Genomic analyses of Mycobacterium tuberculosis from human lung resections reveal a high frequency of polyclonal infections

Polyclonal infections occur when at least two unrelated strains of the same pathogen are detected in an individual. This has been linked to worse clinical outcomes in tuberculosis, as undetected strains with different antibiotic resistance profiles can lead to treatment failure. Here, we examine the amount of polyclonal infections in sputum and surgical resections from patients with tuberculosis in the country of Georgia. For this purpose, we sequence and analyse the genomes of Mycobacterium tuberculosis isolated from the samples, acquired through an observational clinical study (NCT02715271). Access to the lung enhanced the detection of multiple strains (40% of surgery cases) as opposed to just using a sputum sample (0-5% in the general population). We show that polyclonal infections often involve genetically distant strains and can be associated with reversion of the patient's drug susceptibility profile over time. In addition, we find different patterns of genetic diversity within lesions and across patients, including mutational signatures known to be associated with oxidative damage; this suggests that reactive oxygen species may be acting as a selective pressure in the granuloma environment. Our results support the idea that the magnitude of polyclonal infections in high-burden tuberculosis settings is underestimated when only testing sputum samples

Об эпизоотической ситуации по основным гельминтозам крупного рогатого скота в Грузии при разных системах содержания

The purpose of the research is studying the epizootic situation on major helminthoses in cattle under different management systems in Georgia.Materials and methods. The epizootic situation in Georgia on major helminthoses in cattle subject to management systems and the altitudinal zonation of areas location was studied by coprological examination of animals. In 2014–2018, the cattle aged over 2 years held on pasture from March-April until November was studied in homesteads of 59 districts. Similar studies were performed at 19 farms owned by limited liability companies, homesteads and entrepreneurs. The livestock there is presented by Schwyz and Holstein; all processes of care, feeding and milking are mechanized.Results and discussion. Currently, the major helminthoses in pasture cattle in Georgia are paramphistomidosis, fasciolosis, dicrocoeliosis, gastrointestinal strongylatosis and dictyocaulosis which infect 67.5% of the examined cattle. Paramphistomidosis and fasciolosis are found in 59.7 and 21.5% of the examined cattle respectively. With increasing elevation of the altitudinal zonation, the paramphistomidosis and fasciolosis prevalence rates reduce. In case of paramphistomidosis, the infection ranges from 78.4% (low elevation from 0 to 200 m above sea level) to 23.9% (the subalpine area from 1901 to 2300 m above sea level), and in case of fasciolosis, 28.2–8.1% respectively. The rest species of helminths infected cattle to a lesser degree. Dicrocoelium sp. was found in 2.7% of animals, gastrointestinal Strongylata in 6.3%, and Dictyocaulus sp. in 3.9%. Paramphistomum spp., Fasciola sp. and gastrointestinal Strongylata infected 1.2% of the examined cattle in the farms with stabled cattle.Цель исследований: изучение эпизоотической ситуации по основным гельминтозам крупного рогатого скота в Грузии при разных системах содержания.Материалы и методы. Эпизоотическую ситуацию по основным гельминтозам крупного рогатого скота в Грузии с учетом систем содержания, а также вертикальной зональности расположения районов изучали путем копрологического исследования животных. В 2014–2018 гг. в приусадебных хозяйствах 59 районов обследовали скот в возрасте старше двух лет, содержащийся с марта–апреля по ноябрь на пастбище. Аналогичные исследования провели на 19 фермах, принадлежащих обществам ограниченной ответственности, фермерским хояйствам и частным предпринимателям. В них поголовье скота укомплектовано швицкой и голштинской породами; все процессы ухода, кормления и доения животных механизированы.Результаты и обсуждение. В настоящее время, в Грузии в условиях пастбищного содержания основными гельминтозами у крупного рогатого скота являются парамфистомидозы, фасциолез, дикроцелиоз, кишечные стронгилятозы и диктиокаулез, которыми инвазированы 67,5% обследованного скота. Парамфистомидозы и фасциолез зарегистрированы соответственно у 59,7 и 21,5% обследованного скота. С нарастанием вертикальной зональности показатели экстенсивности инвазии парамфистомидами и фасциолами уменьшаются. При парамфистомидозах зараженность варьирует в пределах от 78,4% (низменная зона – от 0 до 200 м над уровнем моря) до 23,9% (субальпийская зона – от 1901 до 2300 м над уровнем моря), при фасциолезе соответственно в пределах 28,2–8,1%. Остальными видами гельминтов скот инвазирован в меньшей степени. Дикроцелии выявлены у 2,7% животных, кишечные стронгилята – у 6,3%, диктиокаулюсы – у 3,9%. В хозяйствах, в которых крупный рогатый скот содержат в стойловых условиях, парамфистомидами, фасциолами и кишечными стронгилятами инвазированы 1,2% обследованного скота

Physics of B_c mesons

In the framework of potential models for heavy quarkonium the mass spectrum for the system ($\bar b c$) is considered. Spin-dependent splittings, taking into account a change of a constant for effective coulomb interaction between the quarks, and widths of radiative transitions between the ($\bar b c$) levels are calculated. In the framework of QCD sum rules, masses of the lightest vector $B_c^*$ and pseudoscalar $B_c$ states are estimated, scaling relation for leptonic constants of heavy quarkonia is derived, and the leptonic constant $f_{B_c}$ is evaluated. The $B_c$ decays are considered in the framework of both the potential models and the QCD sum rules, where the significance of Coulomb-like corrections is shown. The relations, following from the approximate spin symmetry for the heavy quarks in the heavy quarkonium, are analysed for the form factors of the semileptonic weak exclusive decays of $B_c$. The $B_c$ lifetime is evaluated with the account of the corrections to the spectator mechanism of the decay, because of the quark binding into the meson. The total and differential cross sections of the $B_c$ production in different interactions are calculated. The analytic expressions for the fragmentational production cross sections of $B_c$ are derived. The possibility of the practical $B_c$ search in the current and future experiments at electron-positron and hadron colliders is analysed.Comment: 81 page, latex, ihep.sty is required and attached in the end of the file after \end{document}, figures are not availabl

Rifapentine access in Europe: growing concerns over key tuberculosis treatment component

[No abstract available]Support statement: C. Lange is supported by the German Center of Infection Research (DZIF). All other authors have no funding to declare for this study. Funding information for this article has been deposited with the Crossref Funder Registry

About the Epizootic Situation on Major Helminthoses of Cattle Under Different Management Systems in Georgia

The purpose of the research is studying the epizootic situation on major helminthoses in cattle under different management systems in Georgia.Materials and methods. The epizootic situation in Georgia on major helminthoses in cattle subject to management systems and the altitudinal zonation of areas location was studied by coprological examination of animals. In 2014–2018, the cattle aged over 2 years held on pasture from March-April until November was studied in homesteads of 59 districts. Similar studies were performed at 19 farms owned by limited liability companies, homesteads and entrepreneurs. The livestock there is presented by Schwyz and Holstein; all processes of care, feeding and milking are mechanized.Results and discussion. Currently, the major helminthoses in pasture cattle in Georgia are paramphistomidosis, fasciolosis, dicrocoeliosis, gastrointestinal strongylatosis and dictyocaulosis which infect 67.5% of the examined cattle. Paramphistomidosis and fasciolosis are found in 59.7 and 21.5% of the examined cattle respectively. With increasing elevation of the altitudinal zonation, the paramphistomidosis and fasciolosis prevalence rates reduce. In case of paramphistomidosis, the infection ranges from 78.4% (low elevation from 0 to 200 m above sea level) to 23.9% (the subalpine area from 1901 to 2300 m above sea level), and in case of fasciolosis, 28.2–8.1% respectively. The rest species of helminths infected cattle to a lesser degree. Dicrocoelium sp. was found in 2.7% of animals, gastrointestinal Strongylata in 6.3%, and Dictyocaulus sp. in 3.9%. Paramphistomum spp., Fasciola sp. and gastrointestinal Strongylata infected 1.2% of the examined cattle in the farms with stabled cattle

Dynamics of TB mixed infections through space and time

Abstract de la comunicación oral presentada al Scientific Meeting on Mycobacteria. MycoPORTO 2019 Porto (Portugal), 19-20 de septiembre de 2019Pág. 25 del libro de abstracts que se adjunta. Mixed infections happen when at least two unrelated strains of the same pathogen can be detected in an individual. This has been linked to worse clinical outcomes in tuberculosis infections, as undetected strains presenting different antibiotic resistance profiles can lead to treatment failure. Here, we present a study of the extent of mixed infections in Georgia, a high-burden setting in which up to 11% of new TB cases are MDR/RR-TB. We obtained NGS data from cultures derived from surgery and sputum samples from 20 patients. Combined with a customized bioinformatics pipeline we enhanced the detection of multiple strains as opposed to just using a clinical sputum sample, identifying an unprecedented number of mixed infection cases of up to 40% of the patients analyzed. We also characterized transmission using 358 clinical samples and detected transmission clusters, several of which contained a sample from our surgery patients¿ dataset, allowing us to trace the history of several mixed infections. Our results suggest that the magnitude of mixed infections in highburden settings is likely to be underestimated when only using sputum samples and they can be behind discrepancies between DST and WGS predictions if not properly assessed