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Veterinary parasitology2018; 263; 27-33; doi: 10.1016/j.vetpar.2018.10.005

Validation of a new experimental model for assessing drug efficacy against infection with Trypanosoma equiperdum in horses.

Abstract: Trypanosoma equiperdum, the causative agent of dourine, may affect the central nervous system, leading to neurological signs in infected horses. This location protects the parasite from most (if not all) existing chemotherapies. In this context, the OIE terrestrial code considers dourine as a non-treatable disease and imposes a stamping-out policy for affected animals before a country may achieve its dourine-free status. The use of practices as drastic as euthanasia remains controversial, but the lack of a suitable tool for studying a treatment's efficacy against dourine hampers the development of an alternative strategy for dourine infection management. The present study reports on the development of an experimental infection model for assessing drug efficacy against the nervous form of dourine. The model combines the infection of horses by Trypanosoma equiperdum and the search for trypanosomes in the cerebrospinal fluid (CSF) through an ultrasound-guided cervical sampling protocol. After a development phase involving four horses, we established an infection model that consists of inoculating 5 × 10T. equiperdum OVI parasites intravenously into adult Welsh mares (Equus caballus). To evaluate its efficacy, eight horses were infected according to this model. In all these animals, parasites were observed in the blood at 2 days post-inoculation (p.i.) and in CSF (12.5 ± 1.6 days p.i.) and seroconversion was detected (8.25 ± 0.5 days p.i.). All eight animals also developed fever (rectal temperature > 39 °C), low hematocrit (< 27%), and ventral edema (7.9 ± 2.0 days p.i.), together with other inconstant clinical signs such as edema of the vulva (six out of eight horses) or cutaneous plaques (three out of eight horses). This model provides a robust infection protocol that induces an acute trypanosome infection and that allows parasites to be detected in the CSF of infected horses within a period of time compatible with animal experimentation constraints. We conclude that this model constitutes a suitable tool for analyzing the efficacy of anti-Trypanosoma drugs and vaccines.
Publication Date: 2018-10-09 PubMed ID: 30389021DOI: 10.1016/j.vetpar.2018.10.005Google Scholar: Lookup
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  • Journal Article
  • Validation Study

Summary

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The researchers developed and validated a new experimental model for assessing the efficacy of drugs against the infection caused by Trypanosoma equiperdum in horses.

Overview of Research Article

This study focuses on the development and validation of an experimental model for testing how effective drugs are against Trypanosoma equiperdum, a parasite that causes dourine, a disease in horses.

  • The parasite is known to affect the central nervous system, leading to neurological signs in those infected.
  • This location protects the parasite from the majority of existing chemotherapies. Consequently, the OIE terrestrial code considers dourine a non-treatable disease, which typically calls for euthanizing the infected animal.
  • The lack of suitable tools for studying the effectiveness of treatments has impeded the progress of alternative strategies for managing dourine.

Development of the Experimental Infection Model

  • The researchers developed an infection model by infecting horses with Trypanosoma equiperdum and then using an ultrasound-guided cervical sampling protocol to look for trypanosomes in the cerebrospinal fluid (CSF).
  • The model involves inoculating 5 × 10^6 T. equiperdum OVI parasites intravenously into adult Welsh mares.
  • After developing the model with four horses, the researchers tested its efficacy on eight additional horses, introducing the parasites through the same process.

Results of the Experimental Infection Model

  • All eight horses showed parasites in their blood by the second day following inoculation, and in their CSF around 12.5 days afterwards.
  • Seroconversion, the time period during which a specific antibody develops and becomes detectable in the blood, was also detected approximately 8.25 days after inoculation.
  • All horses developed fever and low hematocrit, indicating a low concentration of red blood cells, in addition to ventral edema, a swelling caused by excess fluid accumulated in the horses’ tissues.
  • Less common clinical signs including edema of the vulva and cutaneous plaques were observed in some of the horses.

Conclusion of the Research

The researchers concluded that the model provides a robust infection protocol that creates a severe infection and allows observes parasites in the CSF of infected horses in a timeframe compatible with animal experimentation parameters. It is a suitable tool for analyzing the effectiveness of anti-Trypanosoma drugs and vaccines.

Cite This Article

APA
Hébert L, Guitton E, Madeline A, Géraud T, Carnicer D, Lakhdar L, Pitel PH, Coste M, Laloy E, Giraudet A, Zientara S, Büscher P, Laugier C, Hans A, Petry S, Cauchard J. (2018). Validation of a new experimental model for assessing drug efficacy against infection with Trypanosoma equiperdum in horses. Vet Parasitol, 263, 27-33. https://doi.org/10.1016/j.vetpar.2018.10.005

Publication

ISSN: 1873-2550
NlmUniqueID: 7602745
Country: Netherlands
Language: English
Volume: 263
Pages: 27-33
PII: S0304-4017(18)30342-X

Researcher Affiliations

Hébert, Laurent
  • ANSES, Dozulé Laboratory for Equine Diseases, Bacteriology Unit, 14430, Goustranville, France; ANSES, Dozulé Laboratory for Equine Diseases, Equines Virology and Parasitology Unit, 14430, Goustranville, France. Electronic address: laurent.hebert@anses.fr.
Guitton, Edouard
  • INRA, PFIE, UE1277, 37380, Nouzilly, France.
Madeline, Anthony
  • ANSES, Dozulé Laboratory for Equine Diseases, Bacteriology Unit, 14430, Goustranville, France; ANSES, Dozulé Laboratory for Equine Diseases, Equines Virology and Parasitology Unit, 14430, Goustranville, France.
Géraud, Tristan
  • ANSES, Dozulé Laboratory for Equine Diseases, Equines Virology and Parasitology Unit, 14430, Goustranville, France.
Carnicer, David
  • ANSES, Dozulé Laboratory for Equine Diseases, Epidemiology and pathological anatomy Unit, 14430, Goustranville, France.
Lakhdar, Latifa
  • ANSES, Lyon Laboratory, Plateforme d'Expérimentation Animale, 31 avenue Tony Garnier, 69007, Lyon, France.
Pitel, Pierre-Hugues
  • LABÉO Frank Duncombe, 1 Route de Rosel, 14280, Saint-Contest, France.
Coste, Margaux
  • Laboratoire d'anatomo-cytopathologie, Biopôle Alfort, Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est, Maisons-Alfort, 94700, France.
Laloy, Eve
  • Laboratoire d'anatomo-cytopathologie, Biopôle Alfort, Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est, Maisons-Alfort, 94700, France; UMR Virologie, INRA, Ecole Nationale Vétérinaire d'Alfort, ANSES, Université Paris-Est, Maisons-Alfort, 94700, France.
Giraudet, Aude
  • Laboratoire d'anatomo-cytopathologie, Biopôle Alfort, Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est, Maisons-Alfort, 94700, France.
Zientara, Stéphan
  • UMR Virologie, INRA, Ecole Nationale Vétérinaire d'Alfort, ANSES, Université Paris-Est, Maisons-Alfort, 94700, France.
Büscher, Philippe
  • Institute of Tropical Medicine, Department of Biomedical Sciences, Nationalestraat 155, B-2000, Antwerp, Belgium.
Laugier, Claire
  • ANSES, Dozulé Laboratory for Equine Diseases, 14430, Goustranville, France.
Hans, Aymeric
  • ANSES, Dozulé Laboratory for Equine Diseases, Equines Virology and Parasitology Unit, 14430, Goustranville, France.
Petry, Sandrine
  • ANSES, Dozulé Laboratory for Equine Diseases, Bacteriology Unit, 14430, Goustranville, France.
Cauchard, Julien
  • ANSES, Dozulé Laboratory for Equine Diseases, Bacteriology Unit, 14430, Goustranville, France.

MeSH Terms

  • Anemia
  • Animals
  • Antibodies, Protozoan / blood
  • Disease Models, Animal
  • Dourine / cerebrospinal fluid
  • Dourine / drug therapy
  • Dourine / parasitology
  • Drug Evaluation
  • Female
  • Horse Diseases / drug therapy
  • Horse Diseases / parasitology
  • Horses / parasitology
  • Trypanosoma / drug effects
  • Trypanosoma / isolation & purification

Citations

This article has been cited 4 times.
  1. Desquesnes M, Gonzatti M, Sazmand A, Thévenon S, Bossard G, Boulangé A, Gimonneau G, Truc P, Herder S, Ravel S, Sereno D, Jamonneau V, Jittapalapong S, Jacquiet P, Solano P, Berthier D. A review on the diagnosis of animal trypanosomoses. Parasit Vectors 2022 Feb 19;15(1):64.
    doi: 10.1186/s13071-022-05190-1pubmed: 35183235google scholar: lookup
  2. Verney M, Gautron M, Lemans C, Rincé A, Hans A, Hébert L. Development of a microsphere-based immunoassay for the serological diagnosis of equine trypanosomosis. Sci Rep 2022 Jan 25;12(1):1308.
    doi: 10.1038/s41598-022-05356-ypubmed: 35079068google scholar: lookup
  3. Büscher P, Gonzatti MI, Hébert L, Inoue N, Pascucci I, Schnaufer A, Suganuma K, Touratier L, Van Reet N. Equine trypanosomosis: enigmas and diagnostic challenges. Parasit Vectors 2019 May 15;12(1):234.
    doi: 10.1186/s13071-019-3484-xpubmed: 31092285google scholar: lookup
  4. Hébert L, Froger D, Madeline A, Lecouturier F, Lemans C, Zientara S. European Inter-Laboratory Proficiency Test for Dourine Antibody Detection Using the Complement Fixation Test. Vet Sci 2023 Sep 26;10(10).
    doi: 10.3390/vetsci10100592pubmed: 37888544google scholar: lookup