Abstract
The emergence of drug-resistant tuberculosis (DR-TB) is becoming a challenge to the national TB control programs including Ethiopia. Different risk factors are associated with the emergence of DR-TB. Identifying these risk factors in a local setting is important to strengthen the effort to prevent and control DR-TB. Thus, this study aimed to assess the risk factors associated with drug-resistant TB in Ethiopia. The Preferred Reporting Items for Systematic Reviews and Meta-analysis checklist was followed to conduct this study. We systematically searched the articles from electronic databases and gray literature sources. We used the Joanna Briggs Institute Critical Appraisal tools to assess the quality of studies. Data were analyzed using STATA version 15. We estimated the pooled OR along with 95%CI for each risk factor. The heterogeneity of the studies was assessed using the forest plot and I2 heterogeneity test. Besides, we explored the presence of publication bias through visual inspection of the funnel plot and Egger’s regression test. After intense searching, we found 2238 articles, and 27 eligible studies were included in the final analysis. Based on the pooled analysis of the odds ratio, unemployment (OR; 2.71, 95% CI; 1.64, 3.78), having a history of the previous TB (OR; 4.83, 95% CI; 3.02, 6.64), having contact with a known TB patient (OR; 1.72, 95% CI; 1.05, 2.40), having contact with a known MDR-TB patient (OR; 2.54, 95% CI; 1.46, 3.63), and having pulmonary TB (OR; 1.80, 95% CI; 1.14, 2.45) were found to be the risk factors of drug-resistant TB. While older age TB patients (OR; 0.77, 95% CI; 0.60, 0.95) including age above 45 years OR; (0.76, 95% CI; 0.55, 0.97), and males (OR; 0.86, 95% CI; 0.76, 0.97) were found to had lower risk of DR-TB compared to their counterparts. A previous history of TB treatment is a major risk factor for acquiring DR-TB in Ethiopia that might be due to poor adherence during the first-line anti TB treatment. Besides, having contact with a known TB patient, having contact with a known MDR-TB patient, having pulmonary TB, and being unemployed were the risk factors of DR-TB in Ethiopia. Thus, active screening of TB contacts for DR-TB might help to detect DR-TB cases as early as possible and could help to mitigate its further transmission across the community.
Keywords: Risk factors, Determinants, Drug-resistant tuberculosis, Ethiopia
INTRODUCTION
National tuberculosis (TB) control programs are challenged by the emergence of drug-resistance to more anti-TB drugs resulting in multi-drug resistant tuberculosis (MDR-TB), pre-extensively drug-resistant TB (pre-XDR-TB), and extensively drug-resistant TB (XDR-TB). Globally, about 465, 000 population have rifampicin-resistant TB (RR/TB) (78% MDR-TB), were about 3.5% among new cases and 18% among previously treated cases developed RR/MDR-TB. In addition, about 9% of RR/MDR-TB patients develop XDR-TB (WHO, 2020). The problem is also worse high burden countries including Ethiopia. In Ethiopia, based on the 2019 global TB report there were about 1600 RR/MDR-TB estimated cases where only 741 were laboratory confirmed, and 747 enrolled in treatment (WHO, 2019). In the country, about 12% among previously treated and 0.71% among the new TB cases are estimated to have RR/MDR-TB (WHO, 2020).
The poor treatment adherence during anti-TB treatment such that not taking TB drugs regularly or not taking the full dose of TB drugs result in the emergence of DR-TB. During anti-TB treatment, if there is a poor treatment adherence there is a selective pressure where the drug only kills the drug-susceptible Mycobacterial strain is leaving the resistant ones that could cause a DR-TB onwards (Petrini et al., 1999). The other major mechanism of acquiring DR-TB is through the transmission of drug-resistant Mycobacterial strains among the community. Someone who had contact with a person with DR-TB becomes easily got the disease (WHO, 2012). However, the transmission of DR-TB among the community can be favored by different factors such as demographic, behavioral, clinical, and environmental factors (Li et al., 2015). These risk factors vary from setting to setting and from community to community. Therefore, assessing the major associated risk factors contributing to the emergence of DR-TB based on data-driven from the local setting is important to take appropriate action. Even though there are individual studies that assessed the risk factors of DR-TB in different settings in Ethiopia, their finding is inconclusive and there is limited information that addressed the risk factors of DR-TB at the national level. However, identifying these factors at the national level would be an important input to aid the national TB control program in preventing and controlling the emergence of DR-TB in the country. Thus, this study aimed to assess the risk factors associated with DR-TB in Ethiopia by performing a pooled estimate from individual studies.
METHODS
Search strategy
The study was conducted by following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) checklist designed for systematic review and meta-analysis studies (Hutton et al., 2015; Knobloch et al., 2011) (Additional file 1). A systematic article searching was conducted using an electronic database (PubMed). The search was also performed using the gray literature sources such that WorldCat, Google Scholar and Google. The search was conducted regardless of the publication year. The searching was conducted up to 20 August 2021. Predictors, determinates, risk factors, drug-resistant, multi-drug resistant, rifampicin-resistant, extensively drug-resistant, tuberculosis, and Ethiopia were the keywords used during the searching process. The Boolean operators AND and OR were used accordingly. The search string of the PubMed was (((((((determinants) OR (Predictors)) OR (“Risk Factors” [Mesh])) AND (“Drug Resistance” [Mesh] OR “Tuberculosis, Multidrug-Resistant” [Mesh])) OR (rifampicin resistant)) AND (“Tuberculosis” [Mesh])) OR (TB) AND (“Ethiopia” [Mesh]) (Additional file 2). Two authors (AA, GD) who have previous experience in conducting a systematic review and meta-analysis studies performed the article searching independently under the guidance of a senior librarian at the Ethiopian Public Health Institute. The inconsistencies that arose between two authors were resolved by the third author (ZWB).
Study selection procedure
In the current study, original studies that assessed the risk factors/determinates/predictors of drug-resistant TB at different settings of Ethiopia that are published in the English language were included. Drug-resistant TB in the current study includes either resistance to any of the anti-TB drugs or rifampicin-resistant TB or MDR-TB. While articles that did not reported the risk factors in mixed TB patients both drug-suceptible and drug-resistant TB, incomplete outcomes, commentaris, and without full–text were excluded from the present study. After conducting intense article searching in the available databases and gray literature sources, article screening was conducted through different stages. Primarily the duplicates were removed using the Endnote 8 citation manager. In the second stage, we assessed the articles by title and abstract, and in the third stage, those articles that passed screening by title and abstract were assessed for full-text review. Finally, the eligibility of the individual studies to be included in the final analysis was performed by two independent authors (AA, GD), and the inconsistencies were resolved by the third author (ZWB) through discussion (Figure 1). The PICOS criteria (participants, interventions, comparison, outcome, and study setting) were used to assess the eligibility of the individual studies.