Project title: Risk of Emerging Infections from Insectivorous Bats in Ukraine and Georgia

Project title: Risk of Emerging Infections from Insectivorous Bats in Ukraine and Georgia

Introduction and review

Epidemics of emerging infectious diseases are on the rise. The novel coronavirus strain SARS-CoV-2 (preliminary originated from bat) has resulted in pandemic, the biggest quarantine in human history, the global interruption of all traffic, the international political instability, and the variation in the global economy. Clearly, predicting disease emergence is of critical interest but capacities to anticipate where and when diseases will emerge are limited.

Bats are the hosts of a wide range of emerging zoonotic viral and bacterial pathogens. Bats have unique biology and may play a role in maintenance and transmission of infectious agents to other vertebrates. The significance of bats harboring emerging pathogens that may potentially affect humans in Ukraine and Georgia has been scarcely investigated to date. The project’s objectives are to assess the role of bats as a natural reservoir for pathogens of relevance to human and animal health in Ukraine and Georgia, to investigate factors could influence the assemblage of pathogens in bat populations and how these overall changes can drive to disease emergence in humans and domestic animals; to build capacity to create a sustainable surveillance system (active studies of bats in Ukraine haven’t been conducted) that may help to detect, prevent and predict disease emergence in the region. The project will focus to detect and determine the geographic range of viral (coronaviruses, filoviruses, paramyxoviruses, orthomyxoviruses, lyssaviruses), and bacterial (Brucella spp, Leptospira spp, Yersinia spp) agents circulating in bat populations, as well as determine their evolutionary relationships with pathogens of known relevance for human and animal health and its linkage with different environmental factors. These studies will not only allow the identification of pathogens, assessing the role of bats as the source of zoonotic diseases in Ukraine and Georgia, but also will contribute significantly in the improvement of disease surveillance systems in wildlife.

This project has the potential to advance our understanding on how species assemblages modify host-parasite interactions and how urbanization influences the dilution or amplification effects between biodiversity change and disease emergence as well as data driven risk assessment; Expected findings are of interest for the fields of ecology and evolution of infectious bacterial and viral diseases, early warning systems, and global health; This project is expected to generate data to elucidate the efficacy (or lack thereof) of biodiversity conservation at the local level (e. g., around human settlements) to reduce the burden of infectious diseases.

Creation of a research network for the surveillance and early detection of known and potential high-consequence pathogens for humans and domestic animals in East Europe; Advance Georgia and Ukraine capacity to assess virulence of viral agents found in bats by assessing the evolutionary relationships of novel virus with known high-consequence pathogens; Develop ecological models for the prediction of high-consequence pathogens in unexplored regions of Georgia and Ukraine and neighboring countries based on landscape configuration.

Results obtained will also contribute to the development and implementation of emergency response and preparedness plans in a future. Capacity building will focus on training local scientists in safe and effective techniques for bat capture, sampling, and biosafety measure in the field and in the laboratory. Our project will establish a self-sustainable platform in the both countries for basic pathogen discovery in wildlife using modern laboratory screening technologies while complying with international biosafety requirements.

What is the goal of the project?

The main objectives for this project are: Detect high consequence viral (coronaviruses, filoviruses, paramyxoviruses, lyssaviruses and bunyaviruses, orthomixoviruses) and bacterial (Brucella spp, Leptospira spp and Yersinia spp) agents in bat populations in Ukraine and Georgia; Investigate how landscape biodiversity change (pristine, rural, urbanized settings) could influence the assemblage of high consequence viral and bacterial agents in bat populations and how these overall changes can drive to disease emergence in humans and domestic animals. Tracing the evolutionary relationships between bat borne agents and their known close pathogenic relatives causing disease in humans and animals are also central for this project; Build a sustainable harmonized surveillance network for the early detection, full genomic characterization, data storage and analysis of high consequence viral and bacterial agents associated with bat populations in Ukraine and Georgia, with a long-term vision to expand this working.

What is the problem?

Biodiversity is essential for ecosystem functioning; the globally accelerated biodiversity loss due to urbanization and agriculture will likely create unexpected species assemblages and interactions at different biodiversity scales (macro and microbiota) (Johnson, 2017). Emerging infectious diseases have been linked with biodiversity changes, where most recent epidemics have had a confirmed wildlife origin (Johnson CN, 2017). Nevertheless, the exact point where biodiversity change drive to the emergence of pathogens that affect humans and animals remains unclear (Rohr 2020). The biodiversity-disease relationship has been under intense scrutiny in the field of ecology and evolution during the last decade (Rohr 2020, Randolph 2012, Wood 2013, Lafferty 2013, Wood 2013).

Overwhelming evidence links the emergence of high-consequence pathogens with bat communities and human settlements. Examples include Filoviruses (e. g., Marburg, Ebola viruses) (Leroy 2005, Olival 2014, Towner 2009, 2007, Yang 2017), Lyssaviruses (e. g., rabies, European Bat Lyssavirus 2) (Arai 2003, Aznar-Lopez 2013, Harris 2006, Kuzmin 2006), Paramyxoviruses (e. g., Nipah, Hendra) (Baker 2013, Chua 2002), Coronaviruses (e. g., SARS-CoV, SARS-CoV-2, MERS) (Annan 2013, Li 2005, Memish 2013), Bunyaviruses (CCHF-like viruses) (Mü ller 2016), and Orthomyxoviruses (2 new subtypes: Н17N10 and Н18N11) (Tong, 2013). Strikingly, there is limited comprehensive knowledge of the evolutionary and ecological relationships of these pathogens with the composition of bat species or the levels of habitat degradation.

Additionally, available information is biased towards data generated during epidemics, neglecting the understanding of pathogen circulation and characterization before outbreaks. This reactive instead of preventive approach prevents the understanding of the factors that modify pathogen circulation in the original wildlife reservoir.

The striking abundance and diversity of bat coronaviruses and their close similarity to those found in pandemic respiratory syndromes affecting humans and animals worldwide, corroborate the critical role bats may play as the origin for the global dissemination of high consequence infections. Likewise, more evidence accounting for the extraordinary taxonomical breadth of bat viruses reveals, at least, 248 novel viruses belonging to 24 virus families identified in different parts of the world during the period of 1991-2016 (Young 2016, Mü hldorfer 2011). In addition, several bat-borne high-consequence pathogens found across Europe, Africa, and East Asia also unveil long evolutionary relationships perhaps associated with long-term global disseminations. As an additional example of the global spread of bat viruses, relatives of filoviruses originally thought to be circumscribed to Africa have been discovered in bats in China (Yang 2017). Paramyxovirus, Orthomyxovirus, and Bunyavirus have been also found in bats from different countries around world, suggesting unnoticed and widespread risk of emerging diseases to humans (Conrardy 2014, Mü ller 2016).

What other people do?

Rhinolophidae and Vespertilionidae bat families have been most frequently found infected with high-consequence pathogens and their relatives (Ostfeld 2017, Civitello 2015, Yang 2017). Western Europe is a nucleus of diversity for these bat families. For example, there are between 28 and 30 species of Rhinolophidae and Vespertilionidae bats in Georgia and Ukraine alone, both countries sharing around 80% of the total number of bat species reported (Zagorodniuk 2017, Gorlov 2016). Our recent studies in Georgia revealed circulation of a large diversity of bat-borne pathogens (Bai, 2017), including a striking diversity of SARS- and MERS-like coronaviruses [Urushadze L, Velasco-Villa A. et al. in prep. ]. In the same region, Ukraine reported stable bat-borne pathogen circulation (Klueva 1991, Selimov 1991, Sonntag 2009), and detection of novel viruses, potentially zoonotic, from the Circoviridae family (genus Cyclovirus) [Kemenesi, 2017]. The location of Georgia and Ukraine between Europe and Asia, and the outstanding dispersal of bats (800-1600 km, linked to migration and dispersal after perturbation), make these countries a natural corridor for pathogen exchange and an ideal region to study host-parasite evolution and the biodiversity-disease relationship using high-consequence pathogens in bats as model system.

You are going to do?

Scientific project tasks: Assess the taxonomical diversity of potentially endemic viral (coronaviruses, filoviruses, paramyxoviruses, lyssaviruses and bunyaviruses, orthomixoviruses) and bacterial (Brucella spp, Leptospira spp and Yersinia spp) agents associated with bats living in pristine and urban settings in Ukraine and Georgia (Year 1-3); Investigate the evolutionary relationships between these agents and those known to cause disease in humans and domestic animals using comparative genomics approaches (Year 1-3); Monitor potential seasonal variations in positivity rates, relative composition or overall diversity shifts for bats and their associated bacterial and viral agents (Year 1-3); Assess potential associations between environmental variables and the bacterial/viral agent diversity in Georgia and Ukraine to model risk and disease emergence (or cryptic circulation), by using ecological niche modeling approaches (Year 1-3); Determine the linkages between landscape structure and bat species diversity (Year 2-3); Identify the effect of bat community composition on the occurrence of high-consequence pathogens. (Year 2-3).

Non-scientific project tasks: Foster a sustainable exchange of technology and scientific expertise among institutions from all participating countries to create a solid regional research network; Nurture a culture of biosecurity and biosecurity to improve field and laboratory work with high consequence agents in the region; Improve local capacity for the investigation, early detection of high consequence viral and bacterial agents based on high throughput harmonized standard operating procedures from CDC; Creation a self-sustainable passive surveillance disease network in sick or dead bats across Ukraine and Georgia to complement field studies; Develop local capabilities for the storage, management and analysis of complex genomic data, data interpretation.

What is new?

New information about present or absent of EDPs in bat in Ukraine and Georgia; Standardization and regulation of research methods for EDPs in Ukraine; Spatial representation of the distribution of the studied infections and their causative agents in the defined areas in Ukraine and Georgia; Presentation and publishing new results; State authorities’ (Ukrainian State Veterinary Service, Ukrainian Ministry of Healthcare, Ministry of Environment and Natural Resources Protection of Georgian National Food Agency) notification regarding the results of research will be organized due to the framework of the project; Practical recommendations for improvement of ecological and epidemiological surveillance of bat diseases will be developed based on results obtained by all participants within the project and will be presented to Ukrainian and Georgian governments; The cooperation and joint scientific work between various scientific and diagnostic institutions in Ukraine, Georgia and USA.

Who are you?

National Scientific Center Institute of Experimental and Clinical Veterinary Medicine (NSC IECVM, Ukraine). Leading scientific institution of animal health in Ukraine, coordinates scientific research in dangerous pathogens in Ukraine. The NSC IECVM meets all Ukrainian State Sanitary BS& S rules (DSP 9. 9. 5. 035-99) for working with especial dangerous pathogens (EDPs). NSC IECVM meets Ukrainian State Sanitary permission (No. 47-12, dated 6 April 2012) for working with EDPs. NSC IECVM has accreditation ISO 17025 (№241327, 14. 08. 2017). The NSC IECVM has successfully undertaken several international scientific projects concerning animal diseases, including highly pathogenic avian influenza and Newcastle disease viruses (e. g., STCU projects P-382 and P-382a Immunity concerning AI (2009-2013) USDA funds; P-444, P-444a, P-444b Wildlife epidemiology of HPAI and Newcastle disease (2010-2015) USDA funds, and P-568 Newcastle disease recombinant vaccines (2013-2016) DTRA funds; chlamydial infections in ruminants in Ukraine 2015-2017, Swiss National Science Foundation; two projects UP-4 and UP-10 in frame Ukraine Cooperative Biological Engagement Program (2016-2019). Laboratories have appropriate biosafety and biosecurity level (control access, video-surveillance, negative pressure air ventilation systems, PACS) and are equipped with PCR, DNA-RNA purification and preparation kits, electrophoresis (PAAG, AG), RRT PCR by BSC class 2, low-temperature chambers (refrigerators and freezers), equipment for ELISA, refrigerated centrifuge, water baths, autoclaves, drying chambers, equipment for serological studies, computers. The Commission for Bioethics and Animal Treatment has oversight of all projects involving animals or animal experimentation across the institute.

National Center for Disease Control and Public Health; Richard G. Lugar Center for Public Health Research (NCDC, Georgia) provides national leadership in preventing and controlling communicable and non-communicable diseases, disease surveillance, immunization, laboratory work, research, and responding to public health emergencies. The Lugar center is top-tiered institution in NCDC’s laboratory network and serves as a reference laboratory of the Georgia’s public health system. The Lugar Center’s possesses a BSL-3 facility and BSL-2 space with following laboratories: Bacteriology, Virology, Molecular Biology/Genomics, Cell culture, Parasitology, Entomology, Vivarium, and the National Repository of human and animal EDPs. Since the Lugar Center is Georgia’s only facility where the work with EDPs is conducted, safety and security are our primary concerns. We have robust engineering control in place, with double redundancy for all major facility systems. We have general and EDP-specific emergency response plans, planned emergency drills and identified first responders.

International collaborators: The National Center for Emerging and Zoonotic Infectious Diseases (NCEZID at the Centers for Disease Control and Prevention), The USGS National Wildlife Health Center (NWHC), Virginia Tech, US.

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