This study reviews the epidemiology of thyroid cancer during childhood from the environs of Gomel in Belarus and the clinical data of 64 children aged 4 to 16 years from this area who had been diagnosed with differentiated thyroid carcinoma following the nuclear accident of Chernobyl. One case of thyroid cancer in children (aged < 15 years at diagnosis) was observed during the period 1981-1985 (rate = 0.5; expressed as annual averages per million children under age 15 years in the region of Gomel and period identified) before the Chernobyl accident. Twenty-one cases of thyroid cancer in children were observed during 1986-1990 (rate = 10.5) and 143 (rate 97) during 1991-1994 after the Chernobyl accident. During the first 7 months of 1995, there were 33 more cases of thyroid cancer observed in children. Three children with thyroid cancer were born since 1986 in the Gomel region. A total of 64 children aged 4 to 16 years from this area who had been diagnosed with differentiated thyroid carcinoma had been reviewed by us during the period May to November 1994. The female/male ratio was 1.4:1.0. At the time of the first diagnosis the mean age of the children was 9.4 +/- 2.8 years, and at the time of the accident their mean age was 3.8 +/- 2.4 years. More than 90% of the patients were less than 6 years of age and 3 were still in utero at the time of the accident. The period of latency between the accident and the first diagnosis was 5.6 +/- 1.5 years. Their ages at the time of the first diagnosis and their ages at the time of the accident were significantly correlated (p = 0.001); there was no significant correlation between the age of each child at the time of the accident and the latent period before the onset of carcinoma. The aggressiveness of the tumor, evaluated on the basis of T stage, lymph node status, and lung metastases, did not correlate with age at the time of the first diagnosis or with the age at the time of the accident. The susceptibility of the thyroid to the carcinogenetic effects of radiation, particularly during the first years of life (< 5 years) has clearly been demonstrated. However, there appears to be no correlation between the aggressiveness of the tumor and the age of the patients.

Extrapulmonary and, in particular, spinal tuberculosis (TB) constitutes a minor but significant part of the total TB incidence. In spite of this, almost no studies on the genetic diversity and drug resistance of Mycobacterium tuberculosis isolates from spinal TB patients have been published to date. Here, we report results of the first Russian and globally largest molecular study of M. tuberculosis isolates recovered from patients with tuberculous spondylitis (TBS). The majority of 107 isolates were assigned to the Beijing genotype (n ‫؍‬ 80); the other main families were T (n ‫؍‬ 11), Ural (n ‫؍‬ 7), and LAM (n ‫؍‬ 4). Multidrug resistance (MDR) was more frequently found among Beijing (90.5%) and, intriguingly, Ural (71.4%) isolates than other genotypes (5%; P < 0.001). The extremely drug-resistant (XDR) phenotype was exclusively found in the Beijing isolates (n ‫؍‬ 7). A notable prevalence of the rpoB531 and katG315 mutations in Beijing strains that were similarly high in both TBS (this study) and published pulmonary TB ( Extrapulmonary tuberculosis (EPTB) remains a major health problem due to a significantly high rate of morbidity and mortality in both developing and developed countries and constitutes a significant part of the total TB incidence (1, 2). In Russia, the rate of EPTB decreased from 9.4% in 1992 to 3.4% in 2011, and the EPTB incidence constituted 2.4/100,000 in 2011 (3, 4). At the same time, the rate of tuberculous spondylitis (TBS) among all new EPTB cases increased in Russia from 23% in 2006 to 33% in 2010, which is higher than TB rate for of all other sites of the disease (3, 5).Tuberculous spondylitis constitutes about half of bone and joint TB cases and thus represents the most severe orthopedic disease, frequently leading to irreversible neurological disorders and disability and constituting a serious social and economic problem (6-8). TBS is developed as a result of blood-born dissemination of Mycobacterium tuberculosis. Bacteriological diagnosis of bone and joint TB is a most challenging task, and findings of drug resistance in these isolates may be crucial for adequate management of such cases. Delayed initial diagnosis and confirmation (from 3 months to 10 years after onset of the disease) and the increasing incidence of the multidrug-resistant TBS with spondyloarthropathy in adults require improvement of the etiological diagnostics, taking into account biological and molecular properties of the pathogen (4, 6, 7).M. tuberculosis has a clonal population structure, and it has been demonstrated that not only its large genetic families but also their variants or subgenotypes may play a special role in the disease progression. Russian strain Beijing B0/W148, initially defined by IS6110-restriction fragment length polymorphism (RFLP) analysis (9), presents a remarkable example of a successful clone highly associated with multidrug resistance (MDR) (10). Correlating different typing schemes, 24-locus mycobacterial interspersed repetitive unit-variable-number tandem-repeat (MIRU-VNTR) type 1...

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M ycobacterium tuberculosis isolates of the Beijing 94-32 cluster (also named the Central Asian/Russian Beijing strain) constitute an important component of the population structure of the pathogen in the countries of the Former Soviet Union (1-4). A variable-number tandem-repeat (VNTR)-based analysis suggested that this genotype could speculatively trace its origins to the northwestern regions of China (5). Beijing 94-32 is the largest type within the VNTR-defined CC1 group (6) and falls within the East Europe 1 group as defined by whole-genome sequencing (WGS) (7). Our analysis of all CC1 isolates compiled in the work of Merker et al. (6) demonstrated that type 94-32 presents the largest node in the central position in the phylogenetic network (see Fig. S1 in the supplemental material), and we therefore suggest naming this clonal complex the Beijing 94-32 cluster. The 94-32 cluster isolates were associated with multidrug-resistant/extremely drug-resistant tuberculosis in Russia (8) and in Uzbekistan (termed the Central Asia outbreak strain [2]), and in immigrants in Western Europe (9, 10). This justifies the interest in having a simple tool to rapidly detect this clinically and epidemiologically relevant strain. In this study, DNA of 19 Russian M. tuberculosis isolates of the Beijing genotype was subjected to WGS on the MiSeq platform (Illumina). The next-generation sequencing (NGS) data were deposited in the NCBI Sequence Read Archive (project number PRJNA305488). The fastq and vcf files were subjected to comprehensive bioinformatics

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.