ORCID Profile
0000-0003-3646-1573
Current Organisations
Université de Montréal
,
CHUM Reseach Center
,
Institute Pasteur Madagascascar
,
McGill International TB Center
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Publisher: Centers for Disease Control and Prevention (CDC)
Date: 03-2021
Publisher: Cambridge University Press (CUP)
Date: 2023
DOI: 10.1017/ASH.2023.119
Abstract: We evaluated the added value of infection control-guided, on demand, and locally performed severe acute respiratory coronavirus virus 2 (SARS-CoV-2) genomic sequencing to support outbreak investigation and control in acute-care settings. This 18-month prospective molecular epidemiology study was conducted at a tertiary-care hospital in Montreal, Canada. When nosocomial transmission was suspected by local infection control, viral genomic sequencing was performed locally for all putative outbreak cases. Molecular and conventional epidemiology data were correlated on a just-in-time basis to improve understanding of coronavirus disease 2019 (COVID-19) transmission and reinforce or adapt control measures. Between April 2020 and October 2021, 6 outbreaks including 59 nosocomial infections (per the epidemiological definition) were investigated. Genomic data supported 7 distinct transmission clusters involving 6 patients and 26 healthcare workers. We identified multiple distinct modes of transmission, which led to reinforcement and adaptation of infection control measures. Molecular epidemiology data also refuted (n = 14) suspected transmission events in favor of community acquired but institutionally clustered cases. SARS-CoV-2 genomic sequencing can refute or strengthen transmission hypotheses from conventional nosocomial epidemiological investigations, and guide implementation of setting-specific control strategies. Our study represents a template for prospective, on site, outbreak-focused SARS-CoV-2 sequencing. This approach may become increasingly relevant in a COVID-19 endemic state where systematic sequencing within centralized surveillance programs is not available. clinicaltrials.gov identifier: NCT05411562
Publisher: Cold Spring Harbor Laboratory
Date: 31-10-2022
DOI: 10.1101/2022.10.31.514503
Abstract: Universal access to drug susceptibility testing for newly diagnosed tuberculosis patients is recommended. Access to culture-based diagnostics remains limited and targeted molecular assays are vulnerable to emerging resistance conferring mutations. Improved s le preparation protocols for direct-from-sputum sequencing of Mycobacterium tuberculosis would accelerate access to comprehensive drug susceptibility testing and molecular typing. We assessed a thermo-protection buffer-based direct-from-s le M. tuberculosis whole-genome sequencing protocol. We prospectively processed and analyzed 60 acid-fast bacilli smear-positive sputum s les from tuberculosis patients in India and Madagascar. A ersity of semi-quantitative smear positivity level s les were included. Sequencing was performed using Illumina and MinION (monoplex and multiplex) technologies. We measured the impact of bacterial inoculum and sequencing platforms on M. tuberculosis genomic mean read depth, drug susceptibility prediction performance and typing accuracy. M. tuberculosis was identified from 88% (Illumina), 89% (MinION-monoplex) and 83% (MinION-multiplex) of s les for which sufficient DNA could be extracted. The fraction of M. tuberculosis reads from MinION sequencing was lower than from Illumina, but monoplexing grade 3+ sputum s les on MinION produced higher read depth than Illumina ( p .05) and MinION multiplex ( p .01). No significant difference in overall sensitivity and specificity of drug susceptibility predictions was seen across these sequencing modalities or within each sequencing technology when stratified by smear grade. Lineage typing agreement percentages between direct and culture-based sequencing were 85% (MinION-monoplex), 88% (Illumina) and 100% (MinION-multiplex) M. tuberculosis direct-from-s le whole-genome sequencing remains challenging. Improved and affordable s le treatment protocols are needed prior to clinical deployment.
Publisher: F1000 Research Ltd
Date: 02-12-2019
DOI: 10.12688/WELLCOMEOPENRES.15603.1
Abstract: Two billion people are infected with Mycobacterium tuberculosis , leading to 10 million new cases of active tuberculosis and 1.5 million deaths annually. Universal access to drug susceptibility testing (DST) has become a World Health Organization priority. We previously developed a software tool, Mykrobe predictor , which provided offline species identification and drug resistance predictions for M. tuberculosis from whole genome sequencing (WGS) data. Performance was insufficient to support the use of WGS as an alternative to conventional phenotype-based DST, due to mutation catalogue limitations. Here we present a new tool, Mykrobe , which provides the same functionality based on a new software implementation. Improvements include i) an updated mutation catalogue giving greater sensitivity to detect pyrazinamide resistance, ii) support for user-defined resistance catalogues, iii) improved identification of non-tuberculous mycobacterial species, and iv) an updated statistical model for Oxford Nanopore Technologies sequencing data. Mykrobe is released under MIT license at ykrobe-tools/mykrobe. We incorporate mutation catalogues from the CRyPTIC consortium et al. (2018) and from Walker et al. (2015), and make improvements based on performance on an initial set of 3206 and an independent set of 5845 M. tuberculosis Illumina sequences. To give estimates of error rates, we use a prospectively collected dataset of 4362 M. tuberculosis isolates . Using culture based DST as the reference, we estimate Mykrobe to be 100%, 95%, 82%, 99% sensitive and 99%, 100%, 99%, 99% specific for rif icin, isoniazid, pyrazinamide and ethambutol resistance prediction respectively. We benchmark against four other tools on 10207 (=5845+4362) s les, and also show that Mykrobe gives concordant results with nanopore data. We measure the ability of Mykrobe -based DST to guide personalized therapeutic regimen design in the context of complex drug susceptibility profiles, showing 94% concordance of implied regimen with that driven by phenotypic DST, higher than all other benchmarked tools.
Publisher: American Society for Microbiology
Date: 23-03-2023
DOI: 10.1128/JCM.01578-22
Abstract: Universal access to drug susceptibility testing for newly diagnosed tuberculosis patients is recommended. Access to culture-based diagnostics remains limited, and targeted molecular assays are vulnerable to emerging resistance mutations.
No related grants have been discovered for Simon Grandjean Lapierre.