scholarly journals Drug-resistant Mycobacterium tuberculosis and its genotypes isolated from an outbreak in western Thailand

2020 ◽  
Author(s):  
Janisara Rudeeaneksin ◽  
Benjawan Phetsuksiri ◽  
Chie Nakajima ◽  
Supranee Bunchoo ◽  
Krairerk Suthum ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Variable Number Tandem Repeat ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Drug Resistant ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Extensively Drug Resistant ◽  
Mdr Tb ◽  
Vntr Analysis

Abstract Background Multidrug-resistant TB (MDR-TB) outbreaks have occurred in the Thamaka district, Kanchanaburi province in Thailand. Methods Seventy-two isolates, which included 7% mono-, 30.6% MDR and extensively drug-resistant TB (XDR-TB), were genotyped by spoligotyping, mycobacterial interspersed repetitive unit-variable-number tandem repeat (MIRU-VNTR) and single nucleotide polymorphism genotyping, and their drug resistance was analysed. Results The spoligotyping results showed that Beijing spoligo-international type (SIT)1 was predominant (n=38; 52.8%) while the remaining were non-Beijing sublineages (n=34). The MIRU-VNTR analysis showed that Beijing isolates, most of which belonged to the modern type (n=37), formed 5 clusters and 13 individual patterns. In katG, only mutation Ser315Thr was identified. In rpoB, Ser531Leu was predominant, except for His526Arg and Leu533Pro, which were found in two isolates. A cluster of 14 Beijing strains contained these common mutations and shared the MIRU-VNTR genotype with isolates in the Thamaka district that had spread previously. Two U SIT523 isolates contained the mutations A1400G in rrs and Asp94Gly in gyrA genes, indicating a spread of XDR-TB. Conclusions Most mutations were associated with drug resistance and the specific MDR Beijing and XDR-TB in U SIT523 isolates remain. This genotyping is a key tool for tracking TB transmission in the Thamaka district of Thailand.

scholarly journals Analysis on Drug-Resistance-Associated Mutations among Multidrug-Resistant Mycobacterium tuberculosis Isolates in China

Antibiotics ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1367
Author(s):  
Hongbing Jia ◽  
Yuhui Xu ◽  
Zhaogang Sun
Keyword(s):  
New Technologies ◽  
Gene Mutations ◽  
Multidrug Resistant ◽  
Local Region ◽  
Drug Resistant ◽  
Missense Mutations ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Phenotypic Resistance ◽  
Extensively Drug Resistant

As the causative bacteria of tuberculosis, Mycobacteriumtuberculosis (M. tb) is aggravated by the emergence of its multidrug-resistant isolates in China. Mutations of six of the most frequently reported resistant genes (rpoB, katG, inhA, embB, gyrA, and rpsL) were detected for rifampicin (RIF), isoniazid (INH), ethambutol (EMB), ofloxacin (OFX), and streptomycin (STR) in this study. The amino acid missense mutations (MMs) and their corresponding single nucleotide polymorphism mutations for all drug-resistant (DR) isolates are described in detail. All isolates were divided into non-extensively drug-resistant (Non-XDR) and preXDR/XDR groups. No statistical differences were detected among MMs and linked MMs (LMs) between the two groups, except for rpsL 88 (p = 0.037). In the preXDR/XDR group, the occurrence of MMs in rpoB, katG, and inhA developed phenotypic resistance and MMs of rpoB 531, katG 315, rpsL 43, and rpsL 88 could develop high levels of DR. It is necessary to carry out epidemiological investigations of DR gene mutations in the local region, and thus provide necessary data to support the design of new technologies for rapid detection of resistant M. tb and the optimization of detection targets.

scholarly journals Diagnosis of Multidrug-Resistant Tuberculosis and Extensively Drug-Resistant Tuberculosis: Current Standards and Challenges

2008 ◽  
Vol 19 (2) ◽  
pp. 169-172 ◽  
Author(s):  
Giovanni Battista Migliori ◽  
Alberto Matteelli ◽  
Daniela Cirillo ◽  
Madhukar Pai
Keyword(s):  
Drug Resistance ◽  
Rapid Determination ◽  
Scale Up ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Mdr Tb

INTRODUCTION: The emergence of multidrug-resistant tuberculosis (MDR-TB) and, more recently, extensively drug-resistant TB (XDR-TB) is widely considered a serious threat to global TB control. Over 400,000 new cases of MDR-TB occur each year and, although their rates are currently unknown, XDR-TB cases have been detected in every country where there is capacity to detect them (including Canada).METHODS: The present article provides a narrative overview of the various diagnostic options available for XDR-TB, including conventional tools and newer rapid tests for drug resistance. Available data suggest that automated liquid cultures are highly accurate and their use is rapidly expanding. Newly developed phenotypic tests include TK Medium (Salubris Inc, USA), microscopic-observation drug-susceptibility assay, FASTPlaque-Response bacteriophage assay (Biotec Laboratories Ltd, UK), colorimetric redox indicator methods and the microcolony method. These tests are usually cheaper but not always simple to perform, with some requiring high standards of biosafety and quality control. Among the newly developed phenotypic methods, reverse hybridization-based assays, referred to as line probe assays, represent a useful tool because of their superior accuracy and cost-effectiveness.CONCLUSIONS: To effectively address the threats of MDR-TB and XDR-TB, global initiatives are required to scale-up culture and drug susceptibility testing capacities, especially in high-burden countries where such capacity is scarce. In parallel, efforts are needed to expand the use of novel and emerging technologies (ie, molecular diagnostics) for the rapid determination of drug resistance.

scholarly journals Issues of Tuberculosis Drug-Resistance in Kharkiv Region and in Ukraine

2019 ◽  
pp. 24-28
Author(s):  
O.S. Shevchenko ◽  
O.O. Pohorielova
Keyword(s):  
Drug Resistance ◽  
Statistical Processing ◽  
Multidrug Resistant ◽  
Study Data ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Mdr Tb ◽  
Microsoft Office

Background. Multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis remain severe epidemic problems in the world. That’s why the purpose of our study was to investigate the dynamics of the incidence of multidrug-resistant and extensively drug-resistant tuberculosis, the structure of cases and the effectiveness of treatment in this category of patients in the Kharkiv region and in Ukraine. Materials and methods. To perform the study, data from reporting forms No. 4-2 (TB 07 – MDR TB), No. 8-6 (TB 08) and data from analytical and statistical reference books “Tuberculosis in Ukraine” were used. Statistical processing of information was carried out using Statistica 7.0, Microsoft Office Excel 2007. Results. We found a relatively consistently high incidence rate, prevalence of tuberculosis recurrences among patients with drug-resistant tuberculosis, an increase in the proportion of extensively-drug resistance in patients with treatment failure and interrupted treatment, and low effectiveness of treatment of multidrug-resistant and extensively drug-resistant tuberculosis in patients with repeated cases of treatment. Conclusions. The obtained data once again emphasizes the need for the selection of adequate schemes for antituberculosis chemotherapy and control of anti-tuberculosis drugs.

Bangladesh anthrax outbreaks are probably caused by contaminated livestock feed

2012 ◽  
Vol 141 (5) ◽  
pp. 1021-1028 ◽  
Author(s):  
A. FASANELLA ◽  
G. GAROFOLO ◽  
M. J. HOSSAIN ◽  
M. SHAMSUDDIN ◽  
J. K. BLACKBURN ◽  
...  
Keyword(s):  
Genetic Variance ◽  
Monsoon Season ◽  
Variable Number Tandem Repeat ◽  
Variable Number ◽  
Snp Analysis ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Major Lineage ◽  
Livestock Feed ◽  
Vntr Analysis

SUMMARYIn Bangladesh from 1 July to 30 September 2010 there were 104 animal cases of anthrax and 607 associated human cases. This investigation was conducted in Sirajganj district in December 2010, on eight farms where animal cases had occurred.Bacillus anthraciswas recovered from soil samples and turbinate bones on six farms. Canonical single nucleotide polymorphism (SNP) analysis showed that all the isolates belonged to the major lineage A, sublineage A.Br.001/002 of China and South East Asia while a multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) with 15 VNTRs demonstrated three unique genotypes. The single nucleotide repeat (SNR) analyses showed two SNR types in 97 out of 99 isolates; nevertheless, due to its higher discriminatory power the presence of two isolates with different SNR-type polymorphisms were detected within two MLVA genotypes. The epidemic occurred during the monsoon season, a time of extensive flooding, suggesting that the source was contaminated feed, not grazing, which is supported by the genetic variance.

scholarly journals FIND Tuberculosis Strain Bank: a Resource for Researchers and Developers Working on Tests To Detect Mycobacterium tuberculosis and Related Drug Resistance

2017 ◽  
Vol 55 (4) ◽  
pp. 1066-1073 ◽  
Author(s):  
Belay Tessema ◽  
Pamela Nabeta ◽  
Eloise Valli ◽  
Audrey Albertini ◽  
Jimena Collantes ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Variable Number Tandem Repeat ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Sub Saharan Africa ◽  
Resistance Testing ◽  
Drug Resistant ◽  
Phenotypic Resistance ◽  
Mother And Daughter ◽  
Sub Saharan

ABSTRACT The spread of multidrug-resistant (MDR) tuberculosis (TB) and extensively drug-resistant (XDR) TB hampers global efforts in the fight against tuberculosis. To enhance the development and evaluation of diagnostic tests quickly and efficiently, well-characterized strains and samples from drug-resistant tuberculosis patients are necessary. In this project, the Foundation for Innovative New Diagnostics (FIND) has focused on the collection, characterization, and storage of such well-characterized reference materials and making them available to researchers and developers. The collection is being conducted at multiple centers in Southeast Asia, South America, Eastern Europe, and soon the sub-Saharan Africa regions. Strains are characterized for their phenotypic resistances and MICs to first-line drugs (FLDs) and second-line drugs (SLDs) using the automated MGIT 960 system following validated procedures and WHO criteria. Analysis of resistance-associated mutations is done by whole-genome sequencing (WGS) using the Illumina NextSeq system. Mycobacterial interspersed repetitive-unit–variable-number tandem-repeat analysis and WGS are used to determine strain lineages. All strains are maintained frozen at −80°C ± 10°C as distinct mother and daughter lots. All strains are extensively quality assured. The data presented here represent an analysis of the initial part of the collection. Currently, the bank contains 118 unique strains with extracted genomic DNA and matched sputum, serum, and plasma samples and will be expanded to a minimum of 1,000 unique strains over the next 3 years. Analysis of the current strains by phenotypic resistance testing shows 102 (86.4%), 10 (8.5%), and 6 (5.1%) MDR, XDR, and mono/poly resistant strains, respectively. Two of the strains are resistant to all 11 drugs that were phenotypically tested. WGS mutation analysis revealed FLD resistance-associated mutations in the rpoB , katG , inhA , embB , embA , and pncA genes; SLD resistance in the gyrA , gyrB , rrs , eis , and tlyA genes; and ethionamide resistance in the ethA genes. Most important lineages are represented in the bank, and further collections have been initiated to increase geographic and lineage diversity. The bank provides highly characterized and high-quality strains as a resource for researchers and developers in support of the development and evaluation of new diagnostics and drug resistance detection tools.

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 Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Zhaojing Zong ◽  
Wei Jing ◽  
Jin Shi ◽  
Shu'an Wen ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Significant Difference ◽  
Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

scholarly journals Mycobaterial interspersed repetitive units-variable number of tandem repeats analysis and pattern of drug resistance in extended drug resistant (XDR) TB isolates from pulmonary tuberculosis patients in Bangladesh

2020 ◽  
Vol 46 (1) ◽  
pp. 22-28
Author(s):  
Shirin Tarafder ◽  
Md Bayzid Bin Monir
Keyword(s):  
Drug Resistance ◽  
Molecular Typing ◽  
Tandem Repeats ◽  
Variable Number ◽  
Drug Resistant ◽  
Gyra Gene ◽  
Drug Resistant Tuberculosis ◽  
Tree Analysis ◽  
Resistant Tuberculosis ◽  
Mdr Tb

Background: To investigate the spread of specific genotypes in a defined geographical area and to determine any relationship of these genotypes with drug resistance the most essential method is molecular typing. It allows a rapid and precise species differentiation. Objective: This study was intended to observe the genotypes of XDR mycobacterium tuberculosis by determining 24 loci MIRU-VNTR analysis. Methods: To gain an insight about molecular typing of MTB and drug resistance-associated mutations in XDR-TB isolates a total of 98 multi drug resistant tuberculosis (MDR-TB) isolates collected through Xpert MTB/RIF assay. They were subjected to 2nd line (Fluoroquinolones, kanamycin, capreomycin and amikacin) drug susceptibility testing through line probe assay (LPA) in a view to detect extensively drug resistant tuberculosis (XDR-TB). Genotyping was done for XDR-TB isolates using 24 loci Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) using the online tool at http://www.MIRU-VNTRplus.org.. Out of 98 MDR-TB isolates 11(11.23%)  XDR-TB isolates were typed and analysed. Results: Twenty four loci MIRU-VNTR genotyping involving similarity searching and phylogenetic tree analysis revealed that six (54.60%) XDR-TB isolates belonged to Beijing strain, Other MTB strain also detected were Delhi/CAS two(18.20%), Haarlem two(18.20%) and New-1, one (9.10%) in number. Minimum spanning tree analysis showed two strain of Beijing family form a clonal complex. Beijing strains were more common among younger age group and within urban population. Beijing strains were also predominant in treatment failure patient. Only one new case of XDR-TB belongs to Delhi/CAS family. Second line mycobacterial drug resistance (MTBDRsl) detected by LPA showed the most prevalent mutations involved in Fluoroquinolones drug resistance (FQ) was Asp94Gly in gyrA gene (54.55%) in quinolone resistance determining region (QRDR) and for Injectable 2nd line Drug resistance (ISL) was A1401G, C1402T in 16S rrs gene (100%)..  All XDR-TB isolates showed resistance to Levofloxacin in 2nd line LPA but Moxifloxacin showed low level resistance to some cases. Conclusion: Molecular typing of XDR- TB isolates and pattern of drug resistance associated mutations in XDR-TB isolates in Bangladesh have not been reported previously. The result of this study highlights the need to reinforce the TB policy in Bangladesh with regard to control the spread and transmission as well as detection and treatment strategies regarding XDR-TB. Bangladesh Med Res Counc Bull 2020; 46(1): 22-28

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