Trends in molecular epidemiology of drug-resistant tuberculosis in Republic of Karelia, Russian Federation

Abstract

BackgroundRussian 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.MethodsThe 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.ResultsThe 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.ConclusionsCirculation 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 20th century.

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…43 Furthermore, since full DST profiling and individualised therapy are rarely done, strains with second-line resistance often continue to transmit. Consequently, drug-resistant strains can circulate and persist for decades, as has been shown in Argentina, 99 South Africa, 84 eastern Europe, 82,103 and Portugal. 67 However, our knowledge of the global extent of such The Lancet Respiratory Medicine Commission drug-resistant tuberculosis strains is limited to countries in which culture and molecular strain typing has been done.…”

“…49,82,[99][100][101] In most regions of the world, drug-resistant tuberculosis is now predominantly caused by transmission rather than acquisition of resistance, with an estimated 95·9% of MDR tuberculosis in new tuberculosis cases and 61·3% in previously treated cases being due to transmission. 42 Even the epidemiology of XDR tuberculosis-defined as resistance to isoniazid, rifampicin, a fluoroquinolone, and an injectable agent-is now better understood as reflecting endemics rather than epidemics, 48,95,102,103 and population migration is recognised as a vehicle for spread beyond the region of the strain's origin. Indeed, molecular epidemiological studies have documented the spread of drug-resistant strains within countries, between countries, and even across con tinents (figure 3).…”

“…Red=Beijing strain. 103,104,[105][106][107][108][109][110][111][112] Green=LAM9 strain. 113 Light blue=Haarlem1 strain.…”

Characterization of Mycobacterium Tuberculosis Strains (A 15-Year Survey in Leningrad Region, Russia)

“…у ранее леченных больных ту-беркулезом легких [1]. При этом ранее доказана клиническая значимость и преимущественно эпидемический путь распространения МЛУ штаммов M. tuberculosis генотипа Beijing на тер-ритории России [2,4,6,12,15]. Штаммы дан-ного генотипа характеризует наличие, по мень-шей мере, трех спейсеров 35-43 и отсутствие 1-34 спейсеров в профиле сполиготипирова-ния (табл.…”

Next-Generation Sequencing ofMycobacterium tuberculosis

“…Spoligotype international type (SIT) 266 (Figure, panel A) is an epidemiologically significant genotype. It constitutes a substantial proportion of the population structure of M. tuberculosis in Belarus, a post-Soviet state in Eastern Europe ( 1 , 2 ), and has been described sporadically in the neighboring provinces in northwestern and central Russia ( 2 – 5 ) and in Latvia ( 6 ). More important, it is multidrug resistant (MDR) (and most likely extensively drug resistant).…”