МИКРОЭВОЛЮЦИЯ ВОЗБУДИТЕЛЯ ХОЛЕРЫ В СОВРЕМЕННЫЙ ПЕРИОД

Aim: To carry out comparative molecular genetic analysis of highly pathogenic atypical Vibrio cholerae strains biovar El Tor, isolated in the territory of RF, in order to determine micro-evolutionary alterations of cholera agent in the modern period. Materials and methods: 38 clinical strains have been examined by means of polymerase chain reaction, sequencing and MLVA-analysis. The selected strains were isolated at different periods of time during cholera epidemic complications and differed between each other in virulence. Results: It is demonstrated that new variants have emerged in the course of short-term microevolution. Their genome structure and function differ from those of all previously known strains. The genome alterations have been caused by point mutations in ctxB и tcpA genes associated with virulence and located in CTXφ prophage and pathogenicity island VPI-1 respectively, as well as by the extended deletion in pandemicity island VSP-II. Presented is the dynamics of genome structure and function alterations in modern strains. Conclusion: The discovered genomic alterations in the new variants of the agent evolved in the process of microevolution are indicative of their epidemic potential enhancement and probability of virulence potentiation.Цель исследования: провести сравнительный молекулярно-генетический анализ высокопатогенных атипичных штаммов Vibrio cholerae биовара Эль-Тор, выделенных на территории Российской Федерации, для выявления микроэволюционных изменений возбудителя холеры в современный период. Материалы и методы: исследовали 38 клинических штаммов методами полимеразной цепной реакции, секвенирования и MLVA-анализа. Выбранные штаммы были выделены в разные временные периоды эпидемических осложнений по холере и различались между собой уровнем вирулентности. Рeзультаты: показано, что в ходе непродолжительной микроэволюции возникли новые варианты, структура и функция генома которых отличается от всех известных ранее штаммов. Изменения генома были обусловлены точковыми мутациями в генах ctxB и tcpA, связанных с вирулентностью и входящих в состав профага CTXφ и острова патогенности VPI-1, соответственно, а также протяженной делецией острова пандемичности VSP-II. Представлена динамика изменений структуры и функции генома современных штаммов. Выводы: установленные геномные изменения у новых вариантов возбудителя, возникшие в процессе микроэволюции, указывают на возможность усиления их вирулентности и повышение эпидемического потенциала

КОНЦЕПТУАЛЬНЫЕ ОСНОВЫ БИОЛОГИЧЕСКОЙ БЕЗОПАСНОСТИ. ЧАСТЬ I

Up to date there is a narrow and broad interpretation of the term biological safety (BS) the world over. In the narrow sense it is defined as availability of international regulations applied to diagnostic, manufacturing, or experimental works with pathogenic biological agents (PBA) in accordance with specified levels of biological hazard and BS. In a broader context it has no national, conceptual, terminological or defying basis. Therewith, establishment of this framework has become the core issue of the study. Investigations have revealed that BS should conceptually cover the whole sphere of sanitary-and-epidemiological welfare as well as related fields such as veterinary-sanitary, phytosanitary provision, ecological safety, environmental conditions (occupational, socio-economic and geopolitical infrastructures, ecological system), and be exercised to prevent and control emergency situations (ES) of biological character. It is demonstrated that this type of ES differs from ES in the sphere of public health care of international concern which is formalized in IHR (2005), in the way that it is characterized by high socio-economic and geopolitical significance of the negative influence on human vital activities, comparable with national and international security hazard. Elaborated is the conceptual, terminological and defying toolkit of the BS broad interpretation (27 terms). В современном представлении мирового сообщества существует узкая и широкая трактовка биологической безопасности. Смысл узкого понимания определяется наличием международных требований при работе (диагностической, производственной, экспериментальной) с патогенными биологическими агентами в соответствии с регламентированными уровнями биологической опасности и безопасности. Широкая трактовка биологической безопасности не имеет концептуальной, понятийной, терминологической и определительной основы. Создание концептуальной основы данного понятия и является целью настоящей работы. По результатам исследований установлено, что концептуально биологическая безопасность охватывает всю сферу санитарно-эпидемиологического благополучия, смежные с ней области ветеринарно-санитарного, фитосанитарного обеспечения, экологической безопасности, среду обитания (производственную, социально-экономическую, геополитическую инфраструктуру, экологическую систему) и осуществляется в целях предупреждения и ликвидации чрезвычайных ситуаций биологического характера. Показано, что отличием данной чрезвычайной ситуации от таковой в области общественного здравоохранения, имеющей международное значение, определенной в Международных медико-санитарных правилах (ММСП, 2005), является, как правило, высокая социально-экономическая и геополитическая значимость негативного влияния на жизнедеятельность человека, сопоставимая с угрозой национальной и международной безопасности. Разработанные концептуальные основы биологической безопасности требуют правового (законодательного), нормативного (подзаконного), методического закрепления на территории Российской Федерации, создания соответствующей терминологической базы

АКТУАЛЬНЫЕ ПРОБЛЕМЫ БИОЛОГИЧЕСКОЙ БЕЗОПАСНОСТИ В СОВРЕМЕННЫХ УСЛОВИЯХ. ЧАСТЬ 2. ПОНЯТИЙНАЯ, ТЕРМИНОЛОГИЧЕСКАЯ И ОПРЕДЕЛИТЕЛЬНАЯ БАЗА БИОЛОГИЧЕСКОЙ БЕЗОПАСНОСТИ

In accordance with the established conceptual base for the up-to-date broad interpretation of biological safety, and IHR (2005), developed is the notional, terminological, and definitive framework, comprising 33 elements. Key item of the nomenclature is the biological safety that is identified as population safety (individual, social, national) from direct and (or) human environment mediated (occupational, socio-economic, geopolitical infrastructures, ecological system) exposures to hazardous biological factors. Ultimate objective of the biological safety provision is to prevent and liquidate aftermaths of emergency situations of biological character either of natural or human origin (anthropogenic) arising from direct and indirect impact of the biological threats to the public health compatible with national and international security hazard. Elaborated terminological framework allows for the construction of self-sufficient semantic content for biological safety provision, subject to formalization in legislative, normative and methodological respects and indicative of improvement as regards organizational and structural-functional groundwork of the Russian Federation National chemical and biological safety system, which is to become topical issue of Part 3. (Авторы: Г.Г. Онищенко, В.Ю. Смоленский, Е.Б. Ежлова, Ю.В. Демина, В.П. Топорков, А.В. Топорков, М.Н. Ляпин, В.В. Кутырев)В соответствии с разработанной концептуальной основой современного (широкого) формата биологической безопасности (см. часть 1) и требованиями Международных медико-санитарных правил 2005 г. создана ее понятийная, терминологическая и определительная база, включающая 33 наименования. Ключевым понятием является биологическая безопасность, определяемая как состояние защищенности населения (личности, общества, государства) от прямого и/или опосредованного через среду обитания (производственная, социально-экономическая, геополитическая сфера, экологическая система) воздействия опасных биологических факторов. Конечной целью обеспечения биологической безопасности являются предупреждение и ликвидация последствий чрезвычайных ситуаций биологического характера естественного и искусственного (антропогенного) происхождения, возникающих при прямом и опосредованном воздействии опасных биологических факторов на здоровье населения в масштабе, соизмеримом с угрозой национальной и международной безопасности. Разработанный понятийный аппарат позволяет создать самостоятельное смысловое поле обеспечения биологической безопасности населения, подлежащее закреплению в правовом (законодательном), нормативном (подзаконном) и методическом отношении и позволяющее усовершенствовать организационные и структурно-функциональные основы Национальной системы химической и биологической безопасности Российской Федерации, что будет рассмотрено в Части 3

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Epidemiological features of new coronavirus infection (COVID-19). Communication 1: Modes of implementation of preventive and anti-epidemic measures

The review analyses the information on the epidemiological situation on COVID-19 around the world. Presented is the assessment of the major epidemiological parameters (basic reproductive rate, lethality, incubation period, and serial interval). Demonstrated is the share of severe cases among different age groups and the general structure of incidence by the severity of clinical course. The paper provides the classification of response models internationally depending upon the complex of measures undertaken at different stages of epidemic process. Reviewed are the key response actions to control the COVID-19 transmission in different countries of the world and the Russian Federation and given is the assessment of their effectiveness. © 2020 Russian Research Anti-Plague Institute. All rights reserved

Epidemiological Peculiarities of New Coronavirus Infection (COVID-2019). Communication 2: Peculiarities of epidemic process development in conjunction with performed anti-epidemic measures around the world and in the Russian Federation

The review presents the analysis of the data on the spread of COVID-19 around the world and in Russia available as of June 15, 2020. Dynamics and geographical dissemination of COVID-19 in the Russian Federation is considered. The structure of incidence by gender and age is presented. Assessment of the key epidemiological parameters (morbidity rates and lethality) is provided. The effectiveness of the response measures conducted to control COVID-19 is discussed. © 2020 Russian Research Anti-Plague Institute. All rights reserved

Phylogeny and classification of Yersinia pestis through the lens of strains from the Plague Foci of commonwealth of independent states

The established phylogeny of the etiological agent of plague, Yersinia pestis, is not perfect, as it does not take into account the strains from numerous natural foci of Commonwealth of Independent States (CIS). We have carried out PCR and SNP typing of 359 strains and whole genome sequencing of 51 strains from these plague foci and determined the phylogenetic diversity of the strains circulating here. They belong to 0.ANT3, 0.ANT5, 2.ANT3, 4.ANT branches of antique biovar, 2.MED0, 2.MED1 branches of medieval biovar and to 0.PE2, 0.PE4a. 0.PE4h, 0.PE4t branches. Based on the studies of 178 strains from 23 plague foci of CIS countries, it was determined that the population structure of 2.MED strains is subdivided into Caucasian-Caspian and Central Asian-Chinese branches. In Central-Caucasian high-mountain plague foci in the Russian Federation (RF) the most deeply diverged branch of medieval biovar, 2.MED0, has been found. With the data obtained, the current population structure of Y. pestis species has been refined. New subspecies classification is developed, comprising seven subspecies: pestis, caucasica (0.PE2), angolica (0.PE3), central asiatica (0.PE4), tibetica (0.PE7), ulegeica (0.PE5), and qinghaica (0.PE10). © 2018 Kutyrev, Eroshenko, Motin, Nosov, Krasnov, Kukleva, Nikiforov, Al'khova, Oglodin and Guseva

Comparative Analysis of <i>inv</i> Gene Structure in Strains of Plague and Pseudotuberculosis Agents

Gene inv encoding one of the important pathogenicity factors of pseudotuberculosis agent was analyzed as regards its structure and function in plague microbe of the main and non-main subspecies and pseudotuberculosis microbe. The structure of gene inv was shown to be affected by introduction of insertion sequence IS1541 in all studied Yersinia pestis strains of non-main and main subspecies. This evidences that the loss of functional activity of this gene took place at initial stage of plague agent evolution

Pathogenesis Interrelation of Insufficiency of Erythrocytes Antiradical Protection and Disturbance of Blood Rheological Properties in Bacterial Endotoxicosis

Among the leading pathogenesis factors of disorders of regional blood flow and microcirculation in plague intoxication induced by Y. pestis lipopolysaccharide (LPS) are decreases of blood viscosity at various shift rates, indices of erythrocyte deformation and aggregation that correlate with severity of clinical manifestation. Efferent part of LPS cytopathogenic effects of plague microbe is enhancement of free-radical oxidation and formation of anti-oxidative system deficiency