Whole genome sequencing of drug-resistant Mycobacterium tuberculosis isolates in Victoria, Australia
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved..
OBJECTIVES: Whole genome sequencing (WGS) can identify clusters, transmission patterns, and drug resistance mutations. This is important in low-burden settings such as Australia, as it can assist in efficient contact tracing and surveillance.
METHODS: We conducted a retrospective cohort study using WGS from 155 genomically defined drug-resistant Mycobacterium tuberculosis (DR-TB) isolates collected between 2018-2021 in Victoria, Australia. Bioinformatic analysis was performed to identify resistance-conferring mutations, lineages, clusters and understand how local sequences compared with international context.
RESULTS: Of the 155 sequences, 42% were identified as lineage 2 and 35% as lineage 1; 65.8% (102/155) were isoniazid mono-resistant, 8.4% were multi-drug resistant TB and 5.8% were pre-extensively drug-resistant / extensively drug-resistant TB. The most common mutations were observed in katG and fabG1 genes, especially at Ser315Thr and fabG1 -15 C>T for first-line drugs. Ser450Leu was the most frequent mutation in rpoB gene. Phylogenetic analysis confirmed that Victorian DR-TB were associated with importation events. There was little evidence of local transmission with only five isolate pairs.
CONCLUSION: Isoniazid-resistant TB is the commonest DR-TB in Victoria, and the mutation profile is similar to global circulating DR-TB. Most cases are diagnosed among migrants with limited transmission. This study highlights the value of WGS in identification of clusters and resistance-conferring mutations. This information is crucial in supporting disease mitigation and treatment strategies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 2023 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:138 |
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| Enthalten in: |
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases - 138(2023) vom: 18. Jan., Seite 46-53 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dorji, Thinley [VerfasserIn] |
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| Links: |
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| Themen: |
Antitubercular Agents |
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| Anmerkungen: |
Date Completed 18.12.2023 Date Revised 18.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijid.2023.11.010 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM364592974 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a OBJECTIVES: Whole genome sequencing (WGS) can identify clusters, transmission patterns, and drug resistance mutations. This is important in low-burden settings such as Australia, as it can assist in efficient contact tracing and surveillance | ||
| 520 | |a METHODS: We conducted a retrospective cohort study using WGS from 155 genomically defined drug-resistant Mycobacterium tuberculosis (DR-TB) isolates collected between 2018-2021 in Victoria, Australia. Bioinformatic analysis was performed to identify resistance-conferring mutations, lineages, clusters and understand how local sequences compared with international context | ||
| 520 | |a RESULTS: Of the 155 sequences, 42% were identified as lineage 2 and 35% as lineage 1; 65.8% (102/155) were isoniazid mono-resistant, 8.4% were multi-drug resistant TB and 5.8% were pre-extensively drug-resistant / extensively drug-resistant TB. The most common mutations were observed in katG and fabG1 genes, especially at Ser315Thr and fabG1 -15 C>T for first-line drugs. Ser450Leu was the most frequent mutation in rpoB gene. Phylogenetic analysis confirmed that Victorian DR-TB were associated with importation events. There was little evidence of local transmission with only five isolate pairs | ||
| 520 | |a CONCLUSION: Isoniazid-resistant TB is the commonest DR-TB in Victoria, and the mutation profile is similar to global circulating DR-TB. Most cases are diagnosed among migrants with limited transmission. This study highlights the value of WGS in identification of clusters and resistance-conferring mutations. This information is crucial in supporting disease mitigation and treatment strategies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Australia | |
| 650 | 4 | |a Genomic epidemiology | |
| 650 | 4 | |a MDR-TB | |
| 650 | 4 | |a Multi-drug resistant tuberculosis | |
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| 700 | 1 | |a Horan, Kristy |e verfasserin |4 aut | |
| 700 | 1 | |a Sherry, Norelle L |e verfasserin |4 aut | |
| 700 | 1 | |a Tay, Ee Laine |e verfasserin |4 aut | |
| 700 | 1 | |a Globan, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Viberg, Linda |e verfasserin |4 aut | |
| 700 | 1 | |a Bond, Katherine |e verfasserin |4 aut | |
| 700 | 1 | |a Denholm, Justin T |e verfasserin |4 aut | |
| 700 | 1 | |a Howden, Benjamin P |e verfasserin |4 aut | |
| 700 | 1 | |a Andersson, Patiyan |e verfasserin |4 aut | |
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