WHOLE GENOME SEQUENCING SHEDS LIGHT ON THE TRANSMISSION DYNAMICS OF A MULTIDRUG RESISTANT MYCOBACTERIUM TUBERCULOSIS OUTBREAK OVER 23 YEARS IN A HIGH INCIDENCE SETTING

Introduction. Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem globally, including in Indonesia. Whole-genome sequencing (WGS) analysis has rarely been used for the study of TB and MDR-TB in Indonesia. Aim. We evaluated the use of WGS for drug-susceptibility testing (DST) and to investigate the population structure of drug-resistant Mycobacterium tuberculosis in Java, Indonesia. Methodology. Thirty suspected MDR-TB isolates were subjected to MGIT 960 system (MGIT)-based DST and to WGS. Phylogenetic analysis was done using the WGS data. Results obtained using MGIT-based DST and WGS-based DST were compared. Results. Agreement between WGS and MGIT was 93.33 % for rifampicin, 83.33 % for isoniazid and 76.67 % for streptomycin but only 63.33 % for ethambutol. Moderate WGS–MGIT agreement was found for second-line drugs including amikacin, kanamycin and fluoroquinolone (73.33–76.67 %). MDR-TB was more common in isolates of the East Asian Lineage (63.3%). No evidence of clonal transmission of DR-TB was found among members of the tested population. Conclusion. Our study demonstrated the applicability of WGS for DST and molecular epidemiology of DR-TB in Java, Indonesia. We found no transmission of DR-TB in Indonesia.

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Whole Genome Sequencing Reveals Complex Evolution Patterns of Multidrug-Resistant Mycobacterium tuberculosis Beijing Strains in Patients

PLoS ONE ◽

10.1371/journal.pone.0082551 ◽

2013 ◽

Vol 8 (12) ◽

pp. e82551 ◽

Cited By ~ 81

Author(s):

Matthias Merker ◽

Thomas A. Kohl ◽

Andreas Roetzer ◽

Leona Truebe ◽

Elvira Richter ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Multidrug Resistant ◽

Whole Genome

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Molecular Epidemiology of Mycobacterium tuberculosis To Describe the Transmission Dynamics Among Inuit Residing in Iqaluit Nunavut Using Whole-Genome Sequencing

Clinical Infectious Diseases ◽

10.1093/cid/ciaa420 ◽

2020 ◽

Author(s):

Gonzalo G Alvarez ◽

Alice A Zwerling ◽

Carla Duncan ◽

Christopher Pease ◽

Deborah Van Dyk ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Epidemiological Data ◽

Transmission Dynamics ◽

Homeless Shelter ◽

Whole Genome ◽

Single Nucleotide ◽

Entire Study

Abstract Background In the last decade, tuberculosis (TB) incidence among Inuit in the Canadian Arctic has been rising. Our aim was to better understand the transmission dynamics of TB in this remote region of Canada using whole-genome sequencing. Methods Isolates from patients who had culture-positive pulmonary TB in Iqaluit, Nunavut, between 2009 and 2015 underwent whole-genome sequencing (WGS). The number of transmission events between cases within clusters was calculated using a threshold of a ≤3 single nucleotide polymorphism (SNP) difference between isolates and then combined with detailed epidemiological data using a reproducible novel algorithm. Social network analysis of epidemiological data was used to support the WGS data analysis. Results During the study period, 140 Mycobacterium tuberculosis isolates from 135 cases were sequenced. Four clusters were identified, all from Euro-American lineage. One cluster represented 62% of all cases that were sequenced over the entire study period. In this cluster, 2 large chains of transmission were associated with 3 superspreading events in a homeless shelter. One of the superspreading events was linked to a nonsanctioned gambling house that resulted in further transmission. Shelter to nonshelter transmission was also confirmed. An algorithm developed for the determination of transmission events demonstrated very good reproducibility (κ score .98, 95% confidence interval, .97–1.0). Conclusions Our study suggests that socioeconomic factors, namely residing in a homeless shelter and spending time in a gambling house, combined with the superspreading event effect may have been significant factors explaining the rise in cases in this predominantly Inuit Arctic community.

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Evaluation of a gene-by-gene approach for prospective whole-genome sequencing-based surveillance of multidrug resistant Mycobacterium tuberculosis

Tuberculosis ◽

10.1016/j.tube.2019.02.006 ◽

2019 ◽

Vol 115 ◽

pp. 81-88 ◽

Cited By ~ 2

Author(s):

Rita Macedo ◽

Miguel Pinto ◽

Vítor Borges ◽

Alexandra Nunes ◽

Olena Oliveira ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Multidrug Resistant ◽

Whole Genome

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Transmission of multidrug-resistant Mycobacterium tuberculosis in Shanghai, China: a retrospective observational study using whole-genome sequencing and epidemiological investigation

The Lancet Infectious Diseases ◽

10.1016/s1473-3099(16)30418-2 ◽

2017 ◽

Vol 17 (3) ◽

pp. 275-284 ◽

Cited By ~ 77

Author(s):

Chongguang Yang ◽

Tao Luo ◽

Xin Shen ◽

Jie Wu ◽

Mingyu Gan ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Observational Study ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Multidrug Resistant ◽

Retrospective Observational Study ◽

Whole Genome ◽

Epidemiological Investigation

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Genetic Variation Putatively Associated with Mycobacterium tuberculosis Resistance to Perchlozone, a New Thiosemicarbazone: Clues from Whole Genome Sequencing and Implications for Treatment of Multidrug-Resistant Tuberculosis

Antibiotics ◽

10.3390/antibiotics9100669 ◽

2020 ◽

Vol 9 (10) ◽

pp. 669

Author(s):

Igor Mokrousov ◽

Anna Vyazovaya ◽

Gulnora Akhmedova ◽

Natalia Solovieva ◽

Eugeni Turkin ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Genetic Variation ◽

Whole Genome Sequencing ◽

Treatment Regimen ◽

Genome Sequencing ◽

Multidrug Resistant ◽

Whole Genome ◽

Resistant Tuberculosis ◽

Multidrug Resistant Tuberculosis ◽

Mdr Tb

Perchlozone ([PCZ] 4-thioureido-iminomethylpyridinium perchlorate) is a new thiosemicarbazone approved for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Russia and some other countries. The ethA and hadABC mutations may confer PCZ resistance. At the same time, ethA mutations are known to mediate resistance to ethionamide (ETH) and prothionamide (PTH). We aimed to study the genetic variation underlying Mycobacterium tuberculosis resistance to PCZ through whole genome sequencing (WGS) of consecutive isolates recovered during long-term treatment. This prospective study included patients admitted in 2018–2019 to the regional tuberculosis dispensary, Kaliningrad, Russia, whose treatment regimen included PCZ. Multiple M. tuberculosis isolates were recovered during PCZ treatment, and the bacterial DNA was subjected to WGS followed by bioinformatics analysis. We identified mutations in the genes putatively associated with PCZ resistance, ethA, and hadA. The most frequent one was a frameshift ethA 106 GA > G (seven of nine patients) and most of the other mutations were also likely present before PCZ treatment. In one patient, a frameshift mutation ethA 702 CT > C emerged after six months of PCZ treatment. A frequent presence of cross-resistance mutations to PCZ and ETH/PTH should be taken into consideration when PCZ is included in the treatment regimen of MDR-TB patients.

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