Abstract

Objective:The aim of this systemic review and meta-analysis was to determine demographic, behavioral and clinical risk factors for multiple drug-resistant.

  19 studies were included in the systemic review and meta-analysis.

Materials and Methods:Search engines:PubMed/Medline, Web of Science, Scopus and Google scholar were used to search related literatures on MDR TB and selected determinates of MDRTB. All data were independently extracted. We used a random-effects model according to the DerSimonian and Laird method

Results: The risk of having MDR-TB in patients who have informal education was 0.67 times lowerthan that of patients who have formal education (RR = 0.67; 95% CI, 0.46 to 0.96).

  The risk of having MDR-TB in patients who have Diabetes Mellitus was 1.33 times higher than that of patients who have no Diabetes Mellitus (RR of 1.33and 95% CI, 1.01to 1.77).

Conclusion: This systemic review and meta-analysis indicated that therisk of having MDR-TB in patients who have informal education was 0.67 timeslower than that of patients who have formal education and the risk of having MDR-TB in patients who have Diabetes Mellitus was 1.33 times higher than that of patients who have no Diabetes Mellitus.

  Our review did not showed the presence of association between MDR TB and other selected variables gender, smoking and alcohol.

  We recommend interested researchers on MDR TB to do further research on patient’s educational level as a risk factor for MDR-TB in order to explain the variation in MDR TB among patients with formal education and patients with informal education.

Keywords: Multidrug Resistance Tuberculosis; Alcohol; Smoking; Diabetes Mellitus; Gender; Educational Status

Introduction

• Multidrug resistance tuberculosis is a tuberculosis caused by a tubercle bacilli that isresistant to isoniazid and rifampicin [1].
• Worldwide, an estimated 10.0 million people diseased with TB in 2018 [2].
• In 2018, WHO reported that there were 484,000 incident cases of MDRTB cases and 44.21 (214,000 deaths) [3].
• In the world, MDR-TB among TB patients who arenew cases and previously treated cases was estimated to be 3.5% and 20.5% respectively [4]).
• MDR-TB has received increased attention in Africaand it is under-reported [5,6]
• In Sub-Saharan Africa the magnitude reaches 14% of the world new MDR-TB cases [5].
• In six countries of Africa including (new/retreatment % respectively) Angola (2.6/18%), DR Congo (2.2/17%), Kenya (1.3/9.4%), Nigeria (4.3/25%), Somalia (8.7/47%) and Zimbabwe (4.6/14%) [4].
• In the African Region, the frequency of resistance per country ranged Burundi in the third position with 66% after Rwanda (87%), Democratic Republic of the Congo (68%) [7].
• In Ethiopia prevalence of MDR TB is 2.7% and 14.0% in newly and treated previously TB patients respectively [4].
• In Ethiopia, many of the MDR-TB patients are undiagnosed due to the poorsocioeconomic status of people, low level of knowledgeand decreased access to health service.
• In Ethiopia the number of patients tested for MDR-TB was < 1% of new casesand < 4% of retreatment cases [8].
• Previous studies identified some risk factors associated with MDRTB like gender [9,10], smoking or other substance misuse [11-13] and diabetes [14].
• Previous studies in Ethiopia and China also reportedthat HIV/AIDS smoking cigarette, and drinking alcohol, overcrowding, and poor adherence toDOTS (Directly Observed Treatment Short-course) programare factors associated with MDR-TB[15-20].
• Few authors worldwide had the concern of investigating the patient’s educational level as a risk factor for MDR-TB [21,22].

Aim of the Study

  The aim of this systemic review and meta-analysis was to determine demographic, behavioral and clinical risk factors for multiple drug-resistant TB and for this we have selected two demographic variables gender and educational status, two behavioral factors alcohol and smoking and one clinical factor that is Diabetes Mellitus.

Methodology

  This systematic reviews and meta analyses was done in line withPRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Guideline[23]and we have done the search for different literatures that include data on magnitude ofMDR-TB in relation totwo socio demographic variables gender andeducational status, two behavioral variablesalcohol and smokingand one clinical variable,Diabetes Mellitus.

  Search engines: PubMed/Medline, Web of Science, Scopus and Google scholar were used to search related literatures on MDR TB and selected determinates of MDRTB.

  Combination of words used tosearch were: “MDRTB”, “Gender and MDRTB”, “Diabetes Mellitus and MDRTB”, “alcohol and MDRTB”,“educational status and MDRTB” and“smoking and MDRTB”.

  In addition the reference of selected articles wereused to searchadditionalstudies not foundinour initial search.

  Studies that reported five selected determinants of MDR-TB and this are gender, educational status, alcohol,smoking and Diabetes Mellitusand published in English language regardless of the design and setting were included.

  Studies were included in the review irrespective of their study year.

  MDR-TB is TB that caused by strains of M.tuberculosis that are resistant to isoniazid and RMP[4,24].

  The titles and abstracts were assessed for reporting the outcome and for fulfilling the eligible criteria.

  From studies that fulfill the eligible criteria the following data was extracted using prepared form.: Name ofauthor, prevalence of MDR-TB in the selected variables gender, smoking, alcohol,educational status and Diabetes Mellitus.

  All data were independently extracted. Returned abstracts were reviewed to check whether they contained relevant information.

  Each selected research was assessed using the Newcastle-Ottawa Scale (NOS) for assessing the quality of non randomized studies in meta-analyses [25].

• An outcome of interest was MDR-TB.
• We used a random-effects model according to the DerSimonian and Laird method [26].
• Heterogeneity was assessed by the I² and values greater than 50% considered representing significant heterogeneity.
• When there is heterogeneity between studies we used random-effect models [27]. Results were presented in forest plots. Publication bias was assessed using funnel plots and Beggs and eggers regression test
• Analysis was performed using Rev Man software version 5.3 [28].

Results

• Our initial search using the search terms gave 1170 articles. Out of these, 559 researches which do not match with the aim of the study were excluded after reviewing their titles and abstracts.
• Then the remaining articles were checked for duplications and 77 articles were selected for full text review.
• Of the 77 articles reviewed in full text, 19 articles [29-47] were included in the final analysis based on the inclusion-exclusion criteria and quality assessment and 58 studies were removed prior to analysis for reasons of not reporting at least one variable from the five selected variables to be studied as determinants of MDRTB
• The selection process of study is presented in figure 1.

• 19 studies were included in the systemic review and meta-analysis [29-47].
• 10studies measured magnitude of MDR-TB among Informal and/or formal educated patients[29,30,32,33,35,37,38,44,46,47].
• 16 studies measured magnitude of MDR-TB among male and/or female patients[29-40,43,45-47]
• 7 studies measured magnitude of MDR-TB among Diabetes mellitusand/or no diabetes mellitus patients [29,32,36,38,40,42,45]
• 8 studies measured magnitude of MDR-TB among alcohol drinking patientsand/or no alcohol drinking patients [29-33,35,45,47]
• 13 studies measured magnitude of MDR-TB among Smoking patientsand/or no Smoking patients[29-33,35,37,38,41,42,45-47].

• The meta-analysis of gender and MDR-TB did not demonstrate a statistically significant association of MDR-TB with Gender (An overall RR of 0.96and 95% CI, 0.86 to 1.07).
• As presented in figure 2, except for three studies [30,38,39], all other studies showed no association of MDR-TB to male or female Patients.
• Heterogeneity testing showed significant variation among the studies (I² = 53%).

• The risk of having MDR-TB in patients who have informal education was 0.67 times lowerthan that of patients who have formal education (overall RR = 0.67; 95% CI, 0.46 to 0/96).
• The combined effect size indicated that there isa statistically significant association of MDR-TB with educational status of patients, five studies [30,32,37,46,47] were exceptions.
• There is heterogeneity between the studies(I2 = 84%)(Figure 3).

  There is a statistical significant association between effect size and magnitude of informal education as shown in themoderator analysis as prevalence of informal education increase, the effect size for MDRTB decrease (B=-3.67,p value<0.0001).

  We used Beggs test for asymmetry of funnel plot (p value= 0.531) and Eggers regression test (p value 0.903) to test publication bias and both indicated that there is no publication bias for the meta-analysis of educational status and MDRTB.

• The meta-analysis of Alcohol and MDR-TB did not also demonstrate a statistically significant association of MDR-TB with Drinking Alcohol (overall RR of 0.97 and 95% CI, 0.75 to 1.25).
• As presented in figure 6, except for two studies [32,33], all other studies showed no association of MDR-TB to Alcohol drinking patientsor No alcohol drinking patients.
• There is Heterogeneity between the studies (I² = 74%).

• The meta-analysis of smoking and MDR-TB did not also demonstrate association of MDR-TB with smoking status (an overall RR of 1.18 and 95% CI, 0.87 to 1.60).
• As presented in figure 7, except for five studies [29,32,38,42,47], all other studies showed no association of MDR-TB to smoking patientsor no smoking patients.
• There is Heterogeneity between the studies (I² = 87%).

• The meta-analysis of Diabetes Mellitus and MDR-TB showed that there is a statistically significant association of MDR-TB with Diabetes Mellitus.
• The risk of having MDR-TB in patients who have Diabetes Mellitus was 1.33 times higher than that of patients who have no Diabetes Mellitus (an overall RR of 1.33and 95% CI, 1.01to 1.77).
• As presented in figure 8, except for three studies [29,38,40], all other studies showed no association of MDR-TB to Diabetes Mellitus patientsor no Diabetes Mellitus patients.
• Heterogeneity testing showed significant variation among the studies (I² = 66%).

Discussion

• The finding of this systemic review and meta-analysis showed that there is no statistical significant difference between male and female with respect to Multi Drug Resistance Tuberculosis and our study is similarwith previous studies [29,30,32,33,37,38,48,49].
• Our finding is not similar with previous studies[39,43].
• The explanations for the association between gender and MDRTB in previous studies are socio economic factors, health seeking behavior, prolonged delays in female patients (due to lack of control at household levels onfinancial resources), increased immune suppression with pregnancy, lactation and increased magnitude of HIV.

• This systemic review and meta-analysis did not indicate the presence of association between smoking and Multi Drug Resistance Tuberculosis.
• Further studies need to be done on smoking and resistance to anti-tuberculosis drugs [32].
• This systemic review and meta-analysis is not similar with previous studies [13,38].
• The reason for the difference in findings might be variation in sample size, study design and study participants characteristics.

• Our finding showed that there is no statistical significant association between MDR TB and drinking alcohol andwe could not foundsimilar findings in our search for literature but our findings isnot similar with previous studies [49].
• The explanation for the observed association between alcohol and MDR TB in previous studies is that alcohol drinking is associated with elevated probability ofMDR-TB due to decreasedadherenceimmunosuppressionand adverse drug effects.
• Drinking Alcohol was associated with increased risk ofMDR-TB [37].

  In our systemic review and meta-analysis there is an association between Diabetes Mellitus and MDR TB and our finding is similar with previous studies[29].

• Our systemic review and meta-analysis indicated that the risk of having MDR-TB in patients who have informal education was 0.67 timeslowerthan that of patients who have formal education (overall RR = 0.67; 95% CI, 0.46 to 0/96) and our finding is consistent with previous studies [38,39,42].
• This study is not similar with previous studies [49].
• The possible explanation for difference in findings between our review and other studies might be difference in study participants characteristics, sample size and study areas.

Conclusion

• This systemic review and meta-analysis indicated that therisk of having MDR-TB in patients who have informal education was 0.67 timeslower than that of patients who have formal education and the risk of having MDR-TB in patients who have Diabetes Mellitus was 1.33 times higher than that of patients who have no Diabetes Mellitus.
• Our review did not showed the presence of association between MDR TB and other selected variables gender, smoking and alcohol.
• We recommend interested researchers on MDR TB to do further research on patient’s educational level as a risk factor for MDR-TB in order to explain the variation in MDR TB among patients with formal education and patients with informal education.

Data Availability<> All data are included in the paper.

Conflicts of Interest

  The authors declare that they have no conflicts of interest.

Authors' Contributions

• Kaleab Tesfaye Tegegne was responsible for conceptualization, project administration, software, supervision, and development of the original drafting of the manuscript.
• Kaleab Tesfaye Tegegne, Eleni Tesfaye Tegegne, AbiyuAyalew Assefa,MekibibKassaTessema, BerhanuBifato, AlelignTadele Abebe,Muse Rike and AndualemZenebe were participated in quality assessment of articles, methodology, validation, and screening of research papers
• All authors contributed with data analysis, critically revised the paper, and agreed to be accountable for their contribution.

Acknowledgments

  We would like to thank all the primary authors of the included articles.

Competing of Interest

  The authors have declared that there is no competing interest.

Funding

  Not any funding received for this work.

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Citation

Citation: Kaleab Tesfaye Tegegne., et al. “Determinants of Multidrug Resistance Tuberculosis: A Systematic Review and Meta-analysis". Acta Scientific Cancer Biology 5.6 (2021):49-56.

Copyright

Copyright: © 2021 Kaleab Tesfaye Tegegne.,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.