On the onset and dispersal of a major MDR TB clone among HIV-negative patients, Tunisia
Abstract Background To carry out a whole genome sequencing (WGS)-based investigation on the emergence and spread of the largest multidrug-resistant tuberculosis (MDR TB) outbreak that has been thriving among HIV-negative patients, Tunisia, since the early 2000s. Methods We performed phylogeographic...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Antimicrobial Resistance and Infection Control |
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| Online Access: | https://doi.org/10.1186/s13756-023-01360-7 |
| _version_ | 1797273210815774720 |
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| author | Naira Dekhil Helmi Mardassi |
| author_facet | Naira Dekhil Helmi Mardassi |
| author_sort | Naira Dekhil |
| collection | DOAJ |
| description | Abstract Background To carry out a whole genome sequencing (WGS)-based investigation on the emergence and spread of the largest multidrug-resistant tuberculosis (MDR TB) outbreak that has been thriving among HIV-negative patients, Tunisia, since the early 2000s. Methods We performed phylogeographic analyses and molecular dating based on a WGS dataset representing 68 unique Mycobacterium tuberculosis isolates, covering almost the entire MDR TB outbreak for the time period 2001–2016. Results The data indicate that the ancestor of the MDR TB outbreak emerged in the region of Bizerte, as early as 1974 (95% CI 1951–1985), from where it spread to other regions by 1992 (95% CI 1980–1996). Analysis of a minimum spanning tree based on core genome Multilocus Sequence Typing (cgMLST) uncovered the early spill-over of the fitness-compensated MDR TB strain from the prison into the general population. Indeed, cases with history of incarceration were found to be directly or indirectly linked to up to 22 new outbreak cases (32.35%) among the non-imprisoned population. By around 2008, the MDR TB outbreak strain had acquired additional resistance, leading to an XDR phenotype. Conclusions WGS allowed refining our understanding of the emergence and evolution of the largest MDR TB outbreak in Tunisia, whose causative strain has been circulating silently for almost 26 years before. Our study lends further support to the critical role of prisons-related cases in the early spread of the outbreak among the general population. The shift to an XDR phenotype of such an epidemic clone prompts an urgent need to undertake drastic control measures. |
| first_indexed | 2024-03-07T14:41:18Z |
| format | Article |
| id | doaj.art-f598041a02f446cca5e583907ed07b54 |
| institution | Directory Open Access Journal |
| issn | 2047-2994 |
| language | English |
| last_indexed | 2024-03-07T14:41:18Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Antimicrobial Resistance and Infection Control |
| spelling | doaj.art-f598041a02f446cca5e583907ed07b542024-03-05T20:24:01ZengBMCAntimicrobial Resistance and Infection Control2047-29942024-02-011311810.1186/s13756-023-01360-7On the onset and dispersal of a major MDR TB clone among HIV-negative patients, TunisiaNaira Dekhil0Helmi Mardassi1Unit of Typing and Genetics of Mycobacteria, Laboratory of Molecular Microbiology, Vaccinology, and Biotechnology Development, Pasteur Institute, Tunis, University of Tunis El ManarUnit of Typing and Genetics of Mycobacteria, Laboratory of Molecular Microbiology, Vaccinology, and Biotechnology Development, Pasteur Institute, Tunis, University of Tunis El ManarAbstract Background To carry out a whole genome sequencing (WGS)-based investigation on the emergence and spread of the largest multidrug-resistant tuberculosis (MDR TB) outbreak that has been thriving among HIV-negative patients, Tunisia, since the early 2000s. Methods We performed phylogeographic analyses and molecular dating based on a WGS dataset representing 68 unique Mycobacterium tuberculosis isolates, covering almost the entire MDR TB outbreak for the time period 2001–2016. Results The data indicate that the ancestor of the MDR TB outbreak emerged in the region of Bizerte, as early as 1974 (95% CI 1951–1985), from where it spread to other regions by 1992 (95% CI 1980–1996). Analysis of a minimum spanning tree based on core genome Multilocus Sequence Typing (cgMLST) uncovered the early spill-over of the fitness-compensated MDR TB strain from the prison into the general population. Indeed, cases with history of incarceration were found to be directly or indirectly linked to up to 22 new outbreak cases (32.35%) among the non-imprisoned population. By around 2008, the MDR TB outbreak strain had acquired additional resistance, leading to an XDR phenotype. Conclusions WGS allowed refining our understanding of the emergence and evolution of the largest MDR TB outbreak in Tunisia, whose causative strain has been circulating silently for almost 26 years before. Our study lends further support to the critical role of prisons-related cases in the early spread of the outbreak among the general population. The shift to an XDR phenotype of such an epidemic clone prompts an urgent need to undertake drastic control measures.https://doi.org/10.1186/s13756-023-01360-7Mycobacterium tuberculosisMDR/XDR TBOutbreakXDR phenotypeIncarcerationWhole genome sequencing |
| spellingShingle | Naira Dekhil Helmi Mardassi On the onset and dispersal of a major MDR TB clone among HIV-negative patients, Tunisia Antimicrobial Resistance and Infection Control Mycobacterium tuberculosis MDR/XDR TB Outbreak XDR phenotype Incarceration Whole genome sequencing |
| title | On the onset and dispersal of a major MDR TB clone among HIV-negative patients, Tunisia |
| title_full | On the onset and dispersal of a major MDR TB clone among HIV-negative patients, Tunisia |
| title_fullStr | On the onset and dispersal of a major MDR TB clone among HIV-negative patients, Tunisia |
| title_full_unstemmed | On the onset and dispersal of a major MDR TB clone among HIV-negative patients, Tunisia |
| title_short | On the onset and dispersal of a major MDR TB clone among HIV-negative patients, Tunisia |
| title_sort | on the onset and dispersal of a major mdr tb clone among hiv negative patients tunisia |
| topic | Mycobacterium tuberculosis MDR/XDR TB Outbreak XDR phenotype Incarceration Whole genome sequencing |
| url | https://doi.org/10.1186/s13756-023-01360-7 |
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