Mycobacterium tuberculosis burden, multidrug resistance pattern, and associated risk factors among presumptive extrapulmonary tuberculosis cases at Dessie Referral Hospital, Northeast Ethiopia

Endalkachew Tedla; Getnet Ayalew; Feleke Mekonnen

doi:10.4103/ejcdt.ejcdt_49_19

ORIGINAL ARTICLE

Year : 2020 | Volume : 69 | Issue : 3 | Page : 449-454

Mycobacterium tuberculosis burden, multidrug resistance pattern, and associated risk factors among presumptive extrapulmonary tuberculosis cases at Dessie Referral Hospital, Northeast Ethiopia

Endalkachew Tedla¹, Getnet Ayalew², Feleke Mekonnen BSc ³
¹ Bikat Diagnostic Center, Dessie City, Ethiopia
² Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar City, Amhara, Ethiopia
³ Department of Medical Microbiology, School of Health Sciences, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Amhara, Ethiopia

Date of Submission	25-Feb-2019
Date of Decision	29-Mar-2019
Date of Acceptance	10-Apr-2019
Date of Web Publication	07-Aug-2020

Correspondence Address:
Feleke Mekonnen
BSc in Medical Laboratory Technology, Msc in Medical Microbiology, Department of Medical Microbiology School of Health Sciences, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Amhara
Ethiopia

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ejcdt.ejcdt_49_19

Abstract

Background Tuberculosis (TB) represents one of the major challenges to global health. TB is usually classified based on the disease symptoms and the site of infection. Two types of clinical manifestation of TB are pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB).
Objective This study aimed at determining Mycobacterium tuberculosis and multidrug-resistant tuberculosis (MDR-TB) burden among presumptive EPTB cases and associated risk factors at Dessie Referral Hospital, North West Ethiopia.
Methods A cross-sectional study was conducted from February to April, 2018. A total of 337 presumptive EPTB cases in Dessie Referral Hospital were included using convenient sampling. Data were collected using a prestructured questionnaire. Body fluid specimens were collected and processed. Cytology, GeneXpert, and GenoType MTBDR plus Line Probe Assays were used for the detection of MTB and MDR-TB. Data were entered and cleared by Epi data version 3.1 and analyzed using SPSS, version 21. Multivariate analysis was done. P value less than 0.05 at 95% confidence interval was considered as statistically significant.
Results The overall prevalence of EBTB using GeneXpert and cytopathological technique was 23.4, 27.3%, respectively. TB lymphadenitis (48 and 53.3%, respectively) was the dominant type followed by pleural (27 and 25%, respectively) and peritoneal (24% and 21.7%, respectively) by GeneXpert and cytology. The prevalence of MDR-TB was one (1.3%). Previous history of PTB (P<0.001) and HIV (P<0.001) were significantly associated with EPTB.
Conclusion High prevalence of EPTB (27.3%) was reported, and 1.3% of them were MDR-TB. TB lymphadenitis was dominant. History of previous PTB and HIV was significantly associated with EPTB. Therefore, clinicians, public health professionals, and health programmers should give attention to EPTB case finding, treatment as well as prevention and control of EPTB by adhering guidelines of the ministry of health and WHO recommendations.

Keywords: Dessie Referral Hospital, extrapulmonary tuberculosis, Ethiopia, multidrug-resistant tuberculosis, risk factors

How to cite this article:
Tedla E, Ayalew G, Mekonnen F. Mycobacterium tuberculosis burden, multidrug resistance pattern, and associated risk factors among presumptive extrapulmonary tuberculosis cases at Dessie Referral Hospital, Northeast Ethiopia. Egypt J Chest Dis Tuberc 2020;69:449-54

How to cite this URL:
Tedla E, Ayalew G, Mekonnen F. Mycobacterium tuberculosis burden, multidrug resistance pattern, and associated risk factors among presumptive extrapulmonary tuberculosis cases at Dessie Referral Hospital, Northeast Ethiopia. Egypt J Chest Dis Tuberc [serial online] 2020 [cited 2022 Jun 27];69:449-54. Available from: http://www.ejcdt.eg.net/text.asp?2020/69/3/449/291532

Introduction

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis complex (MTB) groups, which are transmitted from individual to individual from person to person through air born droplets. Globally, most infections of TB are caused by Mycobacterium tuberculosis, which includes more than 150 species. The bacteriology of M. tuberculosis is described as anaerobic, nonmotile, non-spore-forming rod-shaped bacteria, and its staining characteristic showed acid fastness [1]. Based on anatomical position and spectrum of disease symptoms, TB can be usually classified as pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) [2]. TB involving any organs of the body other than the lungs such as pleural, lymph nodes, abdomen, genitourinary tract, skin, joints or bones, and meninges are EPTB [2],[3]. Pathogenesis of TB infection commences when droplet nuclei containing the TB bacteria are inhaled, and which are then internalized by the alveolar macrophages. Within 2–8 weeks of postinfection, M. tuberculosis develops granuloma, consisting of infected macrophages, neutrophils, lymphocytes, and necrotic cells, then the infection becomes controlled and latent tuberculosis infection developed [3],[4],[5],[6]. After years or months, when the immune system fails, the dormant bacilli reactivate, which results in the death of the infected macrophages and formation of a necrotic zone (caseum); this is followed by the disintegrating of the granuloma structure, and the bacilli disseminate to other parts of the lung [3],[7]. The risk factors for the development of EPTB is primarily owing to many exogenous and intrinsic factors, especially the impairment as well as immaturities of the immune system [8]. Age, sex, chronic disease, diabetics, HIV, chemotherapy, organ transplants, genetic factors, alcohol, malnutrition, tobacco smoke, and indoor air pollution among others are factors that accelerate progression to TB disease [9],[10],[11],[12],[13],[14],[15],[16].

Globally, drug resistance poses a serious challenge to TB control. It is a major public health concern in several countries including Ethiopia especially multidrug-resistant tuberculosis (MDR-TB) which is defined as resistance to at least isoniazid and rifampicin (RIF), which increasingly becomes a major problem for mortality and morbidity [17]. The prevalence of MDR-TB is increasing from a baseline rate of 1.6% among new TB cases in 2005 to 2.3% in 2014. Similarly, the rate has been increased from 11.8 to 17.8% among previously treated cases [18],[19],[20]. Studies about TB and MDR-TB among presumptive EPTB cases at northeast Ethiopia are limited. Thus, this study was carried out to determine the burden of TB, MDR-TB, and associated risk factors to certainly provide important information for program managers, health planners, and health care workers, so as to initiate relevant prevention, control, and management of EPTB.

Methods

Study design and area

An institutional-based cross-sectional study was conducted from February to April 2018 at Dessie Referral Hospital. Dessie Referral Hospital is a regional referral hospital with more than 500 beds which gives services like TB/HIV, sexually transmitted infection management, antenatal care, postnatal care, laboratory, pharmacy, integrated maternal, and neonatal care and others for more than five million people living in urban and rural districts of Dessie.

Ethical clearance was obtained from the Research and Ethical Review Committee of the School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar. Study participants were informed about the objectives of the study. Informed written and verbal consent was obtained from each adult study patients and from their parents or caregivers for the pediatric children. Before they were asked to give the sample, they were also informed that all the information and results of their sample were being kept confidential by using codes instead of any personal identities and the results are meant only for the purpose of the study. Moreover, all the patients were aware and agreed that samples may be used in research and that data could be published. The study participants who were GeneXpert positive and had MDR-TB were referred accordingly to the national TB treatment guideline of Ethiopia. Verbal consent was taken from patients and guardians for publication.

Sample size, sampling, and laboratory techniques

A total of 337 patients were selected to collect samples from different body sites by using a single population proportion formula. Sociodemographic information and different clinical specimens such as cerebrospinal, pleural, peritoneal fluids as well as lymph node aspirates were collected by an experienced pathologist from presumptive EPTB cases that came to the hospital. Collected clinical specimens of lymph node aspirate, pleural, peritoneal, and synovial specimens were processed for TB diagnosis. Cytological abnormalities were identified and characterized by a trained experienced pathologist by depositing a drop of the aspirates on a microscope slide, and Wright staining technique was used for differentiation of cells. Moreover, each sample was diagnosed using the GeneXpert MTB/RIF system, which detects MTB complex and RIF resistance. GenoType MTBDR Plus assay was used to detect isoniazid resistance [13],[14],[15],[16],[17].

Statistical analysis

Descriptive statistical analysis was done by SPSS, version 20. Bivariate and multivariate analyses were done to assess the risks. P value less than 0.05 at 95% confidence interval (CI) was considered as statistically significant.

Results

Sociodemographic characteristics

From a total of 337 participants, 197 (58.5%) were male. The mean±SD age was 40.39±1278 years (range, 3–81). Two hundred and four (60.5%) of them were from rural areas, and the majority [149 (44.2%)] were illiterates ([Table 1]).

Table 1 Sociodemographic characteristics and extrapulmonary tuberculosis at Dessie Referral Hospital, Northeast Ethiopia, 2018

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Prevalence of extrapulmonary tuberculosis among presumptive extrapulmonary tuberculosis cases

The overall prevalence of EPTB were 79 (23.4%) and 92 (27.3%) using GeneXpert and cytological methods, respectively. Males [58 (64.6%)] and adults [30 (38%)] were more infected. MDR-TB prevalence was one (1.3%) ([Table 1]).

Comparison of test results by GeneXpert and cytology

From a total of 337 samples, 116 (34.4%) were pleural, 96 (28.5%) peritoneal, 71 (21.1%) cerebrospinal fluid, 53 (15.7%) lymph node aspirate, and one (0.3%) synovial fluids. Pathological examination showed more positive [92/337 (27.3%)] cases than GeneXpert MTB/RIF assay [79/337 (23.4%)] ([Table 2]).

Table 2 Comparison of test results by GeneXpert and cytology based on the sample type among presumptive extrapulmonary tuberculosis cases at Dessie Referral Hospital, Northeast Ethiopia, 2018

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Factors associated with extrapulmonary tuberculosis

Multivariate analysis showed HIV-positive patients were more likely to have EPTB than those who had HIV-negative results (P<0.001, adjusted odds ratio=0.173, 95% CI 0.900–0.331), and previously treated patients with PTB were more likely to have EPTB than those who had no previous history of PTB (adjusted odds ratio=0.008; 95% CI, 0.032–0.299) (P≤0.001) ([Table 3]).

Table 3 Multivariate analysis of sociodemographic characteristics and associated risk factors among the presumptive extrapulmonary tuberculosis cases at Dessie Referral Hospital, Northeast, Ethiopia, 2018

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Discussion

TB remains one of the world’s deadliest communicable diseases. EPTB is one of the common clinical presentations of M. tuberculosis infection, and according to the WHO 2017 report, approximately 32% of all TB infections were to be EPTB. In developing countries, including Ethiopia, it causes high morbidity and mortality because of HIV [17].

The present study showed that the overall prevalence of EPTB was 27.3% (92/337). This finding was almost similar with the burden of EPTB in surveys that were conducted among European Union member countries at different times (22 and 19.3%), Georgia (27.8%), and the study at University of Gondar (26.2%) [3],[21],[22],[23]. On the contrary, our result showed lower prevalence of EPTB compared with the study findings in Spain (37.6%), Portugal (32.6%), India (45.6%), Nepal (48.5%), Oman (37%), Gulf Qatar (54.6%), Egypt (85%), and different parts of Ethiopia (43.9 and 45.9%) [24],[25],[26],[27],[28],[29],[30],[31],[32]. However, it was higher than other studies in Taiwan (13.3%), India (9.1%), North Eastern Nigeria (14.4%), and in Gondar, Ethiopia (9.9%) [8],[33],[34],[35]. This variation might be owing to the difference in the study design, study participants’ socioeconomic difference, and diagnostic modalities.

Male patients showed higher (63.0%) prevalence of EPTB than females (37%.) This was supported by other reports from Brazil (63 vs. 37%), Port Blair (60 vs. 40%), Saudi Arabia (58.8 vs. 41.2%), and from the University of Gondar (58.8 vs. 41.2%) [11],[33],[36],[37]. However, this finding was different from study reports in the USA (9.3% males vs. 16.9% females) [38]. The possible justification for these discrepancies might be owing to underdiagnosis and underreporting of TB in females as a result of various social and cultural factors, which consequently impaired access to health care.

TB lymphadenitis (48.1%) was the most dominant type of EPTB. This was consistent with studies from Gulf Qatar (43.5%), Georgia (27%), India (35%), Bangladesh (28%), Egypt (37.4%), North Eastern Nigeria (28%), Ethiopia (60.8%), Jimma (64.3%), and Gondar (82.4%) [3],[22],[23],[29],[31],[33],[39],[40],[41],[42],[43],[44],[45]. On the contrary, TB pleurisy was predominantly reported from South Africa (39.1%), Eastern Sudan (39%), Port Blair (52.21%), and India (29%) [26],[37],[41],[46]. An equal proportion of TB lymphadenitis and TB pleurisy was seen in Georgia (27%) [23]. This variation in different parts of the world might be owing to the inaccessibility of different body parts, lack of professionals to take the samples from different deep body sites, and the variability of the sensitivity and the specificity of diagnostic methods. The prevalence of MDR-TB in the present study was one (1.3%) case. This finding was similar to a study conducted in North West Ethiopia with one (1.2%) case [47]. However, it was lower than the University of Gondar (2.4%) and Ethiopian MDR-TB Survey (2.3%) [22],[45]. This variation might be owing to the difference of the study participants, the status of the patient, spatial distribution of EPTB, and methods of diagnosis. The previous history of PTB was a risk factor for the development of EPTB in this study, and it was similar to a study from Gondar [22]. This might be owing to the incomplete killing of the bacilli, hence the bacilli may be disseminated from the lung to other distant body sites. HIV was also associated with EPTB, and this was similar to the reports from Brazil, Saudi Arabia, Port Blair, Nigeria, and Ethiopia [11],[22],[36],[37],[48]. This is owing to the fact that immune deficiency owing to the virus confers the dissemination of the bacilli from the lung to other body parts and no granuloma formation of TB-HIV co-infection [49].

Limitation of the study

Fungal culture was not used for confirmation; moreover, as the study is the institutional-based cross-sectional one, it may not fully indicate the burden in the community.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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