scholarly journals Distinguishing Relapse From Reinfection With Whole-Genome Sequencing in Recurrent Pulmonary Tuberculosis: A Retrospective Cohort Study in Beijing, China

2021 ◽  
Vol 12 ◽  
Author(s):  
Jian Du ◽  
Qing Li ◽  
Min Liu ◽  
Yufeng Wang ◽  
Zhongtan Xue ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Chronic Diseases ◽  
Genome Sequencing ◽  
Strong Association ◽  
Drug Susceptibility ◽  
Diabetic Patients ◽  
Whole Genome ◽  
Community Transmission ◽  
Susceptibility Profiles ◽  
Beijing China

Background: Tuberculosis recurrence is still a major problem for the control of tuberculosis, and the cause of the recurrence is still unclear.Methods: We retrospectively recruited 68 pairs of samples of Mycobacterium tuberculosis (MTB) from recurrent TB cases in Beijing Chest Hospital between January 2008 and December 2019. The whole-genome sequencing was conducted to analyze single-nucleotide polymorphism (SNP) and to identify whether recurrent disease was due to relapse or reinfection. The BACTEC MGIT was performed to compare differences in drug susceptibility profiles between two episodes.Results: 62 (91.2%) out of 68 confirmed recurrence were due to relapse, whereas the remaining six (8.8%) were due to reinfection. And there was a strong association between earlier relapse and underlying chronic diseases. In addition, the MTB isolates from non-diabetic patients had a higher mutation rate than those from diabetic patients. A community transmission was also identified in our cohort. Levofloxacin resistance was the most frequently observed drug resistance for 12.9% relapse cases.Conclusion: The relapse of a previous episode in Beijing. The underlying chronic diseases are associated with an earlier TB relapse. MTB isolates were more prone to develop levofloxacin resistance than moxifloxacin resistance after FQ exposure. The patients at high-risk for relapses deserve more careful investigation.

scholarly journals Setup, Validation, and Quality Control of a Centralized Whole-Genome-Sequencing Laboratory: Lessons Learned

2018 ◽  
Vol 56 (8) ◽  
Author(s):  
Cath Arnold ◽  
Kirstin Edwards ◽  
Meeta Desai ◽  
Steve Platt ◽  
Jonathan Green ◽  
...  
Keyword(s):  
Public Health ◽  
Quality Control ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Food Poisoning ◽  
Drug Susceptibility ◽  
Lessons Learned ◽  
Microbial Pathogens ◽  
Whole Genome ◽  
Whole Genome Analysis

ABSTRACT Routine use of whole-genome analysis for infectious diseases can be used to enlighten various scenarios pertaining to public health, including identification of microbial pathogens, relating individual cases to an outbreak of infectious disease, establishing an association between an outbreak of food poisoning and a specific food vehicle, inferring drug susceptibility, source tracing of contaminants, and study of variations in the genome that affect pathogenicity/virulence. We describe the setup, validation, and ongoing verification of a centralized whole-genome-sequencing (WGS) laboratory to carry out sequencing for these public health functions for the National Infection Services, Public Health England, in the United Kingdom. The performance characteristics and quality control metrics measured during validation and verification of the entire end-to-end process (accuracy, precision, reproducibility, and repeatability) are described and include information regarding the automated pass and release of data to service users without intervention.

scholarly journals Low-level rifampin resistance and rpoB mutations in Mycobacterium tuberculosis: An analysis of whole-genome sequencing and drug susceptibility test data in New York

2020 ◽  
Author(s):  
Joseph Shea ◽  
Tanya A. Halse ◽  
Donna Kohlerschmidt ◽  
Pascal Lapierre ◽  
Herns A. Modestil ◽  
...  
Keyword(s):  
New York ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Critical Concentration ◽  
Gene Sequencing ◽  
Drug Susceptibility ◽  
Whole Genome ◽  
Drug Resistant ◽  
Low Level ◽  
Indicator Tube

Rapid and reliable detection of rifampin (RIF) resistance is critical for the diagnosis and treatment of drug-resistant and multi-drug resistant (MDR) tuberculosis. Discordant RIF phenotype/genotype susceptibility results remain a challenge due to the presence of rpoB mutations which do not confer high levels of RIF resistance as have been exhibited in strains with mutations such as Ser450Leu. These strains, termed low-level RIF resistant, exhibit elevated RIF minimum inhibitory concentrations (MICs) compared to fully susceptible strains, however remain phenotypically susceptible by mycobacteria growth indicator tube (MGIT) testing and have been associated with poor patient outcomes. Here we assess RIF resistance prediction by whole-genome sequencing (WGS) among a set of 1779 prospectively tested strains by both prevalence of rpoB gene mutation and phenotype as part of routine clinical testing during a 21/2-year period. During this time, 139 strains were found to have nonsynonymous rpoB mutations, 53 of which were associated with RIF resistance, including both low-level and high-level resistance. Resistance to RIF (1.0 μg/mL in MGIT) was identified in 43 (81.1%) isolates. The remaining 10 (18.9%) strains were susceptible by MGIT, however were confirmed to be low-level RIF resistant by MIC testing. Full rpoB gene sequencing overcame the limitations of critical concentration phenotyping, probe-based genotyping, and partial-gene sequencing methods. Universal clinical WGS with concurrent phenotypic testing provided a more complete understanding of the prevalence and type of rpoB mutations and their association with RIF resistance in New York.

scholarly journals Towards Point-of-Care Diagnosis of Pulmonary Tuberculosis and Drug Susceptibility Testing by Whole Genome Sequencing of DNA Isolated from Sputum

2017 ◽  
Vol 1 (Special Issue-Supplement) ◽  
pp. 267-267
Author(s):  
Kayzad S. Nilgiriwala ◽  
Louise Pankhurst ◽  
Ali Vaughan ◽  
Zamin Iqbal ◽  
Derrick Crook ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Susceptibility Testing ◽  
Point Of Care ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Whole Genome

scholarly journals SARS-CoV-2 Omicron Outbreak in a Dormitory in Saint-Petersburg, Russia

2022 ◽  
Author(s):  
Georgii A. Bazykin ◽  
Daria M. Danilenko ◽  
Andrey B. Komissarov ◽  
Nikita Yolshin ◽  
Olga V. Shneider ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Immune Evasion ◽  
Whole Genome ◽  
Saint Petersburg ◽  
Single Origin ◽  
Rate Of Spread ◽  
Rapid Spread ◽  
Community Transmission

Abstract The B.1.1.529 Omicron variant of SARS-CoV-2 is rapidly spreading, displacing the globally prevalent Delta variant. Before December 16, 2021, community transmission had already been observed in tens of countries globally. However, in Russia, all reported cases had been sporadic and associated with travel. Here, we report an Omicron outbreak at a students’ dormitory in Saint Petersburg, Russia. Out of the 462 sampled residents of the dormitory, 206 (44.6%) tested PCR positive, and 159 (77.1%) of these infections carried the S:ins214EPE insertion, indicating that they were of the Omicron strain. 104 (65%) of Omicron-positive patients have been vaccinated and/or reported previous covid-19. Whole genome sequencing confirmed that the outbreak is caused by the Omicron variant. Phylogenetic analysis showed that the outbreak has a single origin, and belongs to the S:346K sublineage of Omicron which may be characterized by an increased rate of spread, compared to other Omicron sublineages. The rapid spread of Omicron in a population with preexisting immunity to previous variants underlines its propensity for immune evasion.

Diagnostic performance of whole-genome sequencing for identifying drug-resistant TB in Thailand

2021 ◽  
Vol 25 (9) ◽  
pp. 754-760
Author(s):  
P. Kamolwat ◽  
D. Nonghanphithak ◽  
A. Chaiprasert ◽  
S. Smithtikarn ◽  
P. Pungrassami ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Diagnostic Performance ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Whole Genome ◽  
Drug Resistant ◽  
Aminosalicylic Acid ◽  
Promising Tool

BACKGROUND: Whole-genome sequencing (WGS) is a promising tool for the detection of drug-resistant TB (DR-TB). To date, there have been few comparisons of diagnostic performance of WGS and phenotypic drug susceptibility testing (DST) in DR-TB.METHODS: We compared drug resistance-conferring mutations identified by WGS analysis using TB-Profiler and Mykrobe with phenotypic DST profiles based on the Löwenstein-Jensen proportion method using drug-resistant Mycobacterium tuberculosis (n = 537) isolates from across Thailand. Based on available phenotypic DST results, diagnostic performance was analysed for resistance against isoniazid, rifampicin, ethambutol (EMB), streptomycin, ethionamide (ETH), kanamycin, capreomycin (CPM), para-aminosalicylic acid, ofloxacin and levofloxacin.RESULTS: High agreement between the two methods was observed for most drugs (>91%), except EMB (57%, 95% CI 53–61) and ETH (70%, 95% CI 66–74). Also, low specificity was observed for EMB (49%, 95% CI 44–54) and ETH (66%, 95% CI 61–71). Sensitivity was high for most drugs (range 83–98%), except CPM (77%, 95% CI 59–88).CONCLUSION: Low agreement between WGS and phenotypic tests for drug resistance was found for EMB and ETH. The current genomic database is insufficient for the identification of CPM resistance. Challenges remain for routine usage of WGS-based DST, especially for second-line anti-TB drugs.

Whole-genome sequencing differentiates relapse from re-infection in TB

2021 ◽  
Vol 25 (12) ◽  
pp. 995-1000
Author(s):  
A. Nikolenka ◽  
M. Mansjö ◽  
A. Skrahina ◽  
H. Hurevich ◽  
V. Grankov ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Failure ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Drug Susceptibility ◽  
Whole Genome ◽  
Single Nucleotide ◽  
Acquired Drug Resistance ◽  
Resistant Strains

BACKGROUND: Distinguishing TB relapse from re-infection is important from a clinical perspective to document transmission patterns. We investigated isolates from patients classified as relapse to understand if these were true relapses or re-infections. We also investigated shifts in drug susceptibility patterns to distinguish acquired drug resistance from re-infection with resistant strains.METHODS: Isolates from pulmonary TB patients from 2009 to 2017 were analysed using whole-genome sequencing (WGS).RESULTS: Of 11 patients reported as relapses, WGS results indicated that 4 were true relapses (single nucleotide polymorphism difference ≤5), 3 were re-infections with new strains, 3 were both relapse and re-infection and 1 was a suspected relapse who was later categorised as treatment failure based on sequencing. Of the 9 patients who went from a fully susceptible to a resistant profile, WGS showed that none had acquired drug resistance; 6 were re-infected with new resistant strains, 1 was probably infected by at least two different genotype strains and 2 were phenotypically misclassified.CONCLUSIONS: WGS was shown to distinguish between relapse and re-infection in an unbiased way. The use of WGS minimises the risk of false classification of treatment failure instead of re-infection. Furthermore, our study showed that strains without major genetic differences can cause re-infection.

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