09/08/2022

Pathophysiology and Epidemiology of Equine Diseases (PhEED) Unit

Head of Unit: José Carlos Valle-Casuso

The Pathophysiology and Epidemiology of Equine Diseases (PhEED) Unit is based in Normandy. Its expertise in equine health is recognised at national, European and international levels. The work of the PhEED Unit is broken down into four themes: epidemiology, which monitors the appearance and/or spread of major and emerging disorders and analyses their causes; bacteriology, whose research themes focus on bacterial reproductive diseases (including contagious equine metritis) and the bacterial causes of equine mortality; virology, with in particular the study of equine viral arteritis, equine infectious anaemia and equine herpesviruses; and parasitology, whose activities mainly concern the study and characterisation of equine trypanosomoses such as dourine, surra and nagana and their infectious agents (Trypanosoma equiperdum, Trypanosoma evansi and Trypanosoma brucei).

Reference activities

The unit holds five national reference mandates (NRLs) for contagious equine metritis, dourine, equine viral arteritis, equine infectious anaemia and equine herpesviruses.

It is also the European Union Reference Laboratory for equine diseases other than African horse sickness. These include the five diseases for which it is the NRL, as well as surra. This mandate is held jointly with the Virology UMR of the Laboratory for Animal Health.

Lastly, the unit is a World Organisation for Animal Health (WOAH) reference laboratory for dourine and contagious equine metritis.

Surveillance activities

The PhEED Unit monitors the appearance and/or spread of major and emerging equine disorders. It analyses their causes, in particular through the national surveillance network on the causes of equine mortality (Resumeq), which it runs, and through epidemiological investigations in the field. The unit is also involved in a project on the combined use of demographic and health data on horses.

Resumeq

The Normandy site of the ANSES Laboratory for Animal Health has been running and coordinating the national equine mortality surveillance network (Resumeq) since 2015. The network now has 45 members. Its ambition is to centralise all the necropsy results produced by veterinary schools, departmental laboratories and equine veterinarians in France, in order to obtain a precise picture of the causes of equine mortality throughout the country. To date, more than 1400 equine necropsy cases have been recorded in the national database. The epidemiological surveillance scheme has already identified threats at local, regional and national levels and its geographical coverage is gradually expanding. The choice of data collected and the development of various tools for standardising these data were decisive steps in the construction of this network. The PhEED Unit's experience in diagnosing the causes of mortality in Equidae and its historical database (containing necropsy data covering more than twenty years) have enabled it to finely classify the causes of mortality according to several levels, and create the first specific thesaurus for Equidae. This first thesaurus of causes of equine death has been translated and published via an open-access article, with the aim of opening Resumeq up to other countries, especially in Europe. The long-term objective is to establish international collaborations with a view to extending Resumeq and the surveillance of causes of mortality to other European countries.

Research activities

The PhEED Unit specialises in infectious and parasitic diseases of horse reproduction, as well as persistent and/or emerging infections of major importance for the equine sector. Within this framework, it studies and characterises infectious and parasitic agents in horses, and develops diagnostic tools and control measures for these diseases.

 

The themes studied by the PhEED Unit include:

  • Molecular characterisation and typing of isolates of Taylorella equigenitalis, the agent of contagious equine metritis, and Taylorella asinigenitalis, circulating in equine and asinine populations in France and Europe.
  • Ecology study of the agent of contagious equine metritis within the equine genital tract microflora in order to refine detection and control methods.
  • Study of virulence and antimicrobial resistance in pathogenic bacteria of equine origin taken from the necropsy culture collection and epidemiological investigations.
  • Development of new serological and molecular diagnostic methods for dourine and "equine trypanosomoses".
  • Study of the molecular mechanisms underlying the different transmission methods of animal diseases due to parasites of the Trypanozoon sub-genus responsible for fatal diseases in domestic animals and humans.
  • Coordination of the Resumeq equine mortality surveillance network.
  • Structuring of epidemiological surveillance in the equine sector through a project to combine the use of demographic and health data on horses (ValDonEqui).
  • Study of the development of antimicrobial resistance in the main bacterial species responsible for abortion and stillbirth in Equidae.
  • Molecular characterisation (NGS, WGS, etc.) of strains of equine infectious anaemia and equine viral arteritis found in France and Europe.
  • Improvement of serological and molecular diagnostic methods for equine infectious anaemia and equine viral arteritis.
  • Study of host-pathogen interactions in order to better understand the mechanisms of persistence of equine viral arteritis and equine infectious anaemia viruses in horses.
  • Identification of synthetic and/or natural compounds with antimicrobial properties in order to develop targeted treatments against viruses and bacteria infecting Equidae, as an alternative to antibiotic therapy.

The Sabot Joint Technology Unit (UMT)

The Sabot UMT (its name comes from the French for "Equine health and welfare – sector organisation and traceability") was set up in early 2022 for a period of five years. It brings together the PhEED unit and the French Horse and Riding Institute (IFCE) and aims to strengthen their joint research activities with regard to horse health. The unit's work will focus on three main areas: equine census and mortality monitoring, risks associated with parasites and pathogens in the horse environment, and infectious diseases related to reproduction.

Read the news on the creation of the Sabot unit

Main research projects

Funding: 2020 Normandy Interests Network (RIN)

The "Translational antiviral strategies" Chair of Excellence is devoted to the development and validation of innovative diagnostic tools and therapeutic treatments for viral infections. Research is conducted with a translational approach between human and equine viruses. The project has four interrelated objectives:

  • Apply advanced technologies to veterinary medicine to improve diagnostic methods for equine infectious anaemia (EIA) and equine viral arteritis (EVA), for early detection and prevention of viral dissemination,
  • Map the functional interactome of EIA and EVA virus proteins with their host cells, in order to better understand the pathogenesis of infection,
  • Apply a drug repurposing strategy to identify compounds with antiviral activity against EIA and EVA viruses. Identify the most promising compounds and improve their suitability as drugs, in order to maximise their success in future clinical trials,
  • Establish the basis for translational research from equine virology to human viruses, such as HIV or human coronaviruses, including SARS-CoV-2.

Characterisation of Taylorella asinigenitalis: phylogeny, pathogenicity and antimicrobial resistance

Funding: IFCE and Eperon Fund

First reported in 1995, T. asinigenitalis is closely related to the agent of contagious equine metritis (T. equigenitalis). In 2019, the lower virulence of this bacterial species was questioned with the investigation of an outbreak in the Emirates in which three mares had severe and purulent endometritis within five days of insemination with the semen of a donkey positive for T. asinigenitalis. This thesis project is aiming to improve characterisation of this bacterial species through phylogeny, pathogenicity and antimicrobial resistance, in order to determine whether or not it is necessary to report contagious equine metritis regardless of which Taylorella species is isolated.

Acute interstitial pneumonia in foals (AIP): Bring in the [infectious] defendant!

Funding: IFCE

Acute interstitial pneumonia in foals (AIP) is the leading type of pneumonia observed during necropsies on foals aged 1 to 6 months carried out at the ANSES site in Normandy. It is a disease characterised clinically by acute respiratory distress and often results in death, despite treatment. Survivors may have lung damage detectable by X-ray several years after the disease, impacting their sporting careers. As the cause of AIP is still unclear, this project aims to identify known and unknown infectious agents, and determine their role in the pathogenesis of the lesions.

Parasite risk assessment tool for small gastrointestinal strongyls in grazing Equidae to rationalise the use of antiparasitics and prevent the risk of emergence of resistance

Funding: IFCE and the Eperon Fund

Controlling worms in the digestive tract of horses is essentially based on systematic deworming at regular intervals. However, these frequent treatments encourage the development of parasite resistance to deworming agents, which gradually reduces their effectiveness. In order to preserve horse health, there is an urgent need to rationalise this deworming and treat animals only during periods of parasite risk. This project therefore aims to develop a decision-support tool to identify the periods of parasite risk in a group of Equidae, in order to establish when to treat the animals. It will take into account the weather, and breeding and grazing practices.

Equine antivirals – Acellular therapeutic innovation for equines

Funding: 2020 Normandy Interests Network (RIN) and the Eperon Fund

The objective of this study is to characterise the mechanism of action and pharmacological properties of compounds that have been selected by screening and that show an antiviral effect against two equine respiratory viruses: equine viral arteritis (EVA) and equine rhinopneumonitis (EHV-1). This will accelerate the development of effective control strategies for these diseases, which are responsible for major economic losses in the equine sector.

Characterisation of bioaerosols in the horse-rider environment: pilot study

Funding: IFCE

The Equit'Expo project aims to study the exposure of riders and horses to microbiological contaminants (bacteria and mould), by characterising the bioaerosols collected daily during rider training. It is being accompanied by questionnaires and semi-structured interviews on the riders' perception of their environment (dust, breathing problems, etc.) and of the horses' behaviour. The goal is to recommend microbiological indicators of air quality and draw up an initial review of the situations most at risk of exposure for horses and their riders. This will enable future work to target these risk situations, with a view to eventually obtaining tools for assessing and improving air quality in order to preserve human and animal health, well-being and sporting performance during riding.

Assessment of the circulation and characterisation of Clostridium difficile strains in Equidae

Funding: IFCE, Centaure scientific interest group

This project aims to assess the frequency of C. difficile in the equine population necropsied in Normandy, both in the context of carriage and cases of diarrhoea. The isolated strains will be characterised in order to assess the conservation of genotypes between the different reservoirs (equine and others), which would reflect potential widespread or even zoonotic transmissions. Lastly, an assessment of the impact of antibiotic treatments on the development of C. difficile infections in Equidae will be carried out.

Funding: Normandy Region, Centaure scientific interest group for equine health, IFCE, Wellcome Trust, European Commission through DG SANTE (EURL for Equine diseases)

Trypanosoma brucei, Trypanosoma evansi and Trypanosoma equiperdum (BrEvEq) are three flagellate protozoan parasites responsible for nagana, surra and dourine respectively. The differential diagnosis of these diseases remains challenging, particularly due to the lack of specificity of the available diagnostic tools and a lack of knowledge of the intrinsic differences between these parasites. This project, carried out in collaboration with the University of Edinburgh, aims to develop specific serological and molecular diagnostic tools for these equine trypanosomoses and to study the biological differences between the different parasites responsible for these diseases.

Study of Klebsiella pneumoniae isolated from necropsied Equidae and assessment of its zoonotic potential

Funding: IFCE, Centaure scientific interest group

The aim of this project was to conduct a genomic study of K. pneumoniae (the cause of pneumonia in horses) isolated from equine samples between 1996 and 2020. One of the objectives was to characterise and compare the "virulome" and "resistome" of equine strains according to the clinical and lesion context. Another was to carry out a retrospective study of the evolution of the bacterium's virulence and resistance over more than 20 years, and to compare these data with those on human strains isolated from nosocomial  infections.

Study of protein-protein interactions of equine infectious anaemia and African horse sickness viruses with their equine host

Funding: ANSES ("Cross-functional" calls for expressions of interest: inter-laboratories and other departments)

This project sought to perform protein-protein interaction (PPI) mapping for non-structural and accessory proteins of equine infectious anaemia virus (EIAV) and African horse sickness virus (AHSV) with their equine host using the yeast two-hybrid method. The aim was to identify the PPIs likely to be essential for the replication, persistence and/or spread of these viruses. Deciphering and characterising these virus-host molecular interactions opens up new prospects for predicting and simulating future emerging threats and developing effective countermeasures against these diseases, such as new broad-spectrum anti-infective compounds and attenuated strains for these pathogens.

Bacterial growth in stored stallion semen

Funding: IFCE

The transport of stallion semen in liquid form is an alternative to the use of frozen semen. However, bacterial multiplication in diluted semen has been observed in some stallions despite the presence of antibiotics. This project aims to enumerate and characterise the bacterial flora present in the semen of these stallions. Antibiograms will be performed to determine the potential resistance of bacteria to the antibiotics added to the extender.

Antiviral strategies against three equine viruses, EVA, WNV and EHV-1: pharmaco-toxicological study of four candidate compounds in horses

Funding: IFCE

The objective of the SAVE SATELLITE project was to conduct a pharmaco-toxicological study in horses of four compounds likely to be effective against three viral diseases: equine viral arteritis (EVA), West Nile virus (WNV) and equine rhinopneumonitis (EHV-1). This work is an essential preliminary step before conducting an efficacy study in animals, for which specific funding will be requested at a later stage.

Combined use of demographic and health data on horses

Funding: French Horse and Riding Institute (IFCE) and the Eperon Fund

Very little is known about the size, composition and location of the French Equidae population and yet this information is fundamental to better protect their health. In addition, many equine health data are collected separately by different surveillance schemes, and the dispersion of these data hampers an overall assessment or nationwide view of the health situation. In this context, the objective of the ValDonEqui project was to improve knowledge of equine demographics and health by making synergistic use of the data already routinely collected.

Partnerships specific to the PhEED Unit

  • LABEO Franck Duncombe
  • French Institute for Research for Development (IRD)
  • University of Tours
  • Claude Bernard University, Lyon 1
  • French National Institute for Health and Medical Research (Inserm)
  • French National Centre for Scientific Research (CNRS)
  • Ecole Nationale Supérieure de Lyon
  • The Queen's Medical Research Institute, Centre for Inflammation Research, University of Edinburgh (UK)
  • The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh (UK)
  • University of Glasgow (UK)
  • Laboratorio de Diagnóstico, Clínica Equina SRL, Buenos Aires, (Argentina)
  • Center for Microbes, Development and Health, Unit of Discovery and Molecular Characterisation of Pathogens, Institut Pasteur of Shanghai, Chinese Academy of Sciences (China)
  • Albert Einstein College of Medicine, Department of Virology, New York (USA)
  • Pasteur Institut (Paris)