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.