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Parasites & vectors2015; 8; 33; doi: 10.1186/s13071-014-0611-6

Theileria equi isolates vary in susceptibility to imidocarb dipropionate but demonstrate uniform in vitro susceptibility to a bumped kinase inhibitor.

Abstract: The apicomplexan hemoparasite Theileria equi is a causative agent of equine piroplasmosis, eradicated from the United States in 1988. However, recent outbreaks have sparked renewed interest in treatment options for infected horses. Imidocarb dipropionate is the current drug of choice, however variation in clinical response to therapy has been observed. Methods: We quantified the in vitro susceptibility of two T. equi isolates and a lab generated variant to both imidocarb dipropionate and a bumped kinase inhibitor compound 1294. We also evaluated the capacity of in vitro imidocarb dipropionate exposure to decrease susceptibility to that drug. The efficacy of imidocarb dipropionate for clearing infection in four T. equi infected ponies was also assessed. Results: We observed an almost four-fold difference in imidocarb dipropionate susceptibility between two distinct isolates of T. equi. Four ponies infected with the less susceptible USDA Florida strain failed to clear the parasite despite two rounds of treatment. Importantly, a further 15-fold decrease in susceptibility was produced in this strain by continuous in vitro imidocarb dipropionate exposure. Despite a demonstrated difference in imidocarb dipropionate susceptibility, there was no difference in the susceptibility of two T. equi isolates to bumped kinase inhibitor 1294. Conclusions: The observed variation in imidocarb dipropionate susceptibility, further reduction in susceptibility caused by drug exposure in vitro, and failure to clear T. equi infection in vivo, raises concern for the emergence of drug resistance in clinical cases undergoing treatment. Bumped kinase inhibitors may be effective as alternative drugs for the treatment of resistant T. equi parasites.
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Publication Date: 2015-01-20 PubMed ID: 25600252PubMed Central: PMC4311422DOI: 10.1186/s13071-014-0611-6Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article focuses on the susceptibility of a parasitic organism called Theileria equi, which causes equine piroplasmosis, to different treatments including imidocarb dipropionate and compound 1294. The results highlight variations in the effectiveness of these treatments, raising concerns about potential drug resistance.

Research Purpose and Methods

  • The main objective of this study was to observe and quantify the in vitro effectiveness of the drug imidocarb dipropionate and a kinase inhibitor, compound 1294, on two distinct Theileria equi isolates and a lab-generated variant. Another aim was also to evaluate the decrease in susceptibility of the parasite to imidocarb dipropionate after in vitro exposure.
  • The medicinal uptake capacity of imidocarb dipropionate was also evaluated by treating four horses infected with T. equi and analyzing the clearance of the parasite.

Research Findings

  • The researchers observed that the two distinct isolates of T. equi demonstrated an almost four-fold difference in susceptibility to the imidocarb dipropionate treatment. Notably, none of the horses treated with imidocarb dipropionate were able to clear the infection caused by the less susceptible USDA Florida strain, even after two rounds of treatment.
  • An interesting finding was that imidocarb dipropionate’s effectiveness was significantly reduced (further 15-fold) when the strain was exposed to it in vitro repeatedly. This denotes an increased resistance of the parasite to the drug upon repeated exposure.
  • The susceptibility of the T. equi isolates to the bumped kinase inhibitor 1294 treatment, on the other hand, showed no variance. This suggests that these parasites’ resistance may not build up against the kinase inhibitor as it does with imidocarb dipropionate.

Implications of the Study

  • The diverse susceptibility of T. equi to imidocarb dipropionate, as well as the reduction in susceptibility resulting from in vitro exposure, raises concerns about the development of drug resistance in the parasite during clinical treatments.
  • The invariable susceptibility of the parasites to the bumped kinase inhibitor 1294 suggests that it might be a viable alternative treatment, particularly in cases where resistance has been built up. However, this assertion would need further and thorough research to be validated.

Cite This Article

APA
Hines SA, Ramsay JD, Kappmeyer LS, Lau AO, Ojo KK, Van Voorhis WC, Knowles DP, Mealey RH. (2015). Theileria equi isolates vary in susceptibility to imidocarb dipropionate but demonstrate uniform in vitro susceptibility to a bumped kinase inhibitor. Parasit Vectors, 8, 33. https://doi.org/10.1186/s13071-014-0611-6

Publication

Parasites & vectors
ISSN: 1756-3305
NlmUniqueID: 101462774
Country: England
Language: English
Volume: 8
Pages: 33
PII: 33

Researcher Affiliations

Hines, Siddra A
  • Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164-7040, USA. siddra@vetmed.wsu.edu.
Ramsay, Joshua D
  • Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164-7040, USA. jdr105@vetmed.wsu.edu.
Kappmeyer, Lowell S
  • Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164-7040, USA. lkapp@vetmed.wsu.edu.
  • Animal Disease Research Unit, Agricultural Research Service, USDA, Pullman, WA, 99164-6630, USA. lkapp@vetmed.wsu.edu.
Lau, Audrey Ot
  • Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164-7040, USA. laua@vetmed.wsu.edu.
Ojo, Kayode K
  • Division of Allergy and Infectious Diseases and Center for Emerging and Re-emerging Infectious Diseases, School of Medicine, University of Washington, Seattle, WA, 98109-4766, USA. ojo67kk@u.washington.edu.
Van Voorhis, Wesley C
  • Division of Allergy and Infectious Diseases and Center for Emerging and Re-emerging Infectious Diseases, School of Medicine, University of Washington, Seattle, WA, 98109-4766, USA. WVanVoorhis@medicine.washington.edu.
Knowles, Donald P
  • Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164-7040, USA. dknowles@vetmed.wsu.edu.
  • Animal Disease Research Unit, Agricultural Research Service, USDA, Pullman, WA, 99164-6630, USA. dknowles@vetmed.wsu.edu.
Mealey, Robert H
  • Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, 99164-7040, USA. rhm@vetmed.wsu.edu.

MeSH Terms

  • Amino Acid Sequence
  • Animals
  • Antiprotozoal Agents / therapeutic use
  • Cluster Analysis
  • Drug Resistance, Microbial / genetics
  • Flow Cytometry
  • Focal Adhesion Kinase 2 / antagonists & inhibitors
  • Horse Diseases / drug therapy
  • Horse Diseases / parasitology
  • Horses
  • Imidocarb / analogs & derivatives
  • Imidocarb / therapeutic use
  • Inhibitory Concentration 50
  • Molecular Sequence Data
  • Protein Kinase Inhibitors / therapeutic use
  • Sequence Alignment
  • Species Specificity
  • Theileria / genetics
  • Theileriasis / drug therapy
  • Theileriasis / epidemiology
  • Theileriasis / parasitology
  • United States / epidemiology

Grant Funding

  • R01 AI089441 / NIAID NIH HHS
  • R01 AI111341 / NIAID NIH HHS
  • 1 R01 AI089441 / NIAID NIH HHS
  • AI111341-01 / NIAID NIH HHS

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Citations

This article has been cited 19 times.
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