scholarly journals Evaluation of SNP-based genotyping to monitor tuberculosis control in a high MDR-TB setting

2016 ◽  
Author(s):  
N Tukvadze ◽  
I Bergval ◽  
N Bablishvili ◽  
N Bzekalava ◽  
ARJ Schuitema ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Local Level ◽  
Multidrug Resistant ◽  
Added Value ◽  
Multi Drug Resistance ◽  
Reference Laboratory ◽  
Local Staff ◽  
Tb Control ◽  
Treatment History ◽  
Mdr Tb

ABSTRACTMycobacterium tuberculosis (Mtb) lineage identification and typing of clinical isolates in general is performed only retrospectively. The results are rarely linked to drug susceptibility testing (DST) or patient data. Consequently, the association between Mtb lineage, (multi)drug resistance and treatment history is not fully explored at the local level. Here we evaluated a new SNP based typing assay. We furthermore assessed the added value of genotyping of Mtb isolates for epidemiological purposes and guidance of tuberculosis (TB) control. Mtb lineage, DST profile and treatment history were determined for 399 samples at the National TB Reference Laboratory (NRL) in Tbilisi, Georgia by local staff. Data was shared electronically and analysis was performed remotely. Out of 399 isolates, 74 (74/399, 18.5%) were at least multidrug resistant (MDR)-TB, of which 63 (63/74, 85.1%) were members of three different Mtb Beijing lineages. Previous treatment was reported in 38/74 (51.4%) MDR(+) patients. The availability of this data allows associations with lineages. Notably, multidrug resistant TB was more strongly associated with the Beijing lineage than treatment history. Of all MDR-TB Beijing strains 56.7% (42/74) were members of a genetic cluster. This is most easily explained by (ongoing) MDR-TB transmission rather than drug resistance amplification. This knowledge is useful when designing intervention strategies for MDR-TB. Our study provides an example that on-site integrated Mtb genotyping is realistic and could support TB control activities.

scholarly journals Resistance to Isoniazid and Rifampicin and Factors Associated with Resistance Among MDR TB Patients Visiting DOTS PLUS Site

2017 ◽  
Vol 4 (1) ◽  
pp. 14
Author(s):  
Gauri Suhas Kulkarni ◽  
Chetan Mahajan
Keyword(s):  
Socioeconomic Status ◽  
Drug Resistance ◽  
Past History ◽  
Multidrug Resistant ◽  
World Health ◽  
Factors Associated ◽  
Antituberculous Treatment ◽  
Treatment History ◽  
Mdr Tb ◽  
History Of

Introduction: Multidrug-Resistant (MDR-TB) is defined as M tuberculosis resistant to isoniazid and rifampicin with or without resistant to other drugs. Drug resistant TB is known to occur from time of introduction of antituberculosis drugs. MDR TB has become a significant health problem and an obstacle to effective TB control1. Resistance of M. tuberculosis to anti- TB drugs is caused by chromosomal mutations in genes encoding drug targets. Multidrug-resistant strains of M. tuberculosis (MDR-TB) evolve due to sequential accumulation of mutations in target genes. The WHO cites TB as the single most important fatal infection, with around 8.8 million new cases and 1.4 millions deaths per year, 95% in developing countries. According to Global TB report 2015 data of MDR TB as follows2. 50% successfully completed treatment (cure or treatment completed), 16% died, 16% defaulters, 10% treatment failure, 8% without outcome. The MDR-TB is also threatening World Health Organization’s target of tuberculosis elimination by 2050. Study conducted by NIRT and NTI suggest MDR level of 1% to 3% in new cases and around 12% in retreatment cases and revealed an overall emergence to rifampicin in only 2% of patients, despite a high level (18%) of initial resistance to isoniazid, either alone in or in combination with other anti tuberculosis drugs+. Aims and Objectives: 1. To Study the drug resistance to isoniazid and rifampicin among the MDR TB patients visiting DOTS PLUS CENTRE. 2. To Study the various factors associated with resistance to Isoniazid and rifampicin among MDR TB patients. Material and Methods: Present study was conducted at DOTS PLUS Centre in tertiary health care centre. Total 140 of newly diagnosed cases of MDR-TB were included in the present study after satisfying the inclusion and exclusion criteria. Written informed consent was taken from the study participants. Patients’demographic details were noted such as name, age, sex, occupation, socioeconomic status, education. Patients were asked detailed history about smoking, alcohol, tobacco chewing, diabetes mellitus, hypertension, COPD (chronic obstructive pulmonary disease), HIV Status. Details about past history of tuberculosis, treatment history were noted, If the patient was found to have defaulted previous antituberculous treatment, detailed evaluation was done to find out reasons for defaulting the treatment, History of MDR TB contact was noted. The drug resistance pattern of isoniazid and rifampicin was noted. Results: Of the 140 drug resistance tuberculosis patients, MDR Pulmonary tuberculosis was more common in economically productive age group of 21-40 years, distribution of male (60%) and female (40%), 35% patients were found to have defaulted previous antituberculous treatment. Main reasons for defaulting were, becoming asymptomatic, feeling better 40.8% followed by medication side effects 32.65% Conclusion: Isoniazid and rifampicin resistance (74.28%)is more than rifampicin monoresistance (25.72%), there is significant association between addiction of patient and defaulting the previous antituberculous treatment, analysis of patients various factors for drug resistance showed that MDR-TB is more commonly seen in males, age between 21 to 40 years, low socioeconomic status, past history of ATT, Alcoholic and tobacco user.

Current insights into the chemistry and antitubercular potential of benzimidazole and imidazole derivatives

2020 ◽  
Vol 20 ◽  
Author(s):  
Deepa Parwani ◽  
Sushanta Bhattacharya ◽  
Akash Rathore ◽  
Chaitali Mallick ◽  
Vivek Asati ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Multi Drug Resistance ◽  
Benzimidazole Derivatives ◽  
Duration Of Treatment ◽  
Structure Activity ◽  
Mdr Tb ◽  
Low Toxicity ◽  
Extensively Drug Resistance ◽  
Improved Characteristics

: Tuberculosis is a disease caused by Mycobacterium tuberculosis (Mtb), affecting millions of people worldwide. The emergence of drug resistance is a major problem in the successful treatment of tuberculosis. Due to the commencement of MDR-TB (multi-drug resistance) and XDR-TB (extensively drug resistance), there is a crucial need for the development of novel anti-tubercular agents with improved characteristics such as low toxicity, enhanced inhibitory activity and short duration of treatment. In this direction, various heterocyclic compounds have been synthesized and screened against Mycobacterium tuberculosis. Among them, benzimidazole and imidazole containing derivatives found to have potential anti-tubercular activity. The present review focuses on various imidazole and benzimidazole derivatives (from 2015-2019) with their structure activity relationships in the treatment of tuberculosis.

scholarly journals Analysis of drug resistance and mutation profiles in Mycobacterium tuberculosis isolates in a surveillance site in Beijing, China

2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098493
Author(s):  
Jie Zhang ◽  
Yixuan Ren ◽  
Liping Pan ◽  
Junli Yi ◽  
Tong Guan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Drug Testing ◽  
Multidrug Resistant ◽  
High Rate ◽  
Drug Resistant ◽  
Surveillance Site ◽  
Mdr Tb ◽  
Previously Treated Patients ◽  
Beijing China

Objective This study analyzed drug resistance and mutations profiles in Mycobacterium tuberculosis isolates in a surveillance site in Huairou District, Beijing, China. Methods The proportion method was used to assess drug resistance profiles for four first-line and seven second-line anti-tuberculosis (TB) drugs. Molecular line probe assays were used for the rapid detection of resistance to rifampicin (RIF) and isoniazid (INH). Results Among 235 strains of M. tuberculosis, 79 (33.6%) isolates were resistant to one or more drugs. The isolates included 18 monoresistant (7.7%), 19 polyresistant (8.1%), 28 RIF-resistant (11.9%), 24 multidrug-resistant (MDR) (10.2%), 7 pre-extensively drug-resistant (XDR, 3.0%), and 2 XDR strains (0.9%). A higher rate of MDR-TB was detected among previously treated patients than among patients with newly diagnosed TB (34.5% vs. 6.8%). The majority (62.5%) of RIF-resistant isolates exhibited a mutation at S531L in the DNA-dependent RNA polymerase gene. Meanwhile, 62.9% of INH-resistant isolates carried a mutation at S315T1 in the katG gene. Conclusion Our results confirmed the high rate of drug-resistant TB, especially MDR-TB, in Huairou District, Beijing, China. Therefore, detailed drug testing is crucial in the evaluation of MDR-TB treatment.

scholarly journals Increasing prevalence of resistance to second-line drugs among multidrug-resistant Mycobacterium tuberculosis isolates in Kuwait

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Noura M. Al-Mutairi ◽  
Suhail Ahmad ◽  
Eiman Mokaddas
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Mutation Detection ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Genetic Mutations ◽  
Second Line ◽  
Injectable Drugs ◽  
Mdr Tb ◽  
Phenotypic Susceptibility

AbstractMolecular methods detect genetic mutations associated with drug resistance. This study detected resistance-conferring mutations in gyrA/gyrB for fluoroquinolones and rrs/eis genes for second-line injectable drugs (SLIDs) among multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates in Kuwait. Fifty pansusceptible M. tuberculosis and 102 MDR-TB strains were tested. Phenotypic susceptibility testing was performed by MGIT 960 system using SIRE drug kit. GenoType MTBDRsl version 1 (gMTBDRslv1) and GenoType MTBDRsl version 2 (gMTBDRslv2) tests were used for mutation detection. Results were validated by PCR-sequencing of respective genes. Fingerprinting was performed by spoligotyping. No mutations were detected in pansusceptible isolates. gMTBDRslv1 detected gyrA mutations in 12 and rrs mutations in 8 MDR-TB isolates. gMTBDRsl2 additionally detected gyrB mutations in 2 and eis mutation in 1 isolate. Mutations in both gyrA/gyrB and rrs/eis were not detected. gMTBDRslv1 also detected ethambutol resistance-conferring embB mutations in 59 isolates. Although XDR-TB was not detected, frequency of resistance-conferring mutations for fluoroquinolones or SLIDs was significantly higher among isolates collected during 2013–2019 versus 2006–2012. Application of both tests is warranted for proper management of MDR-TB patients in Kuwait as gMTBDRslv2 detected resistance to fluoroquinolones and/or SLIDs in 3 additional isolates while gMTBDRslv1 additionally detected resistance to ethambutol in 58% of MDR-TB isolates.

Exploring the Contribution of Mycobacteria Characteristics in Their Interaction with Human Macrophages

2013 ◽  
Vol 19 (5) ◽  
pp. 1159-1169 ◽  
Author(s):  
Carla Silva ◽  
Joao Perdigao ◽  
Elsa Alverca ◽  
António P. Alves de Matos ◽  
Patricia A. Carvalho ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Envelope ◽  
Treatment Strategies ◽  
Human Monocyte ◽  
Selective Advantage ◽  
Multidrug Resistant ◽  
Structural Features ◽  
Major Health Problem ◽  
Transmission Electron ◽  
Mdr Tb

AbstractTuberculosis (TB) is a major health problem. The emergence of multidrug resistant (MDR)Mycobacterium tuberculosis(Mtb) isolates confounds treatment strategies. In Portugal, cases of MDR-TB are reported annually with an increased incidence noted in Lisbon. The majority of these MDR-TB cases are due to closely related mycobacteria known collectively as theLisboafamily and Q1 cluster. Genetic determinants linked to drug resistance have been exhaustively studied resulting in the identification of family and cluster specific mutations. Nevertheless, little is known about other factors involved in development of mycobacteria drug resistance. Here, we complement genetic analysis with the study of morphological and structural features of theLisboafamily and Q1 cluster isolates by using scanning and transmission electron microscopy. This analysis allowed the identification of structural differences, such as cell envelope thickness, between Mtb clinical isolates that are correlated with antibiotic resistance. The infection of human monocyte derived macrophages allowed us to document the relative selective advantage of theLisboafamily isolates over other circulating Mtb isolates.

scholarly journals Prevalence and Determinant of Depression among Multi-Drug Resistance Tuberculosis: Study in Dr. Kariadi General Hospital

2020 ◽  
Vol 40 (2) ◽  
pp. 88-96
Author(s):  
Mahalul Azam ◽  
Arulita Ika Fibriana ◽  
Fitri Indrawati ◽  
Indah Septiani
Keyword(s):  
Drug Resistance ◽  
General Hospital ◽  
Secondary Data ◽  
Cross Sectional Study ◽  
Multi Drug Resistance ◽  
P Value ◽  
Cross Sectional ◽  
Depression Status ◽  
Prevalence Of Depression ◽  
Mdr Tb

Backgrouds: Multi-drug resistance tuberculosis (MDR-TB) adds the burden of tuberculosis (TB). Depression is a common comorbidity in TB patients. Prevalence of depression among MDR-TB patients was higher, i.e. 11-70%. Prevalence of depression among TB patients in Dr. Kariadi General Hospital was 51.9%. Previous study reported the determinants related to the depression in MDR-TB patients. This study explored the prevalence of depression in MDR-TB patients and its determinants. Methods: This study was a cross-sectional study conducted from July-August 2019. Data consisted of primary and secondary data from Dr. Kariadi General Hospital patients. Sample in this study involved 72 respondents, over 16 years old from 151 registered MDR-TB patients. Depression status was determined using Depression Anxiety Stress Scales obtained from the medical record. Subjects’ characteristics and determinants were collected from primary as well as secondary data. Descriptive data were presented in proportion. Chi-square test continued by Binary logistic regression was performed to determine the association between depression status and its determinants. A P-value

scholarly journals Constraints of Drug Resistance in Mycobacterium tuberculosis - Prospects for Pharmacological Reversion of Susceptibility to Antibiotics

2017 ◽  
Vol 8 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Aleksandr I. Ilin ◽  
Murat E. Kulmanov ◽  
Ilya S. Korotetskiy ◽  
Marina V. Lankina ◽  
Gulshara K. Akhmetova ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Genetic Heterogeneity ◽  
Multidrug Resistant ◽  
Resistance Mutations ◽  
General Increase ◽  
Drug Induced ◽  
Mdr Tb ◽  
Resistant Strains

Emergence of multidrug resistant strains ofMycobacterium tuberculosis(MDR-TB) threatens humanity. This problem was complicated by the crisis in development of new anti-tuberculosis antibiotics. Induced reversion of drug resistance seems promising to overcome the problem. Successful clinical trial of a new anti-tuberculosis nanomolecular complex FS-1 has demonstrated prospectively of this approach in combating MDR-TB. Several clinical MDR-TB cultures were isolated from sputum samples prior and in the process of the clinical trial. Every isolate was tested for susceptibility to antibiotics and then they were sequenced for comparative genomics. It was found that the treatment with FS-1 caused an increase in the number of antibiotic susceptible strains among Mtb isolates that was associated with a general increase of genetic heterogeneity of the isolates. Observed impairing of phthiocerol dimycocerosate biosynthesis by disruptive mutations inppsACDsubunits indicated a possible virulence remission for the sake of persistence. It was hypothesized that the FS-1 treatment eradicated the most drug resistant Mtb variants from the population by aggravating the fitness cost of drug resistance mutations. Analysis of distribution of these mutations in the global Mtb population revealed that many of them were incompatible with each other and dependent on allelic states of many other polymorphic loci. The latter discovery may explain the negative correlation between the genetic heterogeneity of the population and the level of drug tolerance. To the best of our knowledge, this work was the first experimental confirmation of the drug induced antibiotic resistance reversion by the induced synergy mechanism that previously was predicted theoretically.

scholarly journals Prevalence of Multidrug-Resistant Tuberculosis and Associated Factors in Ethiopia: A Systematic Review

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Solomon Weldegebreal Asgedom ◽  
Mebrahtu Teweldemedhin ◽  
Hailay Gebreyesus
Keyword(s):  
Systematic Review ◽  
Risk Factor ◽  
Associated Factors ◽  
Multidrug Resistant ◽  
Previous Exposure ◽  
Tb Control ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Antituberculosis Treatment ◽  
Mdr Tb

Background. Multidrug-resistant tuberculosis (MDR-TB) has continued to be a challenge for tuberculosis (TB) control globally. Ethiopia is one of the countries with high MDR-TB burden. Objective. The main purpose of this study was to determine the prevalence of MDR-TB and associated factors in Ethiopia. Methods. A systematic review of the literatures on prevalence of MDR-TB and associated factors was conducted in the country. Results. In our electronic search, 546 citations were depicted. Among the total 546 citations described, a total of 22 articles met eligibility criteria and were included in the review article. According to our review, the prevalence of MDR-TB ranged from 0 to 46.3%. The average mean rate of MDR-TB in Ethiopia was found to be 12.6±15.9%. The overall prevalence of MDR-TB in all TB cases was estimated to be 1.4%. From a total of 3849 patients studied, 527 had MDR-TB. Previous exposure to antituberculosis treatment was the most commonly identified risk factor of MDR-TB in Ethiopia. Conclusion. Despite relative decline in incidence of MDR-TB, the distribution and prevalence of MDR-TB continued to be a serious challenge for TB control in Ethiopia. Previous exposure to antituberculosis treatment was also the most common risk factor for MDR-TB. Therefore, strong TB and MDR-TB treatment along with tight introduction of follow-up strategies should be applied for better TB control.

scholarly journals Socio-demographic Profile and Drug Sensitivity Pattern of Suspected Drug Resistant Tuberculosis among Patients in Regional Tuberculosis Reference Laboratory (R.T.R.L) of a Tertiary Hospital

2017 ◽  
Vol 18 (2) ◽  
pp. 62-67 ◽  
Author(s):  
Ummay Fatema Khatun ◽  
Robed Amin ◽  
Muna Islam ◽  
Abdur Rob ◽  
Abdur Rahim
Keyword(s):  
Drug Resistance ◽  
Drug Sensitivity ◽  
Reference Laboratory ◽  
Drug Resistant ◽  
Suspected Drug ◽  
Drug Resistant Tuberculosis ◽  
Demographic Profile ◽  
Resistant Tuberculosis ◽  
Sensitivity Pattern ◽  
Mdr Tb

Background: Drug resistant tuberculosis has been reported in all regions of the world. In this study we address the socio-demographic profile and drug sensitivity pattern as well as prevalence of drug resistance tuberculosis in a tertiary center (regional TB reference laboratory) in Bangladesh.Method: This Study was carried out in R.T.R.L. (Regional TB Reference Laboratory) in 250 bedded Chittagong General Hospital. Patients who were referred to R.T.R.L during the period July 2012 to July 2013 were included in the study. Total 100 patients with suspected drug resistant tuberculosis (TB) who had any one of 9 criteria of NTP (National Tuberculosis Control Programme) were selected consecutively. Gene xpert MTB/RIF (Rifampicin resistance) test for all sputum positive cases were performed. Sputum sample of Patients with positive microscopy for AFB or positive Xpert/MTB was sent for culture. The samples with positive sputum culture were sent for drug sensitivity test for 1st line anti- tubercular drug.Result: Among 100 patients 78 were male and 22 were female, majority of the patients (64) were between 15-45 years with poor socio economic condition (73%) and primarily educated. Analysis of our Study result showed that 18% of patients were mono-drug resistant. Among them 13% showed resistance to isoniazid (INH), 4% to streptomycin and only 2% to rifampicin. No patient was found resistant to pyrazinamide (PNZ) and 38% of patient with suspected drug – resistant TB was found to have no drug resistance. 18% of patient had multidrug resistant tuberculosis (MDR-TB) among which 56% were relapse cases (48% after cat -I, 8% after cat II), 24% were non – converter of cat –I, 12% belonged to failure of cat –I, 3% failure of cat –II, 2% return after default and others. 1% of patient had history of contact with MDR –TB patient.Conclusion: Drug-resistance tuberculosis especially MDR-TB, was higher in patients with previously incomplete anti-tuberculosis treatment. A high level of drug resistance among the re-treatment TB patients poses a threat of transmission of resistant strains to susceptible persons in the community. For this reason proper counseling of patients and attention towards the completion of the anti-TB treatment are needed.J MEDICINE July 2017; 18 (2) : 62-67

Sign in / Sign up

Export Citation Format

Share Document