberculosis infection; therefore, identifying infected individuals most likely to progress to disease and treating such subclinical infections to prevent future disease provides a crucial opportunity to interrupt tuberculosis transmission and reduce the global burden of tuberculosis disease. Programmes focusing on single strategies rather than comprehensive programmes that deliver an integrated arsenal for tuberculosis control might continue to struggle. Tuberculosis preventive therapy is a poorly used method that is essential for controlling the reservoirs of disease that drive the epidemic. Comprehensive control strategies that combine preventive therapy for the most high-risk populations and communities with improved case-finding and treatment, control of transmission, and health systems strengthening could ultimately lead to worldwide tuberculosis elimination. In this Series paper we outline challenges to implementation of preventive therapy and provide pragmatic suggestions for overcoming them. We further advocate for tuberculosis preventive therapy as the core of a renewed worldwide focus to implement a comprehensive epidemic control strategy that would reduce new tuberculosis cases to elimination targets. This strategy would be underpinned by accelerated research to further understand the biology of subclinical tuberculosis infections, develop novel diagnostics and drug regimens specifically for subclinical tuberculosis infection, strengthen health systems and community engagement, and enhance sustainable large scale implementation of preventive therapy programmes.
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            Treatment outcomes among patients with extensively drug-resistant tuberculosis: systematic review and meta-analysis.

            . The treatment of extensively drug-resistant tuberculosis (XDR TB) presents a major challenge. Second-line antimycobacterial drugs are less effective, more toxic, and more costly than first-line agents, and XDR TB strains are, by definition, resistant to the most potent second-line options: the injectable agents and fluoroquinolones. We conducted a meta-analysis to assess XDR TB treatment outcomes and to identify therapeutic approaches associated with favorable responses. We searched PubMed and EMBASE databases to identify studies conducted through May 2009 that report XDR TB treatment outcomes. The search yielded 13 observational studies covering 560 patients, of whom 43.7% (95% confidence interval, 32.8%-54.5%) experienced favorable outcomes, defined as either cure or treatment completion, and 20.8% (95% confidence interval, 14.2%-27.3%) died. Random effects meta-analysis and meta-regression showed that studies in which a higher proportion of patients received a later-generation fluoroquinolone reported a higher proportion of favorable treatment outcomes (P=.012). This meta-analysis provides the first empirical evidence that the use of later-generation fluoroquinolones for the treatment of XDR TB significantly improves treatment outcomes, even though drug-susceptibility testing demonstrates resistance to a representative fluoroquinolone. These results suggest that the addition of later-generation fluoroquinolones to XDR TB regimens may improve treatment outcomes and should be systematically evaluated in well-designed clinical studies.
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              Treatment outcome of tuberculosis patients at Gondar University Teaching Hospital, Northwest Ethiopia. A five - year retrospective study

              Background In Gondar University Teaching Hospital standardized tuberculosis prevention and control programme, incorporating Directly Observed Treatment, Short Course (DOTS) started in 2000. According to the proposal of World Health Organization (WHO), treatment outcome is an important indicator of tuberculosis control programs. This study investigated the outcome of tuberculosis treatment at Gondar University Teaching Hospital in Northwest Ethiopia. Methods We analyzed the records of 4000 tuberculosis patients registered at Gondar University Teaching Hospital from September 2003 to May 2008. Treatment outcome and tuberculosis type were categorized according to the national tuberculosis control program guideline. Multivariate analysis using logistic regression model was used to analyse the association between treatment outcome and potential predictor variables. Results From the total of 4000 patients, tuberculosis type was categorized as extrapulmonary in 1133 (28.3%), smear negative pulmonary tuberculosis in 2196 (54.9%) and smear positive pulmonary tuberculosis in 671 (16.8%) cases. Of all patients, treatment outcome was classified as successfully treated in 1181(29.5%), defaulted in 730 (18.3%), died in 403 (10.1%), treatment failed in six (0.2%) and transferred out in 1680 (42.0%) patients. Males had the trend to be more likely to experience death or default than females, and the elderly were more likely to die than younger. The proportion of default rate was increased across the years from 97(9.2%) to 228(42.9%). Being female, age group 15-24 years, smear positive pulmonary tuberculosis and being urban resident were associated with higher treatment success rate. Conclusion The treatment success rate of tuberculosis patients was unsatisfactorily low (29.5%). A high proportion of patients died (10.1%) or defaulted (18.3%), which is a serious public health concern that needs to be addressed urgently.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: MethodologyRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                19 March 2018
                2018
                : 13
                : 3
                : e0194675
                Affiliations
                [1 ] Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
                [2 ] Department of Nursing, College of Health Sciences, Debre Markos University, Debre Markos, Ethiopia
                [3 ] National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
                Rutgers Biomedical and Health Sciences, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-9130-0882
                Article
                PONE-D-17-19776
                10.1371/journal.pone.0194675
                5858841
                29554144
                cac73da3-4cc4-480c-83a3-23faa84b332e
                © 2018 Eshetie et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 24 May 2017
                : 20 February 2018
                Page count
                Figures: 6, Tables: 2, Pages: 18
                Funding
                The authors received no specific funding for this work.
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