Abstract
The aim of the present study was to determine the effective dose of fosfatriclaben through a field study in sheep naturally infected with F. hepatica. Thirty crossbred sheep positive for fluke eggs were selected for inclusion in the trial. On day 0, 5 groups of 6 animals each were formed for treatments: group 1 (G1), G2, and G3 received fosfatriclaben at 4, 6, and 8 mg/kg/IM, respectively. G4 received triclabendazole at 10 mg/kg/PO, and G5 was the untreated control group. Fecal samples of the sheep were analyzed to count the number of fluke eggs to evaluate the percentage of egg reduction. Twenty-one days after treatment, all sheep were humanely euthanized to extract the flukes from the bile ducts. They were counted to assess the percentage of fluke reduction. Fosfatriclaben reduced fluke eggs by 99.6, 99.6, and 100% and flukes by 94.3, 100, and 100%, respectively. Triclabendazole reduced fluke eggs by 95.2% and flukes by 100%. The fosfatriclaben injectable prodrug showed a high fasciolicidal efficacy similar to triclabendazole, with advantages over its predecessor, since only half the dose as compared to triclabendazole was required to remove eggs and flukes in the sheep that were studied.
Similar content being viewed by others
References
Arafa WF, Shokeir KM, Khateib AM (2015) Comparing an in vivo egg reduction test and in vitro egg hatching assay for different anthelmintics against Fasciola species, in cattle. Vet Parasitol 214:152–158. https://doi.org/10.1016/j.vetpar.2015.09.023
Arias-Garcia R, Vera-Montenegro Y, Flores-Ramos M, Castillo R, Hernandez-Campos A, Ibarra-Velarde F (2020) Efficiency comparison of experimental fosfatriclaben with three commercial fasciolicides in experimentally infected sheep. Parasitol Res 119:2687–2693. https://doi.org/10.1007/s00436-020-06705-4
Baggot JD (1992) Clinical pharmacokinetics in veterinary medicine. Clin Pharmacokinet 22(4):254–273. https://doi.org/10.2165/00003088-199222040-00002
Belew S, Suleman S, Wynendaele E, Duchateau L, De Spiegeleer B (2021) Environmental risk assessment of the anthelmintic albendazole in Eastern Africa, based on a systematic review. Environ Pollut 269:116106. https://doi.org/10.1016/j.envpol.2020.116106
Brockwell YM, Elliott TP, Anderson GR, Stanton R, Spithill TW, Sangster NC (2014) Confirmation of Fasciola hepatica resistant to triclabendazole in naturally infected Australian beef and dairy cattle. Int J Parasitol Drugs Drug Res 4(1):48–54. https://doi.org/10.1016/j.ijpddr.2013.11.005
Bϋscher, G., Bowen, FL., Strong, MB., Crowfoot, PD (1999). 17th International Conference of the WAAVP, Copenhagen, Denmark, August 1999. Efficacy of triclabendazole, its metabolites and other compounds in sheep. Abstract c7.40.
Ceballos L, Canton C, Pruzzo C, Sanabria R, Moreno L, Sanchis J, Suarez G, Ortiz P, Fairweather I, Lanusse C, Alvarez L, Martinez-Valladares M (2019) The egg hatch test: a useful tool for albendazole resistance diagnosis in Fasciola hepatica. Vet Parasitol 271:7–13. https://doi.org/10.1016/j.vetpar.2019.06.001
Fairweather I (2011a) Raising the bar on reporting ‘triclabendazole resistance.’ Vet Rec 168:514–515. https://doi.org/10.1136/vr.d2867
Fairweather I (2011b) Reducing the future threat from (liver) fluke: realistic prospect or quixotic fantasy? Vet Parasitol 180:133–143. https://doi.org/10.1016/j.vetpar.2011.05.034
Fairweather I, Boray JC (1999) Fasciolicides: efficacy, actions, resistance and its management. Vet J 158(2):81–112. https://doi.org/10.1053/tvjl.1999.0377
Fairweather I, Brennan GP, Hanna REB, Robinson MW, Skuce PJ (2020) Drug resistance in liver flukes. Int J Parasitol Drugs Drug Resist 12:39–59. https://doi.org/10.1016/j.ijpddr.2019.11.003
Fernández V, Estein S, Ortiz P, Luchessi P, Solano V, Solana HA (2015) A single aminoacid substitution in isozyme GSTmu in Triclabendazole resistant Fasciola hepatica (sligo strain) can substantially influence the manifestation of anthelmintic resistance. Exp Parasitol 159:274–279. https://doi.org/10.1016/j.exppara.2015.10.007
Flores M, Ibarra F, Jung H, Hernández A, Vera Y, Castillo R (2017) Novel triclabendazole prodrug: a highly water soluble alternative for the treatment of fasciolosis. Bioorg Med Chem Lett 27:616–619. https://doi.org/10.1016/j.bmcl.2016.12.004
Hanna REB, McMahon C, Ellison S, Edgar HW, Kajugu PE, Gordon A, Irwin D, Barley JP, Malone FE, Brennan GP, Fairweather I (2015) Fasciola hepatica: a comparative survey of adult fluke resistance to triclabendazole, nitroxynil and closantel on selected upland and lowland sheep farms in Northern Ireland using fecal egg counting, coproantigen ELISA testing and fluke histology. Vet Parasitol 207:34–43. https://doi.org/10.1016/j.vetpar.2014.11.016
Hutchinson GW, Dawson K, Fitzgibbon CC, Martin PJ (2009) Efficacy of an injectable combination anthelmintic (nitroxynil + clorsulon + ivermectin) against early immature Fasciola hepatica compared to triclabendazole combination flukicides given orally or topically to cattle. Vet Parasitol 162:278–284. https://doi.org/10.1016/j.vetpar.2009.03.032
Kamaludeen J, Graham-Brown J, Stephens N, Miller J, Howell A, Beesley N, Hodgkinson J, Learmount J, Williams D (2019) Lack of efficacy of triclabendazole against Fasciola hepatica is present on sheep farms in three regions of England, and Wales. Vet Rec 184:502–507. https://doi.org/10.1136/vr.105209
Keiser J, Kirchofer C, Haschke M, Huwyler J, Dong Y, Vennerstrom L, Vanhoff K, Kaminsky R, Malikides N (2010) Efficacy, safety and pharmacokinetics of 1,2,4- trioxalane OZ78 against an experimental infection with Fasciola hepatica in sheep. Vet Parasitol 173:228–235. https://doi.org/10.1016/j.vetpar.2010.06.031
Kelley JM, Elliot TP, Beddoe T, Anderson G, Skuce P, Spithill W (2016) Current threat of triclabendazole resistance in Fasciola hepatica. Trends Parasitol 32(6):458–469. https://doi.org/10.1016/j.pt.2016.03.002
Kelley JM, Rathinasamy V, Elliott TP, Rawlin G, Beddoe T, Stevenson MA, Spithill TW (2020) Determination of the prevalence and intensity of Fasciola hepatica infection in dairy cattle from six irrigation regions of Victoria, south-easter Australia, further identifying significant triclabendazole resistance on three properties. Vet Parasitol 277:109019. https://doi.org/10.1016/j.vetpar.2019.109019
Khadka P, Ro J, Kim H, Kim I, Kim JT, Kim H, Cho JM, Yun G, Lee J (2014) Pharmaceutical particle technologies: an approach to improve drug solubility, dissolution and bioavailability. Asian J Pharm Sci 9(6):304–316. https://doi.org/10.1016/j.ajps.2014.05.005
Martínez-Valladares M, Famularo MDR, Fernández-Pato N, Castañón-Ordonez L, Cordero-Pérez C, Rojo-Vázquez FA (2010) Efficacy of nitroxynil against Fasciola hepatica resistant to triclabendazole in a naturally infected sheep flock. Parasitol Res 107:1205–1211. https://doi.org/10.1007/s00436-010-1989-5
Martínez-Valladares M, Cordero-Pérez C, Rojo-Vázquez FA (2014) Efficacy of an anthelmintic combination in sheep infected with Fasciola hepatica resistant to albendazole and clorsulon. Exp Parasitol 136:59–62. https://doi.org/10.1016/j.exppara.2013.10.010
Mas-Coma S, Bargues MD, Valero MA (2018) Human fascioliasis infection sources, their diversity, incidence factors, analytical methods and prevention measures. Parasitology 145:1665–1699. https://doi.org/10.1017/S0031182018000914
McKellar QA (1997) Ecotoxicology and residues of anthelmintic compounds. Vet Parasitol 72:413–435. https://doi.org/10.1016/S0304-4017(97)00108-8
Mehmood K, Zhang H, Sabir AJ, Abbas RZ, Ijaz M, Durrani AZ, Saleem MH, Ur Rehman M, Iqbal MK, Wang Y, Ahmad HI, Abbas T, Hussain R, Ghori MT, Ali S, Khan AU, Li J (2017) A review on epidemiology, global prevalence and economical losses of fasciolosis in ruminants. Microb Pathog 109:253–262. https://doi.org/10.1016/j.micpath.2017.06.006
Novobilský A, Höglund J (2015) First report of closantel treatment failure against Fasciola hepatica in cattle. Int J Parasitol Drugs Drug Resist 5(3):172–177. https://doi.org/10.1016/j.ijpddr.2015.07.003
Novobilský A, Björk Averpilb H, Höglund J (2012) The field evaluation of albendazole and triclabendazole efficacy against Fasciola hepatica by coproantigen ELISA in naturally infected sheep. Vet Parasitol 190:272–276. https://doi.org/10.1016/j.vetpar.2012.06.022
Overend DJ, Bowen FL (1995) Resistance of Fasciola hepatica to triclabendazole. Aust Vet J 72:275–276. https://doi.org/10.1111/j.1751-0813.1995.tb03546.x
Porto RS, Rodrigues-Silva C, Schneider J, Rath S (2019) Benzimidazoles in wastewater: analytical method development, monitoring and degradation by photolysis and ozonation. J Environ Manage 232:729–737. https://doi.org/10.1016/j.jenvman.2018.11.121
Rojas-Campos T, Vera-Montenegro Y, Flores-Ramos M, Castillo R, Hernández-Campos A, Ibarra-Velarde F (2019) Effectiveness of the experimental Fosfatriclaben in comparison with two commercial fasciolicides in cattle. Pharmacology & Pharmacy 10(11):498–506. https://doi.org/10.4236/pp.2019.1011041
Taylor M, Coop R, Wall R (2015) Veterinary parasitology, 4th edn. Wiley-Blackwell, Hoboken Wolff K, Eckert J, Schneiter G, Lutz H (1983) Efficacy of triclabendazole against Fasciola hepatica in sheep and goats. Vet Parasitol 13:145–150. https://doi.org/10.1016/0304-4017(83)90074-2
Wolff K, Eckert J, Schneiter G, Lutz H (1983) Efficacy of triclabendazole against Fasciola hepatica in sheep and goats. Vet Parasitol 13:145–150. https://doi.org/10.1016/0304-4017(83)90074-2
Wood IB, Amaral NK, Bairden K, Duncan JL, Kassai T, Malone JB Jr, Pankavich JA, Reinecke RK, Slocombe O, Taylor SM, Vercruysse J (1995) World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) second edition of guidelines for evaluating the efficacy of anthelmintics in ruminants (bovine, ovine, cap- rine). Vet Parasitol 58:181–213. https://doi.org/10.1016/0304-4017(95)00806-2
Acknowledgements
Grateful acknowledgement for assistance is due to Dr. Ignacio Olave-Leyva from Facultad Veterinaria de Tulancingo, Hgo., Gerardo Francisco-Márquez from Facultad de Medicina Veterinaria y Zootecnia – UNAM. M. Flores-Ramos is very grateful to Dirección General de Asuntos del Personal Académico (DGAPA-UNAM) for the Postdoctoral fellowship granted.
Funding
This work was supported by the project PAPIIT, DGAPA, UNAM-IT201018.
All procedures performed in this work are in agreement with the ethical standards of institutional guidelines on the care and use of animals.
Author information
Authors and Affiliations
Corresponding author
Additional information
Section Editor: Georg von Samson-Himmelstjerna.
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ibarra-Velarde, F., Rojas-Campos, T., Vera-Montenegro, Y. et al. Field study on the determination of the effective dose of injectable fosfatriclaben prodrug in sheep naturally infected with Fasciola hepatica. Parasitol Res 121, 433–440 (2022). https://doi.org/10.1007/s00436-021-07366-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00436-021-07366-7