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Parasitology Research

, Volume 103, Issue 3, pp 517–522 | Cite as

Efficacy and safety of artemether against a natural Fasciola hepatica infection in sheep

  • Jennifer KeiserEmail author
  • Laura Rinaldi
  • Vincenzo Veneziano
  • Laura Mezzino
  • Marcel Tanner
  • Jürg Utzinger
  • Giuseppe Cringoli
Original Paper

Abstract

Triclabendazole is the current drug of choice against Fasciola spp. infections in livestock, but resistance has become a major problem. In this study, we assessed the efficacy and safety of artemether, a derivative of artemisinin, in sheep with a low natural Fasciola hepatica infection. Artemether was administered orally or intramuscularly; sheep were monitored for 8 h posttreatment and then once daily for adverse events, and drug efficacy was estimated by fecal egg count reductions and worm burden reductions. Single 40- and 80-mg/kg oral doses of artemether showed no effect on F. hepatica egg and worm burden. Treatment with a single 160-mg/kg intramuscular dose of artemether significantly reduced the egg burden (64.9%) and worm burden (91.3%). At half this dose, a worm burden reduction of 65.3% was obtained, which was still statistically significant (P < 0.05). The lowest intramuscular dose of artemether investigated (40 mg/kg) yielded no effect on egg counts and worm burden. There were no adverse events due to artemether; however, two abortions were observed 7 days posttreatment. In conclusion, artemether shows interesting fasciocidal properties in sheep, but embryotoxicity is of concern. Further studies are warranted to assess the potential of additional artemisinin derivatives and other peroxidic compounds for the treatment of Fasciola spp. infections in different ruminants.

Keywords

Artemisinin Artesunate Worm Burden Artemether Artemisinin Derivative 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We are grateful to the farmer Mr. Massimo Lullo for his kind collaboration, and thank Dafra Pharma and Kunming Pharmaceutical Cooperation for the supply of artemether powder. We thank Prof. Xiao Shuhua for his collaboration and many discussions on the anti-trematocidal activities of the artemisinins. This investigation received financial support from the Swiss Tropical Institute, the Swiss National Science Foundation via projects PPOOA-114941 (to J. Keiser) and PPOOB-102883 and PPOOB-119129 (to J. Utzinger).

References

  1. Adam I, Elwasila E, Mohammed Ali DA, Elansari E, Elbashir MI (2004) Artemether in the treatment of Plasmodium falciparum malaria during pregnancy in eastern Sudan. Trans R Soc Trop Med Hyg 98:509–513PubMedCrossRefGoogle Scholar
  2. Alvarez-Sanchez MA, Mainar-Jaime RC, Perez-Garcia J, Rojo-Vazquez FA (2006) Resistance of Fasciola hepatica to triclabendazole and albendazole in sheep in Spain. Vet Rec 159:424–425PubMedGoogle Scholar
  3. Chen LJ, Wang MY, Sun WK, Liu MZ (1984) Embryotoxicity and teratogenicity studies on artemether in mice, rats and rabbits. Zhongguo Yaoli Xuebao 5:118–122PubMedGoogle Scholar
  4. Clark RL, White TE, A Clode S, Gaunt I, Winstanley P, Ward SA (2004) Developmental toxicity of artesunate and an artesunate combination in the rat and rabbit. Birth Defects Res B Dev Reprod Toxicol 71:380–394PubMedCrossRefGoogle Scholar
  5. Cringoli G (2006) FLOTAC, a novel apparatus for a multivalent faecal egg count technique. Parassitologia 48:381–384PubMedGoogle Scholar
  6. Cringoli G, Rinaldi L, Veneziano V, Capelli G, Scala A (2004) The influence of flotation solution, sample dilution and the choice of McMaster slide area (volume) on the reliability of the McMaster technique in estimating the faecal egg counts of gastrointestinal strongyles and Dicrocoelium dendriticum in sheep. Vet Parasitol 123:121–131PubMedCrossRefGoogle Scholar
  7. Davis TM, Karunajeewa HA, Ilett KF (2005) Artemisinin-based combination therapies for uncomplicated malaria. Med J Aust 182:181–185PubMedGoogle Scholar
  8. Fairweather I, Boray JC (1999) Mechanism of fasciolide action and drug resistance in Fasciola hepatica. In: Dalton JP (ed) Fasciolosis. CABI Publishing, Dublin, Ireland, pp 225–276Google Scholar
  9. Formentini EA, Mestorino N, Errecalde JO (2005) Pharmacokinetics of ricobendazole after its intravenous, intraruminal and subcutaneous administration in sheep. Vet Res Commun 29:595–608PubMedCrossRefGoogle Scholar
  10. Hien TT, Truong NT, Minh NH, Dat HD, Dung NT, Hue NT, Dung TK, Tuan PQ, Campbell JI, Farrar JJ, Day JN (2008) A randomized controlled pilot study of artesunate versus triclabendazole for human fascioliasis in central Vietnam. Am J Trop Med Hyg 78:388–392PubMedGoogle Scholar
  11. Huo JZ, Xia WJ, Xue M, Zhou ZT (1991) Pharmacokinetics and metabolism of artesunate in cows. Yao Xue Xue Bao 26:225–227 (in Chinese)PubMedGoogle Scholar
  12. Keiser J, Utzinger J (2007) Advances in the discovery and development of novel trematocidal drugs. Expert Opin Drug Discov 2(Suppl 1):9–23CrossRefGoogle Scholar
  13. Keiser J, Engels D, Büscher G, Utzinger J (2005) Triclabendazole for the treatment of fascioliasis and paragonimiasis. Expert Opin Invest Drugs 14:1513–1526CrossRefGoogle Scholar
  14. Keiser J, Xiao SH, Tanner M, Utzinger J (2006a) Artesunate and artemether are effective fasciolicides in the rat model and in vitro. J Antimicrob Chemother 57:1139–1145PubMedCrossRefGoogle Scholar
  15. Keiser J, Utzinger J, Tanner M, Dong Y, Vennerstrom JL (2006b) The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola hepatica. J Antimicrob Chemother 58:1193–1197PubMedCrossRefGoogle Scholar
  16. McGready R, Cho T, Keo NK, Thwai KL, Villegas L, Looareesuwan S, White NJ, Nosten F (2001) Artemisinin antimalarials in pregnancy: a prospective treatment study of 539 episodes of multidrug-resistant Plasmodium falciparum. Clin Infect Dis 33:2009–2016PubMedCrossRefGoogle Scholar
  17. McManus DP, Dalton JP (2006) Vaccines against the zoonotic trematodes Schistosoma japonicum, Fasciola hepatica and Fasciola gigantica. Parasitology 133(Suppl):43–61CrossRefGoogle Scholar
  18. Molina EC, Gonzaga EA, Lumbao LA (2005) Prevalence of infection with Fasciola gigantica and its relationship to carcase and liver weights, and fluke and egg counts in slaughter cattle and buffaloes in southern Mindanao, Philippines. Trop Anim Health Prod 37:215–221PubMedCrossRefGoogle Scholar
  19. Nontprasert A, Pukrittayakamee S, Dondorp AM, Clemens R, Looareesuwan S, White NJ (2002) Neuropathologic toxicity of artemisinin derivatives in a mouse model. Am J Trop Med Hyg 67:423–429PubMedGoogle Scholar
  20. Rioux MC, Carmona C, Acosta D, Ward B, Ndao M, Gibbs BF, Bennett HP, Spithill TW (2007) Discovery and validation of serum biomarkers expressed over the first twelve weeks of Fasciola hepatica infection in sheep. Int J Parasitol 38:123–136PubMedCrossRefGoogle Scholar
  21. Schweizer G, Braun U, Deplazes P, Torgerson PR (2005) Estimating the financial losses due to bovine fasciolosis in Switzerland. Vet Rec 157:188–193PubMedGoogle Scholar
  22. Silamut K, Newton PN, Teja-Isavadharm P, Suputtamongkol Y, Siriyanonda D, Rasameesoraj M, Pukrittayakamee S, White NJ (2003) Artemether bioavailability after oral or intramuscular administration in uncomplicated falciparum malaria. Antimicrob Agents Chemother 47:3795–3798PubMedCrossRefGoogle Scholar
  23. Utzinger J, Xiao SH, Tanner M, Keiser J (2007) Artemisinins for schistosomiasis and beyond. Curr Opin Invest Drugs 8:105–116Google Scholar
  24. Vandamme TF, Ellis KJ (2004) Issues and challenges in developing ruminal drug delivery systems. Adv Drug Deliv Rev 56:1415–1436PubMedCrossRefGoogle Scholar
  25. Vennerstrom JL, Arbe-Barnes S, Brun R, Charman SA, Chiu FC, Chollet J, Dong Y, Dorn A, Hunziker D, Matile H, McIntosh K, Padmanilayam M, Santo Tomas J, Scheurer C, Scorneaux B, Tang Y, Urwyler H, Wittlin S, Charman WN (2004) Identification of an antimalarial synthetic trioxolane drug development candidate. Nature 430:900–904PubMedCrossRefGoogle Scholar
  26. 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, caprine). Vet Parasitol 58:181–213PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Jennifer Keiser
    • 1
    Email author
  • Laura Rinaldi
    • 2
  • Vincenzo Veneziano
    • 2
  • Laura Mezzino
    • 2
  • Marcel Tanner
    • 3
  • Jürg Utzinger
    • 3
  • Giuseppe Cringoli
    • 2
  1. 1.Department of Medical Parasitology and Infection BiologySwiss Tropical InstituteBaselSwitzerland
  2. 2.Department of Pathology and Animal Health, CREMOPAR Regione CampaniaUniversity of Naples “Federico II”NaplesItaly
  3. 3.Department of Public Health and EpidemiologySwiss Tropical InstituteBaselSwitzerland

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