FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
International journal for parasitology. Drugs and drug resistance2025; 27; 100580; doi: 10.1016/j.ijpddr.2025.100580

3′-deoxytubercidin: A potent therapeutic candidate for the treatment of Surra and Dourine.

Abstract: Surra and Dourine are widespread diseases caused by two protozoan parasites Trypanosoma brucei evansi and Trypanosoma brucei equiperdum, respectively. A wide range of animals including camels, horses, cattle and buffaloes are susceptible to infection. These diseases pose a significant socio-economic burden, primarily due to the limited therapeutic options and the complications associated with toxicity and drug resistance, making disease management particularly challenging. This study evaluated the potential of 3'-deoxytubercidin, a previously identified antitrypanosomal nucleoside, as a therapeutic candidate for Surra and Dourine using mouse models. Mice infected with either T. b. evansi or T. b. equiperdum were treated with 3'-deoxytubercidin at a dosage of 6.25 mg kg administrated intraperitoneally once daily for five consecutive days. The treatment resulted in full cure, as confirmed by both microscopic examination and quantitative PCR, without any observed toxicity. Given the importance of considering the One Health concept in developing new antiparasitic drugs for veterinary use, the environmental impact of 3'-deoxytubercidin was assessed through the ecotoxicity tests on aquatic organisms, conducted in accordance with OECD guidelines. The compound showed some toxicity to Daphnia (EC = 0.54 mg L in acute Daphnia test) but had no significant adverse effects on green alga at concentrations tested (up to 50 mg L). This study confirms the suitability of 3'-deoxytubercidin as an effective and safe therapeutic candidate for further development in the treatment of Surra and Dourine, highlighting its potential for improving disease management in affected regions.
Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.
Get Full Text
Publication Date: 2025-01-10 PubMed ID: 39827514PubMed Central: PMC11787584DOI: 10.1016/j.ijpddr.2025.100580Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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.

Overview

  • This study investigates 3′-deoxytubercidin as a promising drug candidate to treat Surra and Dourine, two serious parasitic diseases affecting various livestock.
  • Using mouse infection models, the research confirms the compound’s efficacy and safety while also evaluating its environmental impact.

Background and Importance

  • Surra and Dourine: Diseases caused by Trypanosoma brucei evansi (Surra) and Trypanosoma brucei equiperdum (Dourine).
  • Affected species: These parasites infect animals such as camels, horses, cattle, and buffaloes, which are critical for agriculture and transportation in many regions.
  • Socio-economic Burden: Infections lead to significant economic losses due to decreased productivity and mortality.
  • Challenges in Treatment: Existing treatments have limitations including toxicity and emerging drug resistance, complicating effective disease management.

Research Objectives

  • To evaluate 3′-deoxytubercidin, an antitrypanosomal nucleoside, as a therapeutic candidate for Surra and Dourine.
  • To assess the efficacy, safety, and potential environmental impact of this compound when used as a veterinary treatment.

Methodology

  • Experimental Model: Mouse models infected with either T. b. evansi or T. b. equiperdum to simulate Surra and Dourine infections.
  • Treatment Regime: Administered 3′-deoxytubercidin intraperitoneally at 6.25 mg/kg once daily for five consecutive days.
  • Evaluation of Efficacy:
    • Parasite clearance was monitored by microscopic examination of blood samples.
    • Quantitative PCR was used to confirm the absence of parasites at a molecular level.
  • Safety Assessment: Monitored for any signs of toxicity in treated mice during and after therapy.
  • Environmental Impact: Ecotoxicity tests conducted on aquatic organisms following OECD guidelines:
    • Acute toxicity to Daphnia species showed some effects at an EC50 (median effective concentration) of 0.54 mg/L.
    • No significant toxicity observed on green algae at concentrations up to 50 mg/L, indicating low environmental risk to this organism.

Key Findings

  • The treatment with 3′-deoxytubercidin led to a full cure in mouse models infected with T. b. evansi and T. b. equiperdum.
  • No observable toxicity in mice, indicating a favorable safety profile for the drug candidate.
  • Environmental testing revealed some toxicity toward Daphnia but minimal impact on green algae, suggesting manageable ecological risks when used with environmental considerations.

Significance and Conclusions

  • 3′-deoxytubercidin exhibits strong potential as a safe and effective treatment for Surra and Dourine, diseases with few effective therapies.
  • Its promising safety profile in animal models and controlled environmental impact makes it a suitable candidate for further veterinary development.
  • The study highlights the importance of the One Health approach, integrating animal health, human health, and environmental safety in drug development.
  • Successful development of this treatment could substantially improve disease control and reduce socio-economic losses in affected regions.

Cite This Article

APA
Ilbeigi K, Mabille D, Roy R, Bundschuh M, Van de Velde E, Hulpia F, Van Calenbergh S, Caljon G. (2025). 3′-deoxytubercidin: A potent therapeutic candidate for the treatment of Surra and Dourine. Int J Parasitol Drugs Drug Resist, 27, 100580. https://doi.org/10.1016/j.ijpddr.2025.100580

Publication

International journal for parasitology. Drugs and drug resistance
ISSN: 2211-3207
NlmUniqueID: 101576715
Country: Netherlands
Language: English
Volume: 27
Pages: 100580
PII: 100580

Researcher Affiliations

Ilbeigi, Kayhan
  • Laboratory of Microbiology, Parasitology and Hygiene, Infla-Med Centre of Excellence, University of Antwerp, 2610, Wilrijk, Belgium.
Mabille, Dorien
  • Laboratory of Microbiology, Parasitology and Hygiene, Infla-Med Centre of Excellence, University of Antwerp, 2610, Wilrijk, Belgium.
Roy, Rajdeep
  • iES Landau, Institute for Environmental Sciences, University of Kaiserslautern-Landau (RPTU), 76829, Landau, Germany.
Bundschuh, Mirco
  • iES Landau, Institute for Environmental Sciences, University of Kaiserslautern-Landau (RPTU), 76829, Landau, Germany.
Van de Velde, Ewout
  • Laboratory for Medicinal Chemistry (Campus Heymans), Ghent University, 9000, Gent, Belgium.
Hulpia, Fabian
  • Laboratory for Medicinal Chemistry (Campus Heymans), Ghent University, 9000, Gent, Belgium.
Van Calenbergh, Serge
  • Laboratory for Medicinal Chemistry (Campus Heymans), Ghent University, 9000, Gent, Belgium.
Caljon, Guy
  • Laboratory of Microbiology, Parasitology and Hygiene, Infla-Med Centre of Excellence, University of Antwerp, 2610, Wilrijk, Belgium. Electronic address: Guy.Caljon@uantwerpen.be.

MeSH Terms

  • Animals
  • Mice
  • Trypanocidal Agents / therapeutic use
  • Trypanocidal Agents / pharmacology
  • Trypanocidal Agents / administration & dosage
  • Trypanocidal Agents / toxicity
  • Trypanosoma brucei brucei / drug effects
  • Trypanosomiasis, African / drug therapy
  • Trypanosomiasis, African / parasitology
  • Trypanosomiasis, African / veterinary
  • Female
  • Disease Models, Animal

Conflict of Interest Statement

Declaration of competing interest 3′-Deoxytubercidin is subject of the patent “Nucleoside analogues for the treatment of parasitic infections”. Approval number: US11072628, date: January 01, 2021.

References

This article includes 26 references
  1. Aregawi WG, Agga GE, Abdi RD, Buscher P. Systematic review and meta-analysis on the global distribution, host range, and prevalence of Trypanosoma evansi.. Parasites Vectors 2019;12(1):67.
    doi: 10.1186/s13071-019-3311-4pmc: PMC6357473pubmed: 30704516google scholar: lookup
  2. ASTM. Standard guide for conducting acute toxicity tests on test materials with fishes, macroinvertebrates, and amphibians.. 2007.
  3. Brun R, Hecker H, Lun ZR. Trypanosoma evansi and T. equiperdum: distribution, biology, treatment and phylogenetic relationship (a review). Vet. Parasitol. 1998;79(2):95–107.
    doi: 10.1016/s0304-4017(98)00146-0pubmed: 9806490google scholar: lookup
  4. Buscher P, Gonzatti MI, Hebert L, Inoue N, Pascucci I, Schnaufer A, Suganuma K, Touratier L, Van Reet N. Equine trypanosomosis: enigmas and diagnostic challenges.. Parasites Vectors 2019;12(1):234.
    doi: 10.1186/s13071-019-3484-xpmc: PMC6518633pubmed: 31092285google scholar: lookup
  5. Calistri P, Narcisi V, Atzeni M, De Massis F, Tittarelli M, Mercante MT, Ruggieri E, Scacchia M. Dourine reemergence in Italy.. J. Equine Vet. Sci. 2013;33(2):83–89.
    doi: 10.1016/j.jevs.2012.05.057google scholar: lookup
  6. Dean S, Gould MK, Dewar CE, Schnaufer AC. Single point mutations in ATP synthase compensate for mitochondrial genome loss in trypanosomes.. Proc. Natl. Acad. Sci. U. S. A. 2013;110(36):14741–14746.
    doi: 10.1073/pnas.1305404110pmc: PMC3767566pubmed: 23959897google scholar: lookup
  7. Desquesnes M, Dargantes A, Lai DH, Lun ZR, Holzmuller P, Jittapalapong S. Trypanosoma evansi and surra: a review and perspectives on transmission, epidemiology and control, impact, and zoonotic aspects.. BioMed Res. Int. 2013;2013.
    doi: 10.1155/2013/321237pmc: PMC3789323pubmed: 24151595google scholar: lookup
  8. Eissa N, Hussein H, Wang H, Rabbi MF, Bernstein CN, Ghia JE. Stability of reference genes for messenger RNA quantification by real-time PCR in mouse dextran sodium sulfate experimental colitis.. PLoS One 2016;11(5).
    doi: 10.1371/journal.pone.0156289pmc: PMC4886971pubmed: 27244258google scholar: lookup
  9. Garric J, Vollat B, Duis K, Pery A, Junker T, Ramil M, Fink G, Ternes TA. Effects of the parasiticide ivermectin on the cladoceran Daphnia magna and the green alga Pseudokirchneriella subcapitata.. Chemosphere 2007;69(6):903–910.
    doi: 10.1016/j.chemosphere.2007.05.070pubmed: 17624408google scholar: lookup
  10. Gizaw Y, Megersa M, Fayera T. Dourine: a neglected disease of equids.. Trop. Anim. Health Prod. 2017;49(5):887–897.
    doi: 10.1007/s11250-017-1280-1pmc: PMC5432633pubmed: 28439783google scholar: lookup
  11. Gonzalez-Andrade P, Camara M, Ilboudo H, Bucheton B, Jamonneau V, Deborggraeve S. Diagnosis of trypanosomatid infections: targeting the spliced leader RNA.. J. Mol. Diagn. 2014;16(4):400–404.
    doi: 10.1016/j.jmoldx.2014.02.006pubmed: 24814957google scholar: lookup
  12. Gutierrez C, Desquesnes M, Touratier L, Buscher P. Trypanosoma evansi: recent outbreaks in Europe.. Vet. Parasitol. 2010;174(1–2):26–29.
    doi: 10.1016/j.vetpar.2010.08.012pubmed: 20851526google scholar: lookup
  13. Hebert L, Guitton E, Madeline A, Geraud T, Zientara S, Laugier C, Hans A, Buscher P, Cauchard J, Petry S. Melarsomine hydrochloride (Cymelarsan((R))) fails to cure horses with Trypanosoma equiperdum OVI parasites in their cerebrospinal fluid.. Vet. Parasitol. 2018;264:47–51.
    doi: 10.1016/j.vetpar.2018.11.005pubmed: 30503091google scholar: lookup
  14. Hulpia F, Mabille D, Campagnaro GD, Schumann G, Maes L, Roditi I, Hofer A, de Koning HP, Caljon G, Van Calenbergh S. Combining tubercidin and cordycepin scaffolds results in highly active candidates to treat late-stage sleeping sickness.. Nat. Commun. 2019;10(1):5564.
    doi: 10.1038/s41467-019-13522-6pmc: PMC6895180pubmed: 31804484google scholar: lookup
  15. Ilbeigi K, Barata C, Barbosa J, Bertram MG, Caljon G, Costi MP, Kroll A, Margiotta-Casaluci L, Thore ESJ, Bundschuh M. Assessing environmental risks during the drug development process for parasitic vector-borne diseases: a critical reflection.. ACS Infect. Dis. 2024;10(4):1026–1033.
    doi: 10.1021/acsinfecdis.4c00131pmc: PMC11019539pubmed: 38533709google scholar: lookup
  16. Kim J, Alvarez-Rodriguez A, Li Z, Radwanska M, Magez S. Recent progress in the detection of surra, a neglected disease caused by trypanosoma evansi with a one Health impact in large parts of the tropic and sub-tropic world.. Microorganisms 2023;12(1).
    doi: 10.3390/microorganisms12010044pmc: PMC10819111pubmed: 38257871google scholar: lookup
  17. Kumar R, Jain S, Kumar S, Sethi K, Kumar S, Tripathi BN. Impact estimation of animal trypanosomosis (surra) on livestock productivity in India using simulation model: current and future perspective.. Vet Parasitol Reg Stud Reports 2017;10:1–12.
    doi: 10.1016/j.vprsr.2017.06.008pubmed: 31014579google scholar: lookup
  18. Lai DH, Hashimi H, Lun ZR, Ayala FJ, Lukes J. Adaptations of Trypanosoma brucei to gradual loss of kinetoplast DNA: Trypanosoma equiperdum and Trypanosoma evansi are petite mutants of T. brucei.. Proc. Natl. Acad. Sci. U. S. A. 2008;105(6):1999–2004.
    doi: 10.1073/pnas.0711799105pmc: PMC2538871pubmed: 18245376google scholar: lookup
  19. Liebig M, Fernandez AA, Blubaum-Gronau E, Boxall A, Brinke M, Carbonell G, Egeler P, Fenner K, Fernandez C, Fink G, Garric J, Halling-Sorensen B, Knacker T, Krogh KA, Kuster A, Loffler D, Cots MA, Pope L, Prasse C, Duis K. Environmental risk assessment of ivermectin: a case study.. Integrated Environ. Assess. Manag. 2010;6(Suppl. l):567–587.
    doi: 10.1002/ieam.96pubmed: 20821718google scholar: lookup
  20. Luckins AG. Trypanosoma evansi in Asia.. Parasitol. Today 1988;4(5):137–142.
    doi: 10.1016/0169-4758(88)90188-3pubmed: 15463067google scholar: lookup
  21. Mabille D, Ilbeigi K, Hendrickx S, Ungogo MA, Hulpia F, Lin C, Maes L, de Koning HP, Van Calenbergh S, Caljon G. Nucleoside analogues for the treatment of animal trypanosomiasis.. Int J Parasitol Drugs Drug Resist 2022;19:21–30.
    doi: 10.1016/j.ijpddr.2022.05.001pmc: PMC9111543pubmed: 35567803google scholar: lookup
  22. . OECD Test No. 202: Daphnia sp. Acute Immobilisation Test.. 2004.
    doi: 10.1787/9789264069947-engoogle scholar: lookup
  23. . OECD Test No. 201: freshwater alga and cyanobacteria, growth inhibition test.. 2011.
    doi: 10.1787/9789264069923-engoogle scholar: lookup
  24. . OECD Test No. 211: Daphnia magna reproduction test.. 2012.
    doi: 10.1787/9789264185203-engoogle scholar: lookup
  25. Ranjithkumar M, Saravanan BC, Yadav SC, Kumar R, Singh R, Dey S. Neurological trypanosomiasis in quinapyramine sulfate-treated horses--a breach of the blood-brain barrier?. Trop. Anim. Health Prod. 2014;46(2):371–377.
    doi: 10.1007/s11250-013-0498-9pubmed: 24197687google scholar: lookup
  26. Tamarit A, Gutierrez C, Arroyo R, Jimenez V, Zagala G, Bosch I, Sirvent J, Alberola J, Alonso I, Caballero C. Trypanosoma evansi infection in mainland Spain.. Vet. Parasitol. 2010;167(1):74–76.
    doi: 10.1016/j.vetpar.2009.09.050pubmed: 19864069google scholar: lookup

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 100,280 horse owners like you who receive our email updates on horse health and nutrition.