Beijing Lineage of MDR<i>Mycobacterium tuberculosis</i>in Bulgaria, 2007–2011

Panaiotov, Stefan; Bachiyska, Elizabeta; Yordanova, Stanislava; Atanasova, Yuliana; Brankova, Nadia; Levterova, Victoria; Sengstake, Sarah; Anthony, Richard; Bergval, Indra; Sola, Christophe; Kantardjiev, Todor

doi:10.3201/eid2011.140468

Cited by 5 publications

(4 citation statements)

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“…This may be expected given the overwhelming dominance of the Beijing family strain in most regions in China [ 19 , 20 ]. Consistent with previous reports [ 21 – 23 ], the results of genotyping indicate that Beijing family of strains is also overrepresented in this population. While different from the previous study [ 22 ], the member within Beijing family exhibit the close-relatedness with similarity more than 80 % and the 11 clones were identified with the majority clone comprised by 90 Mtb isolates, which all belong to Beijing genotype.…”

Section: Discussionsupporting

confidence: 92%

Drug resistance characteristics and cluster analysis of M. tuberculosis in Chinese patients with multiple episodes of anti-tuberculosis treatment

Zhao

Werngren

et al. 2015

BMC Infect Dis

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BackgroundTuberculosis (TB) patients with multiple episodes of anti-TB treatment represent an important source of TB transmission, as well as a serious threat to the control of drug resistant TB, due to the high risk of multidrug and extensively drug resistance (MDR/XDR) and elongating infectiousness of this patient group. In this study we analyzed the possible risk of development and transmission of MDR and XDR in TB patients with multiple episodes of previous treatment history.MethodsThe study subjects were pulmonary TB patients who had at least two episodes of previous anti-TB treatment. A total of 166 eligible patients were identified from 10 counties/districts distributed in east, west, north, south and central China. Drug susceptibility test (DST) was performed by proportion method on LJ-media for the 1st line anti-TB drugs and a line probe assay was used to detect mutations related to resistance of the key 2nd-line drugs. Genotyping of M. tuberculosis (Mtb) was performed with MIRU-VNTR and Spoligotyping.ResultsResistances to 1st-line drugs was observed in 122 (73.5 %) of the 166 Mtb isolates with 97 (58.4 %) being MDR-TB. Mutations relevant to 2nd-line drug resistance was seen in 63 isolates, including 35 MDR-TB isolates (30 pre-XDR, 5 XDR-TB). The Spoligotyping revealed 83.1 % Mtb isolates belonged to the Beijing family. The MIRU-VNTR based genotyping revealed 32 (19.3 %) of patients were infected with more than one strain. The number of previous TB treatment episode was found being significantly associated with the risk of MDR-TB and XDR-TB. Among the remaining 134 patients infected with a single Mtb strain, MIRU-VNTR revealed a high homogeneity of strain especially within Beijing family despite the polymorphic variations along with geographic locations.ConclusionsThe high genetic relatedness and risk of MDR-TB and subsequent pre-XDR and XDR-TB among repeatedly treated patients suggest the establishment of M/XDR Mtb in this specific patient population. It highlights the urgent needs of providing DST of both 1st- and 2nd-line drugs before and during the medication in China’s MDR-TB control program. Furthermore, the possibility of infection with multiple strains should also be considered to be associated with the drug resistance, which calls for the modification of treatment regimen.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-1331-z) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Drug resistance characteristics and cluster analysis of M. tuberculosis in Chinese patients with multiple episodes of anti-tuberculosis treatment

Zhao

Werngren

et al. 2015

BMC Infect Dis

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“…Although the Beijing lineage keeps the second position of distribution in EU/EEA (about 30% of the sequenced strains) in Bulgaria, it represents only 3% amongst the MDR-TB cases. [3] The trend of scarce spreading remains steady with the years (3.2% for the period of 2007-2011) [12] and could be explained with the small numbers of imported TB cases in the country.…”

Section: Discussionmentioning

confidence: 99%

Whole genome sequencing of Bulgarian rifampicin resistant Mycobacterium tuberculosis strains

Yordanova¹,

Bachiyska²,

Tagliani³

et al. 2022

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Introduction: The transmission of drug-resistant tuberculosis is one of the greatest challenges facing the global tuberculosis control. Aim: The aim of the study was to investigate the resent transmission of rifampicin resistant tuberculosis in Bulgaria and to describe the mutations related to the antimicrobials’ resistance using whole genome sequencing. Materials and methods: As part of an ECDC funded pilot study for evaluation of the systematic use of whole genome sequencing (WGS) of Mycobacterium tuberculosis (MTB) surveillance (EUSeqMyTB), Bulgaria provided 65 rifampicin resistant isolates over a three years’ timeframe (2017-2019) representing 87.5% of the notified rifampicin resistant cases. Drug resistance prediction and relatedness analysis of the resistant isolates was performed in collaboration with San Raffaele Scientific Institute, Milan, Italy. Results: Almost all of the isolates were identified as Euro-American lineage (96.9%); 18.5% of the isolates were found to be resistant to fluoroquinolones, but no mutations conferring resistance to bedaquiline or linezolid could be identified. Less than half (43.3%) of the isolates were clustered (<5 SNPs distance) into a total of seven national SNP-based clusters, while a total of six isolates were found to be part of different cross-border clusters. All clustered cases originated from Bulgaria. Conclusions: WGS has proven to be a reliable tool for surveillance and tracing of recent transmission of tuberculosis and has the potential for resistance prediction for most of the antituberculosis drugs.

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“…In the Beijing sublineage, 70% were MDR with a probability odds ratio of 2.6. Our previous study demonstrated that the first imported TB case in Bulgaria was from Moldova in 2007-2009 [65]. Not all detected cases of TB caused by the Beijing genotype resulted from human migration.…”

Section: Resultsmentioning

confidence: 99%

Biodiversity of Mycobacterium tuberculosis in Bulgaria Related to Human Migrations or Ecological Adaptation

2022

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Bulgaria is among the 18 high-priority countries of the WHO European Region with high rates of tuberculosis. The causative agent of tuberculosis is thought to have emerged in Africa 70,000 years ago, or during the Neolithic age, and colonized the world through human migrations. The established main lineages of tuberculosis correlate highly with geography. The goal of our study was to investigate the biodiversity of Mycobacterium tuberculosis in Bulgaria in association with human migration history during the last 10 centuries. We analyzed spoligotypes and MIRU-VNTR genotyping data of 655 drug-sensitive and 385 multidrug-resistant M. tuberculosis strains collected in Bulgaria from 2008 to 2018. We assigned the genotype of all isolates using SITVITWEB and MIRU-VNTRplus databases and software. We investigated the major well-documented historical events of immigration to Bulgaria that occurred during the last millennium. Genetic profiles demonstrated that, with the exceptions of 3 strains of Mycobacterium bovis and 18 strains of Lineage 2 (W/Beijing spoligotype), only Lineage 4 (Euro-American) was widely diffused in Bulgaria. Analysis of well-documented immigrations of Roma from the Indian subcontinent during the 10th to the 12th centuries, Turkic peoples from Central Asia in the medieval centuries, and more recently Armenians, Russians, and Africans in the 20th century influenced the biodiversity of M. tuberculosis in Bulgaria but only with genotypes of sublineages within the L4. We hypothesize that these sublineages were more virulent, or that ecological adaptation of imported M. tuberculosis genotypes was the main driver contributing to the current genetic biodiversity of M. tuberculosis in Bulgaria. We also hypothesize that some yet unknown local environmental factors may have been decisive in the success of imported genotypes. The ecological factors leading to local genetic biodiversity in M. tuberculosis are multifactorial and have not yet been fully clarified. The coevolution of long-lasting pathogen hosts should be studied, taking into account environmental and ecological changes.

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Beijing Lineage of MDRMycobacterium tuberculosisin Bulgaria, 2007–2011

Cited by 5 publications

References 10 publications

Drug resistance characteristics and cluster analysis of M. tuberculosis in Chinese patients with multiple episodes of anti-tuberculosis treatment

Drug resistance characteristics and cluster analysis of M. tuberculosis in Chinese patients with multiple episodes of anti-tuberculosis treatment

Whole genome sequencing of Bulgarian rifampicin resistant Mycobacterium tuberculosis strains

Biodiversity of Mycobacterium tuberculosis in Bulgaria Related to Human Migrations or Ecological Adaptation

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