Microevolution of extensively drug-resistant tuberculosis in Russia.

Extensively drug-resistant (XDR) tuberculosis (TB), which is resistant to both first- and second-line antibiotics, is an escalating problem, particularly in the Russian Federation. Molecular fingerprinting of 2348 Mycobacterium tuberculosis isolates collected in Samara Oblast, Russia, revealed that 72%belonged to the Beijing lineage, a genotype associated with enhanced acquisition of drug resistance and increased virulence. Whole-genome sequencing of 34 Samaran isolates, plus 25 isolates representing global M. tuberculosis complex diversity, revealed that Beijing isolates originating in Eastern Europe formed a monophyletic group. Homoplasic polymorphisms within this clade were almost invariably associated with antibiotic resistance, indicating that the evolution of this population is primarily driven by drug therapy. Resistance genotypes showed a strong correlation with drug susceptibility phenotypes. A novel homoplasic mutation in rpoC, found only in isolates carrying a common rpoB rifampicin-resistance mutation, may play a role in fitness compensation. Most multidrug-resistant (MDR) isolates also had mutations in the promoter of a virulence gene, eis, which increase its expression and confer kanamycin resistance. Kanamycin therapy may thus select for mutants with increased virulence, helping preserve bacterial fitness and promoting transmission of drug-resistant TB strains. The East European clade was dominated by two MDR clusters, each disseminated across Samara. Polymorphisms conferring fluoroquinolone resistance were independently acquired multiple times within each cluster, indicating that XDR TB is currently not widely transmitted. © 2012 by Cold Spring Harbor Laboratory Press

COMPLEX PROCESSING OF CELLULOSE WASTE FROM POULTRY AND SUGAR PRODUCTION

Summary.To solve the problem of disposing of huge volumes of cellulose waste from sugar production in the form of beet pulp and waste of poultry farms in the form of poultry manure is proposed to use the joint use of two methods of thermal processing of waste - pyrolysis and gasification. The possibility of using pyrolysis applied to the waste are confirmed by experimental results. Based on the results of laboratory studies of the properties of by-products resulting from the thermal processing of the feedstock, it is proposed complex processing to produce useful products, to be implemented in the form of marketable products, and the organization's own process energy utilization. Developed flow diagram of an integrated processing said waste comprises 3 sections, which successively carried out: pyrolytic decomposition of the feedstock to obtain a secondary product in the form of solid, liquid and gas fractions, the gasification of solids to obtain combustible gas and separating the liquid fraction by distillation to obtain valuable products. The main equipment in the first region is the pyrolysis reactor cascade condensers; the second section - gasifiers layers and stream type; the third - one or more distillation columns with the necessary strapping. Proper power supply installation is organized by the use of the heat produced during combustion of the synthesis gas for heating and gasification reactor. For the developed scheme presents calculations of the heat balance of the installation, supporting the energy efficiency of the proposed disposal process. Developments carried out in the framework of the project the winner of the Youth Prize Competition Government of Voronezh region to support youth programs in the 2014-2015

Rapid diagnostics of tuberculosis and drug resistance in the industrialized world: clinical and public health benefits and barriers to implementation

In this article, we give an overview of new technologies for the diagnosis of tuberculosis (TB) and drug resistance, consider their advantages over existing methodologies, broad issues of cost, cost-effectiveness and programmatic implementation, and their clinical as well as public health impact, focusing on the industrialized world. Molecular nucleic-acid amplification diagnostic systems have high specificity for TB diagnosis (and rifampicin resistance) but sensitivity for TB detection is more variable. Nevertheless, it is possible to diagnose TB and rifampicin resistance within a day and commercial automated systems make this possible with minimal training. Although studies are limited, these systems appear to be cost-effective. Most of these tools are of value clinically and for public health use. For example, whole genome sequencing of Mycobacterium tuberculosis offers a powerful new approach to the identification of drug resistance and to map transmission at a community and population level

Evolution and transmission of drug-resistant tuberculosis in a Russian population

The molecular mechanisms determining the transmissibility and prevalence of drug-resistant tuberculosis in a population were investigated through whole-genome sequencing of 1,000 prospectively obtained patient isolates from Russia. Two-thirds belonged to the Beijing lineage, which was dominated by two homogeneous clades. Multidrug-resistant (MDR) genotypes were found in 48% of isolates overall and in 87% of the major clades. The most common rpoB mutation was associated with fitness-compensatory mutations in rpoA or rpoC, and a new intragenic compensatory substitution was identified. The proportion of MDR cases with extensively drug-resistant (XDR) tuberculosis was 16% overall, with 65% of MDR isolates harboring eis mutations, selected by kanamycin therapy, which may drive the expansion of strains with enhanced virulence. The combination of drug resistance and compensatory mutations displayed by the major clades confers clinical resistance without compromising fitness and transmissibility, showing that, in addition to weaknesses in the tuberculosis control program, biological factors drive the persistence and spread of MDR and XDR tuberculosis in Russia and beyond

INVASIVE ASPERGILLOSIS AND MUCORMYCOSIS IN ONCOHEMATOLOGICAL PATIENTS

In the retrospective multicenter study during 2007–2017 we included 59 oncohematological patients with mucormycosis and 541 patients with invasive aspergillosis. Our study showed that mucomorhycosis more often developed in children and adolescents (p = 0.001), and after «graft versus host» disease development (p = 0.0001). Patients with mucormycosis were more immunosuppressed: severe neutropenia was in 88 % vs. 82 %, median duration of neutropenia ‒ 30 days vs. 14 days, p = 0.0001, lymphocytopenia – 77 % vs. 65 %, median duration of lymphocytopenia – 25 days vs. 14 days, p = 0.001. The main sites of infection were lungs, nevertheless in patients with mucormycosis it was less frequent (73 % vs. 97 %, p = 0.02), but more frequent were ≥2 organs involvement (42 % vs. 8 %, p = 0.001) and paranasal sinuses involvement (15 % vs. 6 %, p = 0.04). Typical clinical features of mucomorhycosis were localized pain syndrome (53 % vs. 5 %, p = 0.0001), hemoptysis (32 % vs. 6 %, p = 0.001), on lung computed tomography scan – pleural effusion (53 % vs. 7 %, p = 0.003), lesions with destruction (38 % vs. 8 %, p = 0.0001) and “a reverse halo” symptom (17 % vs. 3 %). The overall 12-week survival was significantly lower in patients with mucormycosis (49 % vs. 81 %, p = 0.0001). In both groups unfavorable prognosis factors were: ≥2 organs involvement (p = 0.0009) and concomitant bacterial or viral infection (p = 0.001 and p = 0.008 respectively). In mucormycosis patients favorable prognosis factor was remission of underlying disease (p = 0.006), in invasive aspergillosis patients – early bronchoscopy (p = 0.003), voriconazole use (p = 0.0007) and secondary antifungal prophylaxis (p = 0.0001)