Canine leptospirosis is a zoonotic disease, spread through contact with infected urine, which is of concern from both veterinary and human public health perspectives. Diagnosis of acute leptospirosis in dogs is problematic, due to antigenic variation of the pathogen and difficulty in differentiating infected from vaccinated animals (DIVA). The microscopic agglutination test (MAT) is the most widely used diagnostic assay, despite its limitations, which include having to handle live pathogenic organisms, considerable inter-laboratory variability, subjective interpretation of results and interference by vaccine responses. Epidemiological information on the different Leptospira serovars currently circulating in the pet dog population is limited; there are considerable geographical differences in the prevalence of different serovars, with the potential for emerging disease as a result of animals entering the UK that are shedding leptospira organisms of serovars that are not currently present. Recognition that the traditional bivalent canine leptospirosis vaccine was not providing protection against emerging disease led to the introduction of L4 mutivalent vaccines. However, it is estimated that at least 15% of clinical cases are infected by serovars not included in current vaccines and there is currently no formal surveillance process in place to detect and react to changes in serovar prevalence.
In partnership with MSD Animal Health and the Animal & Plant Health Agency (APHA), we will take an interdisciplinary approach to studying canine leptospirosis, with a focus on developing improved diagnostics and increasing our understanding of the epidemiology of the disease in the UK dog population. We will evaluate the genetic diversity in lipopolysaccharide (LPS) synthesis genes and outer membrane proteins (OMPs including LipL21, LipL32, LipL41, LigA/B/C), by resequencing and comparing vaccine and field strains currently identified in the UK. We hypothesise that genetic variation will impact on B cell epitopes of these surface antigens. Selected proteins and peptides will be taken forward for production of serovar specific antigens, which will be assessed in serological assays. We will develop techniques for measuring serum IgM (more likely during the acute phase of infection) and IgG (more likely following vaccination) against serovar specific LPS and OMPs. We hypothesise that this approach will be more effective for diagnostic testing and discriminating between acute infection and vaccine immunity. LPS will be purified from the most common Leptospira serovars and pooled or used individually in ELISA. Recombinant OMPs will be produced as fusion proteins with a nanoluciferase tag. These will be used in a liquid-phase luciferase immunoprecipitation (LIPS) assay. Residual serum samples that have previously been tested by MAT by APHA and of known leptospira antibody status will be made available for this part of the study. We will access the VetCompass database of clinical cases and APHA database of canine leptospirosis serology results to estimate the frequency of leptospirosis in dogs attending first opinion veterinary practices and the associated risk factors, explore the geographical and temporal distribution of clinical cases of leptospirosis and quantify trends in vaccination uptake for canine leptospirosis in the UK.
Interested applicants are encouraged to contact Prof. Brian Catchpole (email@example.com) in advance of the deadline.
Closing date is 19th January. Please ensure that you read the Guidelines before submitting an application. Your application and supporting documents should be sent in a single email to LIDo.Admissions@ucl.ac.uk
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