TickTools: Development of tools to monitor and control tick-borne diseases of humans and livestock

Lead Research Organisation: ANIMAL AND PLANT HEALTH AGENCY
Department Name: Virology


Tick-borne diseases cause a significant health burden on both the human and domestic livestock populations within the United Kingdom (UK). This includes the recently detected tick-borne encephalitis virus, a common cause of encephalitis in humans across Europe, and the livestock disease caused by louping ill virus. Both are types of flaviviruses and are closely related, and both are now endemic within the UK. Many questions remain concerning the biology of these viruses and there are key gaps in understanding virus distribution within tick vector populations, fundamental questions on flavivirus virus pathogenesis and a clear lack of serological tests that can distinguish between antibodies to either virus in order to tell which is circulating in the different host species. To address these gaps, the TickTools project aims to conduct a series of studies, each coordinated by one of the project partners. The Animal and Plant Health Agency (APHA) will conduct field surveys for adult ticks from across the UK and determine the microbiological make-up present within each sample, which will identify all viruses and bacteria present. This approach will also capture the genome of each tick that can be used to assess the relationships between tick-populations within the country, which in turn could reveal the interactions between these populations and how ticks, and their pathogens disperse. APHA will support the University of Glasgow Centre for Virus Research (CVR) in establishing a virus infection model to determine the pathogenesis of tick-borne flaviviruses. This will be achieved by comparing the virulent virus with an attenuated virus. This approach will identify potential therapeutic targets for prevention and control of flavivirus infection with the aim of preventing the most severe manifestations of virus infection. From these studies, CVR will supply organ tissue (spleen) to the University of Nottingham (UoN) to support their development of scFv antibodies that can be used to further study both viruses but also have potential as treatments for people or pets that become infected. The UoN will also develop antigen (peptide) panels that will discriminate between serological responses to infection with either TBEV or LIV. Using assays developed by UoN, serological surveillance in both human and animal populations will be possible.

Technical Summary

The TickTools proposal will enhance the ability of the United Kingdom (UK) to respond to the emergence and spread of tick-borne diseases caused by flaviviruses. This includes the recently emerged tick-borne encephalitis virus (TBEV) and the endemic pathogen of sheep, louping ill virus (LIV). This will be achieved through the acquisition of fundamental knowledge of the tick microbiome and the generation of an interactome map of endosymbionts, both bacterial and viral, and pathogenic viruses. A pilot study has shown the great diversity of microbial agents present in tick populations within the south of England and the discovery of novel viruses. In addition, the genetic structure of UK tick populations will be determined and used to reveal the interrelationships between different populations. This offers the potential to understand both tick and virus dispersal. The development of a murine pathogenesis model for both virulent and attenuated viruses, generated by re-encoding for non-optimised codons, will identify cytokine/chemokine responses and potential therapeutic targets at the molecular level. This approach has previously identified the cytokine IL-6 as a target for control during tick-borne virus infection. A further challenge is the discrimination of serological responses to closely related tick-borne viruses such as TBEV and LIV. The project will develop the Soluble Phage Array (SPAr) linked to next generation sequencing, a process termed next generation phage display (NGDP) to generate peptide panels that achieve this within a single serological test. Preliminary results have provided proof-of-principle of this method. The TickTools project will further validate these findings and through collaboration with all three partners develop a surveillance tool to accurately monitor serological responses to tick-borne flaviviruses in both human and animal populations.


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Title Nucleic acids DNA/RNA 
Description RNA and DNA samples have been extracted from 30 tick samples from locations in England and Wales. Illumina sequence data is available for each sample. Bioinformatic analysis is currently being conducted. 
Type Of Material Biological samples 
Year Produced 2023 
Provided To Others? No  
Impact Analysis of these samples has contributed to two research communications: 1. "Sequences related to Chimay rhabdoviruses are widely distributed in Ixodes ricinus ticks across England and Wales" submitted to the journal Viruses, in review. 2, Draft manuscript "Investigation utilising metagenomics reveals microbiome diversity within the common sheep tick (Ixodes ricinus) sampled in the UK" in preparation 
Description Gap-DC2 
Organisation Animal and Plant Health Agency
Country United Kingdom 
Sector Public 
PI Contribution The TickTools consortium has contributed preliminary data to support a publication prepared by the GAP-DC2 project
Collaborator Contribution The partner has prepared the draft of a manuscript entitle "Sequences related to Chimay rhabdovirus are widely distributed in Ixodes ricinus ticks across England and Wales" by Dr Mirjam Schilling, a researcher within the Genomics for Animal and Plant Disease Centre (GAP-DC2) funded by the Department for Environment Food and Rural Affairs.
Impact A draft manuscript on viruses detected in British common sheep ticks (Ixodes ricinus).
Start Year 2023
Description OpTick (BBSRC/Defra funded One Health Vector Borne Disease Control) BB/X017974/1 
Organisation UK Centre for Ecology & Hydrology
Country United Kingdom 
Sector Public 
PI Contribution Organised field survey in south west England including visit to APHA Starcross Veterinary Investigation Centre and field site in Blackdown Hills. Shared APHA data on tick-borne disease detection. Gave presentation on "Diagnostics of tickborne diseases" for an OpTick webinar (https://www.optick.ceh.ac.uk/optick-events). Joined monthly workpackage meetings. Contribute to survey development for farmer/veterinary attitudes to tick and tick-borne disease.
Collaborator Contribution The OpTick partners have supplied inteligence on ticks and tick-borne diseases in the two study regions (SW England and North Wales).
Impact This collaboration is a multi-disciplinary effort from UK CEH, UK HSA, University of Liverpool, Moredun Institute and Animal and Plant Health Agency.
Start Year 2023
Description University of Aix Marseille 
Organisation Aix-Marseille University
Country France 
Sector Academic/University 
PI Contribution The TickTools consortium (Kohl Group - Liverpool School of Tropical Medicine) is the recipient of support from this collaboration.
Collaborator Contribution The University of Aix Marseille, France, through the group of Professor Xavier de Lamballerie is contributing experience and protocols to successfully recover re-sequence virus genomes.
Impact Results of virus genome resequencing is pending.
Start Year 2024
Description University of Nottingham 
Organisation University of Nottingham
Department School of Veterinary Medicine and Science Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution The TickTools project has hosted a post-doctoral student from the University of Nottingham for three months to investigate exposure of deer to tick-borne pathogens at a hotspot for tick-borne disease in southern England. The TickTools partner (Animal and Plant Health Agency) has supplied the University of Nottingham partner with a panel of tick-borne encephalitis virus seropositive and seronegative deer sera.
Collaborator Contribution The University of Nottingham partner will use the sera panel to investigate methods to distinguish seropositivity between tick-borne encephalitis virus and louping ill virus. The University of Nottingham has written a draft scientific manuscript entitled "Detection of Babesia species in wild deer from south-west England" and submitted it to the journal Current Research in Parasitology & Vector-Borne Diseases.
Impact The manuscript is in review, outcome pending.
Start Year 2023
Description University of Oxford 
Organisation University of Oxford
Department Department of Biology
Country United Kingdom 
Sector Academic/University 
PI Contribution The TickTools project has obtained mass sequencing data on a small panel of Hippoboscidae (flatflies / deer keds) removed from birds. This will support a post-doctoral project to investigate transmission of avipox in birds by ectoparasites hosted by the University of Oxford.
Collaborator Contribution The University of Oxford has supplied a large panel of ectoparasites removed from birds, some with obvious signs of disease caused by avian poxviruses.
Impact The data generated from this collaboration is multi-disciplinary (virology/biology/bioinformatics) and will support a post-doctoral project and a manuscript on the microbiome of ectoparasites of birds.
Start Year 2023
Description Vector Borne Disease Data Hub 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Engagement with seminars announcing the creation of the VBD datahub, recently funded by BBSRC/Defra.
Collaborator Contribution The TickTools consortium has shared the data management plan of the project with the VBD Hub. Future meetings are planned to discuss how datasets generated by TickTools can be shared with the Hub project.
Impact No outputs have been identified.
Start Year 2024
Description Field sampling for ticks within England and Wales for ticks where livestock are present and engagement with farmers. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact Farm and livestock locations were visited during the tick activity season in 2023. Sites in the counties of Cornwall, Devon, Hampshire and Powys were visited. Farm owners were interviewed for knowledge on tick distribution.
Year(s) Of Engagement Activity 2023
Description Press release concerning TickTools project 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact This press release, issued by Defra, highlighted the project with the following text release: "The funding will support two APHA-led projects, including TickTools - a three-year project backed by £1.2 million to develop the tools to monitor and control tick-borne diseases. APHA will bring together researchers from the University of Nottingham and the Centre for Virus Research at the University of Glasgow and investigate the basic biology of tick-borne pathogen - from tick host interactions, improved vaccines to prevent disease and diagnostic methods to detect infection."
Year(s) Of Engagement Activity 2023
URL https://www.gov.uk/government/news/additional-funding-for-research-on-diseases-spread-by-mosquitoes-...