|FULL LENGTH ARTICLE
|Year : 2016 | Volume
| Issue : 3 | Page : 324-327
More than half of presumptive multidrug-resistant cases referred to a tuberculosis referral laboratory in the Tigray region of Ethiopia are multidrug resistant
Kebede Tesfay1, Shinesh Tesfay2, Etsay Nigus3, Araya Gebreyesus1, Dawit Gebreegziabiher1, Kelemework Adane1
1 Department of Medical Microbiology and Immunology, Institute of Biomedical Sciences, College of Health Sciences, Mekelle University, Mekelle, Ethiopia
2 Department of Clinical Laboratory, Mekelle Regional Hospital, Mekelle, Ethiopia
3 Department of Clinical Laboratory, Ayder Referral Hospital, Mekelle University, Mekelle, Ethiopia
|Date of Web Publication||13-Feb-2017|
Department of Medical Microbiology and Immunology, Institute of Biomedical Sciences, College of Health Sciences, Mekelle University, Mekelle
Source of Support: None, Conflict of Interest: None
Objective/background: Generating epidemiological data on multidrug-resistant tuberculosis (MDR-TB) is essential to assess the magnitude and trends of anti-TB drug resistance. This study determined the prevalence of MDR-TB among presumptive MDR cases referred to a TB referral laboratory in the Tigray region of Ethiopia. Methods: A retrospective cross-sectional study was conducted on 262 culture-positive presumptive MDR-TB samples submitted to the Tigray Regional Research Laboratory for MDR testing between January 2013 and August 2014. Relevant data were recorded using a structured recording format. Results: Out of 262 Mycobacterium tuberculosis isolates, 143 (54.6%) were MDR, 28 (10.7%) were resistant to rifampicin only, and 19 (7.3%) were resistant to isoniazid only. The prevalence of MDR-TB among newly infected cases was 66.7% (8/12) and that among previously treated cases was 54.1% (97/179). Of the variables tested, being a male was found to be associated with the development of MDR-TB (p = .003). Conclusion: More than half of the presumptive MDR cases referred to the Tigray Regional Research Laboratory were MDR. The prevalence was high in both newly infected and previously treated cases. Hence, re-enforcing the TB prevention methods, and strengthening the directly observed treatment short-course (DOTS) strategy and the capacity of laboratories to undertake drug susceptibility testing (DST) in the region are imperative in order to curb the emergence and transmission of MDR-TB.
Keywords: Ethiopia, Multidrug-resistant tuberculosis, Previously treated
|How to cite this article:|
Tesfay K, Tesfay S, Nigus E, Gebreyesus A, Gebreegziabiher D, Adane K. More than half of presumptive multidrug-resistant cases referred to a tuberculosis referral laboratory in the Tigray region of Ethiopia are multidrug resistant. Int J Mycobacteriol 2016;5:324-7
|How to cite this URL:|
Tesfay K, Tesfay S, Nigus E, Gebreyesus A, Gebreegziabiher D, Adane K. More than half of presumptive multidrug-resistant cases referred to a tuberculosis referral laboratory in the Tigray region of Ethiopia are multidrug resistant. Int J Mycobacteriol [serial online] 2016 [cited 2021 Sep 17];5:324-7. Available from: https://www.ijmyco.org/text.asp?2016/5/3/324/200073
| Introduction|| |
Multidrug-resistant tuberculosis (MDR-TB) is a form of TB caused by bacteria that are resistant to at least two of the most powerful first-line anti-TB drugs, isoniazid (INH) and rifampicin (RIF) . The emergence of MDR-TB has been a global health problem threatening the progress made in TB care and control . Globally, the prevalence of MDR-TB was reported to be 3.5% among new TB cases and 20.5% among previously treated TB cases in 2013 .
The impact of MDR-TB is much worse in low-income countries such as Ethiopia, where the socioeconomic status of the people is low, TB burden is high, and well-equipped health care facilities are limited . A national drug-resistance survey conducted in Ethiopia in 2011 reported the prevalence of MDR-TB to be 2.7% and 17.9% among new and retreatment cases, respectively .
Previous drug resistance surveys involving presumptive MDR cases reported MDR proportions of 36.3%  and 33%, respectively, in the Amhara and Oromia regions  of Ethiopia. However, these studies might not be representative of cases from other regions of the country owing to differences in lifestyle and environmental conditions across different regions of Ethiopia . Besides, regions differ in their TB control and prevention performance. In the annual performance report of the year 2013/2014, for example, the TB case detection rates in the Amhara and Oromia regions were about 58% and 61%, respectively, while this figure was about 66% in the Tigray region . The TB cure rates were 75%, 78%, and 64% in the Amhara, Oromia, and Tigray regions, respectively . These variations could affect the distribution of MDR strains, and hence quantifying the burden of MDR-TB regionally is justifiable. This study, therefore, determined the prevalence of MDR-TB among presumptive MDR cases referred to a tuberculosis referral laboratory in the Tigray region of Ethiopia.
| Methods|| |
Study design and setting
This was a health facility-based retrospective cross-sectional study conducted in the Tigray Regional Research Laboratory located in Mekelle, the capital of the Tigray region. This regional research laboratory is the only laboratory that provides MDR testing service in the Tigray region and is a referral site for presumptive MDR cases from all parts of Tigray (North Ethiopia).
Study population and sampling technique
Relevant data were recorded conveniently for all presumptive MDR cases (treatment failure and relapse cases, defaulters, and a few new cases) referred to the Tigray Regional Research Laboratory for MDR testing between January 2013 and August 2014, using a structured recording format. MDR testing was performed in the regional laboratory by the genotypic method (Genotype MTBDRplus test, Hain Lifescience) following the manufacturer's instructions and standard operating procedures. Data on the sociodemographic characteristics, INH and RIF resistance outcome, previous history of treatment, and previous treatment subcategories were then extracted from a total of 262 presumptive MDR cases.
Data were entered using Epi Data entry version 3.1 (DenmarkInfo @ EpiData.dk) software and analyzed using SPSS version 21 (Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp). Differences between the MDR and non-MDR cases with respect to the patients' baseline characteristics were assessed using the chi-square test. A p value≤.05 was considered statistically significant.
This study was approved by the ethical review committees of the College of Health Sciences, Mekelle University. A letter of cooperation was written to the Tigray Regional Research Laboratory authority. Furthermore, confidentiality of patient information was safeguarded throughout the research activities.
| Results|| |
Characteristics of the study population
Out of the 262 culture-positive presumptive MDR cases included in this study, 79.4% (208/262) were males and 20.6% (54/262) females with a mean age of 36 years. The majority of them (179 [68.3%]) were previously treated cases, while a few (12 [4.5%]) were newly infected cases. With regard to their retreatment subcategories, 55.3% (99/179) were relapse cases, 41% (77/179) treatment failure cases, and 3.7% (3/179) defaulters. However, the TB treatment history was unknown for a substantial proportion of cases (71 [27.2%]).
Rifampicin and isoniazid resistance patterns
Out of the 262 Mycobacterium tuberculosis isolates, 143 (54.6%) were MDR, 28 (10.7%) were resistant to RIF only, and 19 (7.3%) were resistant to INH only. The prevalence of MDR-TB among newly infected cases was 66.7% (8/12) and that among the previously treated cases was 54.1% (97/179). Within the previously treated cases, relapse cases had the highest MDR-TB prevalence (55.6% [55/179]), but the difference was not statistically significant. Of the variables tested, being a male was found to be associated with the development of MDR-TB (p = .003) ([Table 1]). The prevalence of MDR-TB in those with an unknown treatment history was 64.8% (46/71).
|Table 1: Association of baseline characteristics with MDR-TB among presumptive MDR-TB cases referred to a tuberculosis referral laboratory in the Tigray region of Ethiopia between January 2013 and August 2014, as analyzed by the Chi-square test.|
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| Discussion|| |
In this study, more than half of M. tuberculosis isolates (54.6%) were MDR strains. This is notably higher than that documented in similar reports from the Amhara regional state (36.3%)  and Oromia region (33%) . The difference could partly be attributed to differences in the TB clinical screening quality, and case detection and TB cure rates in the regions. In the annual performance report of the year 2013/2014, the TB case detection rates in the Amhara and Oromia regions were about 58% and 61%, respectively, while this figure was about 66% in the Tigray region . This implies that the number of missed MDR cases in the two regions could be more than that observed in the Tigray region. In the same report, the TB cure rate was higher in the Amhara (75%) and Oromia regions (78%) than in the Tigray region (64%) , indicating that we can expect more MDR cases in Tigray. This indicates that MDR-TB is a serious public health problem in Ethiopia. Our figure is, however, comparable to an MDR rate of 53% reported among presumptive MDR cases in India .
We report a high rate of MDR in both newly infected and previously treated cases. The MDR rate among newly infected cases (66.6%) is much higher than that documented in previous reports from Ethiopia ,,. The difference could be due to differences in sample size in that a lower number of new cases were included in our study. When compared with studies from other countries, our figure is also higher than those reported in Kenya , Uganda , and India . This discrepancy might be due to differences in sample size, study time, and geographical variation. The high MDR rate in new cases suggests the existence of active person-to-person transmission of MDR strains in the region and could indicate weakness in TB prevention and control measures.
In the present study, being a male was a risk factor for the development of MDR-TB. This is in agreement with the report from Addis Ababa . This association could be due to differences in the adherence behavior of males and females to anti-TB treatment. A study in Nigeria, for example, showed that being a male was a risk factor for defaulting from anti-TB medication , thus increasing their risk of developing MDR-TB. In contrast to the previous reports from Ethiopia ,, in our study, a previous history of TB treatment was not associated with the development of MDR-TB.
The proportion of monoresistance to RIF in this study (10.7%) was also higher than that demonstrated in previous reports from different parts of Ethiopia ,,. The possible explanation for this difference could be that our study was conducted in a TB laboratory that is a referral site for presumptive MDR cases from all parts of Tigray, while the previous studies involved TB patients seeking routine TB treatment. Since RIF is the most important drug to treat TB, emergence of resistance to this drug has huge implications for TB control policies. This high proportion of monoresistance suggests that the precursors of MDR-TB are increasing in the study region as monoresistance to these drugs predicts MDR. This could negatively impact the effectiveness of the new RIF-based 6-month treatment regimen adopted by the Federal Ministry of Health of Ethiopia. Hence, efforts are needed to ensure proper use of this drug in the study region.
To mention some of the limitations, due to the fact that our study was retrospective in nature, data on the previous history of treatment were missing for a substantial proportion of presumptive MDR cases. Furthermore, since our study included presumptive MDR cases, generated data might not be representative of the situation in the general population of the Tigray region.
| Conclusion|| |
In conclusion, this study revealed that more than half of the presumptive MDR cases referred to the Tigray Regional Research Laboratory were MDR. The prevalence was high in both newly infected and previously treated cases. Hence, re-enforcing the TB prevention methods, and strengthening the DOTS strategy and the capacity of laboratories to undertake DST in the region are imperative in order to curb the emergence and transmission of MDR-TB.
| Conflicts of interest|| |
| Acknowledgments|| |
The authors would like to acknowledge the College of Health Sciences of Mekelle University for the financial support. K.T., S.T., and E.N. were involved in the study design, data collection, data analysis, and drafting of the manuscript. D.G., A.G., and K.A. were involved in the design, data analysis, writing, and review of the manuscript.
| References|| |
World Health Organization, Guidelines for the Programmatic Management of Drug-Resistant Tuberculosis, Emergency Update 2008, WHO, 2008. Geneva, Switzerland.
World Health Organization, Towards Universal Access to Diagnosis and Treatment of Multidrug-resistant and Extensively Drug-resistant Tuberculosis by 2015, WHO, 2011. Geneva, Switzerland.
World Health Organization, Global Tuberculosis Report, WHO, 2014. Geneva, Switzerland.
P.D. Davies, The world-wide increase in tuberculosis: how demographic changes, HIV infection and increasing numbers in poverty are increasing tuberculosis, Ann. Med. 35 (2003) 235–243.
S.H. Lemma, in: Proceedings of the 9th TB-Research Annual Conference (TRAC), March 21–23, Hawassa University Conference Center, Hawassa, Ethiopia, 2014.
D. Mekonnen, A. Admassu, W. Mulu, et al, Multidrugresistant and heteroresistant Mycobacterium tuberculosis
and associated gene mutations in Ethiopia, Int. J. Infect. Dis. 39 (2015) 34–38.
G. Mulisa, T. Workneh, N. Hordofa, et al, Multidrug-resistant Mycobacterium tuberculosis
and associated risk factors in Oromia Region of Ethiopia, Int. J. Infect. Dis. 39 (2015) 57–61.
J.G. Abbink, New configurations of Ethiopian ethnicity: the challenge of the South, Northeast Afr. Stud. 5 (1) (1998) 59–81.
Federal Ministry of Health of Ethiopia, Health Sector Development Programme IV, Annual Performance Report, WHO, 2014. Addis Ababa, Ethiopia.
N. Pradhan, S. Desai, A. Kagal, et al, Patterns of TB drugresistance in a tertiary care facility in Pune, India, Clin. Microbiol. 2 (2013) 123.
K. Adane, G. Ameni, S. Bekele, et al, Prevalence and drug resistance profile of Mycobacterium tuberculosis
isolated from pulmonary tuberculosis patients attending two public hospitals in East Gojjam zone, northwest Ethiopia, BMC Public Health 15 (2015) 572.
G. Abebe, K. Abdissa, A. Abdissa, et al, Relatively low primary drug resistant tuberculosis in southwestern Ethiopia, BMC Res. Notes 5 (2012) 225.
S.A. Yimer, M. Agonafir, Y. Derese, et al, Primary drug resistance to anti-tuberculosis drugs in major towns of Amhara region, Ethiopia, APMIS 120 (2012) 503–509.
P.W. Ndung'u, S. Kariuki, G. Revathi, Resistance patterns of Mycobacterium tuberculosis
isolates from pulmonary tuberculosis patients in Nairobi, J. Infect. Dev. Ctries. 6 (2011) 33–39.
B.B. Asiimwe, S. Ghebremichael, G. Kallenius, et al, Mycobacterium tuberculosis
spoligotypes and drug susceptibility pattern of isolates from tuberculosis patients in peri-urban Kampala, Uganda, BMC Infect. Dis. 8 (2008) 101.
A. Gupta, J.P. Mathuria, S.K. Singh, et al, Antitubercular drug resistance in four healthcare facilities in North India, J. Health Popul. Nutr. 29 (2011) 583–592.
S. Hirpa, G. Medhin, B. Girma, et al, Determinants of multidrug-resistant tuberculosis in patients who underwent first-line treatment in Addis Ababa: a case control study, BMC Public Health 13 (2013) 782.
O. Daniel, O. Oladapo, O. Alausa, Default from tuberculosis treatment programme in Sagamu, Nigeria, Niger J. Med. 15 (2005) 63–67.
W. Mulu, D. Mekkonnen, M. Yimer, et al, Risk factors for multidrug resistant tuberculosis patients in Amhara National Regional State, Afr. Health Sci. 15 (2015) 368–377.
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