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GenES_VBD network (Genomic Epidemiology tools for the Surveillance of Vector Borne Diseases: applied to tick species, reservoirs, and pathogens

Lead Research Organisation: London School of Hygiene and Tropical Medicine
Department Name: Infectious and Tropical Diseases

Abstract

Ticks are widespread ectoparasites that feed on the blood of mammals, birds, and sometimes reptiles and amphibians. Globally, ticks can transmit a variety of pathogens to humans and animals. In the UK, they are responsible for spreading many pathogens including the bacteria Borrelia burgdorferi sensu lato, which is responsible for >2,000 cases of Lyme disease per year. Other tick-borne pathogens established in the UK include Anaplasma phagocytophilium, Babesia spp. and louping-ill virus, which cause disease in farm and companion animals, and potentially affecting humans.

The changing climate and human activities have contributed to changes in tick distribution and activity and increased the risk of importation and establishment of new pathogens and tick species into the UK. In the past 20 years, bacteria Rickettsia helvetica, tick-borne encephalitis virus (TBEV), and Theileria luwenshuni parasites have been detected in the UK.

Currently, the surveillance of ticks and tick-borne diseases (TBDs) in the UK is carried out by the UK Health Surveillance Agency (UKHSA) through their Tick Surveillance Scheme (TSS), while the UKHSA Rare and Imported Pathogens Laboratory (RIPL) is a specialist centre for advice and diagnosis for a wide range of infections. The Animal and Plant Health Agency (APHA) is involved in surveillance of TBDs that affect livestock.

Surveillance and diagnostics are currently based on tick identification and the use of molecular (PCR) and serological tests, as well as histology and bacterial cultures. All these approaches have limitations, including high-cost, and unsuitable for large-scale surveillance of multiple pathogens. Thus, new cost- effective tools are required for high throughput testing of a wide range of tick species and tick-borne pathogens to improve surveillance of TBDs that affect humans and animals.

With the advances in genomics technologies there is a unique opportunity to improve the capacity of large-scale TBDs surveillance at reduced cost and obtain information on the genetic material of tick and pathogens. The proposed project will have four related objectives: (1) to complete the DNA sequences of the main UK tick species and create genetic barcodes to be used for surveillance of ticks and pathogens they carry; (2) to test these barcodes in a highly targeted approach of amplicon sequencing, establish protocols for laboratory and field assays, and screen >8,000 UKHSA TSS tick samples; (3) to study the genetic diversity of UK ticks and pathogens they transmit, as well as the relationship between ticks, pathogens and vertebrate hosts they feed on, and pair this data with geospatial analysis to allow for better prevention and targeting of interventions; and (4) to develop capacity for the genomic investigation of ticks and tick-borne pathogens, including development of bioinformatics tools to be used by researchers and stakeholders such as UKHSA and APHA. This work will allow us to generate genetic epidemiological data which will also support forecasting of TBD emergence and spread, as well as create tools for timely detection of any imported ticks and pathogens they transmit.

Technical Summary

Ticks are ectoparasites that feed on blood of a variety of vertebrates and transmit pathogens to humans and animals globally. In the UK, ticks are vectors and reservoirs of pathogens, such as Borrelia burgdorferi s.l., which is responsible for >2k cases of Lyme disease each year. Other tick-borne pathogens established in the UK include Anaplasma phagocytophilium, Babesia spp. and louping-ill virus, affecting farm and companion animals. Changing climate and human activities have increased the risk of importation and establishment of new tick species and pathogens, such as tick-borne encephalitis virus and Theileria luwenshuni that were detected in UK in the last decade.
Tick-borne disease (TBD) surveillance in the UK is carried out by the UKHSA through their Tick Surveillance Scheme (TSS) and Rare and Imported Pathogens Laboratory, and the Animal and Plant Health Agency (APHA). With advances in genomics-based technologies and their reducing costs, there is a unique opportunity to improve the capacity of large-scale surveillance of TBDs. The aim of our work is to enhance existing UK tick and pathogen surveillance through application of genomic methods, including protocols to determine species and geographic origin, and detect presence of pathogens, generating genetic epidemiological data to support forecasting of TBD emergence and spread. The proposed project will have four related objectives, to: (1) identify genetic barcodes for surveillance of ticks and pathogens; (2) validate the barcodes for amplicon sequencing, screen TSS ticks, and establish protocols for laboratory and field assays; (3) perform a geospatial-phylo-genomic-epidemiological analysis across ticks, their pathogens and hosts; (4) develop capacity in genomic investigation of ticks and pathogens, including through sharing informatics tools for use by researchers and stakeholders for decision making. Our work will also provide a template for the genomics surveillance of other vector borne infections.

Publications

10 25 50
 
Title Methods for extraction of high molecular weight (HMW) DNA from ticks 
Description We developed a method that allow us to extract HMW DNA from ticks , by using a combination of lyse buffers and beads. Using this protocol we can now sequence the genome of individual ticks and build reference genomes. This method is being used to build reference genomes for UK ticks. 
Type Of Material Technology assay or reagent 
Year Produced 2024 
Provided To Others? No  
Impact To buld reference genomes of any organisms it is necessary to have HMW DNA. With the method we developed we can now extract HMW DNA from individual ticks and we have started to build reference genomes for UK ticks. 
 
Title Multiplex assay for screening pathogens 
Description A multiplex assay to run on NGS technology, such as nanopore platform, was developed to screening pathogens in thousand of tick samples and detect possible viruses or bacteria that can cause disease in humans or animals. 
Type Of Material Technology assay or reagent 
Year Produced 2024 
Provided To Others? No  
Impact We will be able to screen thousand of ticks in paralell and it will be cost effective. 
 
Title Bioinformatic pipeline to generate and annotate reference genomes 
Description We have developed a bioinformatic pipeline that can be used to successfully build reference genomes from raw sequence data (long reads- MinION and Pacbio platforms) and also to performe genome annotations. 
Type Of Material Data analysis technique 
Year Produced 2024 
Provided To Others? No  
Impact With this pipeline we are now building reference genomes from three tick species native from the UK. 
 
Title Genomic data available for UK ticks 
Description WE have generated long reads for three different tick species in the UK. 
Type Of Material Database/Collection of data 
Year Produced 2024 
Provided To Others? No  
Impact This data will be available for researcher that will be able to use it to design assays and make population genomic analysis. 
 
Description UKHSA 
Organisation UK Health Security Agency
Country United Kingdom 
Sector Public 
PI Contribution Our research team is contributing to this collaboration by sequencing the genomes of three tick species in the UK that are key vectors for human and animal diseases. This work will generate the first reference genomes for UK ticks, providing a crucial resource for understanding their genetics, vector capacity, and potential for disease transmission. Additionally, we have organized a genomic analysis course that included participants from UKHS, further strengthening capacity-building efforts in this field.A.
Collaborator Contribution Our partners are contributing to this collaboration by collecting tick samples and designing targeted amplicons for selected pathogens. These amplicons will be used in a multiplex assay to screen thousands of ticks rapidly and cost-effectively, enhancing our ability to detect and monitor tick-borne diseases.
Impact Genomic data for ticks in the UK has been generated as well as a multiplex amplicon assay to screen for pathogens in ticks. A genomic analysis course was conducted to strengthen capacity-building efforts in this field. The work was presented at the UK VBD meeting in Liverpool, 2024.
Start Year 2024
 
Description Genomics workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact We organized at LSHTM a Genomic Analysis course with participants from UKHSA, as well as many participants from other national and international Universities.
Year(s) Of Engagement Activity 2024
 
Description Meeting at LSHTM 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact The team from UKHSA visit the facilities at LSHTM and we had the opportunity to discuss the progress of the project.
Year(s) Of Engagement Activity 2025
 
Description Meeting at UKHSA 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact The team from LSHTM visit the facilities at UKHSA and we had the opportunity to discuss the progress of the project.
Year(s) Of Engagement Activity 2024
 
Description UK vector meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact Our team, together with our collaborators from UKHSA, presented our work to numerous researchers in the field of vector-borne diseases (VBD) in the UK.
Year(s) Of Engagement Activity 2024