title: Trends in molecular epidemiology of drug-resistant tuberculosis in Republic of Karelia, Russian Federation.
abstract: BACKGROUND
  Russian Republic of Karelia is located at the Russian-Finnish border. It contains most of the historical Karelia land inhabited with autochthonous Karels and more recently migrated Russians. Although tuberculosis (TB) incidence in Karelia is decreasing, it remains high (45.8/100 000 in 2014) with the rate of multi-drug resistance (MDR) among newly diagnosed TB patients reaching 46.5 %. The study aimed to genetically characterize Mycobacterium tuberculosis isolates obtained at different time points from TB patients from Karelia to gain insight into the phylogeographic specificity of the circulating genotypes and to assess trends in evolution of drug resistant subpopulations.
  
  
  METHODS
  The sample included 150 M. tuberculosis isolates: 78 isolated in 2013-2014 ("new" collection) and 72 isolated in 2006 ("old" collection). Drug susceptibility testing was done by the method of absolute concentrations. Spoligotyping was used to test genotype-specific markers of a Latin-American-Mediterranean (LAM) family and its sublineages as well as a Beijing B0/W148-cluster.
  
  
  RESULTS
  The largest spoligotypes were SIT1 (Beijing family, n = 42) and SIT40 (T family, n = 5). Beijing family was the largest (n = 43) followed by T (n = 11), Ural (n = 10) and LAM (n = 8). Successful Russian clone, Beijing В0/W148, was identified in 15 (34.9 %) of 43 Beijing isolates; all В0/W148 isolates were drug-resistant. Seven of 8 LAM isolates belonged to the RD115/LAM-RUS branch, 1 - to the LAM RD174/RD-Rio sublineage. MDR was found in Beijing (32/43), Ural (3/10), and LAM (3/8). In contrast, all T isolates were pansusceptible. Comparison of drug resistant subgroups of the new and old collections showed an increasing prevalence of the B0/W148 clonal cluster, from 18.0 % (mainly polyresistant) in 2006 to 32.6 % in 2014 (mainly MDR and pre-XDR). The West-east increasing gradient is observed for the Ural genotype that may be defined a 'Russian' strain. In contrast, the spoligotype SIT40 of the T family appears to be a historical Karelian strain.
  
  
  CONCLUSIONS
  Circulation of the MDR M. tuberculosis isolates of the Beijing genotype and its B0/W148 cluster continues to critically influence the current situation with the MDR-TB control in northwestern Russia including the Republic of Karelia. Revealed phylogeographic patterns of some genotypes reflect a complex demographic history of Karelia within the course of the 20(th) century.
authors.affiliation: Laboratory of Molecular Microbiology, St. Petersburg Pasteur Institute, 14 Mira street, St. Petersburg, 197101, Russia. imokrousov@mail.ru.
authors.forename: Igor
authors.initials: I
authors.lastname: Mokrousov
authors.affiliation: Laboratory of Molecular Microbiology, St. Petersburg Pasteur Institute, 14 Mira street, St. Petersburg, 197101, Russia. elmtree2001@mail.ru.
authors.forename: Anna
authors.initials: A
authors.lastname: Vyazovaya
authors.affiliation: Laboratory of Etiological Diagnostics, Research Institute of Phthisiopulmonology, St. Petersburg, Russia. baclab@spbniif.ru.
authors.forename: Natalia
authors.initials: N
authors.lastname: Solovieva
authors.affiliation: Republican Tuberculosis Dispensary, Petrozavodsk, Republic of Karelia, Russia. sun-tatjana@mail.ru.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Sunchalina
authors.affiliation: Petrozavodsk State University, Petrozavodsk, Republic of Karelia, Russia. markelov@psu.karelia.ru.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Markelov
authors.affiliation: Laboratory of Etiological Diagnostics, Research Institute of Phthisiopulmonology, St. Petersburg, Russia. echernya@gmail.com.|Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg, Russia. echernya@gmail.com.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Chernyaeva
authors.affiliation: Laboratory of Etiological Diagnostics, Research Institute of Phthisiopulmonology, St. Petersburg, Russia. melnikovanatalii@mail.ru.
authors.forename: Natalia
authors.initials: N
authors.lastname: Melnikova
authors.affiliation: Laboratory of Etiological Diagnostics, Research Institute of Phthisiopulmonology, St. Petersburg, Russia. marine-md@mail.ru.
authors.forename: Marine
authors.initials: M
authors.lastname: Dogonadze
authors.affiliation: Laboratory of Molecular Microbiology, St. Petersburg Pasteur Institute, 14 Mira street, St. Petersburg, 197101, Russia. dariastarkova13@gmail.com.
authors.forename: Daria
authors.initials: D
authors.lastname: Starkova
authors.affiliation: Laboratory of Etiological Diagnostics, Research Institute of Phthisiopulmonology, St. Petersburg, Russia. sagievanr@gmail.com.
authors.forename: Neliya
authors.initials: N
authors.lastname: Vasilieva
authors.affiliation: Laboratory of Molecular Microbiology, St. Petersburg Pasteur Institute, 14 Mira street, St. Petersburg, 197101, Russia. kantarelle@mail.ru.
authors.forename: Alena
authors.initials: A
authors.lastname: Gerasimova
authors.affiliation: Republican Tuberculosis Dispensary, Petrozavodsk, Republic of Karelia, Russia. tub@onego.ru.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Kononenko
authors.affiliation: Laboratory of Etiological Diagnostics, Research Institute of Phthisiopulmonology, St. Petersburg, Russia. jouravlev-slava@mail.ru.
authors.forename: Viacheslav
authors.initials: V
authors.lastname: Zhuravlev
authors.affiliation: Laboratory of Molecular Microbiology, St. Petersburg Pasteur Institute, 14 Mira street, St. Petersburg, 197101, Russia. onarvskaya@gmail.com.|Laboratory of Etiological Diagnostics, Research Institute of Phthisiopulmonology, St. Petersburg, Russia. onarvskaya@gmail.com.
authors.forename: Olga
authors.initials: O
authors.lastname: Narvskaya
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000494:pharmacology*; D004269:DNA, Bacterial / Q000032:analysis; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D058974:Phylogeography; D012426:Russia / Q000453:epidemiology; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology* / Q000382:microbiology*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D004269:DNA, Bacterial