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LIDo iCASE Studentship: Canine leptospirosis at home and abroad

Employer
Royal Veterinary College
Location
Camden, London/Hawstead, Hertfordshire
Closing date
10 Jan 2023

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LIDo iCASE Studentship: Canine leptospirosis at home and abroad: Matching the vaccine with the infection

RVC - studentship

RVC Supervisor(s): Prof. Brian CatchpoleDr Kim Stevens

Department:  Pathobiology and Population Sciences

RVC supervisors: Professor Brian Catchpole and Dr Kim Stevens

Non-RVC supervisor: MSD Animal Health (industrial partner)

Project Summary:

Background, aims and objectives:

Leptospirosis is a zoonotic disease, which is of concern from both veterinary and human public health perspectives. Dogs are often infected by leptospira serovars from other mammalian species (e.g. rodents, production animals or horses), then pose a risk of direct or indirect infection to the human population, particularly in countries such as Nigeria, where drinking water sources are at risk of contamination from infected urine.

Diagnosis of leptospirosis is somewhat challenging, due to antigenic variation of the pathogen and difficulty in differentiating infected from vaccinated animals (DIVA). The standard microscopic agglutination test (MAT) is a serological assay that has many drawbacks. Furthermore, clinical samples are not routinely evaluated beyond the ‘PCR positive’ stage. As a result of these diagnostic test deficiencies, epidemiological information regarding the different serovars currently circulating in the pet dog population is limited.

There are considerable geographical differences in the prevalence of different serovars, which is problematic when using a ‘standard’ vaccine, designed from historical data generated either in the USA or mainland Europe.

Recognition that the traditional bivalent leptospirosis vaccine was not providing adequate protection against emerging disease led to the introduction of an L4 mutivalent vaccine in 2013. However, even then it was estimated that at least 15% of clinical cases in the UK were from serovars not included in the vaccine and there are currently no surveillance processes in place to detect and react to changes in serovar prevalence from spatial and temporal perspectives.

In partnership with MSD Animal Health, and in collaboration with the Animal and Plant Health Agency (APHA), the aim is to take an interdisciplinary approach to studying canine leptospirosis. We will focus on developing improved molecular and immunological diagnostic tests and increasing our epidemiological understanding of this infectious disease in the UK and Nigerian dog populations, with a view to informing vaccine design.

The project will provide insight into antigenic variation of this pathogen at the genetic, molecular and host response levels. Companion animals enjoy a close relationship with the human population and control of infectious disease is particularly important for zoonotic pathogens such as leptospira in a One Health context. Not only will this research address questions of fundamental importance for understanding the host pathogen interaction, but will also inform vets of the risk factors for leptospirosis and enable commercial companies to tailor their vaccines more specifically to those leptospira serovars currently circulating and emerging in the dog population

Project plan

Samples: PCR+ and MAT+ samples will be provided via MSD Animal Health and APHA, as well as collaborating commercial diagnostic laboratories. Collaborators at the Faculty of Veterinary Medicine, University of Ibadan will be responsible for recruiting leptospirosis cases/samples in Nigeria.

Molecular diagnostics: PCR+ samples will be genotyped by multi-locus sequence typing and further evaluated by next generation sequencing (MinION, Oxford Laboratories). The PubMLST and LeptoDB databases will determine the genomospecies and likely maintenance host/source of infection.

Serology: Pre/post vaccination and MAT+ sera will be evaluated in our established luciferase immunoprecipitation assay against the outer membrane proteins (OMPs) LipL32 and LipL41. We will attempt to develop a DIVA assay, based on detection of antibodies against LigA-C. Epitope prediction software will be employed to identify peptides from these three OMPs that will form the basis of a chimeric LigA-C epitope target for the immunoassay.

Epidemiology: Multivariable regression models will identify risk factors for serovar prevalence. Spatial analysis will map the distribution of serovars and identify any spatio-temporal clustering. Spatial modelling will identify agro-ecological risk factors associated with the distribution of individual serovars. Risk maps will be generated to identify areas of high risk for the transmission of different serovars.

References

  1.  Taylor C, O'Neill DG, Catchpole B, Brodbelt DC. Leptospirosis vaccination in dogs attending UK primary care practices: vaccine uptake and factors associated with administration. BMC Vet Res. 2022 Jul 22;18(1):285.
  2.  Taylor C, Brodbelt DC, Dobson B, Catchpole B, O'Neill DG, Stevens KB. Spatio-temporal distribution and agroecological factors associated with canine leptospirosis in Great Britain. Prev Vet Med. 2021 Aug;193:105407.
  3. Taylor C, O'Neill DG, Catchpole B, Brodbelt DC. Incidence and demographic risk factors for leptospirosis in dogs in the UK. Vet Rec. 2022 Mar;190(6):e512.

Requirements

Essential:

Desirable:

  • MSc level qualification
  • Veterinary qualified graduate

This is a 4 year fully-funded LIDo iCASE project, open to applicants eligible for "Home" fees. International applicants are welcome to apply, but there are a limited number of international places on this studentship programme. 

The programme will commence October 2023. 

If you are interested in applying for this position, please follow the link below.  Please use your personal statement to demonstrate any previous skills or experience you have in using both qualitative and quantitative research methods.

How to Apply

To apply for this project please do so via the LIDo website via the APPLY button

Please do not apply through the RVC website. Any application submitted via the RVC form will not be considered.

We welcome informal enquiries - these should be directed to Professor Brian Catchpole (bcatchpole@rvc.ac.uk)

The deadline is Tuesday 10th January 2023. The portal will close promptly at 5pm on 10th January and all applications must be complete including both references by this deadline

 

 

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