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

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 The unpublished studies have been retrieved from the grey literature through Google and Google Scholar.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.


Rationale
3 Describe the rationale for the review in the context of what is already known.

3-5
Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

METHODS
Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.

N/A
Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.

6
Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

6
Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.

6
Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).
6 Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators. 8 Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

7-8
Risk of bias in individual studies 12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.

8
Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

RESULTS
Study selection 17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.

9-10
Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

9-10 S2_Table
Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12).

NI
Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.

9-13
Synthesis of results 21 Present results of each meta-analysis done, including confidence intervals and measures of consistency.

9-13
Risk of bias across studies 22 Present results of any assessment of risk of bias across studies (see Item 15).

DISCUSSION
Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their relevance to key groups (e.g., healthcare providers, users, and policy makers).

13-19
Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

19
Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research.

FUNDING
Funding 27 Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.

N/A
Key: N/A, not applicable; NI, not indicated.