scholarly journals Molecular characterisation of multidrug-resistantMycobacterium tuberculosisisolates from a high-burden tuberculosis state in Brazil

2019 ◽  
Vol 147 ◽  
Author(s):  
R. S. Salvato ◽  
S. Schiefelbein ◽  
R. B. Barcellos ◽  
B. M. Praetzel ◽  
I. S. Anusca ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Molecular Characterisation ◽  
Drug Resistant ◽  
Isoniazid Resistance ◽  
High Burden ◽  
Brics Countries ◽  
Mdr Tb

AbstractTuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131Mycobacterium tuberculosis (M.tb)DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of thekatG,inhA andrpoB genes and RDRiosublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRiodeletion was observed in 42 (32%) of theM.tbisolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%)M.tbisolates, we found mutations associated with rifampicin (RIF) resistance inrpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance inkatG andinhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in therpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.

scholarly journals Tuberculosis Drug Susceptibility, Treatment, and Outcomes for Belarusian HIV-Positive Patients with Tuberculosis: Results from a National and International Laboratory

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Daria N. Podlekareva ◽  
Dorte Bek Folkvardsen ◽  
Alena Skrahina ◽  
Anna Vassilenko ◽  
Aliaksandr Skrahin ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Reference Laboratory ◽  
Drug Resistant ◽  
Second Line ◽  
High Burden ◽  
Tb Treatment ◽  
Mdr Tb

Background. To cure drug-resistant (DR) tuberculosis (TB), the antituberculous treatment should be guided by Mycobacterium tuberculosis drug-susceptibility testing (DST). In this study, we compared conventional DST performed in Minsk, Belarus, a TB DR high-burden country, with extensive geno- and phenotypic analyses performed at the WHO TB Supranational Reference Laboratory in Copenhagen, Denmark, for TB/HIV coinfected patients. Subsequently, DST results were related to treatment regimen and outcome. Methods. Thirty TB/HIV coinfected patients from Minsk were included and descriptive statistics applied. Results. Based on results from Minsk, 10 (33%) TB/HIV patients had drug-sensitive TB. Two (7%) had isoniazid monoresistant TB, 8 (27%) had multidrug-resistant (MDR) TB, 5 (17%) preextensive drug-resistant (preXDR) TB, and 5 (17%) had extensive drug-resistant (XDR) TB. For the first-line drugs rifampicin and isoniazid, there was DST agreement between Minsk and Copenhagen for 90% patients. For the second-line anti-TB drugs, discrepancies were more pronounced. For 14 (47%) patients, there were disagreements for at least one drug, and 4 (13%) patients were classified as having MDR-TB in Minsk but were classified as having preXDR-TB based on DST results in Copenhagen. Initially, all patients received standard anti-TB treatment with rifampicin, isoniazid, pyrazinamide, and ethambutol. However, this was only suitable for 40% of the patients based on DST. On average, DR-TB patients were changed to 4 (IQR 3-5) active drugs after 1.5 months (IQR 1-2). After treatment adjustment, the treatment duration was 8 months (IQR 2-11). Four (22%) patients with DR-TB received treatment for >18 months. In total, sixteen (53%) patients died during 24 months of follow-up. Conclusions. We found high concordance for rifampicin and isoniazid DST between the Minsk and Copenhagen laboratories, whereas discrepancies for second-line drugs were more pronounced. For patients with DR-TB, treatment was often insufficient and relevant adjustments delayed. This example from Minsk, Belarus, underlines two crucial points in the management of DR-TB: the urgent need for implementation of rapid molecular DSTs and availability of second-line drugs in all DR-TB high-burden settings. Carefully designed individualized treatment regimens in accordance with DST patterns will likely improve patients’ outcome and reduce transmission with drug-resistant Mycobacterium tuberculosis strains.

scholarly journals Mortality of Drug-resistant Tuberculosis in High-burden Countries: Comparison of Routine Drug Susceptibility Testing with Whole-genome Sequencing

2020 ◽  
Author(s):  
Martina L. Reichmuth ◽  
Kathrin Zürcher ◽  
Marie Ballif ◽  
Chloé Loiseau ◽  
Sonia Borrell ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Whole Genome ◽  
Drug Resistant ◽  
Hiv Status ◽  
High Burden

AbstractBackgroundDrug-resistant Mycobacterium tuberculosis (Mtb) strains threaten tuberculosis (TB) control. We compared data on drug resistance obtained at clinics in seven high TB burden countries during routine care with whole-genome sequencing (WGS) carried out centrally.MethodsWe collected pulmonary Mtb isolates and clinical data from adult TB patients in Africa, Latin America, and Asia, stratified by HIV status and drug resistance, from 2013 to 2016. Participating sites performed drug susceptibility testing (DST) locally, using routinely available methods. WGS was done using Illumina HiSeq 2500 at laboratories in the USA and Switzerland. We used TBprofiler to analyse the genomes. We used multivariable logistic regression adjusted for sex, age, HIV-status, history of TB, sputum positivity, and Mtb-lineage to analyse mortality.FindingsWe included 582 TB patients. The median age was 32 years (interquartile range: 27-43 years), 225 (39%) were female, and 247 (42%) were HIV-positive. Based on WGS, 339 (58%) isolates were pan-susceptible, 35 (6%) monoresistant, 146 (25%) multidrug-resistant, and 24 (4%) pre-/ extensively drug-resistant (pre-XDR/XDR-TB). The local DST results were discordant compared to WGS results in 130/582 (22%) of patients. All testing methods identified isoniazid and rifampicin resistance with relatively high agreement (kappa 0.69 for isoniazid and 0.88 rifampicin). Resistance to ethambutol, pyrazinamide, and second-line drugs was rarely tested locally. Of 576 patients with known treatment, 86 (15%) patients received inadequate treatment according to WGS results and the World Health Organization treatment guidelines. The analysis of mortality was based on 530 patients; 63 patients (12%) died and 77 patients (15%) received inadequate treatment. Mortality ranged from 6% in patients with pan-susceptible Mtb (18/310) to 39% in patients with pre-XDR/XDR-TB (9/23). The adjusted odds ratio for mortality was 4.82 (95% CI 2.43-9.44) for under-treatment and 0.52 (95% CI 0.03-2.73) for over-treatment.InterpretationIn seven high-burden TB countries, we observed discrepancies between drug resistance patterns from local DST and WGS, which resulted in inadequate treatment and higher mortality. WGS can provide accurate and detailed drug resistance information, which is required to improve the outcomes of drug-resistant TB in high burden settings. Our results support the WHO’s call for point-of-care tests based on WGS.

scholarly journals The epidemiological characteristics and profile of drug-resistant tuberculosis among children with tuberculosis in Sichuan, China, 2015-2018: A retrospective study

2020 ◽  
Author(s):  
Yuanhong Xu ◽  
Qingfeng Li ◽  
Ma Zhu ◽  
Xueqi Wu ◽  
Dongmei Wang ◽  
...  
Keyword(s):  
Clinical Information ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
History Of ◽  
Epidemiological Characteristics

Abstract Background: The aim of this study was to investigate the epidemiological characteristics and profile of drug-resistant tuberculosis (DR-TB) among children with TB in Sichuan province of China.Methods: From January 2015 to December 2018, microbiological culture-confirmed child TB cases (aged<15 years old) were enrolled retrospectively. Epidemiological and clinical information from these cases, and the drug susceptibility testing (DST) results of the isolates were collected and analyzed.Results: Of 317 culture-confirmed child TB cases, 16.7% (53/317) were aged under 5 years old. 54.9% were Tibetans, and 31.9% had clear history of contact with TB patients. More than half (53.9%) weren’t vaccinated by Calmette–Guérin bacillus (BCG). 30% (n=95) were diagnosed as severe TB, and 92.4% (n=293) were new cases. The ratio of severe TB in BCG vaccinated group was significant lower than that observed in unvaccinated group (p<0.01). Significantly higher proportion of severe TB among Tibetans than Han child TB cases was observed in BCG unvaccinated group (p<0.01). The overall rate of DR-TB in this study was 24.3% (77/317) and 17 multidrug-resistant tuberculosis (MDR-TB) cases were identified with rate of MDR-TB at 5.4% (17/317). No XDR case was found. 13 out of 17 MDR-TB cases (76.4%) were Tibetan children. The ratio of any resistance to four first-line drugs identified were: INH, 15.5%; RIF, 9.1%; EMB, 0.6% and SM, 6.0%, respectively. More than half of MDR patterns were resistant to INH+RIF (9/17), followed by at least resistance to INH+RIF+SM (n=7). Conclusions: This was the first investigation on the epidemiological characteristics and profiles of DR-TB among child TB cases in Southwest of China. Our findings indicated a potentially high risk of TB infection to Tibetan children in the concentrated Tibetan communities of Sichuan.

scholarly journals EXTENSIVELY DRUG RESISTANT TUBERCULOSIS (XDR TB)

2019 ◽  
Vol 5 (2) ◽  
pp. 26
Author(s):  
Sarah Rahmayani Siregar
Keyword(s):  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Tuberculosis Programme ◽  
Mdr Tb ◽  
Directly Observed Treatment

Tuberkulosis adalah penyakit infeksi kronis menular yang masih merupakan masalah kesehatan masyarakat di dunia termasuk Indonesia. Tuberkulosis (TB) sebagian besar akan mengalami penyembuhan dengan pengobatan. Namun tidak semua penyakit TB sembuh dengan pengobatan. Hal ini disebabkan pengobatan dari TB yang belum terlaksana dengan baik sehingga dapat pula menyebabkan terjadinya resistensi terhadap Obat Anti Tuberkulosis (OAT), berupa Multidrug Resistant Tuberkulosis (MDR TB) dan Extensively Drug Resistant Tuberculosis (XDR TB). XDR TB adalah TB yang disebabkan oleh strain yang resistensi terhadap isoniazid dan rifampisin, disertai resisten terhadap salah satu fluorokuinolon dan salah satu dari tiga obat injeksi lini kedua (amikasin, kapreomisin atau kanamisin). XDR TB diperkenalkan tahun 2006 ketika terjadi epidemi yang sangat fatal di Afrika Selatan. XDR-TB dapat ditularkan melalui bakteri yang disebarkan oleh orang yang sudah terkena resistensi obat. Diagnosis XDR-TB ditegakkan dengan uji sensitiviti obat atau Drug Susceptibility Testing (DST), bukan sekedar berdasarkan gambaran foto toraks dan adanya faktor resiko yang ada pada seseorang. WHO telah merancang strategi Directly Observed Treatment Short Course (DOTS-Plus) untuk mengelola TB M/XDR di negara-negara miskin sumber daya. Revisi National Tuberculosis Programme (RNTCP) di bawah DOTS-Plus akan menggunakan rejimen pengobatan standar (STR) kategori IV, yang terdiri dari 6 obat (kanamisin, levofloxacin, etionamid, sikloserin, pirazinamid, dan etambutol) selama 6-9 bulan fase intensif dan 4 obat (levofloxacin, ethionamide, cycloserine, dan ethambutol) selama 18 bulan dari fase lanjutan. Penyembuhan tergantung pada tingkat resistensi obat, tingkat keparahan penyakit dan apakah sistem kekebalan pasien terganggu.

Effectiveness of GenoType MTBDRsl in excluding TB drug resistance in a clinical trial

2021 ◽  
Vol 25 (10) ◽  
pp. 839-845
Author(s):  
M. Ejo ◽  
A. Van Deun ◽  
A. Nunn ◽  
S. Meredith ◽  
S. Ahmed ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Central Laboratory ◽  
Mdr Tb ◽  
Smear Negative ◽  
Probe Assay ◽  
Standard Treatment Regimen

OBJECTIVES: To assess the performance of the GenoType MTBDRsl v1, a line-probe assay (LPA), to exclude baseline resistance to fluoroquinolones (FQs) and second-line injectables (SLIs) in the Standard Treatment Regimen of Anti-tuberculosis Drugs for Patients With MDR-TB 1 (STREAM 1) trial.METHODS: Direct sputum MTBDRsl results in the site laboratories were compared to indirect phenotypic drug susceptibility testing (pDST) results in the central laboratory, with DNA sequencing as a reference standard.RESULTS: Of 413 multidrug-resistant TB (MDR-TB) patients tested using MTBDRsl and pDST, 389 (94.2%) were FQ-susceptible and 7 (1.7%) FQ-resistant, while 17 (4.1%) had an inconclusive MTBDRsl result. For SLI, 372 (90.1%) were susceptible, 5 (1.2%) resistant and 36 (8.7%) inconclusive. There were 9 (2.3%) FQ discordant pDST/MTBDRsl results, of which 3 revealed a mutation and 5 (1.3%) SLI discordant pDST/MTBDRsl results, none of which were mutants on sequencing. Among the 17 FQ- and SLI MTBDRsl-inconclusive samples, sequencing showed 1 FQ- and zero SLI-resistant results, similar to frequencies among the conclusive MTBDRsl. The majority of inconclusive MTBDRsl results were associated with low bacillary load samples (acid-fast bacilli smear-negative or scantily positive) compared to conclusive results (P < 0.001).CONCLUSION: MTBDRsl can facilitate the rapid exclusion of FQ and SLI resistances for enrolment in clinical trials.

scholarly journals Use of Genotype MTBDRplus Assay for Diagnosis of Multidrug-Resistant Tuberculosis in Nepal

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Elina Maharjan ◽  
Narayan Dutt Pant ◽  
Sanjeev Neupane ◽  
Jyoti Amatya ◽  
Bhawana Shrestha
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Conventional Drug ◽  
Mdr Tb ◽  
Genotype Mtbdrplus

The main aims of this study were to study the patterns of mutations in rpoB, katG, and inhA genes in Mycobacterium tuberculosis strains isolated from patients from Nepal and to evaluate the performance of genotype MTBDRplus assay, taking conventional drug susceptibility testing as gold standard for diagnosis of MDR-TB. A total of 69 Mycobacterium tuberculosis strains isolated from 73 smear positive sputum samples from patients suspected of suffering from multidrug-resistant tuberculosis were used in our study. The drug susceptibility pattern of Mycobacterium tuberculosis isolated from these sputum specimens was determined by using genotype MTBDRplus assay taking conventional drug susceptibility testing as reference. The sensitivity and specificity of the genotype MTBDRplus assay for the detection of MDR-TB were found to be 88.7% and 100%, respectively. 88.7% of the rifampicin resistant isolates had mutations in rpoB gene. Similarly, 79.7% and 9.4% of isoniazid resistant isolates had mutations in katG and inhA genes, respectively. Genotype MTBDRplus assay was found to be very rapid and highly sensitive and specific method for diagnosis of MDR-TB and will be very helpful for early diagnosis of MDR-TB in high tuberculosis burden countries.

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