ArticleBMC infectious diseases2020
A retrospective genomic analysis of drug-resistant strains of M. tuberculosis in a high-burden setting, with an emphasis on comparative diagnostics and reactivation and reinfection status.
Article in BMC infectious diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Methods for Detecting Mycobacterial Mixed Strain Infections-A Systematic Review.Frontiers in genetics · 2020Pooled it
- Multidrug-Resistant Tuberculosis in Central and Eastern Europe: Implementation and Maturity of Whole-Genome Sequencing for Surveillance.Diseases (Basel, Switzerland) · 2026Review
- Host-intrinsic and host-extrinsic factors modulate immunity to Mtb infection, reinfection, and noncanonical vaccination routes.Cell reports. Medicine · 2025Review
- The recent rapid expansion of multidrug resistant Ural lineage Mycobacterium tuberculosis in Moldova.Nature communications · 2024Article
- Unraveling tuberculosis patient cluster transmission chains: integrating WGS-based network with clinical and epidemiological insights.Frontiers in public health · 2024Article
- CD4bioRxiv : the preprint server for biology · 2023Article
- Strain structure analysis of Mycobacterium tuberculosis circulating among HIV negative, positive and drug resistant TB patients attending chest clinics in Western Kenya.BMC pulmonary medicine · 2023Article
- Advantages of analysing both pairwise SNV-distance and differing SNVs betweenMicrobial genomics · 2023Article
- Combining Radiological and Genomic TB Portals Data for Drug Resistance Analysis.IEEE access : practical innovations, open solutions · 2023Article
- Patterns of genomic interrelatedness of publicly available samples in the TB portals database.Tuberculosis (Edinburgh, Scotland) · 2022Article
- Phylogeography and transmission of M. tuberculosis in Moldova: A prospective genomic analysis.PLoS medicine · 2022Article
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Authors and funding
11 authors.
Funding
Abstract
backgroundRecurrence of drug-resistant tuberculosis (DR-TB) after treatment occurs through relapse of the initial infection or reinfection by a new drug-resistant strain. Outbreaks of DR-TB in high burden regions present unique challenges in determining recurrence status for effective disease management and treatment. In the Republic of Moldova the burden of DR-TB is exceptionally high, with many cases presenting as recurrent.
methodsWe performed a retrospective analysis of Mycobacterium tuberculosis from Moldova to better understand the genomic basis of drug resistance and its effect on the determination of recurrence status in a high DR-burden environment. To do this we analyzed genomes from 278 isolates collected from 189 patients, including 87 patients with longitudinal samples. These pathogen genomes were sequenced using Illumina technology, and SNP panels were generated for each sample for use in phylogenetic and network analysis. Discordance between genomic resistance profiles and clinical drug-resistance test results was examined in detail to assess the possibility of mixed infection.
resultsThere were clusters of multiple patients with 10 or fewer differences among DR-TB samples, which is evidence of person-to-person transmission of DR-TB. Analysis of longitudinally collected isolates revealed that many infections exhibited little change over time, though 35 patients demonstrated reinfection by divergent (number of differences > 10) lineages. Additionally, several same-lineage sample pairs were found to be more divergent than expected for a relapsed infection. Network analysis of the H3/4.2.1 clade found very close relationships among 61 of these samples, making differentiation of reactivation and reinfection difficult. There was discordance between genomic profile and clinical drug sensitivity test results in twelve samples, and four of these had low level (but not statistically significant) variation at DR SNPs suggesting low-level mixed infections.
conclusionsWhole-genome sequencing provided a detailed view of the genealogical structure of the DR-TB epidemic in Moldova, showing that reinfection may be more prevalent than currently recognized. We also found increased evidence of mixed infection, which could be more robustly characterized with deeper levels of genomic sequencing.
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