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Echinococcus metacestodes as laboratory models for the screening of drugs against cestodes and trematodes

  • A. HEMPHILL (a1), B. STADELMANN (a1), S. SCHOLL (a1), J. MÜLLER (a1), M. SPILIOTIS (a1), N. MÜLLER (a1), B. GOTTSTEIN (a1) and M. SILES-LUCAS (a2)...

Summary

Among the cestodes, Echinococcus granulosus, Echinococcus multilocularis and Taenia solium represent the most dangerous parasites. Their larval stages cause the diseases cystic echinococcosis (CE), alveolar echincoccosis (AE) and cysticercosis, respectively, which exhibit considerable medical and veterinary health concerns with a profound economic impact. Others caused by other cestodes, such as species of the genera Mesocestoides and Hymenolepis, are relatively rare in humans. In this review, we will focus on E. granulosus and E. multilocularis metacestode laboratory models and will review the use of these models in the search for novel drugs that could be employed for chemotherapeutic treatment of echinococcosis. Clearly, improved therapeutic drugs are needed for the treatment of AE and CE, and this can only be achieved through the development of medium-to-high throughput screening approaches. The most recent achievements in the in vitro culture and genetic manipulation of E. multilocularis cells and metacestodes, and the accessability of the E. multilocularis genome and EST sequence information, have rendered the E. multilocularis model uniquely suited for studies on drug-efficacy and drug target identification. This could lead to the development of novel compounds for the use in chemotherapy against echinococcosis, and possibly against diseases caused by other cestodes, and potentially also trematodes.

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Corresponding author

*Corresponding author: Andrew Hemphill, Institute of Parasitology Vetsuisse Faculty, University of BerneLänggass-Strasse 122, CH-3012Berne, Switzerland. Tel: +41 31 6312384. Fax: +41 31 6312477. Email: hemphill@ipa.unibe.ch

References

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Ali-Khan, Z., Siboo, R., Gomersall, M. and Faucher, M. (1983). Cystolytic events and the possible role of germinal cells in metastasis in chronic alveolar hydatidosis. Annals of Tropical Medicine and Parasitology 77, 497512.
Ammann, R. and Eckert, J. (1995). Clinical diagnosis and treatment of echinococcosis in humans. In Echinococcosis and Hydatid Disease (ed. Thompson, R. C. A. and Lymbery, A. J.), pp. 411430. CAB International, Wallmingford.
Angelucci, F., Basso, A., Bellelli, A., Brunori, M., Pica Maattoccia, L. and Valle, C. (2007). The anti-schistosomal drug praziquantel is an adenosine antagonist. Parasitology 134, 215–1221.
Becker, B., Mehlhorn, H., Andrews, P. and Thomas, H. (1981). Ultrastructural investigations on the effect of praziquantel on the tegument of five species of cestodes. Zeitschrift für Parasitenkunde 64, 257269.
Blanton, R. E., Wachira, T. M., Zeyhle, E., Njoroge, E. M., Magambo, J. K. and Schantz, P. M. (1988). Oxfendazole treatment of cystic hydatid disease in naturally infected animals. Antimicrobial Agents and Chemotherapy 42, 601605.
Brehm, K. and Spiliotis, M. (2008 a). Recent advances in the in vitro cultivation and genetic manipulation of Echinococcus multilocularis metacestodes and germinal cells. Experimental Parasitology 119, 506515.
Brehm, K. and Spiliotis, M. (2008 b). The influence of host hormones and cytokines on Echinococcus multilocularis signalling and development. Parasite 15, 286289.
Brehm, K., Spiliotis, M., Zavala-Gongora, R., Konrad, C. and Frosch, M. (2006). The molecular mechanisms of larval cestode development: first steps into an unknown world. Parasitology International 55, S15S21.
Bresson-Hadni, S., Delabrousse, E., Blagosklonov, O., Bartholomot, B., Koch, S., Miguet, J. P., André Mantion, G. and Angèle Vuitton, D. (2006). Imaging aspects and non-surgical interventional treatment in human alveolar echinococcosis. Parasitology International 55 (Suppl.), S267S272.
Bresson-Hadni, S., Vuitton, D. A., Bartholomot, B., Heyd, B., Godart, D., Meyer, J. P., Hrusovsky, S., Becker, M. C., Mantion, G., Lenys, D. and Miguet, J. P. (2000). A twenty year history of alveolar echinococcosis: analysis of a series of 117 patients from eastern France. European Journal of Gasteroenterology and Hepatology 12, 327336.
Britos, L., Dominguez, L., Ehrlich, R. and Marin, M. (2000). Effect of praziquantel on the strobilar development of Mesocestoides corti in vitro. Journal of Helminthology 74, 295299.
Brunetti, E., Troia, G., Garlaschelli, A. L., Gulizia, R. and Filice, C. (2004). Twenty years of percutaneous treatments for cystic echinococcosis: a preliminary assessment of their use and safety. Parassitologia 46, 367370.
Budke, C. M. (2006). Global socioeconomic impact of cystic echinococcosis. Emerging Infectious Diseases 12, 296303.
Chappell, L. H., Wastling, J. M. and Hurd, H. (1989). Action of cyclosporin A on the tapeworms Hymenolepis microstoma, H. diminuta and Mesocestoides corti in vivo. Parasitology 98, 291299.
Casado, N., Urrea-Paris, M. A., Moreno, M. J. and Rodriguez-Caabeiro, F. (2001). Combined praziquantel and albendazole chemoprophylaxis in experimental hydatidosis. Parasitology Research 87, 787789.
Chai, J., Menghebat Wie, J., Deyu, S., Bin, L., Jincao, S., Chen, F., Xiong, L., Yiding, M., Xiuling, W., Dolikun, , Guliber, , Yanchun, W., Fanghua, G. and Shuhua, X. (2004). Observations on clinical efficacy of albendazole emulsion in 264 cases of hepatic cystic echinococcosis. Parasitology International 53, 3–10.
Chinnery, J. B. and Morris, D. L. (1986). Effects of albendazole sulphoxide on viability of hydatid protoscoleces in vitro. Transactions of the Royal Society of Tropical Medicine and Hygiene 80, 815817.
Cobo, F., Yarnoz, C., Sesma, B., Fraile, P., Aizcorbe, M., Trujillo, R., Diaz-de-Liano, A. and Ciga, M. A. (1998). Albendazole plus praziquantel versus albendazole alone as preoperative treatment in intra-abdominal hydatidosis caused by Echinococcus granulosus. Tropical Medicine and International Health 3, 462466.
Colebrook, A. L., Jenkins, D. J., Jones, M. K., Tatarczuch, L. and Lightowlers, M. W. (2004). Effect of cyclosporin A on the survival and ultrastructure of Echinococcus granulosus protoscoleces in vitro. Parasitology 129, 497504.
Craig, P. S., McManus, D. P., Lightowlers, M. W., Chabalgoity, J. A., Garcia, H. H., Gavidia, C. M., Gilman, R. H., Gonzalez, A. E., Lorca, M., Naquira, C., Nieto, A. and Schantz, P. M. (2007). Prevention and control of cystic echinococcosis. Lancet Infectious Diseases 7, 385394.
Dubey, R., Abuzar, S., Sharma, S., Chatterjee, R. K. and Katiyar, J. C. (1985). Synthesis and anthelmintic activity of 5(6)-(benzimidazol-2-ylcarbamoyl) and (4-substituted piperazin-1-yl)benzimidazoles. Journal of Medical Chemistry 28, 17481750.
Dueger, E. L., Moro, P. L. and Gilman, R. H. (1999). Oxfendazole treatment of sheep with naturally acquired hydatid disease. Antimicrobial Agents and Chemotherapy 43, 22632267.
Eckert, J. and Deplazes, P. (2004). Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis of increasing concern. Clinical Microbiology Reviews 17, 107135.
Eckert, J. and Pohlenz, J. (1976). On the effect of mebendazole on metacestodes of Mesocestoides corti and Echinococcus multilocularis. Tropenmedizin und Parasitologie 27, 247262.
Eckert, J., Thompson, R. C. A. and Mehlhorn, H. (1983). Proliferation and metastases formation of larval Echinococcus multilocularis. I. Animal model, macroscopical and histological findings. Zeitschrift für Parasitenkunde 69, 737748.
Elissondo, M. C., Albani, C. M., Gende, L., Eguaras, M. and Denegri, G. (2008). Efficacy of thymol against Echinococcus granulosus protoscoleces. Parasitology International 57, 185190.
Elissondo, M. C., Ceballos, L., Alvarez, L., Sánchez Bruni, S., Lanusse, C. and Denegri, G. (2009). Flubendazole and ivermectin in vitro combination therapy produces a marked effect on Echinococcus granulosus protoscoleces and metacestodes. Parasitology Research. doi. 10.1007/s00436-009-1469-y
Elissondo, M., Ceballos, L., Dopchiz, M., Andresiuk, V., Alvarez, L., Sanchez Bruni, S., Lanusse, C. and Denegri, G. (2007). In vitro and in vivo effects of flubendazole on Echinococcus granulosus metacestodes. Parasitology Research 100, 10031009.
Elissondo, M. C., Dopchiz, M. C., Ceballos, L., Alvarez, L., Sanchez Bruni, S., Lanusse, C. and Denegri, G. (2006). In vitro effects of flubendazole on Echinococcus granulosus protoscoleces. Parasitology Research 98, 317323.
El-On, J. (2002). Benzimidazole treatment of cystic echinococcosis. Acta Tropica 85, 243252.
Emery, I., Bories, C., Liance, M., and Houin, R. (1995). In vitro quantitative assessment of Echinococcus multilocularis metacestode viability after in vivo and in vitro maintenance. International Journal for Parasitology 25, 275278.
Franchi, C., DiVico, B. and Teggi, A. (1999). Long term evaluation of patients with hydatidosis treated with benzimidazole carbamates. Clinical Infectious Diseases 29, 304309.
Frayha, G. J., Bikhazi, K. J. and Kachachi, T. A. (1981). Treatment of hydatid cysts (Echinococcus granulosus) by Cetrimide. Transactions of the Royal Society of Tropical Medicine and Hygiene 75, 447450.
Garcia, H. H., Gonzales, A. E., Evans, C. A. W. and Gilman, R. H. (2003). Taenia solium cysticercosis. The Lancet 361, 547556.
Garcia-Dominguez, C., Correa, D., Rabiela, M. T. and Flisser, A. (1991). Praziquantel treatment of muscle Taenia solium cysticercosis. 4. Reversible in vitro effect. Parasitology Research 77, 691696.
Garcia-Llamazares, J. L., Alvarez-de-Felipe, A. I., Redondo-Cardena, P., Voces-Alonso, J. A. and Prieto-Fernandez, J. G. (1997). In vivo inhibition of the regenerative capacity of hydatid material after treatment with netobimin. Parasitology Research 83, 105108.
Gavidia, C. M., Gonzalez, A. E., Lopera, L., Jayashi, C., Angelats, R., Barron, E. A., Ninaquispe, B., Villareal, L., Garcia, H. H., Verastegui, M. R. and Gilman, R. (2009). Evaluation of nitazoxanide and oxfendazole efficacy against cystic echinococcosis in naturally infected sheep. American Journal of Tropical Medicine and Hygiene 80, 367372.
Gelmedin, V., Caballero-Gamiz, R. and Brehm, K. (2008). Characterization and inhibition of a p38-like mitogen-activated protein kinase (MAPK) from Echinococcus multilocularis: Antiparasitic activities of a p38 MAPK inhibitors. Biochemical Pharmacology 76, 10681081.
Gnanasekar, M., Salunkhe, A. M., Mallia, A. K., He, Y. X. and Kalyanasundaram, R. (2009). Prazquantel affects the regulatory myosin light chain of Schistosoma mansoni. Antimicrobial Agents and Chemotherapy 53, 10541060.
Gottstein, B. and Hemphill, A. (1997). Immunopathology of echinococcosis. Chemical Immunology 66, 177208.
Gupta, S., Katiyar, J. C. and Sen, A. B. (1981). Effect of mode of infection on the development and chemotherapeutic response of Hymenolepis nana in rats. Journal of Helminthology 55, 101107.
Heath, D. D., Christie, M. J. and Chevis, R. A. (1975). The lethal effect of mebendazole on secondary Echinococcus granulosus, cysticerci of Taenia pisiformis and tetrathyridia of Mesocestoides corti. Parasitology 70, 273285.
Hemphill, A. and Gottstein, B. (1995). Immunological and morphological studies on the proliferation of in vitro cultivated Echinococcus multilocularis metacestodes. Parasitology Research 81, 605614.
Hemphill, A. and Kern, P. (2008). Special issue: experimental studies in echinococcosis. Experimental Parasitology 119, 437438.
Hemphill, A. and Mueller, J. (2009). Alveolar and cystic echinococcosis: towards novel chemotherapeutical treatment options. Journal of Helminthology 83, 99–111.
Hemphill, A., Mueller, J. and Esposito, M. (2006). Nitazoxanide, a broad-spectrum thiazolide anti-infective agent for the treatment of gastrointestinal infections. Expert Opinion in Pharmacotherapy 7, 953964.
Hemphill, A., Spicher, M., Stadelmann, B., Mueller, J., Naguleswaran, A., Gottstein, B. and Walker, M. (2007). Innovative chemotherapeutical treatment options for alveolar and cystic echinococcosis. Parasitology 134, 16571670.
Hemphill, A., Stettler, M., Walker, M., Siles-Lucas, M., Fink, R. and Gottstein, B. (2002). Culture of Echinococcus multilocularis metacestodes; an alternative to animal use. Trends in Parasitology 18, 445449.
Holmes, E., Tsang, T. M., Huang, J. T., Leweke, F. M., Koethe, D., Gerth, C. W., Nolden, B. M., Gross, S., Schreiber, D., Nicholson, J. K. and Bahn, S. (2006). Metabolic profiling of CSF: evidence that early intervention may impact on disease progression and outcome in schizophrenia. PloS Medicine 3, e327. doi:10.1371/journal.pmed.0030327.
Horton, R. J. (1997). Albendazole in the treatment of human cystic echinococcosis: 12 years of experience. Acta Tropica 64, 7993.
Hosch, W., Junghanss, T., Stojkovic, M., Brunetti, E., Heye, T., Kauffmann, G. W. and Hull, W. E. (2008). Metabolic viability assessment of cystic echinococcosis using high field 1H MRS of cyst contents. NMR in Biomedicine 21, 734754.
Hrckova, G. and Velebny, S. (1995). Effects of free and liposomized praziquantel on worm burden and antibody response in mice infected with Mesocestoides corti tetrathyridia. Journal of Helminthology 69, 213221.
Hrckova, G. and Velebny, S. (1997). Effect of praziquantel and liposome-incorporated praziquantel on peritoneal macrophage activation in mice infected with Mesocestoides corti tetrathyridia (Cestoda). Parasitology 114, 475482.
Hrckova, G., Velebny, S. and Corba, J. (1998). Effects of free and liposomized praziquantel on the surface morphology and motility of Mesocestoides vogae tetrathyridia (syn. M. corti; Cestoda: Cyclophyllidea) in vitro. Parasitology Research 84, 230238.
Hurd, H., Mackenzie, K. S. and Chappell, L. H. (1993). Anthelmintic effects of cyclosporin A on protoscoleces and secondary hydatid cysts of Echinococcus granulosus in the mouse. International Journal for Parasitology 23, 315320.
Ingold, K., Bigler, P., Thormann, W., Cavaliero, T., Gottstein, B. and Hemphill, A. (1999). Efficacies of albendazole sulfoxide and albendazole sulfone against in vitro cultivated Echinococcus multilocularis metacestodes. Antimicrobial Agents and Chemotherapy 43, 10521061.
Jain, M. K., Gupta, S., Katiyar, J. C., Maitra, S. C., Singh, J. and Bhakuni, D. S. (1989). Methyl 5(6)-(alpha-hydroxyphenyl methyl) benzimidazole-2-carbamate and cysticercosis: chemotherapeutic and electron microscopic studies. Indian Journal of Experimental Biology 27, 454459.
Jeziorski, M. C. and Greenberg, R. M. (2006). Voltage-cated calcium channel subunits from platyhelminths: potential role in praziquantel action. International Journal for Parasitology 36, 625632.
Jura, H., Bader, A. and Frosch, M. (1998). In vitro activities of benzimidazoles against Echinococcus multilocularis metacestodes. Antimicrobial Agents and Chemotherapy 42, 10521056.
Jura, H., Bader, A., Hartmann, M., Maschek, H. and Frosch, M. (1996). Hepatic tissue culture model for study of host-parasite interactions in alveolar echinococcosis. Infection and Immunity 64, 34843490.
Kammerer, W. S. and Perez-Esandi, M. V. (1975). Chemotherapy of experimental Echinococcus granulosus infection. Trials in CF1 mice and jirds (Meriones unguiculatus). American Journal of Tropical Medicine and Hygiene 24, 9095.
Keiser, J., Chollet, J., Xiao, S. H., Mei, J. Y., Jiao, P. Y., Utzinger, J. and Tanner, M. (2009). Mefloquine – an aminoalcohol with promising antischistosomal properties in mice. PLOS Neglected Tropical Diseases 3, 110.
Keiser, J. and Utzinger, J. (2007 a). Food-borne trematodiasis: current chemotherapy and advance with artemisinins and synthetic trioxolanes. Trends in Parasitology 23, 555562.
Keiser, J. and Utzinger, J. (2007 b). Artemisinins and synthetic trioxolanes in the treatment of helminthic infections. Current Opinions in Infectious Diseases 20, 605612.
Kern, P. (2003). Echinococcus granulosus infection: clinical presentation, medical treatment and outcome. Langenbecks Archives of Surgery 388, 413420.
Kern, P. (2006). Medical treatment of echinococcosis under the guidance of Good Clinical Practice (GCP/ICH). Parasitology International 55 (Suppl.), S273S282.
Kern, P., Abboud, P., Kern, W. V., Stich, A., Bresson-Hadni, S., Guerin, B., Buttenschoen, K., Gruener, B., Reuter, S. and Hemphill, A. (2008). Critical appraisal of nitazoxanide for the treatment of alveolar echinococcosis. American Journal of Tropical Medicine and Hygiene 79, 119.
King, C. H. (2007). Lifting the burden of schistosomiasis – defining elements of infection-associated disease and the benefits of anti-parasite treatment. Journal of Infectious Diseases 196, 653655.
Kohn, A. B., Roberts-Misterly, J. M., Anderson, P. A. V., Khan, N. and Greenberg, R. M. (2003). Specific sites in the beta interaction domain of schistosome Ca2+ channel -subunit are key to its role in sensitivity to the anti-schistosomal drug praziquantel. Parasitology 127, 349356.
Launchbury, A. P. and Habboubi, N. (1993). Epirubicin and doxorubicin: a comparison of their characteristics, therapeutic activity and toxicity. Cancer Treatment Reviews 19, 197228.
Lawton, P., Hemphill, A., Deplazes, P., Gottstein, B., and Sarciron, M. E. (1997). Echinococcus multilocularis metacestodes: immunological and immunocytochemical analysis of the relationships between alkaline phosphatase and the Em2 antigen. Experimental Parasitology 87, 142149.
Lawton, P., Walchshofer, N. and Sarciron, M. E. (2001). In vitro effects of isoprinosine and a dipeptide methyl ester on Echinococcus multilocularis protoscoleces. Journal of Helminthology 75, 251257.
Li, J. V., Wang, Y. L., Saric, J., Nicholson, J. K., Dirnhofer, S., Singer, B. H., Tanner, M., Wittlin, S., Holmes, E. and Utzinger, J. (2008). Gobal metabolic responses of NMRI mice to an experimental Plasmodium berghei infection. Journal of Proteome Research 7, 39483956.
Liance, M., Bresson-Hadni, S., Vuitton, D. A., Lenys, D., Carbillet, J. P. and Houin, R. (1992). Effects of cyclosporin A on the course of murine alveolar echinococcosis and on specific cellular and humoral immune responses against Echinococcus multilocularis. International Journal for Parasitology 22, 2328.
Liance, M., Nemati, F., Bories, C. and Couvreur, P. (1993). Experience with doxorubicin-bound polyisohexylcyanoacrylate nanoparticles on murine alveolar echinococcosis of the liver. International Journal for Parasitology 23, 427429.
Maki, J. and Yanagisawa, T. (1985). Anthelmintic effects of bithionol, paromomycin sulphate, flubendazole and mebendazole on mature and immature Hymenolepis nana in mice. Journal of Helminthology 59, 211216.
Martin, F. P. J., Verdu, E. F., Wang, Y. L., Dumas, M. E., Yap, I. K. S., Cloarec, O., Bergonzelli, G. E., Corthesy-Theulaz, I., Kochhar, S., Holmes, E., Lindon, J. C., Collins, S. M. and Nicholson, J. K. (2006). Transgenomic interactions in a mouse disease model: interaction of Trichinella spiralis infection with dietary Lactobacillus paracasei supplementation. Journal of Proteome Research 5, 21852193.
Martinez, J., Perez-Serrano, J., Bernadina, W. E. and Rodriguez-Caabeiro, F. (1999). Echinococcus granulosus: in vivo effects of ivermectin and praziquantel on hsp60 and hsp70 levels. Experimental Parasitology 93, 171180.
Martinez Zedillo, G., Hoyo Badillo, C., Amezcua, J. and Gonzalez Barranco, D. (1992). Verapamil does not block the spastic response of praziquantel on the larvae of Taenia pisiformis. Archives of Medical Research 23, 7377.
Marchiondo, A. A., Ming, R., Andersen, F. L., Slusser, J. H. and Conder, G. A. (1994). Enhanced larval cyst growth of Echinococcus multilocularis in praziquantel-treated jirds (Meriones unguiculatus). American Journal of Tropical Medicine and Hygiene 50, 120127.
Mathis, A., Wild, P., Boettger, E. C., Kapel, C. M. O. and Deplazes, P. (2005). Mitochondrial ribosome as the target for the macrolide antibiotic clarithromycin in the helminth Echinococus multilocularis. Antimicrobial Agents and Chemotherapy 49, 32513255.
Matsumoto, J., Müller, N., Hemphill, A., Oku, Y., Kamiya, M. and Gottstein, B. (2006). 14-3-3- and II/3-10 gene expression as molecular markers to address viability and growth activity of Echinococcus multilocularis metacestodes. Parasitology 392, 98–105.
Matsumoto, J., Sakamoto, K., Shiniyo, N., Kido, Y., Yamamoto, N., Yagi, K., Miyoshi, H., Nonaka, N., Katakura, K., Kita, K. and Oku, Y. (2008). Anaerobic NADH-fumarate reductase system is predominant in the respiratory chain of Echinococcus multilocularis providing a novel target for the chemotherapy of alveolar echinococcosis. Antimicrobial Agents and Chemotherapy 52, 164170.
McManus, D. P., Wenbao, Z., Jun, L. and Bartley, P. B. (2003). Echinococcosis. The Lancet 362, 12951304.
McTigue, M. A., Williams, D. R. and Tainer, J. A. (1995). Crystal structures of a schistosomal drug and vaccine target: glutathione S-transferase from Schistosoma japonica and its complex with the leading anti-schistosomal drug praziquantel. Journal of Molecular Biology 246, 2127.
Mehlhorn, H., Eckert, J. and Thompson, R. C. A. (1983). Proliferation and metastases formation of larval Echinococcus multilocularis II. Ultrastructural investigations. Zeitschrift für Parasitenkunde 69, 749763.
Miyaji, S., Katakura, K., Matsufuji, S., Murakami, Y., Hayashi, S., Oku, Y., Okamoto, M. and Kamiya, M. (1993). Failure of treatment with alpha-difluoromethylornithine against secondary multilocular echinococcosis in mice. Parasitology Research 79, 7576.
Moreno, M. J., Casado, N., Urrea-París, M. A. and Rodríguez-Caabeiro, F. (2002). Could ivermectin have a synergic effect with albendazole in hydatidosis therapy? Parasitology Research 88, 563567.
Morris, D. L., Chinnery, J. B. and Ubhi, C. (1987). A comparison of the effects of albendazole, its sulphone metabolite, and mebendazole on the viability of protoscoleces of Echinococcus granulosus in an in vitro culture system. Transactions of the Royal Society of Tropical Medicine and Hygiene 81, 804806.
Morris, D. L., Richards, K. S. and Chinnery, J. B. (1986). Protoscolicidal action of praziquantel – in vitro and electron microscopical studies on Echinococcus granulosus. Journal of Antimicrobial Chemotherapy 18, 687691.
Morseth, D. J. (1967). Fine structure of the hydatid cyst and protoscolex of Echinococcus granulosus. Journal of Parasitology 53, 312325.
Müller, J., Naguleswaran, A., Müller, N. and Hemphill, A. (2008 a). Neospora caninum: functional inhibition of protein disulfide isomerase by the broad-spectrum anti-parasitic drug nitazoxanide and other thiazolides. Experimental Parasitology 118, 8088.
Müller, J., Sidler, D., Nachbur, U., Wastling, J., Brunner, T. and Hemphill, A. (2008 b). Thiazolides inhibit growth and induce glutathione-S-transferase Pi (GSTP1)-dependent cell death in human colon cancer cells. International Journal of Cancer 123, 17971806.
Naguleswaran, A., Spicher, M., Vonlaufen, N., Ortega-Mora, L. M., Torgerson, P., Gottstein, B. and Hemphill, A. (2006). In vitro metacestodicidal activities of genistein and other isoflavones against Echinococcus multilocularis and Echinococcus granulosus. Antimicrobial Agents and Chemotherapy 50, 37703778.
Nakao, M., McManus, D. P., Schantz, P. M., Craig, P. S. and Ito, A. (2007) A molecular phylogeny of the genus Echinococcus inferred from complete mitochondrial genomes. Parasitology 134, 713722.
Nessim, N. G., Hassan, S. I., William, S. and El-Baz, H. (2000). Efffect of the broad spectrum antheminthic drug flubenadazole upon Schistosoma mansoni experimentally infected mice. Arztneimittelforschung 50, 11291133.
Nogi, T., Zhang, D., Chan, J. D., and Marchant, J. S. (2009). A novel bological activity of praziqunatel requiring voltage-operated Ca2+ channel beta subunits: subversion of flatworm regenerative polarity. PloS Neglected Tropical Diseases 3, e464.
Novak, M. and Blackburn, B. J. (1985). Comparison of the effects of imidazo[1,2-a]pyridine-2-carbamates and benzimidazole-2-carbamates on the development of Hymenolepis nana in Tribolium confusum. Experientia 41, 687689.
Ochieng'-Mitula, P. J. and Burt, M. D. (1996). The effects of ivermectin on the hydatid cyst of Echinococcus granulosus after direct injection at laparotomy. Journal of Parasitology 82, 155157.
Ordovas, J. M. and Mooser, V. (2006). Metagenomics: the role of the microbiome in cardivascular diseases. Current Opinion in Lipidology 17, 157161.
Palomares-Alonso, F., Piliado, J. C., Palencia, G., Ortiz-Plata, A. and Jung-Cook, H. (2007). Efficacy of nitazoxanide, tizoxanide, and tizoxanide/albendazole sulphoxide combination against Taenia crassiceps cysts. Journal of Antimicrobial Chemotherapy 59, 212218.
Perez Serrano, J., Casado, N., Guillermo, , Denegri, , Rodriguez-Caabeiro, F. (1994). The effects of albendazole and albendazole sulphoxide combination-therapy on Echinococcus granulosus in vitro. International Journal for Parasitology 24, 219224.
Rausch, R. L. (1995). Life cycle patterns and geographic distribution of Echinococcus species. In Echinococcosis and Hydatid Disease (ed. Thompson, R. C. A. and Lymbery, A. J.), pp. 8999. Wallmingford: CAB International.
Reuter, S., Buck, A., Grebe, O., Nüssle-Kügele, K., Kern, P. and Manfras, B. (2003 b). Salvage treatment with amphotericin B in progressive human alveolar echinococcosis. Antimicrobial Agents and Chemotherapy 47, 35863591.
Reuter, S., Buck, A., Manfras, B., Kratzer, W., Seitz, H. M., Darge, K., Reske, S. N. and Kern, P. (2004). Structured treatment interuption in patients with alveolar echinococcosis. Hepatology 39, 509517.
Reuter, S., Jensen, B., Buttenschoen, K., Kratzer, W. and Kern, P. (2000). Benzimidazoles in the treatment of alveolar echinococcosis. Journal of Antimicrobial Chemotherapy 46, 451460.
Reuter, S., Manfras, B., Merkle, M., Harter, G. and Kern, P. (2006). In vitro activities of itraconazole, methiazole, and nitazoxanide versus Echinococcus multilocularis larvae. Antimicrobial Agents and Chemotherapy 50, 29662970.
Reuter, S., Merkle, M., Brehm, K., Kern, P. and Manfras, B. (2003 a). Effect of amphotericin B on larval growth of Echinococcus multilocularis. Antimicrobial Agents and Chemotherapy 47, 620625.
Robinson, M. W., Hoev, E. M., Fairweather, I., Dalton, J. P., McGonigle, S. and Trudgett, A. (2001). Characterization of a beta tubulin gene from the liver fluke Fasciola hepatica. International Journal for Parasitology 31, 12641268.
Rodriguez-Caabeiro, F., Casado, N. and Juarez-Pelaez, E. (1989). Efecto in vitro de praziquantel, mebendazole y oxfendazole sobre protoscolex de Echinococcus granulosus. Revista Iberica Parasitologica 49, 7783.
Rogan, M. T. and Richards, K. S. (1986). Echinococcus granulosus: in vivo effect of monensin on the tegument of the protoscolex. Parasitology 93, 347355.
Saldana, J., Marin, M., Fernandez, C. and Dominguez, L. (2001). In vitro taurocholate-induced segmentation and clustering of Mesocestoides vogae (syn. corti) tetrathyridia (Cestoda) – inhibition by cestocidal drugs. Parasitology Research 87, 281286.
Sarciron, E. M., Bresson-Hadni, S., Mercier, M., Lawton, P., Duranton, C., Lenys, D., Petavy, A. F. and Vuitton, D. A. (1997). Antibodies against Echinococcus multi locularis phosphatase as markers for the specific diagnosis and the serological monitoring of alveolar echinococcosis. Parasite Immunology 19, 6168.
Sarciron, M. E., Hamoud, W., Azzar, G., and Petavy, A. F. (1991). Alkaline phosphatase from Echinococcus multilocularis: purification and characterization. Compendium of Biochemistry and Physiology 100, 253258.
Saric, J., Li, J. V., Wang, Y., Keiser, J., Bundy, J. G., Holmes, E. and Utzinger, J. (2008). Metabolic profiling of an Echinostoma caproni infection in the mouse for biomarker discovery. PloS Neglected Tropcial Diseases 2, e254. doi: 10.1371/journal.pntd.0000254
Schantz, P. M., Chai, J., Craig, P. S., Eckert, J., Jenkins, D. J., Macpherson, C. N. L. and Thakur, A. (1995). Epidemiology and control of hydatid disease. In Echinococcosis and Hydatid Disease (ed. Thompson, R. C. A. and Lymbery, A. J.),pp. 233245. Wallmingford: CAB International.
Schipper, H. G., Koopmans, R. P., Nagy, J., Butter, J. J., Kaeger, P. A. and Van Boxtel, C. J. (2000). Effect of dose increase or cimetidine co-administration on albendazole bioavailability. American Journal of Trpocial Medicine and Hygiene 63, 270273.
Schmidt, J. (1998). Effects of benzimidazole antheminthics as microtubule-active drugs on the synthesis of surface glycoconjugates in Echinostoma caproni, Hymenolepis microstoma and Schistosoma mansoni. Parasitology Research 84, 362368.
Schumacher, G. and Neuhaus, P. (2001). The physiological estrogen metabolite 2-methoxyestradiol reduces tunor growth and induces apoptosis in human solid tunors. Journal of Cancer Research and Clinical Oncology 127, 405410.
Shandera, W. X. and Kass, J. S. (2006). Neurocysticercosis: current knowledge and advances. Current Neurology and Neuroscience Reports 6, 453459.
Siles-Lucas, M. and Hemphill, A. (2002). Cestode parasites: Application of in vivo and in vivo models for studies on the host-parasite relationship. Advances in Parasitology 51, 133230.
Spicher, M., Naguleswaran, A., Ortega-Mora, L. M., Mueller, J., Gottstein, B. and Hemphill, A. (2008 a). In vitro and in vivo effects of 2-methoxyestradiol, either alone, or combined with albendazole, against Echinococcus metacestodes. Experimental Parasitology 119, 475482.
Spicher, M., Roethlisberger, C., Lany, C., Stadelmann, B., Keiser, J., Ortega-Mora, L. M., Gottstein, B. and Hemphill, A. (2008 b). In vitro and in vivo treatments of Echinococcus protoscoleces and metacestodes with artemisinin derivatives. Antimicrobial Agents and Chemotherapy 52, 34473450.
Spiliotis, M. and Brehm, K. (2008). Axenic in vitro cultivation of Echinococcus multilocularis metacestode vesicles and the generation of primary cell cultures. In Host Pathogen Interactions (ed. Rupp, S. and Sohn, K.),pp. 245262. Humana Press.
Spiliotis, M., Lechner, S., Tappe, D., Scheller, D., Krohne, G. and Brehm, K. (2008). Transient tranfection of Echinococcus multilocularis primary cells and complete in vitro regeneration of metacestode vesicles. International Journal for Parasitology 38, 10251039.
Spiliotis, M., Tappe, D., Sesterhenn, L. and Brehm, K. (2004). Long-term in vitro cultivation of Echinococcus multilocularis metacestodes under axenic conditions. Parasitology Research 92, 430432.
Stettler, M., Fink, R., Walker, M., Gottstein, B., Geary, T. G., Rossignol, J. F. and Hemphill, A. (2003). In vivo parasiticidal effect of nitazoxanide against Echinococcus multilocularis metacestodes. Antimicrobial Agents and Chemotherapy 47, 467474.
Stettler, M., Rossignol, J. F., Fink, R., Walker, M., Gottstein, B., Merli, M., Theurillat, R., Thormann, W., Dricot, E., Segers, R. and Hemphill, A. (2004). Secondary and primary murine alveolar echinococcosis: combined albendazole/nitazoxanide chemotherapy exhibits profound anti-parasitic activity. International Journal for Parasitology 34, 615624.
Stettler, M., Siles-Lucas, M., Sarciron, E., Lawton, P., Gottstein, B. and Hemphill, A. (2001). Echinococcus multilocularis alkaline phosphatase as a marker for metacestode damage induced by in vitro drug treatment with albendazole sulphoxide and albendazole sulfone. Antimicrobial Agents and Chemotherapy 45, 22562262.
Stey, C. and Jost, R. (1993). Rezidivierende, lebensbedroliche Anaphylaxie als Erstmanifestation eines Echinococcus cysticus (granulosus) der Leber. Schweizerische Medizinische Wochenzeitschrift 123, 14451450.
Tallima, H. and El Ridi, R. (2007). Praziquantel binds Schistosoma mansoni adult worm actin. International Journal of Antimicrobial Agents 29, 570575.
Taylor, D. H. and Morris, D. L. (1988). In vitro culture of Echinococcus multilocularis: protoscolicidal action of praziquantel and albendazole sulphoxide. Transactions of the Royal Society of Tropical Medicine and Hygiene 82, 265267.
Taylor, D. H., Richards, K. S. and Morris, D. L. (1989). Rapid recovery of Echinococcus granulosus following ‘successful’ albendazole therapy in a gerbil model. Journal of Helminthology 63, 349352.
Tellez-Giron, E., Ramos, M. C. and Montante, M. (1981). Effect of flubendazole on Cysticercus cellulosae in pigs. American Journal of Tropical Medicine and Hygiene 30, 135138.
Tellez-Giron, E., Ramos, M. C., Dufour, L., Montante, M., Tellez, E. Jr.Rodriguez, J., Gomez-Mendez, F. and Mireles, E. (1984). Treatment of neurocysticercosis with flubendazole. American Journal of Tropical Medicine and Hygiene 33, 627631.
Terenina, N. V., Kosovatova, L. A., Gerasimova, E. I. and Shalaeva, N. M. (1998). The effect of anthelmintics on the serotonin content of cestodes. Meditsinskaia parazitologiia i parazitarnye bolezni 1, 1015.
Thompson, R. C. A. (1986). Biology and systematics of Echinococcus. In The Biology of Echinococcus and Hydatid Disease (ed. Thompson, R. C. A.), pp. 5–17. Allen & Unwin, London.
Urrea-Paris, M. A., Casado, N., Moreno, M. J. and Rodriguez-Caabeiro, F. (2001). Chemoprophylactic praziquantel treatment in experimental hydatidosis. Parasitology Research 87, 510512.
Urrea-Paris, M. A., Moreno, M. J., Casado, N. and Rodriguez-Caabeiro, F. (1999). Echinococcus granulosus: praziquantel treatment against the metacestode stage. Parasitology Research 85, 999–1006.
Utzinger, J., Chollet, J., Tu, Z., Xiao, S. and Tanner, M. (2002). Comparative study of the effects of artemether and artesunate on juvenile and adult Schistosoma mansoni in experimentally infected mice. Transactions of the Royal Society of Tropical Medicine and Hygiene 96, 318323.
Varcasia, A., Garippa, G., Pipia, A. P., Scala, A., Brianti, E., Giannetto, S., Battelli, G., Poglayen, G. and Micagni, G. (2008) Cystic echinococcosis in equids in Italy. Parasitology Research 102, 815818.
Verheyen, A., Vanparijs, O., Borgers, M. and Thienpont, D. (1978). Scanning electron microscopic observations of Cysticercus fasciolaris (=Taenia taeniaeformis) after treatment of mice with mebendazole. Journal of Parasitology 64, 411425.
Voelker, R. (2009). Attention sought for negelected diseases. Journal of the American Medical Association 301, 17551756.
Vuitton, D. (2009). Benzimidazoles for the treatment of cystic and alveolar echinococcosis: what is the consensus? Expert Review in Anti-Infective Therapy 7, 145149.
Vutova, K., Mechkov, G., Vachkov, P., Petkov, R., Georgiev, P., Handjiev, S., Ivanov, A. and Todorov, T. (1999). Effect of mebendazole on human cystic echinococcosis: the role of dosage and treatment duration. Annals of Tropical Medicine and Parasitology 93, 357365.
Walker, M., Rossignol, J. F., Torgerson, P. and Hemphill, A. (2004). In vivo effects of nitazoxanide on Echinococcus granulosus protoscoleces and metacestodes. Journal of Antimicrobial Chemotherapy 54, 609616.
Wang, Y. L., Holmes, E., Nicholson, J. K., Cloarec, O., Chollet, J., Tanner, M., Singer, B. H. and Utzinger, J. (2004). Metabolomic investigations in mice infected with Schistosoma mansoni: an approach for biomarker identification. Proceedings of the National Academy of Sciences, USA 101, 1267612681.
Wang, Y. L., Utzinger, J., Saric, J., Li, J. V., Burckhardt, J., Dirnhofer, S., Nicholson, J. K., Singer, B. H., Brun, R. and Holmes, E. (2008). Global metabolic responses of mice to Trypanosoma brucei brucei infection. Proceedings of the National Academy of Sciences, USA 105, 61276132.
Wang, Y. L., Utzinger, J., Xiao, S. H., Xue, J., Nicholson, J. K., Tanner, M., Singer, B. H. and Holmes, E. (2006). System level metabolic effects of a Schistosoma japonicum infection in the Syrian hamster. Molecular and Biochemical Parasitology 146, 19.
Wen, H., New, R. R., Muhmut, M., Wang, J. H., Wang, Y. H., Zhang, J. H., Shao, Y. M. and Craig, P. S. (1996). Pharmacology and efficacy of liposome-entrapped albendazole in experimental secondary alveolar echinococcosis and effect of co-administration with cimetidine. Parasitology 113, 111121.
Wiest, P. M., Li, Y., Olds, R. and Bowen, W. D. (1992). Inhibition of phosphoinositide turnover by praziquantel in Schistosoma mansoni. Journal of Parasitology 78, 753755.
Williams, S., Guirgus, F. and Nessim, N. G. (2003). Effect of simultaneous and/or consective administration of the broad spectrum anthelminthic flubendazole together with praziquantel in experimental Schistosoma mansoni infection. Arztneimittelforschung 53, 532537.
Winning, A., Braslins, P. and McCarthy, J. S. (2009). Case report: nitazoxanide for the treatment of refractory bony hydatid disease. American Journal of Tropical Medicne and Hygiene 80, 176178.

Keywords

Echinococcus metacestodes as laboratory models for the screening of drugs against cestodes and trematodes

  • A. HEMPHILL (a1), B. STADELMANN (a1), S. SCHOLL (a1), J. MÜLLER (a1), M. SPILIOTIS (a1), N. MÜLLER (a1), B. GOTTSTEIN (a1) and M. SILES-LUCAS (a2)...

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