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Veterinary parasitology1999; 82(3); 205-210; doi: 10.1016/s0304-4017(99)00020-5

Determination of the activity of pyrimethamine, trimethoprim, sulfonamides, and combinations of pyrimethamine and sulfonamides against Sarcocystis neurona in cell cultures.

Abstract: Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome in horses from the Americas and is usually caused by infection with the apicomplexan parasite, Sarcocystis neurona. The activities of pyrimethamine, trimethoprim, sulfachloropyridazine, sulfadiazine, sulfadimethoxine, sulfamethoxazole, sulfamethazine, and sulfathiazole were examined against developing S. neurona merozoites in bovine turbinate cell cultures. A microtiter plate host cell lesion based assay was used to determine the effects of agents on developing merozoites. A cell culture flask assay was used to determine if selective concentrations of the agents killed or only inhibited development of S. neurona. Pyrimethamine was coccidiocidal at 1.0 microg/ml and trimethoprim was coccidiocidal at 5.0 microg/ml. None of the sulfonamides had activity when used alone at 50.0 or 100.0 microg/ml. Combinations of sulfonamides (5.0 or 10.0 microg/ml) with 0.1 microg/ml pyrimethamine demonstrated improved activity.
Publication Date: 1999-05-29 PubMed ID: 10348099DOI: 10.1016/s0304-4017(99)00020-5Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research article discusses the impact of various medicines, including pyrimethamine, trimethoprim, sulfonamides, and their combinations on the apicomplexan parasite, Sarcocystis neurona, which often causes Equine protozoal myeloencephalitis (EPM) in horses from the Americas. The experiment was conducted using the bovine turbinate cell cultures and presented methods to evaluate the drug activities against S. neurona.

Objective of the Research

  • The aim of this research was to assess the efficacy of different drugs – pyrimethamine, trimethoprim, sulfonamides, and their combinations – against the parasite Sarcocystis neurona that causes EPM syndrome in horses.

Methodology and Approach

  • Multiple drugs were screened for their effect against developing S. neurona merozoites in bovine turbinate cell cultures.
  • Two types of assays were conducted – a microtiter plate host cell lesion based assay and a cell culture flask assay to reveal the impacts of these agents on the merozoites.
  • The microtiter plate assay focused on determining the effect of the drugs on the developing merozoites.
  • The cell culture flask assay concentrated on identifying if selective concentrations of the agents killed or merely stopped the development of the S. neurona.

Key Findings

  • Result analysis demonstrated that pyrimethamine at 1.0 microg/ml concentration and trimethoprim at 5.0 microg/ml concentration were effective against the parasite.
  • Sulfonamides did not display any significant effect when used alone at high concentrations of (50.0 or 100.0 microg/ml).
  • However, the experiment indicated that a combination of sulfonamides with a minimal concentration of pyrimethamine (0.1 microg/ml) shown improved activity against S. neurona.

Cite This Article

APA
Lindsay DS, Dubey JP. (1999). Determination of the activity of pyrimethamine, trimethoprim, sulfonamides, and combinations of pyrimethamine and sulfonamides against Sarcocystis neurona in cell cultures. Vet Parasitol, 82(3), 205-210. https://doi.org/10.1016/s0304-4017(99)00020-5

Publication

ISSN: 0304-4017
NlmUniqueID: 7602745
Country: Netherlands
Language: English
Volume: 82
Issue: 3
Pages: 205-210

Researcher Affiliations

Lindsay, D S
  • Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg 24061-0342, USA. lindsayd@vt.edu
Dubey, J P

    MeSH Terms

    • Animals
    • Anti-Infective Agents / pharmacology
    • Anti-Infective Agents / standards
    • Anti-Infective Agents / therapeutic use
    • Antimetabolites / pharmacology
    • Antimetabolites / standards
    • Antimetabolites / therapeutic use
    • Antiprotozoal Agents / pharmacology
    • Antiprotozoal Agents / standards
    • Antiprotozoal Agents / therapeutic use
    • Cattle
    • Cells, Cultured
    • Drug Combinations
    • Encephalomyelitis / drug therapy
    • Encephalomyelitis / parasitology
    • Encephalomyelitis / veterinary
    • Enzyme-Linked Immunosorbent Assay / veterinary
    • Horse Diseases / drug therapy
    • Horse Diseases / parasitology
    • Horses
    • Pyrimethamine / pharmacology
    • Pyrimethamine / standards
    • Pyrimethamine / therapeutic use
    • Sarcocystis / drug effects
    • Sarcocystosis / drug therapy
    • Sarcocystosis / parasitology
    • Sarcocystosis / veterinary
    • Sulfonamides / pharmacology
    • Sulfonamides / standards
    • Sulfonamides / therapeutic use
    • Trimethoprim / pharmacology
    • Trimethoprim / standards
    • Trimethoprim / therapeutic use
    • Turbinates / cytology
    • Turbinates / parasitology

    Citations

    This article has been cited 6 times.
    1. Bowden GD, Land KM, O'Connor RM, Fritz HM. High-throughput screen of drug repurposing library identifies inhibitors of Sarcocystis neurona growth.. Int J Parasitol Drugs Drug Resist 2018 Apr;8(1):137-144.
      doi: 10.1016/j.ijpddr.2018.02.002pubmed: 29547840google scholar: lookup
    2. Güzel Bayülken D, Bostancıoğlu RB, Koparal AT, Ayaz Tüylü B, Dağ A, Benkli K. Assessment of in vitro cytotoxic and genotoxic activities of some trimethoprim conjugates.. Cytotechnology 2018 Jun;70(3):1051-1059.
      doi: 10.1007/s10616-018-0187-7pubmed: 29335807google scholar: lookup
    3. Fayer R, Esposito DH, Dubey JP. Human infections with Sarcocystis species.. Clin Microbiol Rev 2015 Apr;28(2):295-311.
      doi: 10.1128/CMR.00113-14pubmed: 25715644google scholar: lookup
    4. Slesak G, Schäfer J, Langeheinecke A, Tappe D. Prolonged clinical course of muscular sarcocystosis and effectiveness of cotrimoxazole among travelers to Tioman Island, Malaysia, 2011-2014.. Clin Infect Dis 2015 Jan 15;60(2):329.
      doi: 10.1093/cid/ciu791pubmed: 25301217google scholar: lookup
    5. Baroni EE, Díaz DC, Picco E, Waxman S, Rodríguez C, San Andrés MI, Boggio JC. Effects of age on the pharmacokinetics of single dose sulfamethazine after intravenous administration in cattle.. Vet Res Commun 2008 Oct;32(7):509-19.
      doi: 10.1007/s11259-008-9053-ypubmed: 18481189google scholar: lookup
    6. Elsheikha HM, Mansfield LS. Determination of the activity of sulfadiazine against Besnoitia darlingi tachyzoites in cultured cells.. Parasitol Res 2004 Aug;93(5):423-6.
      doi: 10.1007/s00436-004-1133-5pubmed: 15205942google scholar: lookup