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Pathogens (Basel, Switzerland)2020; 9(12); 1035; doi: 10.3390/pathogens9121035

Imidocarb Dipropionate Lacks Efficacy against Theileria haneyi and Fails to Consistently Clear Theileria equi in Horses Co-Infected with T. haneyi.

Abstract: Control of , the primary cause of equine theileriosis, is largely reliant on acaracide use and chemosterilization with imidocarb dipropionate (ID). However, it is currently unknown if ID is effective against , the recently identified second causative agent of equine theileriosis, or if the drug maintains effectiveness against in the presence of co-infection. The purpose of this study was to address these questions using ID treatment of the following three groups of horses: (1) five infected horses; (2) three - infected horses; and (3) three - infected horses. Clearance was first evaluated using nPCR for each sp. on peripheral blood samples. ID failed to clear in all three groups of horses, and failed to clear in two of three horses in group two. For definitive confirmation of infection status, horses in groups two and three underwent splenectomy post-treatment. The -nPCR-positive horses in group two developed severe clinical signs and were euthanized. Remaining horses exhibited moderate signs consistent with . Our results demonstrate that ID therapy lacks efficacy against , and - co-infection may interfere with ID clearance of .
Publication Date: 2020-12-10 PubMed ID: 33321715PubMed Central: PMC7764667DOI: 10.3390/pathogens9121035Google Scholar: Lookup
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  • Journal Article

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.

The research article discusses a study investigating the effectiveness of the drug imidocarb dipropionate (ID) in treating a disease in horses known as equine theileriosis, caused by two types of pathogens; Theileria equi and Theileria haneyi. The study findings indicate that ID treatment is ineffective in eradicating these pathogens, particularly in horses co-infected with both.

Study Objective and Methodology

  • The study aims to explore the efficacy of the drug, imidocarb dipropionate (ID), popularly used for controlling Theileria equi, the main causative agent of equine theileriosis. The researchers also aimed to determine if the drug remains effective against Theileria equi in horses co-infected with a newly identified pathogen, Theileria haneyi.
  • The researchers executed their study by treating three groups of horses with ID. The first group consisted of five horses infected with Theileria equi, the second group had three horses infected with Theileria haneyi, and the third group comprised three horses co-infected with both pathogens.
  • The researchers evaluated the clearance of the disease by taking peripheral blood samples and testing them with a technique called nPCR
  • For final confirmation of infection statuses, the horses from the second and third groups underwent a surgical procedure called a splenectomy (removal of the spleen) after the ID treatment.

Main Findings

  • The results indicated that ID could not eliminate Theileria haneyi from any of the horses in the three groups. In the second group, it failed to eliminate Theileria equi from two out of three horses. These findings suggest a potential inadequacy in the current treatment approach for equine theileriosis.
  • Horses tested positive for Theileria haneyi nPCR from the second group developed severe clinical signs following the splenectomy and were subsequently euthanized. Remaining horses developed moderate symptoms consistent with Theileria equi.

Conclusion

  • Findings from the study show that imidocarb dipropionate lacks efficacy in treating infections caused by Theileria haneyi and has inconsistent results in eradicating Theileria equi, especially in horses co-infected with both pathogens.
  • This research uncovers potential gaps in the current best-practice treatment for equine theileriosis, indicating the need for further research on therapeutic options to more effectively manage and treat this common equine disease.

Cite This Article

APA
Sears K, Knowles D, Dinkel K, Mshelia PW, Onzere C, Silva M, Fry L. (2020). Imidocarb Dipropionate Lacks Efficacy against Theileria haneyi and Fails to Consistently Clear Theileria equi in Horses Co-Infected with T. haneyi. Pathogens, 9(12), 1035. https://doi.org/10.3390/pathogens9121035

Publication

ISSN: 2076-0817
NlmUniqueID: 101596317
Country: Switzerland
Language: English
Volume: 9
Issue: 12
PII: 1035

Researcher Affiliations

Sears, Kelly
  • Department of Veterinary Microbiology and Pathology, Program in Vector-borne Diseases, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
Knowles, Donald
  • Department of Veterinary Microbiology and Pathology, Program in Vector-borne Diseases, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
Dinkel, Kelcey
  • Department of Veterinary Microbiology and Pathology, Program in Vector-borne Diseases, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
Mshelia, Philip W
  • Department of Veterinary Microbiology and Pathology, Program in Vector-borne Diseases, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
  • Department of Veterinary Medicine, Ahmadu Bello University, Zaria 810253, Nigeria.
Onzere, Cynthia
  • Department of Veterinary Microbiology and Pathology, Program in Vector-borne Diseases, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
Silva, Marta
  • Department of Veterinary Microbiology and Pathology, Program in Vector-borne Diseases, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
  • CureVac AG, 72076 Tubingen, Germany.
Fry, Lindsay
  • Department of Veterinary Microbiology and Pathology, Program in Vector-borne Diseases, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
  • Animal Disease Research Unit, USDA-ARS, Pullman, WA 99164, USA.

Grant Funding

  • 2090-320000-034-00D / Agricultural Research Service
  • No number / Washington State University, College of Veterinary Medicine Equine Infectious Disease Research Program

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 39 references
  1. Wise LN, Pelzel-McCluskey AM, Mealey RH, Knowles DP. Equine piroplasmosis.. Vet Clin North Am Equine Pract 2014 Dec;30(3):677-93.
    doi: 10.1016/j.cveq.2014.08.008pubmed: 25300637google scholar: lookup
  2. Scoles GA, Ueti MW. Vector ecology of equine piroplasmosis.. Annu Rev Entomol 2015 Jan 7;60:561-80.
  3. Camino E, Pozo P, Dorrego A, Carvajal KA, Buendia A, Gonzalez S, de Juan L, Dominguez L, Cruz-Lopez F. Importance of equine piroplasmosis antibody presence in Spanish horses prior to export.. Ticks Tick Borne Dis 2020 Mar;11(2):101329.
    doi: 10.1016/j.ttbdis.2019.101329pubmed: 31734215google scholar: lookup
  4. Wise LN, Kappmeyer LS, Mealey RH, Knowles DP. Review of equine piroplasmosis.. J Vet Intern Med 2013 Nov-Dec;27(6):1334-46.
    doi: 10.1111/jvim.12168pubmed: 24033559google scholar: lookup
  5. Guimarães AM, Lima JD, Tafuri WL, Ribeiro MFB, Sciavicco CJS, Botelho ACC. Clinical and histopathological aspects of splenectomized foals infected by Babesia equi.. J. Equine Vet. Sci. 1997;17:211–216.
  6. Kuttler KL, Gipson CA, Goff WL, Johnson LW. Experimental Babesia equi infection in mature horses.. Am J Vet Res 1986 Aug;47(8):1668-70.
    pubmed: 3530065
  7. Singh B, Banerjee DP, Gautam OP, Gupta RKP. Clinicopathological changes in splenectomised donkeys infected with Babesia equi.. Indian J. Parasitol. 1980;4:77–80.
  8. Ueti MW, Mealey RH, Kappmeyer LS, White SN, Kumpula-McWhirter N, Pelzel AM, Grause JF, Bunn TO, Schwartz A, Traub-Dargatz JL, Hendrickson A, Espy B, Guthrie AJ, Fowler WK, Knowles DP. Re-emergence of the apicomplexan Theileria equi in the United States: elimination of persistent infection and transmission risk.. PLoS One 2012;7(9):e44713.
  9. Ambawat HK, Malhotra DV, Kumar S, Dhar S. Erythrocyte associated haemato-biochemical changes in Babesia equi infection experimentally produced in donkeys.. Vet Parasitol 1999 Sep 1;85(4):319-24.
    doi: 10.1016/S0304-4017(99)00110-7pubmed: 10488734google scholar: lookup
  10. Cunha CW, McGuire TC, Kappmeyer LS, Hines SA, Lopez AM, Dellagostin OA, Knowles DP. Development of specific immunoglobulin Ga (IgGa) and IgGb antibodies correlates with control of parasitemia in Babesia equi Infection.. Clin Vaccine Immunol 2006 Feb;13(2):297-300.
  11. Lewis MJ, Wagner B, Woof JM. The different effector function capabilities of the seven equine IgG subclasses have implications for vaccine strategies.. Mol Immunol 2008 Feb;45(3):818-27.
  12. Knowles DP Jr, Kappmeyer LS, Stiller D, Hennager SG, Perryman LE. Antibody to a recombinant merozoite protein epitope identifies horses infected with Babesia equi.. J Clin Microbiol 1992 Dec;30(12):3122-6.
  13. Bishop RP, Kappmeyer LS, Onzere CK, Odongo DO, Githaka N, Sears KP, Knowles DP, Fry LM. Equid infective Theileria cluster in distinct 18S rRNA gene clades comprising multiple taxa with unusually broad mammalian host ranges.. Parasit Vectors 2020 May 19;13(1):261.
    doi: 10.1186/s13071-020-04131-0pmc: PMC7236219pubmed: 32430015google scholar: lookup
  14. Knowles DP, Kappmeyer LS, Haney D, Herndon DR, Fry LM, Munro JB, Sears K, Ueti MW, Wise LN, Silva M, Schneider DA, Grause J, White SN, Tretina K, Bishop RP, Odongo DO, Pelzel-McCluskey AM, Scoles GA, Mealey RH, Silva JC. Discovery of a novel species, Theileria haneyi n. sp., infective to equids, highlights exceptional genomic diversity within the genus Theileria: implications for apicomplexan parasite surveillance.. Int J Parasitol 2018 Aug;48(9-10):679-690.
    doi: 10.1016/j.ijpara.2018.03.010pubmed: 29885436google scholar: lookup
  15. Sears KP, Kappmeyer LS, Wise LN, Silva M, Ueti MW, White S, Reif KE, Knowles DP. Infection dynamics of Theileria equi and Theileria haneyi, a newly discovered apicomplexan of the horse.. Vet Parasitol 2019 Jul;271:68-75.
    doi: 10.1016/j.vetpar.2019.06.009pubmed: 31303207google scholar: lookup
  16. Coultous RM, McDonald M, Raftery AG, Shiels BR, Sutton DGM, Weir W. Analysis of Theileria equi diversity in The Gambia using a novel genotyping method.. Transbound Emerg Dis 2020 May;67(3):1213-1221.
    doi: 10.1111/tbed.13454pubmed: 31845493google scholar: lookup
  17. Bhoora RV, Collins NE, Schnittger L, Troskie C, Marumo R, Labuschagne K, Smith RM, Dalton DL, Mbizeni S. Molecular genotyping and epidemiology of equine piroplasmids in South Africa.. Ticks Tick Borne Dis 2020 Mar;11(2):101358.
    doi: 10.1016/j.ttbdis.2019.101358pubmed: 31870636google scholar: lookup
  18. Mshelia PW, Kappmeyer L, Johnson WC, Kudi CA, Oluyinka OO, Balogun EO, Richard EE, Onoja E, Sears KP, Ueti MW. Molecular detection of Theileria species and Babesia caballi from horses in Nigeria.. Parasitol Res 2020 Sep;119(9):2955-2963.
    doi: 10.1007/s00436-020-06797-ypmc: PMC7431391pubmed: 32647992google scholar: lookup
  19. Frerichs WM, Allen PC, Holbrook AA. Equine piroplasmosis (Babesia equi): therapeutic trials of imidocarb dihydrochloride in horses and donkeys.. Vet Rec 1973 Jul 21;93(3):73-5.
    doi: 10.1136/vr.93.3.73pubmed: 4748680google scholar: lookup
  20. Grause JF, Ueti MW, Nelson JT, Knowles DP, Kappmeyer LS, Bunn TO. Efficacy of imidocarb dipropionate in eliminating Theileria equi from experimentally infected horses.. Vet J 2013 Jun;196(3):541-6.
    doi: 10.1016/j.tvjl.2012.10.025pubmed: 23199699google scholar: lookup
  21. Meyer C, Guthrie AJ, Stevens KB. Clinical and clinicopathological changes in 6 healthy ponies following intramuscular administration of multiple doses of imidocarb dipropionate.. J S Afr Vet Assoc 2005 Mar;76(1):26-32.
    doi: 10.4102/jsava.v76i1.390pubmed: 15900897google scholar: lookup
  22. Adams LG. Clinicopathological aspects of imidocarb dipropionate toxicity in horses.. Res Vet Sci 1981 Jul;31(1):54-61.
    doi: 10.1016/S0034-5288(18)32521-9pubmed: 7313320google scholar: lookup
  23. Kutscha J, Sutton DG, Preston T, Guthrie AJ. Equine piroplasmosis treatment protocols: specific effect on orocaecal transit time as measured by the lactose 13C-ureide breath test.. Equine Vet J Suppl 2012 Dec;(43):62-7.
  24. Wise LN, Kappmeyer LS, Silva MG, White SN, Grause JF, Knowles DP. Verification of post-chemotherapeutic clearance of Theileria equi through concordance of nested PCR and immunoblot.. Ticks Tick Borne Dis 2018 Feb;9(2):135-140.
    doi: 10.1016/j.ttbdis.2017.08.007pubmed: 28887100google scholar: lookup
  25. Hines SA, Ramsay JD, Kappmeyer LS, Lau AO, Ojo KK, Van Voorhis WC, Knowles DP, Mealey RH. Theileria equi isolates vary in susceptibility to imidocarb dipropionate but demonstrate uniform in vitro susceptibility to a bumped kinase inhibitor.. Parasit Vectors 2015 Jan 20;8:33.
    doi: 10.1186/s13071-014-0611-6pmc: PMC4311422pubmed: 25600252google scholar: lookup
  26. Pasolini MP, Pagano TB, Costagliola A, Biase D, Lamagna B, Auletta L, Fatone G, Greco M, Coluccia P, Vincenzo V, Pirozzi C, Raso GM, Santoro P, Manna G, Papparella S, Paciello O. Inflammatory Myopathy in Horses With Chronic Piroplasmosis.. Vet Pathol 2018 Jan;55(1):133-143.
    doi: 10.1177/0300985817716262pubmed: 28718360google scholar: lookup
  27. Butler CM, Werners AH, de Haseth OB, van Maanen C. Strain variations might determine the effectiveness of multiple high doses of imidocarb dipropionate treatment in T. equi carrier horses. Proceedings of the 6th Congress of the European College of Equine Internal Medicine; Le Touquet, France. 7–9 February 2013; pp. 696–710.
  28. De Waal DT, Van Heerden J, Van den Berg SS, Stegmann GF, Potgieter FT. Isolation of pure Babesia equi and Babesia caballi organisms in splenectomized horses from endemic areas in South Africa.. Onderstepoort J Vet Res 1988 Mar;55(1):33-5.
    pubmed: 3353098
  29. Bushman M, Morton L, Duah N, Quashie N, Abuaku B, Koram KA, Dimbu PR, Plucinski M, Gutman J, Lyaruu P, Kachur SP, de Roode JC, Udhayakumar V. Within-host competition and drug resistance in the human malaria parasite Plasmodium falciparum.. Proc Biol Sci 2016 Mar 16;283(1826):20153038.
    doi: 10.1098/rspb.2015.3038pmc: PMC4810865pubmed: 26984625google scholar: lookup
  30. Hansen J, Day T. Coinfection and the evolution of drug resistance.. J Evol Biol 2014 Dec;27(12):2595-604.
    doi: 10.1111/jeb.12518pubmed: 25417787google scholar: lookup
  31. Karvonen A, Jokela J, Laine AL. Importance of Sequence and Timing in Parasite Coinfections.. Trends Parasitol 2019 Feb;35(2):109-118.
    doi: 10.1016/j.pt.2018.11.007pubmed: 30578150google scholar: lookup
  32. Gimenez F, Hines SA, Evanoff R, Ojo KK, Van Voorhis WC, Maly DJ, Vidadala RSR, Mealey RH. In vitro growth inhibition of Theileria equi by bumped kinase inhibitors.. Vet Parasitol 2018 Feb 15;251:90-94.
  33. G Silva M, Knowles DP, Antunes S, Domingos A, Esteves MA, Suarez CE. Inhibition of the in vitro growth of Babesia bigemina, Babesia caballi and Theileria equi parasites by trifluralin analogues.. Ticks Tick Borne Dis 2017 Jun;8(4):593-597.
    doi: 10.1016/j.ttbdis.2017.04.002pubmed: 28416183google scholar: lookup
  34. Silva MG, Villarino NF, Knowles DP, Suarez CE. Assessment of Draxxin(®) (tulathromycin) as an inhibitor of in vitro growth of Babesia bovis, Babesia bigemina and Theileria equi.. Int J Parasitol Drugs Drug Resist 2018 Aug;8(2):265-270.
  35. Bowden GD, Reis PM, Rogers MB, Bone Relat RM, Brayton KA, Wilson SK, Di Genova BM, Knoll LJ, Nepveux V FJ, Tai AK, Ramadhar TR, Clardy J, O'Connor RM. A conserved coccidian gene is involved in Toxoplasma sensitivity to the anti-apicomplexan compound, tartrolon E.. Int J Parasitol Drugs Drug Resist 2020 Dec;14:1-7.
  36. O'Connor RM, Nepveux V FJ, Abenoja J, Bowden G, Reis P, Beaushaw J, Bone Relat RM, Driskell I, Gimenez F, Riggs MW, Schaefer DA, Schmidt EW, Lin Z, Distel DL, Clardy J, Ramadhar TR, Allred DR, Fritz HM, Rathod P, Chery L, White J. A symbiotic bacterium of shipworms produces a compound with broad spectrum anti-apicomplexan activity.. PLoS Pathog 2020 May;16(5):e1008600.
  37. Bertone JGH, Sislak M, Agnic H, Heidmiller M, Stanley S, Wickler S. Pharmacokinetics, Pharmacodynamics, and Safety of N-Butylscopolammonium Bromide Administered Intramuscularly Versus Intravenously. Proceedings of the American Association of Equine Practitioners; Baltimore, MD, USA. 4–8 December 2010; pp. 279–280.
  38. Ueti MW, Palmer GH, Scoles GA, Kappmeyer LS, Knowles DP. Persistently infected horses are reservoirs for intrastadial tick-borne transmission of the apicomplexan parasite Babesia equi.. Infect Immun 2008 Aug;76(8):3525-9.
    doi: 10.1128/IAI.00251-08pmc: PMC2493223pubmed: 18490466google scholar: lookup
  39. Roberts MC, Groenendyk S. Splenectomy in the horse.. Aust Vet J 1978 Apr;54(4):196-7.

Citations

This article has been cited 4 times.
  1. Onzere CK, Hulbert M, Sears KP, Williams LBA, Fry LM. Tulathromycin and Diclazuril Lack Efficacy against Theileria haneyi, but Tulathromycin Is Not Associated with Adverse Clinical Effects in Six Treated Adult Horses.. Pathogens 2023 Mar 14;12(3).
    doi: 10.3390/pathogens12030453pubmed: 36986375google scholar: lookup
  2. Paulino PG, Peckle M, Mendonça LP, Massard CL, Antunes S, Couto J, Domingos A, Guedes Junior DDS, Cabezas-Cruz A, Santos HA. Differential Expression of Immune Genes in the Rhipicephalus microplus Gut in Response to Theileria equi Infection.. Pathogens 2022 Dec 6;11(12).
    doi: 10.3390/pathogens11121478pubmed: 36558812google scholar: lookup
  3. Sears KP, Knowles DP, Fry LM. Clinical Progression of Theileria haneyi in Splenectomized Horses Reveals Decreased Virulence Compared to Theileria equi.. Pathogens 2022 Feb 16;11(2).
    doi: 10.3390/pathogens11020254pubmed: 35215197google scholar: lookup
  4. Bastos RG, Sears KP, Dinkel KD, Kappmeyer L, Ueti MW, Knowles DP, Fry LM. Development of an Indirect ELISA to Detect Equine Antibodies to Theileria haneyi.. Pathogens 2021 Feb 27;10(3).
    doi: 10.3390/pathogens10030270pubmed: 33673478google scholar: lookup