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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 11  |  Issue : 4  |  Page : 429-434

Line probe assay test in new cases of tuberculosis with rifampicin resistance not detected by Xpert MTB/RIF


1 Department of Pulmonology and Respiratory Medicine, Airlangga University; Sub-Pulmonology Department of Internal Medicine, Faculty of Medicine, Hang Tuah University, Surabaya, Indonesia
2 Department of Clinical Microbiology, Faculty of Medicine; Tuberculosis Study Group, Institute of Tropical Disease, Airlangga University, Surabaya, Indonesia
3 Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Airlangga University, Surabaya, Indonesia
4 Department of Pulmonology and Respiratory Medicine; Tuberculosis Study Group, Institute of Tropical Disease, Airlangga University, Surabaya, Indonesia

Date of Submission02-Aug-2022
Date of Decision24-Oct-2022
Date of Acceptance01-Nov-2022
Date of Web Publication10-Dec-2022

Correspondence Address:
Soedarsono Soedarsono
Jl. Mayjen Prof. Dr. Moestopo, No. 47, Surabaya 60131
Indonesia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmy.ijmy_176_22

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  Abstract 


Background: In Indonesia, the National guideline for tuberculosis only recommended taking the DST to check INH resistance only for re-treatment cases of rifampicin-susceptible TB (RS-TB) detected by Xpert MTB/RIF. This study was conducted mainly to evaluate the proportion of isoniazid resistance in new cases of RS-TB according to the Xpert MTB/RIF. Methods: This was an observational descriptive study in RS-TB new patients diagnosed by Xpert MTB/RIF. Sputum samples were examined using first-line LPA and evaluated by culture-based DST. Results of first-line LPA and culture-based DST were compared and presented. Results: Fifty-four new cases of RS-TB (according Xpert MTB/RIF) were enrolled in this study. INH resistance was detected in 4 (7.4%) using FL-LPA and in 5 (9.3%) using culture-based DST. RIF resistance was also found in 1 (1.9%) using FL-LPA and in 2 (3.7%) using culture-based DST. Ethambutol resistance was also detected in 4 (7.4%) using culture-based DST. Conclusion: First-line LPA successfully revealed 4 (7.4%) of Hr-TB in new RS-TB cases detected by the Xpert MTB/RIF. In new cases with RS-TB detected by the Xpert MTB/RIF, FL- LPA can be used as rapid molecular DST to detect RIF and INH resistance followed by culture-based DST to examine other drug resistance.

Keywords: Culture-based drug susceptibility test, drug-resistant tuberculosis, first-line line probe assay, isoniazid-resistant tuberculosis, Xpert MTB/RIF


How to cite this article:
Soedarsono S, Mertaniasih NM, Hasan H, Kusmiati T, Permatasari A, Kusumaningrum D, Wijaksono W. Line probe assay test in new cases of tuberculosis with rifampicin resistance not detected by Xpert MTB/RIF. Int J Mycobacteriol 2022;11:429-34

How to cite this URL:
Soedarsono S, Mertaniasih NM, Hasan H, Kusmiati T, Permatasari A, Kusumaningrum D, Wijaksono W. Line probe assay test in new cases of tuberculosis with rifampicin resistance not detected by Xpert MTB/RIF. Int J Mycobacteriol [serial online] 2022 [cited 2023 Feb 5];11:429-34. Available from: https://www.ijmyco.org/text.asp?2022/11/4/429/363165




  Introduction Top


Tuberculosis (TB) remains a global health problem, caused 9.9 million people fell ill with TB in 2020 and 1.3 million deaths in 2020.[1] Drug-resistant TB (DR-TB) continues to be a public health threat. There were an estimated 465,000 DR-TB cases globally. Indonesia ranks 5th for high DR-TB burden with 24,000 DR-TB cases.[2] Resistance to isoniazid (INH) and rifampicin (RIF) (the two most effective first-line [FL] drugs) is of greatest concern; resistance to both the drugs is defined as multidrug-resistant TB (MDR-TB). Globally, the best estimate of the proportion of people diagnosed with TB for the first time who had MDR/RR-TB has remained at about 3%–4%, and the best estimate for those previously treated for TB has remained at about 18%–21%.[1]

In recent years, rapid and sensitive molecular tests have become available to replace or complement existing conventional tests for detecting Mycobacterium tuberculosis (MTB) and drug resistance. The Xpert MTB/RIF is the fully automated cartridge-based nucleic acid amplification test for simultaneous identification of MTB complex and rifampicin resistance (RR) in <2 h and is recommended by the World Health Organization (WHO). This examination is the FL diagnostic tool for TB diagnosis for suspected TB cases.[3],[4],[5] The results of the RIF resistance test on the Xpert MTB/RIF assay were used as a surrogate marker for the MDR-TB without testing for INH.[6],[7] Based on the current regulation of MDR-TB treatment program in Indonesia, patient's with RIF resistance, determined by Xpert MTB/RIF assay with considered as MDR-TB and are treated with second-line anti-TB drugs.[8] Although RIF and INH resistance often occur concurrently such as in MDR-TB strains, resistance to each of these agents arises independently from each other, and resistance to one agent can occur without resistance to the other.[6] Indeed, testing only for RIF resistance might unnecessarily deny access to INH for patients with low-level INH resistance or no INH resistance (i.e., RIF-monoresistant TB). On the other hand, if RIF resistance is not detected on Xpert MTB/RIF, but actually resistance to INH is present unknowingly, treatment with standard regimens of first-line TB drugs can lead to treatment failure, and acquisition of MDR.[9]

In Indonesia, the MDR-TB treatment program has been implemented since 2009 and is currently being planned for TB treatment program of INH monoresistant TB (Hr-TB), one of the most potent drugs for TB treatment apart from RIF, but it is still limited to retreatment cases. Globally, there were about half a million new cases of RR-TB, of which 78% had MDR-TB in 2018. In addition, an estimated 830,000 people had TB disease caused by MTB with resistance to INH and susceptibility to RIF, referred to as INH-resistant TB (Hr-TB).[3] It is very important to know the proportion of Hr-TB in new cases, where the results of the Xpert MTB/RIF examination showed RIF resistance not detected. Therefore, the TB program should not only focus on retreatment cases.

For those patients with results of MTB detected and RIF resistance not detected (according to the result of Xpert MTB/RIF), the WHO recommended consider taking the drug susceptibility test (DST) for INH if there is a high prevalence of INH resistance not associated with RIF resistance (i.e., INH mono- or polyresistance) in this setting.[3] In Indonesia, the current guideline recommended checking INH resistance only for retreatment cases with Xpert MTB/RIF results of MTB detected and RIF resistance not detected, while new cases with Xpert MTB/RIF results of MTB detected and RIF resistance not detected are directly diagnosed as drug-susceptible TB (DS-TB) and treated with FL anti-TB drugs regimen.[4],[10]

The increased recognition of drug resistance and improved access to rapid molecular testing have led more programs to test for at least RR at the start of TB treatment. In 2020, the WHO approved line probe assays (LPAs) as one of the rapid tests for diagnosis of TB and DR-TB. FL-LPAs such as GenoType MTBDRplus (HAIN Lifescience, Nehren, Germany) and NTM + MDRTB Detection Kit (NIPRO Corporation, Osaka, Japan) allow the detection of resistance to RIF, INH, and ethambutol (EMB). The WHO recommends using FL-LPA for persons with a sputum smear-positive specimen or a cultured isolate of MTBC; commercial molecular LPAs may be used as the initial test instead of phenotypic culture-based DST to detect resistance to RIF and INH.[3] In addition to Xpert MTB/RIF for RIF, a LPA can detect mutations commonly associated with resistance to RIF, INH (FL-LPA), fluoroquinolones, and second-line injectable agents (second-line LPA).[11]

The resistance pattern of MTB varies widely in various geographic locations. The control and treatment of DR-TB require an accurate and rapid diagnosis and also changes in TB therapy regimen to avoid potential resistance-amplifying regimens. The selected TB diagnostic method in an area should be based on the prevalence and local resistance patterns.[12] This study was conducted to evaluate the examination of FL-LPA mainly to detect INH resistance in new cases of rifampicin-susceptible TB (RS-TB) detected by Xpert MTB/RIF. The results of this study can be used to re-evaluate the policy of INH monoresistant diagnosis program only for RS-TB of re-treatment TB cases based on the results of Xpert MTB/RIF.


  Methods Top


Patients and study design

This was an observational descriptive study in Dr. Soetomo Hospital Surabaya (one of the main referral hospitals for MDR-TB services in eastern Indonesia) from March 2021 to December 2021. Sputum samples were taken from new cases of RS-TB detected by Xpert MTB/RIF. New cases are patients who have never been treated for TB or have taken anti-TB drugs for <1 month.[13]

Data collection

Sputum samples were examined using FL-LPA (RIF and INH) as a molecular rapid assay. Samples were evaluated for RIF and INH resistance based on culture-based DST using MGIT 960 BACTEC System which can also evaluate other anti-TB drugs including EMB. FL-LPA used in this study was Genoscholar™. NTM + MDRTB II (Nipro Corporation Limited, Thailand). Xpert MTB/RIF examination was conducted in the clinical microbiology laboratory, Dr. Soetomo Hospital Surabaya. Culture-based DST using MGIT 960 BACTEC System was carried out at the Surabaya Health Laboratory Center, which has been certified by the WHO. The examination of FL-LPA was conducted at the Institute of Tropical Diseases, Universitas Airlangga. Results of FL-LPA and culture-based DST were compared and presented as frequencies and percentages.


  Results Top


According to Xpert MTB/RIF results, this study included 54 new cases of RS-TB with a mean age of 43.3 years, consisting of 38 (70.4%) men and 16 (29.6%) women. Diabetes mellitus (DM) was the most common comorbid in TB patients with the number of 11 (20.4%), while 20 (37%) patients were smokers. [Table 1] shows the characteristics of study subjects.
Table 1: Characteristic of study subjects

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According to the results of FL-LPA and culture-based DST for INH resistance detection [Table 2], it was shown that FL-LPA successfully detected INH resistance in 4 (7.4%) new cases of RS-TB, while culture-based DST detected INH resistance in 5 (9.3%) new cases of RS-TB.
Table 2: Results of first-line line probe assay and culture-based drug susceptibility test for detection of isoniazid resistance in new cases of rifampicin-susceptible-tuberculosis based on Xpert MTB/RIF

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[Table 3] shows the results of FL-LPA and culture-based DST for RIF resistance detection. It was shown that FL-LPA found RIF resistance in 1 (1.9%) new case of RS-TB, while culture-based DST detected RIF resistance in 2 (3.7%) new cases of RS-TB. In this study, FL-LPA can only detect RIF and INH resistance, while culture-based DST can also detect EMB resistance in 4 (7.4%) new TB cases, as presented in [Table 4].
Table 3: Results of first-line line probe assay and culture-based drug susceptibility test for detection of rifampicin resistance in new cases of rifampicin-susceptible tuberculosis based on Xpert MTB/RIF

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Table 4: Results of first-line line probe assay and culture-based drug susceptibility test for detection of ethambutol resistance in new cases of rifampicin-susceptible tuberculosis based on Xpert MTB/

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  Discussion Top


Our study enrolled 54 new cases of RS-TB (according to Xpert MTB/RIF results). DM was the most common comorbid with 11 (20.4%), and 20 (37%) of RS-TB patients are smokers. Previous studies reported DM and smoking as individual risk factors for active TB.[14] Human immunodeficiency virus (HIV) infection was reported as the risk factor for TB, especially in HIV patients with a long duration of HIV infection, smoking, and nonuses of antiretroviral treatment.[15],[16],[17]

The current WHO guideline recommended to consider taking the DST for INH if there is a high prevalence of INH resistance for those patients with results of MTB detected and RIF resistance not detected (according to result of Xpert MTB/RIF).[3] In Indonesia, the current guideline by Indonesian National TB Program (NTP) recommended to check INH resistance only for retreatment cases with Xpert MTB/RIF results of MTB detected and RIF resistance not detected. However, the new TB cases with the same Xpert MTB/RIF results are directly diagnosed as DS-TB and treated with the FL anti-TB drugs standard regimen.[4],[10]

Specifically, a positive molecular test for RR can be considered diagnostic for MDR-TB, because in most countries, >90% of RIF-resistant strains are also resistant to INH.[18] However, there were about half a million new cases of RR-TB, of which 78% had MDR-TB in 2018. In addition, an estimated 830,000 people had Hr-TB.[3] The incidence of Hr-TB was 6.9% in Asia, 6.8% in Europe, 5.4% in Africa, and 6.3% in Canada.[19] In Indonesia, a study in suspected TB cases using a culture-based DST using Lowenstein–Jensen media showed 49/70 (70%) samples were monoresistance to INH.[20] These reports showed that the results of RIF resistance not detected (according to the results of Xpert MTB/RIF) did not rule out the presence of INH resistance. The examination of drug resistance is crucial to determine the treatment regimen, as the treatment for DS-TB, Hr-TB, and MDR/RR-TB is different.[3],[11]

In the current study, FL-LPA detected 4 (7.4%) INH resistance and 1 (1.9%) RIF resistance cases, while culture-based DST detected 5 (9.3%) INH resistance and 2 (3.7%) RIF resistance cases [Table 2] and [Table 3]. This showed the importance of taking the DST for INH and RIF resistance for all new cases of RS-TB patients detected by Xpert MTB/RIF. A study by Stephen et al. reported that LPA such as the GenoType® MTBDRplus version 2.0 (Hain Lifescience, Nehren, Germany) assay had a sensitivity, specificity, positive predictive value, and negative predictive value of 100% for INH and RIF resistance. Due to its ability to detect RIF and INH resistance more accurately and in a shorter period of time, it can be used as an alternative platform of diagnosis.[21]

Our study found INH monoresistant TB (Hr-TB) in 4 (7.4%) detected by FL-LPA and 5 (9.3%) detected by culture-based DST [Table 2]. In this study, FL-LPA and culture-based DST have discordance results. A study by Idrees et al. (2017) in Pakistan reported that there were no discrepancies between phenotypic drug susceptibility testing and LPA for INH and RIF resistance in patients, and its use in clinical practice would lead to rapid detection and effective management.[22] Whereas, Joob and Wiwanitkit stated that although MTBDRplus LPA can be useful, there are many considerations, such as the cost of test and the diagnostic property of the test. The problem of the accuracy of the diagnosis is still another big problem in using MTBDRplus LPA.[23] A study in South Africa also reported the discordance between these two methods. Mahomed et al. reported that LPA showed high sensitivity and specificity of 93% and 95%, respectively, for INH testing. This study is merely to show that discordance does exist between different methods of testing.[24] Molecular assays detect resistance at a genetic level and thus do not detect the eventual phenotypic expression. Furthermore, there is an inability of molecular assays to detect mutations outside targeted “hotspots” and resistance determining regions.[24]

A previous study also reported that the MTBDRplus assay was unable to detect INH resistance in the two isolates that were detected by the MGIT system. This might be due to an undiscovered mutation in a genomic area that is not targeted by this assay (such as ahpc, kasA, or furA). Discordant results between phenotypic and genotypic DST may be due to the fact that not all mutations conferring resistance to anti-TB drugs are included in the LPA assay. Being sensitive by phenotypic technique but resistant by genotypic technique might be linked to false RIF resistance, which is caused by a silent mutation that causes the probe to fail to hybridize on a strip and is misinterpreted as RIF resistant.[25] Another common reason for discordant results is the presence of mixed infections and heteroresistance. Mixed infections with multiple strains of MTB create a challenge for DR-TB testing and treatment as attending clinicians receive results that are dependent on the level of detection of the assay utilized. Furthermore, clinicians may receive conflicting results if populations of both sensitive and resistance MTB strains are present in the patient's sample. Heteroresistance can arise as a result of within-host diversification following a single infection with both DR-TB and DS-TB infection which can be spontaneous or driven by antibiotic selection pressure.[24]

New cases of RS-TB were known to have INH resistance according to the results of FL-LPA and culture-based DST. This finding highlighted the importance to take the DST for INH resistance, although Xpert MTB/RIF for those patients showed RIF resistance not detected (RS-TB). Therefore, the DST for INH resistance should also be tested in all new cases of RS-TB. The result of this study also showed that FL-LPA can be implemented as rapid molecular DST to detect RIF and INH resistance for the diagnosis of Hr-TB and MDR/RR-TB in new TB cases.

DR-TB can develop in two different ways called primary and secondary resistance. Primary resistance is caused by person-to-person transmission of drug-resistant bacteria; this referred to new cases of DR-TB. Secondary or acquired resistance occurs when the patient does not receive an adequate regimen, does not take the prescribed medication, or due to other contributing factors such as mal-absorption or drug-to-drug interactions. This refers to the term re-treatment cases of DR-TB.[26] Transmission of DR-TB is associated both with the virulence of the DR strain and with the susceptibility of the population.[27] Factors associated with Hr-TB are not significant enough to efficiently screen TB patients at risk of Hr-TB. Although several studies conducted in different countries have tried to address this question, no risk factor associated with Hr-TB has been clearly identified so far. The systematic implementation of rapid molecular testing on clinical samples remains the only effective way to make the early diagnosis of Hr-TB and adapt treatment.[28]

Rapid molecular testing is making it increasingly feasible to detect MDR/RR-TB and other types of resistance and to use the results to guide treatment decisions. The WHO recommends the use of the approved rapid molecular DST as the initial test to detect drug resistance before the initiation of appropriate therapy for all TB patients, including new patients and patients with a previous history of TB treatment.[11] The use of FL-LPA to detect the resistance of RIF and INH can thus be used to decide upon the initial regimen for treatment of Hr-TB and MDR/RR-TB. Apart from its rapidity, LPA can also provide information on the mutation patterns, which can influence the choice of treatment (e.g., if only the inhA mutation is present, it is likely that INH can still be effective at high dose, whereas if the katG mutation alone or both inhA and katG are present, INH is no longer effective, even at high dose). If RR is detected, rapid molecular tests for resistance to INH and fluoroquinolones should be performed promptly, to inform the decision on which regimen to use for the treatment.[11] Although the result of culture-based DST can be delayed for 4 to 12 weeks and up to 15% samples may be contaminated, conventional culture-based DST for INH may still be used to evaluate cases with INH resistance from LPA result. This is particularly important for populations with a high pretest probability of resistance to INH.[3],[29]

In the current study, FL-LPA can only detect RIF and INH resistance, while culture-based DST used in this study can also detect EMB resistance in 4 (7.4%) new TB cases. According to the WHO guideline for DR-TB treatment, regimen for Hr-TB treatment consisted of INH, RIF, EMB, pyrazinamide, and levofloxacin.[11] However, the finding of EMB resistance could become a concern as EMB is one component in the regimen for Hr-TB treatment.


  Conclusions Top


First line - line probe assay successfully revealed 4 (7.4%) Hr-TB in new cases of RS-TB (according to the Xpert MTB/RIF). Taking the DST for INH resistance is also important for all new cases of RS-TB. In new cases with RS-TB detected by the Xpert MTB/RIF, FL-LPA can be used as rapid molecular DST to detect RIF and INH resistance followed by culture-based DST to examine other drug resistance. This can be used to re-evaluate the policy of INH monoresistant diagnosis program only for RS-TB of re-treatment TB cases based on the results of Xpert MTB/RIF. In the future, a study with a bigger sample can be conducted in Indonesia to analyze the prevalence of Hr-TB in new TB cases.

Limitation of study

This study used Genoscholar™ NTM + MDRTB II which has been approved by the WHO to examine the resistance to RIF and INH. Meanwhile, to check resistance to pyrazinamide, an additional test kit is needed, which is separate from the Genoscholar™ NTM + MDRTB II kit, called Genoscholar PZA TB II. Targeted sequencing to confirm the results of LPA and culture-based DST and the examination for EMB and pyrazinamide using LPA are needed to be conducted in the future study.

Ethical policy and institutional review board statement

This study was approved by the ethics committee with ethical clearance number 1492/KEPK/IX/2019 on September 9, 2019. This study was conducted in accordance with the Declaration of Helsinki.

Patient declaration of consent statement

All participants included had given their written informed consent to participate in this study. In cases of decreased consciousness and severe illness, written informed consent was represented by next of kin.

Financial support and sponsorship

This study was supported by a grant from Faculty of Medicine, Universitas Airlangga (Penelitian Unggulan Fakultas 2019).

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
World Health Organization (WHO). Global Tuberculosis Report 2021. Geneva: World Health Organization; 2021.  Back to cited text no. 1
    
2.
World Health Organization (WHO). Global Tuberculosis Report 2020. Geneva: World Health Organization; 2020.  Back to cited text no. 2
    
3.
World Health Organization (WHO). Consolidated Guidelines on Tuberculosis. Module 3 : Diagnosis – Rapid Diagnostics for Tuberculosis Detection. Geneva: World Health Organization; 2020.  Back to cited text no. 3
    
4.
Ministry of Health of Republic of Indonesia. Temukan TB Obati Sampai Sembuh Penatalaksanaan Tuberkulosis Resistan Obat di Indonesia. Jakarta: Ministry of Health of Republic of Indonesia; 2020.  Back to cited text no. 4
    
5.
Sanker P, Kottuthodi R, Ambika A, Santhosh VT, Balakrishnan R, Mrithunjayan SK, et al. Predictable repeatability issues with GeneXpert-Xpert MTB/RIF (version 4) derived rifampicin resistant tuberculosis results from South India: Appreciating the limits of a technological marvel! Biomed Biotechnol Res J 2017;1:76-80.  Back to cited text no. 5
    
6.
Malenfant JH, Brewer TF. Rifampicin mono-resistant tuberculosis – A review of an uncommon but growing challenge for global tuberculosis control. Open Forum Infect Dis 2021;8:ofab018.  Back to cited text no. 6
    
7.
Lawn SD, Nicol MP. Xpert® MTB/RIF assay: Development, evaluation and implementation of a new rapid molecular diagnostic for tuberculosis and rifampicin resistance. Future Microbiol 2011;6:1067-82.  Back to cited text no. 7
    
8.
Ministry of Health of Republic of Indonesia. Petunjuk Teknis. Jakarta: Ministry of Health of Republic of Indonesia; 2020.  Back to cited text no. 8
    
9.
Bisimwa BC, Nachega JB, Warren RM, Theron G, Metcalfe JZ, Shah M, et al. Xpert Mycobacterium tuberculosis/rifampicin-detected rifampicin resistance is a suboptimal surrogate for multidrug-resistant tuberculosis in eastern Democratic Republic of the Congo: Diagnostic and clinical implications. Clin Infect Dis 2021;73:e362-70.  Back to cited text no. 9
    
10.
Ministry of Health of Republic of Indonesia. Perubahan Alur Diagnosis dan Pengobatan Tuberkulosis di Indonesia. Jakarta: Ministry of Health of Republic of Indonesia; 2021.  Back to cited text no. 10
    
11.
World Health Organization. WHO Operational Handbook on Tuberculosis. Module 4: Drug-Resistant Tuberculosis Treatment. Geneva: World Health Organization; 2020.  Back to cited text no. 11
    
12.
Mokrousov I, Bhanu NV, Suffys PN, Kadival GV, Yap SF, Cho SN, et al. Multicenter evaluation of reverse line blot assay for detection of drug resistance in Mycobacterium tuberculosis clinical isolates. J Microbiol Methods 2004;57:323-35.  Back to cited text no. 12
    
13.
World Health Organization (WHO). Who Revised Definitions and Reporting Framework for Tuberculosis. Vol. 18. Geneva: World Health Organization; 2013.  Back to cited text no. 13
    
14.
Patra J, Jha P, Rehm J, Suraweera W. Tobacco smoking, alcohol drinking, diabetes, low body mass index and the risk of self-reported symptoms of active tuberculosis: Individual participant data (IPD) meta-analyses of 72,684 individuals in 14 high tuberculosis burden countries. PLoS One 2014;9:e96433.  Back to cited text no. 14
    
15.
Awadalla H, El-Samani F, Soghaier MA, Makki M. Risk factors associated with the development of tuberculosis among HIV-infected patients in Khartoum in 2010. AIMS Public Health 2015;2:784-92.  Back to cited text no. 15
    
16.
Cui Z, Lin M, Nie S, Lan R. Risk factors associated with Tuberculosis (TB) among people living with HIV/AIDS: A pair-matched case-control study in Guangxi, China. PLoS One 2017;12:e0173976.  Back to cited text no. 16
    
17.
Adhikari N, Bhattarai RB, Basnet R, Joshi LR, Tinkari BS, Thapa A, et al. Prevalence and associated risk factors for tuberculosis among people living with HIV in Nepal. PLoS One 2022;17:e0262720.  Back to cited text no. 17
    
18.
Seung KJ, Keshavjee S, Rich ML. Multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. Cold Spring Harb Perspect Med 2015;5:a017863.  Back to cited text no. 18
    
19.
Edwards BD, Edwards J, Cooper R, Kunimoto D, Somayaji R, Fisher D. Incidence, treatment, and outcomes of isoniazid mono-resistant Mycobacterium tuberculosis infections in Alberta, Canada from 2007-2017. PLoS One 2020;15:e0229691.  Back to cited text no. 19
    
20.
Nikmawati A, Windarwati W, Hardjoeno H. Resistensi Mycobacterium tuberculosis terhadap obat anti tuberkulosis. Indones J Clin Pathol Med Lab 2018;12:58.  Back to cited text no. 20
    
21.
Stephen S, Muzhizhizhi D, Dhibi N, Chidemo T, Samaneka W, Matubu TA, et al. Validation of the GenoType® MTBDRplus Ver 2.0 assay for detection of rifampicin and isoniazid resistance in Mycobacterium tuberculosis complex isolates at UZCHS-CTRC TB research laboratory. Int J Mycobacteriol 2019;8:83-8.  Back to cited text no. 21
[PUBMED]  [Full text]  
22.
Idrees F, Irfan M, Jabeen K, Farooqi J, Hasan R. Diagnostic performance of genoType® MTBDRplus line probe assay in bronchoalveolar lavage for pulmonary tuberculosis diagnosis in sputum scarce and smear-negative patients. Int J Mycobacteriol 2017;6:122-6.  Back to cited text no. 22
[PUBMED]  [Full text]  
23.
Joob B, Wiwanitkit V. Diagnostic performance of GenoType® MTBDRplus line probe assay. Int J Mycobacteriol 2017;6:322.  Back to cited text no. 23
[PUBMED]  [Full text]  
24.
Mahomed S, Mlisana K, Cele L, Naidoo K. Discordant line probe genotypic testing vs. culture-based drug susceptibility phenotypic testing in TB endemic KwaZulu-Natal: Impact on bedside clinical decision making. J Clin Tuberc Other Mycobact Dis 2020;20:100176.  Back to cited text no. 24
    
25.
Diriba G, Kebede A, Tola HH, Alemu A, Yenew B, Moga S, et al. Utility of line probe assay in detecting drug resistance and the associated mutations in patients with extrapulmonary tuberculosis in Addis Ababa, Ethiopia. SAGE Open Med 2022;10:1-10.  Back to cited text no. 25
    
26.
Centers for Disease Control and Prevention (CDC). Core Curriculum on Tuberculosis : What the Clinician Should Know Core Curriculum On Tuberculosis. 7th ed. Atlanta: Centers for Disease Control and Prevention (CDC); 2021.  Back to cited text no. 26
    
27.
Caminero JA. Multidrug-resistant tuberculosis: Epidemiology, risk factors and case finding. Int J Tuberc Lung Dis 2010;14:382-90.  Back to cited text no. 27
    
28.
Bachir M, Guglielmetti L, Tunesi S, Billard-Pomares T, Chiesi S, Jaffré J, et al. Isoniazid-monoresistant tuberculosis in France: Risk factors, treatment outcomes and adverse events. Int J Infect Dis 2021;107:86-91.  Back to cited text no. 28
    
29.
Mbelele PM, Mohamed SY, Sauli E, Mpolya EA, Mfinanga SG, Addo KK, et al. Meta-narrative review of molecular methods for diagnosis and monitoring of multidrug-resistant tuberculosis treatment in adults. Int J Mycobacteriol 2018;7:299-309.  Back to cited text no. 29
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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