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| ORIGINAL ARTICLE |
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| Year : 2020 | Volume
: 9
| Issue : 4 | Page : 391-396 |
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Pattern of primary tuberculosis drug resistance and associated risk factors at Dubai health authority in Dubai
Maya Habous1, Maimona Elimam1, Laila AlDabal2, Bindu Chidambaran1, Zulfa AlDeesi1
1 Department of Pathology, Rashid Hospital, Dubai, United Arab Emirates
2 Medical Affairs Department, Infectious Diseases Unit, Rashid Hospital, Dubai, United Arab Emirates
| Date of Submission | 09-Sep-2020 |
| Date of Decision | 29-Sep-2020 |
| Date of Acceptance | 03-Oct-2020 |
| Date of Web Publication | 15-Dec-2020 |
Correspondence Address:
Maya Habous
Department of Pathology, Rashid Hospital, Dubai
United Arab Emirates
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijmy.ijmy_170_20
Background: The objective of this study is to determine the initial drug resistance pattern among new tuberculosis (TB) cases and assess the extent of association with human immunodeficiency virus (HIV) and diabetes mellitus (DM). Method: This is a retrospective analysis of 1116 clinical isolates were collected from patients who were newly diagnosed with TB at TB Laboratory between January 2016 and November 2019 and used for determining drug-resistance profiles against five first-line and five second-line anti-TB drugs; and the results were assessed the association between TB risk factors and primary drug resistance TB. Results: Of the 1116 newly diagnosed TB patients, 193 (17.3%) showed resistance to at least one or more of the first-line drugs by different patterns, 105 (9.4%) showed resistance to one drug, 38 (3.40%) showed polyresistance, 50 (4.5%) showed multidrug resistant (MDR), and one patient had extensively drug resistant. Mono-resistance to isoniazid (INH), STR, pyrazinamide, and rifampicin were seen in 40 (3.6%), 33 (2.95%), 29 (2.59%), and 3 (0.3%) of isolates, respectively. INH showed the highest percentage of resistance among the patients. Of 1116 newly diagnosed TB patients, 256 (22.9%) were TB-DM cases and 135 (12.9%) were TB-no DM cases. The rates of drug resistance-TB 46/1116 (4.12%), monoresistance 25 (2.24%), polyresistance 9 (0.8%), and MDR 12 (1.07%) among TB-DM group were higher than TB-no DM group. Conclusion: Our study confirms that resistance to INH was the most common phenomenon. We found that diabetes was identified as a risk factor of TB drug resistance. We did not find a significant association between HIV co-infection and TB drug-resistance
Keywords: Multidrug resistance tuberculosis, Mycobacterium tuberculosis, primary drug resistance, risk factor
How to cite this article:
Habous M, Elimam M, AlDabal L, Chidambaran B, AlDeesi Z. Pattern of primary tuberculosis drug resistance and associated risk factors at Dubai health authority in Dubai. Int J Mycobacteriol 2020;9:391-6 |
How to cite this URL:
Habous M, Elimam M, AlDabal L, Chidambaran B, AlDeesi Z. Pattern of primary tuberculosis drug resistance and associated risk factors at Dubai health authority in Dubai. Int J Mycobacteriol [serial online] 2020 [cited 2023 Mar 23];9:391-6. Available from: https://www.ijmyco.org/text.asp?2020/9/4/391/303444 |
| Introduction | |  |
The World Health Organization (WHO) global tuberculosis (TB) Report 2019 stated that TB causes 10 million cases and 1.2 million deaths annually among human immunodeficiency virus (HIV)-negative people, and there were an additional 251 000 deaths from TB among HIV-positive people. TB is one of the most significant contagious pathogens in the world and remains the top infectious killer worldwide. It is the leading killer of people with HIV and a major cause of deaths related to antimicrobial resistance.[1]
TB is an infectious disease caused by bacterial strains belonging to the Mycobacterium tuberculosis complex. Diagnosis, treatment, and prevention of TB have become more complex because of resistance to commonly used antituberculous drugs.
Multidrug resistant (MDR) and extensively drug-resistant (XDR) TB has been rapidly spreading in recent years; it is multifactorial and fueled by improper treatment of patients and continues to be a public health Threat.[2] In 2018, there were about half a million new cases of rifampicin-resistant (RR) TB (of which 78% had multidrug-resistant TB). 186,772 cases of MDR/RR-TB were detected and notified in 2018. Of these, a total of 156,071 people were enrolled and started on treatment with a second-line regimen.[1] Recently, epidemiological studies and whole-genome sequencing analysis of M. tuberculosis provided evidence that the majority of drug-resistant TB cases were due to primary infection of resistant TB strains.[3],[4]
WHO end TB strategy calls for the early diagnosis of TB including universal drug susceptibility testing (DST); universal access to DST is defined as providing DST for at least rifampicin (RIF) for all patients with bacteriologically confirmed TB and providing further DST for at least fluoroquinolones and second-line injectable agents for all TB patients with RR TB.[5]
Early detection of resistance to TB drugs is intended to ensure initiation of appropriate drug regimen from the start, increase the likelihood of treatment success and prevent the acquisition of additional resistance and to control spread of resistant strains of M. tuberculosis especially MDR-TB.[2],[6],[7] Therefore, DST should be obtained from all newly diagnosed TB patients to allow tailoring of treatment to individual resistance profiles.[8],[9]
Resistance to RIF and concomitant resistance to INH and RIF have the most effect on the outcome of treatment. Therefore, information about drug resistance prevalence is necessary for more effective treatment of new cases and for national strategic planning.[10]
International studies have identified the various risk factors for TB; it may be divided into issues related to host immunity and issues related to environmental exposure to infection. Many new cases of TB are attributable to undernourishment, HIV infection, smoking, diabetes mellitus (DM), and alcohol use.[11],[12]
In 2018, an estimated 2.3 million TB cases were attributable to undernourishment, 0.9 million to smoking, 0.8 million to alcohol abuse, 0.8 million to HIV infection, and 0.4 million to diabetes.[1]
Systematic reviews have shown that undernutrition,[13] smoking,[14] diabetes,[15],[16],[17] and alcohol misuse[18] are the individual risk factors that can double or triple the risk of development of active TB.
TB disease is much higher among people infected with HIV; it is greatly increases the risk of active TB and coinfection leads to an acceleration of both diseases. In 2018, there were 477,461 TB reported cases of TB among people living with HIV, of whom 86% on antiretroviral therapy.[1] Recent studies indicate that co-infected HIV-positive TB patients are at increased risk of MDR-TB compared to HIV-negative patients. This could partly be because of more rapid disease progression in HIV-infected individuals.[19],[20]
Diabetes has long been recognized as one of the key risk factors for the development of TB. In the latest WHO Global TB Report, diabetes was estimated to have caused around 400,000 people to fall ill with TB globally in 2018.[1] People with diabetes, compared to nondiabetic controls, were two to three-fold more likely to develop TB.[16],[21]
Impaired immunity in diabetic patients is thought to contribute to the evolution of latent TB infection to active cases. Moreover, people with TB who have DM have a poorer response to treatment than do those without DM and are therefore at a higher risk of TB treatment failure, death, and relapse after cure.[22],[23] Previous study had found that 10%–23% of MDR-TB patients had concomitant diabetes.[24] Due to global increases in MDR-TB and DM, it was a necessity to explore the relationship between diabetes and primary drug resistance of TB.[1],[24],[25]
Our aim of this study is to determine the initial drug resistance pattern among new pulmonary and extrapulmonary TB cases and assess the extent of association with HIV and DM.
| Method | | |
Study type, population, and sampling
This is a retrospective study from January 2016 to November 2019; it was conducted in TB Laboratory of Dubai Health Authority, UAE. It included inpatients and outpatients presenting with suspected TB from four hospitals and all public health centers in Dubai. All new TB cases were defined as any pulmonary or extrapulmonary TB patient with no history of treatment or a history of anti-TB therapy for <1 month, for all age category and both gender (male-female). Among 1116 new TB patients, 987 (88.5%) were pulmonary TB and 129 (11.5%) were extrapulmonary TB. The respiratory samples (n = 965) and nonrespiratory samples (n = 151) with 828 (74.20%) males and 288 (25.80%) female. The age groups of 26–35 (39.3%) years old were the most affected by TB. A comprehensive detail of the characteristic status of study participants is given in [Table 1]. This study involved 1116 new TB cases with drug-susceptibility data, and information on diabetes and HIV were included.
Our study was approved by the Dubai Scientific Research Ethics Committee of Dubai Health Authority (Ref: DSREC-08/2019_15) and was performed in accordance with all national regulations.
Isolation and identification drug-susceptibility testing of mycobacterium
All clinical samples suspected of TB were included in our study. Each sample was processed for smear microscopy by Ziehl-Neelsen and auramine-O stains and conventional cultured in MGIT Bactec 960 liquid medium and Lowenstein–Jensen solid (LJ) media. Drug phenotypic-susceptibility testing was done on MGIT 960.
First-line DST was run on all new TB cases isolates. Second-line DST was run on all RR and/or multidrug-resistant TB isolates.
The respiratory and nonrespiratory specimens, including sputum, bronchial lavage, chest secretion, biopsy, biological fluids, and pus, were processed using the standard N-acetyl-L-cysteine decontamination and concentration method. Tissues and biopsies were first, grinded firmly with a small amount of sterile saline by a tissue grinder (Omni Bead Ruptor), and then processed similar to other specimens. Freshly prepared Mycoprep ™NALC-NaOH solution (Becton Dickinson, Sparks, MD, USA) was added to the specimen at equal volume (1:1), mixed on vortex, and left for 15 min for digestion at the room temperature. A double amount (twice the amount of mixture) of sterile phosphate buffer (pH 6.8) (Becton Dickinson, Sparks, MD, USA) was then added to the mixture and centrifuged for 15 min at 3000 rpm. The supernatant was then removed, and the sediment was dissolved in 2.5 ml of sterile phosphate buffer for further study. Decontamination was not required for sterile specimens such as cerebrospinal fluid (CSF), synovial fluid, pleural fluid, pericardial fluid, peritoneal fluid, and other sterile fluids. Since sterility is not always guaranteed, it was always recommended to streak a drop of the resuspended sediment on blood agar. If there was growth in blood agar, then decontamination was performed in the next day, where the sediment was resuspended processed similar to sputum samples.
Each sample was processed for smear microscopy by Ziehl-Neelsen and auramine-O stains and conventional cultured in both MGIT Bactec 960 liquid medium (Becton Dickinson Microbiology System, USA) and LJ solid media (Becton Dickinson BBLTM Prepared Culture Media). Identification of MTB is isolated from the solid or liquid cultures by the immune chromatographic assay for rapid species identification (Becton Dickinson MGITTM TBc Identification Test). Phenotypic culture-based DST methods on MGIT 960 (Becton Dickinson Microbiology System, USA), using the WHO recommended critical concentrations, with anti-TB agents and critical concentrations for testing (first-line and second-line drugs).
Drug susceptibility was tested on MGIT medium-containing isoniazid (INH); 0.1 μg/ml, RIF; 1.0 μg/ml, ethambutol (EMB); 5.0 μg/ml, streptomycin (SM); 1.0 μg/ml, pyrazinamide (PZA) 100 μg/ml, and second-line drugs including kanamycin (KAN); 2.5 μg/ml, capreomycin (CAP); 2.5 μg/ml, amicacin 1.0 μg/ml, ofloxacin; 2.0 μg/ml and moxifloxacin; 0.25 μg/ml according to the proportion method based on the WHO guideline.[26],[27]
Any drug resistance was defined as resistance to one or more first-line TB drugs (INH, RIF, EMB, PZA, and SM). Resistance to only one first-line TB drug was defined as monoresistance, whereas resistance to at least two or more first-line TB drugs except the INH and RIF combination was defined as polyresistance. MDR-TB was defined as the resistance to the two key first-line TB drugs, INH and RIF. Furthermore, XDR-TB was defined as resistant to INH, RIF, any fluoroquinolone, and to at least one of three second-line injectable drugs (amikacin, CAP, and KAN).[28]
The diagnosis of diabetes mellitus has been based on glycated haemoglobin =6.5 as per the WHO criteria for the diagnosis of diabetes.[29]
| Results | | |
Among clinical samples with new positive growth of M. tuberculosis, sputum samples predominated with 909 (81.50%) followed by 48 (4.20%) pleural fluid, 45 (4%) bronchial lavage, 28 (2.50%) pus, 30 (2.70%) biopsy, 16 (1.40%) CSF, 11 (1%) chest secretion, 11 (1%) peritoneal fluid, 7 (0.60%) pericardial fluid, 4 (0.20%) urine, 1 (0.10%) synovial fluid, 2 (0.20%) other fluid, 1 (0.10%) stool, 1 (0.10%) blood, 1 (0.10%) bone marrow, and 1 (0.10%) gastric lavage.
Drug-susceptibility testing patterns among new TB patients
DST of M. tuberculosis isolates for 1116 clinical samples were performed on first line anti-TB drugs (INH, RIF, EMB, PZA and SM). DST showed that 923 (82.70%) isolates were sensitive to all the tested drugs and 193 (17.3%) showed drug resistance to at least one or more of the first line drugs by different patterns.
The prevalence of overall resistance to one drug was 105 (9.4%). The highest proportion of mono resistance was observed against INH 40 (3.6%) followed by STR 33 (2.95%), PZA 29 (2.59%), and RIF 3 (0.3%). There was no primary mono-resistance to EMB among the new isolates. The pattern of combined resistant toward two drugs was 36 (3.22%), and the pattern of combined resistant toward three drugs was 2 (0.2%). However, 77/1116 (6.9%) isolates were INH resistant without concurrent rifampicin resistance. INH showed the highest percentage of resistance among the patients. Furthermore, 50 (4.5%) patients were diagnosed with MDR-TB. A comprehensive detail of the mono, poly drug resistance, and MDR pattern is given in [Table 2].
Drug-resistance profiles of multidrug-resistant tuberculosis clinical isolates
Among 50 MDR-TB clinical isolates, 10 (20%) were resistant to just rifampicin and INH, 21 (42%) to three first-line anti-TB drugs, and 19 (38%) were resistant to five first-line anti-TB drugs. The DST against five second-line anti-TB drugs was performed for 23 MDR isolates, the results of 23 MDR showed that 16 (32%) isolates were sensitive to all the tested drugs, 1 (2%) was resistant to one drug, 5 (10%) isolates were resistant to two drugs. In addition, 1 (2%) isolate was XDR-TB [Table 3].
The association between diabetes mellitus and primary drug-resistance profile
Of 1116 newly diagnosed TB patients, 256 (22.9%) were TB-DM cases, 135 (12.9%) were TB-no DM cases, and 725 (65%) were TB cases without information on diabetes. Among 256/1116 (22.9%) TB-DM cases, 210/1116 (18.8%) were fully susceptible, 46/1116 (4.12%) were resistance to at least one or more of the first-line drugs, 25 (2.24%) were monoresistance, 9 (0.8%) were polyresistance, 12 (1.07%) were MDR, and among 135 (12.9%) TB-no DM cases 108/1116 (9.67%) were fully susceptible, 27/1116 (2.41%) were resistance to at least one or more of the first-line drugs, 12 (1.07%) were monoresistance, 8 (0.7%) were polyresistance, and 7 (0.62%) were MDR [Table 4]. | Table 4: Drug-resistant profile among tuberculosis-diabetes mellitus patients and tuberculosis-No diabetes mellitus patients and tuberculosis-human immunodeficiency virus patients and tuberculosis-No human immunodeficiency virus patients
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The association between human immunodeficiency virus and primary drug-resistance profile
Among 1116 new TB cases, 33/1116 (2.95%) were HIV positive and 1083/1116 (97.04%) were HIV negative. Out of the 33 HIV positive 27/1116 (2.41%) were fully susceptible, 4/1116 (0.3%) were monoresistance, 1/1116 (0.08%) was polyresistance, and 1/1116 (0.08%) was MDR [Table 4]. There was no evidence of an association between HIV and any type of primary drug-resistance profile.
| Discussion | | |
This is the first study of initial drug-resistance pattern among new TB patients in Dubai; it has generated valuable information regarding the primary drug-resistant TB situation among new cases.
In our study, resistance to at least one or more first-line anti-TB drugs was 17.3%. This is relatively higher than previous reports from other countries in Middle East region, such as Oman (6%) and lower than reports from Jordan (32.4%).[30]
Our data showed that the rate of monoresistance was 9.4%; it is higher than reports from Iraq (2.6%) and lower than reports from Saudi Arabia (27%)[30] and from Sudan (22.46%).[31]
We observed that the highest rate of monoresistance and any resistance were associated with INH. The global averages of INH resistance without concurrent rifampicin resistance were 7.2% in new TB cases.[1] In our study, the prevalence of monoresistance and any resistance to INH excluding MDR-TB was 3.6% and 6.9%, respectively. Our finding is similar to a rate of resistance 4% and 7.5% reported in other Gulf countries such as Saudi Arabia, respectively.[32]
Drug-resistant TB is prevalent in different parts of the world, and according to the WHO global report, it was estimated that 3.4% of the new TB patients had MDR-TB in 2018. Compared with the global report, the prevalence rate of MDR-TB was found in 4.5% of the new TB cases which shows increasing trend.
Furthermore, the prevalence rate of MDR-TB in this study was high in comparison with what has been reported from the other parts of the gulf country, for example, Kuwait (1.5%), Oman (2.9%), and Saudi Arabia (2.6%), and was low in comparison with what has been reported from Bahrain (5.1%) (WHO report 2019).
The diabetes is more prevalent in the Middle East region than other regions, as per International Diabetes Federation, the national prevalence of diabetes in adults in United Arab Emirates is 15.4%,[33] and the global prevalence of diabetes among patients with active TB is 15·3%.[34] In our study, we observed that the prevalence of diabetes among new TB cases in Dubai was 22.9%. Our finding is higher than other Middle East countries, such as Libya (6.1%), Tunisia (7.6%), Yemen (9.5%), and Egypt (15.8%), and lower than Kuwait (29.8%) and Saudi Arabia (42.2%).[34]
The association between DM and TB has been known for many years, but studies in the last 10–15 years have highlighted that DM increases the risk of active TB and that patients with dual disease have worse TB treatment outcomes compared with those who have just TB alone. Few previous published studies have examined the risk factors and primary drug-resistant profile of TB-DM cases. Our study indicated that TB-DM groups 46/1116 (4.12%) had a higher proportion of drug resistance than TB-no DM groups 27/1116 (2.41%), and diabetes was significantly associated with INH resistance among new cases.
Recent studies indicate that co-infected HIV-positive TB patients are at increased risk of MDR-TB compared to HIV-negative patients.[19],[20],[35] We found that among new TB cases, there was no evidence of an association between HIV and any type of primary drug-resistance profile.
In spite of limitations, our study provides relevant initial data about drug resistance in Dubai. To the best of our knowledge, the present study is the first investigation of risk factors for drug-resistant TB in the United Arab Emirates.
| Conclusion | | |
Our study confirms that resistance to INH was the most common phenomenon. The resistance pattern identified in this study could assist clinicians in providing appropriate treatment regimen to TB patients and improve their clinical outcome. We found that diabetes was identified as a risk factor of total drug resistance and MDR among newly diagnosed TB cases. Good management of diabetes and TB infection screening program among DM patients might be necessary for improving TB control in Dubai.
We did not find a significant association between HIV co-infection and drug-resistance, but the association between diabetes and drug-resistant TB should be further explored.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]
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