Evolution and emergence of multidrug-resistant <i>Mycobacterium tuberculosis</i> in Chisinau, Moldova

Brown, Tyler S.; Eldholm, Vegard; Brynildsrud, Ola Brønstad; Osnes, Magnus N; Stennis, Natalie; Stimson, James A.; Colijn, Caroline; Alexandru, Sofia; Noroc, Ecaterina; Ciobanu, Nelly; Crudu, Valeriu; Cohen, Ted; Mathema, Barun

doi:10.1101/2021.02.04.21251152

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…Disponibilitatea tot mai mare a metodelor de secvențiere, împreună cu dezvoltarea abordărilor analitice pentru integrarea datelor genomice, spațiale și epidemiologice de înaltă rezoluție, a transformat capacitatea noastră de a descrie transmiterea agenților patogeni în populații (11,12,13,14). Studiile genomice anterioare ale M. tuberculosis din aceste regiuni au descris apariția și evoluția unor linii specifice responsabile pentru o proporție exagerată de TB MDR în aceste țări (15,16,17,18).…”

Section: Introducereunclassified

Geographical analysis and evaluation of M. tuberculosis genome sequencing at the national level

Crudu¹,

Codreanu²,

Alexandru³

et al. 2023

BulMed

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Tuberculosis, one of the ancient infections that especially affects humans, the main target organ of this disease being the lung, is caused by M. tuberculosis and remains one of the most important public health problems, especially in developing countries. The emergence of multidrug-resistant and extensively drug-resistant tuberculosis is considered a serious threat to tuberculosis control worldwide. The burden of drug-resistant tuberculosis remains increasing in countries endemic for this infection. The risk factors that influence this situation and that are elucidated more frequently in the specialized literature are the abusive use of drugs, the failure of the therapeutic regimen, the relapse of tuberculosis, the difficulty of obtaining drug sensitivity testing in a fast time. In Moldova, but also in other regions of Eastern Europe, drug resistance represents a serious obstacle in the effective control of this disease. There is evidence that the transmission of resistant strains, as opposed to the acquisition of resistance mutations through inadequate treatment of drug-susceptible tuberculosis, is the main driver of the high level of multidrug-resistant and extensively drug-resistant tuberculosis in these countries.

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Section: Introducereunclassified

Geographical analysis and evaluation of M. tuberculosis genome sequencing at the national level

Crudu¹,

Codreanu²,

Alexandru³

et al. 2023

BulMed

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“…Various combination therapy is available to treat TB [6]. However, there is an emergence of multidrug-resistant TB (MDR-TB) [7]. Presently, the MDR-TB has a cumulative incidence rate globally.…”

Section: Introductionmentioning

confidence: 99%

Genetic diversity assessment of the Mycobacterium tuberculosis isolates of patients with tuberculosis in Karaj, Iran

Farnad

Momtaz

Mosavari

et al. 2021

Preprint

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Background Tuberculosis (TB) is an old issue that is presently measured as a significant challenge. Molecular characterization of Mycobacterium tuberculosis has contributed to TB control. The present survey was aimed to assess the genetic diversity of M. tuberculosis strains isolated from patients with TB in Karaj, Iran. Methods Seventeen M. tuberculosis isolates from 2012 to 2013 were collected and subjected to an IS6110 restriction fragment length polymorphism (IS6110-RFLP) analysis. Demographically, 6 females and 14 males who had Iranian citizenship were included in this study. Results Sixteen different genetic types were obtained after enzymatic digestion and RFL analysis. Copy numbers of IS6110 in each isolate ranged from 0 to 12. The majority of isolates (66%) harbored copy numbers between 6 and 12. Each isolates harbored 6.9 copies of the IS6110 marker. Nine isolates harbored 10 to 12 copies of the IS6110 marker, 5 isolates harbored 6 to 10 copies, and 2 others harbored copies less than 6. No copy of IS6110 was found among the 4 isolates. No relationship was found between gender and copy numbers. Conclusions The high genetic diversity found amongst the M. tuberculosis isolates maybe show different sources of infection and the importance of reemerging of the TB. However, further surveys should perform to assess other molecular epidemiologic aspects of M. tuberculosis in Iran.

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Phylogeography and transmission of M. tuberculosis in Moldova

Yang

Sobkowiak

Naidu

et al. 2021

Preprint

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Background The incidence of multidrug-resistant tuberculosis (MDR-TB) remains critically high in countries of the former Soviet Union, where >20% of new cases and >50% of previously-treated cases have resistance to rifampin and isoniazid. Transmission of resistant strains, as opposed to resistance selected through inadequate treatment of drug-susceptible TB, is the main driver of incident MDR-TB in these countries. Methods We conducted a prospective, genomic analysis of all culture-positive TB cases diagnosed in 2018 and 2019 in the Republic of Moldova. We used phylogenetic methods to identify putative transmission clusters; spatial and demographic data were analyzed to further describe local transmission of M. tuberculosis. Results Of 2236 participants, 779 (36%) had MDR-TB, of whom 386 (50%) had never been treated previously for TB. 92% of MDR M. tuberculosis strains belonged to putative transmission clusters. Phylogenetic reconstruction identified three large clades that were comprised nearly uniformly of MDR-TB; two of these clades were of Beijing lineage and one of Ural lineage, and each had additional distinct clade-specific second-line drug resistance mutations and geographic distributions. Spatial and temporal proximity between pairs of cases within a cluster was associated with greater genomic similarity. Conclusions The MDR-TB epidemic in Moldova is the result of local transmission of multiple M. tuberculosis strains, including distinct clades of highly drug-resistant M. tuberculosis with varying geographic distributions and drug resistance profiles. This study demonstrates the role of comprehensive genomic surveillance for understanding the transmission of M. tuberculosis and highlights the urgency of interventions to interrupt transmission of highly drug-resistant M. tuberculosis.

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Evolution and emergence of multidrug-resistant Mycobacterium tuberculosis in Chisinau, Moldova

Cited by 3 publications

References 21 publications

Geographical analysis and evaluation of M. tuberculosis genome sequencing at the national level

Geographical analysis and evaluation of M. tuberculosis genome sequencing at the national level

Genetic diversity assessment of the Mycobacterium tuberculosis isolates of patients with tuberculosis in Karaj, Iran

Phylogeography and transmission of M. tuberculosis in Moldova

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