Abstract
The aim of the present work was to determine the in vitro protoscolicidal effect of flubendazole (FLBZ) against Echinococcus granulosus. Protoscoleces of E. granulosus were incubated with FLBZ at concentrations of 10, 5 and 1 μg/ml. The first signs of FLBZ-induced damage were observed 3 days post-incubation. A clear protoscolicidal effect, reducing the vitality of protoscoleces to 35.6±0.7%, was observed after 18 days of incubation. After 25 days of FLBZ incubation (5 μg/ml), the percentage of vital protoscoleces was 13.9±5.9%. Protoscolex mortality was 100% (10 and 1 μg/ml) and 0.7±0.7% (5 μg/ml) after FLBZ incubation for 30 days. Results of vitality tests were consistent with the tissue damage observed at the ultrastructural level. The primary site of damage was the tegument of the parasite. The morphological changes included contraction of the soma region, formation of blebs on the tegument, rostellar disorganization, loss of hooks and destruction of microtriches. The data reported in this article demonstrate a clear in vitro effect of FLBZ against E. granulosus protoscoleces.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bekhti A, Schaaps JP, Capron M, Dessaint JP, Santoro F, Capron A (1977) Treatment of hepatic hydatid disease with mebendazole—preliminary results in four cases. Br Med J 2:1047–1051
Borgers M, De Nollin S (1975) Ultrastuctural changes in Ascaris suum intestine after mebendazole treatment in vivo. J Parasitol 61:110–122
Campbell WC, Blair LS (1974) Treatment of the cystic stage of Taenia crassiceps and Echinococcus multilocularis in laboratory animals. J Parasitol 60:1053–1054
Casado N, Rodríguez-Caabeiro F, Hernández S (1986) In vitro survival of Echinococcus granulosus protoescolices in several media, at 4°C and 37°C. Z Parasitenkd 72:273–278
Casado N, Rodríguez-Caabeiro F, Jiménez A, Criado A, De Armas C (1989) In vitro effects of levamisol and ivermectin against Echinococcus granulosus protoscoleces. Int J Parasitol 19:945–947
Casado N, Pérez-Serrano J, Denegri G, Rodríguez-Caabeiro F (1996) Development of a chemotherapeutic model for in vitro drug screening in Echinococcus granulosus cysts: assessment of the effects of albendazole and albendazole sulphoxide combination-therapy. Int J Parasitol 26:59–65
Chinnery JB, Morris DL (1986) Effect of albendazole sulphoxide on viability of hydatid protoscoleces in vitro. Trans R Soc Trop Med Hyg 80:815–817
Davis A, Pawlowski ZS, Dixon H (1986) Multicenter trials of benzimidazole-carbamates in human echinococcosis. Bull World Health Org 64:333–388
Eckert J, Schantz PM, Gasser RB, Torgerson PR, Bessonov AS, Movsessian SO, Thakur A, Grimm F, Nikogossian MA (2001) Geographic distribution and prevalence. In: J Eckert, Gemmell MA, Meslin FX, Pawlowski ZS (ed) WHO/OIE manual on echinococcosis in humans and animals: a public health problem of global concern. WHO/WOAH, Paris, pp 100–142
El-On J (2003) Benzimidazole treatment of cystic echinococcosis. Acta Trop 85:243–252
Franchi C, Di Vico B, Teggi A (1999) Long-term evaluation of patients with hydatidosis treated with benzimidazole carbamates. Clin Infect Dis 29:304–309
Friedman PA, Platzer EG (1978) Interaction of anthelmintic benzimidazoles and benzimidazole derivatives with bovine brain tubulin. Biochim Biophys Acta 544:605–614
Heath DD, Chevis RAF (1974) Mebendazole and hydatid cysts. Lancet 2:218–219
Horton J (2003) Albendazole for the treatment of echinococcosis. Fundam Clin Pharmacol 17:205–212
Jenkins DJ, Power K (1996) Human hydatidosis in New South Wales and the Australian Capital Territory 1987–1992. Med J Aust 164:18–21
Kassis AI, Tanner CE (1986) The role of complement in hydatid disease: in vitro studies. Int J Parasitol 6:25–35
Lacey E (1988) The role of the cytoskeletal protein, tubulin, in the mode of action and mechanism of drug resistance to benzimidazoles. Int J Parasitol 18:885–936
Lubega G, Prichard R (1991) Interaction of benzimidazole anthelmintics with Haemonchus contortus tubulin: binding affinity and anthelmintic efficacy. Exp Parasitol 73:203–209
Luider PJ, Robotti G, Meister FP, Bircher J (1985) High oral doses of Mebendazole interfere with growth of larval Echinococcus multilocularis lesions. J Hepatol 1:369–377
Morris DL, Chinnery JB, Ubhi C (1987) A comparison of the effects al albendazole, its sulphone metabolite, and mebendazole on the viability of protoscoleces of Echinococcus granulosus in an in vitro culture system. Trans R Soc Trop Med Hyg 81:804–806
Pérez-Serrano J, Casado N, Denegri G, Rodríguez-Caabeiro F (1994) The effects of albendazole and albendazole sulphoxide combination-therapy on Echinococcus granulosus in vitro. Int J Parasitol 24:219–224
Pérez-Serrano J, Martínez J, Denegri G, Casado N, Bodega G, Rodríguez-Caabeiro F (2001) In vitro effect of albendazole and albendazole sulphoxide on 70 and 60 kDa heat shock proteins in Echinococcus granulosus protoscolices. Res Rev Parasitol 61:67–71
Recco P, Hornus E, Frejevus J, Micheau P, Bessieres MH, Roques C, Linas, MD (1984) Hydatidose pleurale disseminee et hydatidoses hepatiques. Traitment post-operatoire par flubendazole a propos de 3 cas. Bull Soc Fran Parasitol 3:115–118
Richards KS, Morris DL, Daniels D, Riley EM (1988) Echinococcuc granulosus: the effects of praziquantel, in vivo and in vitro, on the ultrastructure of equine strain murine cysts. Parasitology 96:323–336
Rodríguez-Caabeiro F, Casado N, Juárez-Peláez E (1989) Efecto in vitro de praziquantel, mebendazole y oxfendazole sobre protoescólex de Echinococcus granulosus. Rev Iber Parasitol 49:77–83
Smyth JD, Howkins AB, Barton N (1966) Factors controlling the differentiation of hydatid organism. Echinococcus granulosus, into cysts or strobilar stages in vitro. Nature 211:1374–1377
Teggi A, Lastilla GM, De Rosa F (1993) Therapy of human hydatid disease with mebendazole and albendazole. Antimicrob Agents Chemother 37:1679–1684
Thompson RCA, Reynoldson JA, Riddler CR (1986) Praziquantel adversely affects protoscoleces of Echinococcus granulosus in vitro. J Helminthol 60:279–286
Torgerson PR, Budke CM (2003) Echinococcosis: an international public health challenge. Res Vet Sci 74:191–202
Urrea-Paris MA, Moreno MJ, Casado N, Rodríguez-Caabeiro F (1999) Echinococcus granulosus: praziquantel treatment against the metacestode stage. Parasitol Res 85:999–1006
Urrea-Paris MA, Moreno MJ, Casado N, Rodríguez-Caabeiro F (2000) In vitro effect of praziquantel and albendazole combination therapy of the larval stage of Echinococcus granulosus. Parasitol Res 86:957–964
Verheyen A (1982) Echinococcus granulosus: the influence of Mebendazole therapy on the ultrastructural morphology of the germinal layer of hydatid cysts in man and in mice. Z Parasitenkd 67:55–65
Acknowledgements
The authors acknowledge Dr. Leo Van Leemput (Janssen, Animal Health, Beerse, Belgium) and Dr. Gustavo Viana (Janssen, Buenos Aires, Argentina) for providing FLBZ used in the present experimental work and Dr. Kathleen Vlaminck (Janssen, Animal Health, Beerse, Belgium) for her critical review of this manuscript. The help of Dr. Gonzalez, Dr. Tessi and Sr. Chasma is gratefully appreciated. This work was supported by the PICT 02 No. 01-12535, BID 1201/OC-AR. Partial financial support of this work was provided by Fundación Alberto J. Roemmers, Argentina.
Author information
Authors and Affiliations
Corresponding author
Additional information
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
Rights and permissions
About this article
Cite this article
Elissondo, M., Dopchiz, M., Ceballos, L. et al. In vitro effects of flubendazole on Echinococcus granulosus protoscoleces. Parasitol Res 98, 317–323 (2006). https://doi.org/10.1007/s00436-005-0026-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00436-005-0026-6