title: Treatment outcomes for multidrug-resistant tuberculosis under DOTS-Plus: a systematic review and meta-analysis of published studies.
abstract: BACKGROUND
  Anti-tuberculosis drug resistance is a major public health problem that threatens the progress made in tuberculosis care and control worldwide. Treatment success rates of multidrug-resistant tuberculosis (MDR-TB) is a key issue that cannot be ignored. There is a paucity of evidence that assessed studies on the treatment of MDR-TB, which focus on the effectiveness of the directly observed treatment, short-course (DOTS)-Plus program. Therefore, it is crucial to assess and summarize the overall treatment outcomes for MDR-TB patients enrolled in the DOTS-Plus program in recent years. The purpose of this study was to thus assess and summarize the available evidence for MDR-TB treatment outcomes under DOTS-Plus.
  
  
  METHODS
  A systematic review and meta-analysis of published literature was conducted. Original studies were identified using the databases MEDLINE®/PubMed®, Hinari, and Google Scholar. Heterogeneity across studies was assessed using the Cochran's Q test and I2statistic. Pooled estimates of treatment outcomes were computed using the random effect model.
  
  
  RESULTS
  Based on the 14 observational studies included in the meta-analysis, it was determined that 5 047 patients reported treatment outcomes. Of these, the pooled prevalence, 63.5% (95% CI: 58.4-68.5%) successfully completed full treatment (cured or treatment completed) with a pooled cure rate of 55.6%, whereas 12.6% (95% CI: 9.0-16.2%) of the patients died, 14.2% (95% CI: 11.6-16.8%) defaulted from therapy, and 7.6% (95% CI: 5.6-9.7%) failed therapy. Overall 35.4% (95% CI: 30-40.8%) of patients had unsuccessful treatment outcomes. An unsatisfactorily high percentage 43% (95% CI: 32-54%) of unsuccessful treatment outcomes was observed among patients who were enrolled in standardized treatment regimens.
  
  
  CONCLUSIONS
  This study revealed that patients with MDR-TB exhibited a very low treatment success rate compared to the World Health Organization 2015 target of at least 75 to 90%. The high default rate observed by conducting this literature review could possibly explain the spread of the MDR-TB strain in various populations. A better treatment success rate was observed among patients in individualized treatment regimens than in standardized ones. Conducting further individual-based meta-analysis is recommended to identify potential factors for defaulting treatment using large-scale and multi-center studies.
authors.affiliation: Department of Public Health, College of Medical and Health Sciences, Wollega University, P. O. Box 395, Nekemte, Ethiopia. ktwu27@gmail.com.
authors.forename: Kelemu Tilahun
authors.initials: KT
authors.lastname: Kibret
authors.affiliation: Department of Public Health, College of Medical and Health Sciences, Haramaya University, P. O. Box 135, Harar, Ethiopia.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Moges
authors.affiliation: College of Health, Department of Public Health, University of West Florida, Florida, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Memiah
authors.affiliation: Public Health Research Consultant, P. O. Box 24414, Addis Ababa, Ethiopia.
authors.forename: Sibhatu
authors.initials: S
authors.lastname: Biadgilign
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023801:Directly Observed Therapy; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents
keywords: DOTS-Plus; Multidrug resistance; Multidrug-resistant tuberculosis; Treatment outcomes; Tuberculosis