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Alveolar and cystic echinococcosis: towards novel chemotherapeutical treatment options

Published online by Cambridge University Press:  01 June 2009

A. Hemphill  and
J. Müller
A. Hemphill*
Affiliation:
Institute of Parasitology, Vetsuisse Faculty, University of Berne, Berne, Switzerland
J. Müller
Affiliation:
Institute of Parasitology, Vetsuisse Faculty, University of Berne, Berne, Switzerland
*
*Fax: +41 31 6312477 E-mail: hemphill@ipa.unibe.ch
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Abstract

Echinococcus granulosus and Echinococcus multilocularis are cestode parasites, of which the metacestode (larval) stages cause the neglected diseases cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. The benzimidazoles albendazole and mebendazole are presently used for the chemotherapeutical treatment, alone or prior to and after surgery. However, in AE these benzimidazoles do not appear to be parasiticidal in vivo. In addition, failures in drug treatments as well as the occurrence of side-effects have been reported, leading to discontinuation of treatment or to progressive disease. Therefore, new drugs are needed to cure AE and CE. Strategies that are currently employed in order to identify novel chemotherapeutical treatment options include in vitro and in vivo testing of broad-spectrum anti-infective drugs or drugs that interfere with unlimited proliferation of cancer cells. The fact that the genome of E. multilocularis has recently been sequenced has opened other avenues, such as the selection of novel drugs that interfere with the parasite signalling machinery, and the application of in silico approaches by employing the Echinococcus genome information to search for suitable targets for compounds of known mode of action.

Type
Review Article
Information
Journal of Helminthology , Volume 83 , Special Issue 2: Symposium and related papers from the 10th European Multicolloquium of Parasitology , June 2009 , pp. 99 - 111
Copyright
Copyright © Cambridge University Press 2009

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References

Ali-Khan, Z., Siboo, R., Gomersall, M. & 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, 497–512.Google Scholar
Ammann, R. & Eckert, J. (1995) Clinical diagnosis and treatment of echinococcosis in humans. pp. 411–430in Thompson, R.C.A. & Lymbery, A.J. (Eds) Echinococcosis and hydatid disease. Wallingford, CAB International.Google Scholar
Attalla, H., Makela, T.P., Adlercreutz, H. & Andersson, L.C. (1996) 2-Methoxy-estradiol arrests cells in mitosis without depolymerizing tubulin. Biochemical and Biophysical Research Communications 228, 467–473.CrossRefGoogle ScholarPubMed
Bartholomot, G., Vuitton, D.A., Harraga, S., Shi, D.Z., Giraudoux, P., Barnish, G., Wang, Y.H., MacPherson, C.N. & Craig, P.S. (2002) Combined ultrasound and serologic screening for hepatic alveolar echinococcosis in central China. American Journal for Tropical Medicine and Hygiene 66, 23–29.CrossRefGoogle ScholarPubMed
Blanton, R.E., Wachira, T.M., Zeyhle, E.E., Njoroge, E.M., Magambo, J.K. & Schantz, P.M. (1998) Oxfendazole treatment for cystic hydatid disease in naturally infected animals. Antimicrobial Agents and Chemotherapy 42, 601–605.CrossRefGoogle ScholarPubMed
Blum, G., Perkhofer, S., Haas, H., Schrettl, M., Würzner, R., Dierich, M. & Lass-Flörl, C. (2008) Potential basis for amphotericin B resistance in Aspergillus terreus. Antimicrobial Agents and Chemotherapy 52, 1353–1355.CrossRefGoogle ScholarPubMed
Brehm, K. & Spiliotis, M. (2008) Recent advances in the in vitro cultivation and genetic manipulation of Echinococcus multilocularis metacestodes and germinal cells. Experimental Parasitology 119, 506–515.Google Scholar
Brehm, K., Kronthaler, K., Jura, H. & Frosch, M. (2000) Cloning and characterization of beta-tubulin genes from Echinococcus multilocularis. Molecular and Biochemical Parasitolology 107, 297–302.CrossRefGoogle ScholarPubMed
Brehm, K., Spiliotis, M., Zavala-Gongora, R., Konrad, C. & Frosch, M. (2006) The molecular mechanisms of larval cestode development: first steps into an unknown world. Parasitology International 55, S15–S21.Google Scholar
Bresson-Hadni, S., Laplante, J.J., Lenys, D., Rohmer, P., Gottstein, B., Jacquier, P., Mercet, P., Meyer, J.P., Miguet, J.P. & Vuitton, D.A. (1994) Sero-epidemiologic screening of Echinococcus multilocularis infection in a European area endemic for alveolar echinococcosis. American Journal of Tropical Medicine and Hygiene 51, 837–846.CrossRefGoogle Scholar
Brunetti, E., Troia, G., Garlaschelli, A.L., Gulizia, R. & Filice, C. (2004) Twenty years of percutaneous treatments for cystic echinococcosis: a preliminary assessment of their use and safety. Parassitologia 46, 367–370.Google ScholarPubMed
Casado, N., Rodriguez-Caabeiro, F., Jiménez, A., Criado, A. & de Armas, C. (1989) In vitro effects of levamisole and ivermectin against Echinococcus granulosus protoscoleces. International Journal of Parasitology 19, 945–947.Google Scholar
Casado, N., Urrea-Paris, M.A., Moreno, M.J. & Rodriguez-Caabeiro, F. (2001) Combined praziquantel and albendazole chemoprophylaxis in experimental hydatidosis. Parasitology Research 87, 787–789.Google ScholarPubMed
Chai, J., Menghebat, , Wei, J., Deyu, S., Bin, L., Jincao, S., Chen, F., Xiong, L., Yiding, M., Xiuling, W., Dolikun, , Guliber, , Yanchun, W., Fanghua, G. & Shuhua, X. (2004) Observations on clinical efficacy of albendazole emulsion in 264 cases of hepatic cystic echinococcosis. Parasitology International 53, 3–10.Google Scholar
Cobo, F., Yarnoz, C., Sesma, B., Fraile, P., Aizcorbe, M., Trujillo, R., Diaz-de-Liano, A. & 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, 462–466.Google Scholar
Dakora, F.D. & Phillips, D.A. (1996) Diverse functions of isoflavonoids in legumes transcend anti-microbial definitions of phytoalexins. Physiological and Molecular Plant Pathology 49, 1–20.CrossRefGoogle Scholar
Driscoll, M., Dean, E., Reilly, E., Bergholz, E. & Chalfie, M. (1989) Genetic and molecular analysis of a Caenorhabditis elegans β-tubulin that conveys benzimidazole sensitivity. Journal of Cell Biology 109, 2993–3003.Google Scholar
Dueger, E.L., Moro, P.L. & Gilman, R.H. (1999) Oxfendazole treatment of sheep with naturally acquired hydatid disease. Antimicrobial Agents and Chemotherapy 43, 2263–2267.Google Scholar
Eckert, J. & Deplazes, P. (2004) Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis of increasing concern. Clinical Microbiology Reviews 17, 107–135.Google Scholar
Eckert, J., Thompson, R.C.A. & Mehlhorn, H. (1983) Proliferation and metastases formation of larval Echinococcus multilocularis. I. Animal model, macroscopical and histological findings. Zeitschrift für Parasitenkunde 69, 737–748.CrossRefGoogle ScholarPubMed
El-On, J. (2002) Benzimidazole treatment of cystic echinococcosis. Acta Tropica 85, 243–252.CrossRefGoogle Scholar
Esposito, M., Mueller, N. & Hemphill, A. (2007) Structure-activity relationships from in vitro efficacies of the thiazolide series against the intracellular apicomplexan protozoan Neospora caninum. International Journal for Parasitology 37, 183–190.CrossRefGoogle ScholarPubMed
Fernandez, V., Chalar, C., Martinez, C., Musto, H., Zaha, A. & Fernandez, C. (2000) Echinococcus granulosus: molecular cloning and phylogenetic analysis of an inducible glutathione-S-transferase. Experimental Parasitology 96, 190–194.CrossRefGoogle ScholarPubMed
Frayha, G.J., Bikhazi, K.J. & Kachachi, T.A. (1981) Treatment of hydatid cysts (Echinococcus granulosus) by Cetrimide. Transactions of the Royal Society of Tropical Medicine and Hygiene 75, 447–450.CrossRefGoogle ScholarPubMed
Garcia-Llamazares, J.L., Alvarez-de-Felipe, A.I., Redondo-Cardena, P., Voces-Alonso, J.A. & Prieto-Fernandez, J.G. (1997) In vivo inhibition of the regenerative capacity of hydatid material after treatment with netobimin. Parasitology Research 83, 105–108.Google Scholar
Gelmedin, V., Zavala-Gongora, R., Fernandez, C. & Brehm, K. (2005) Echinococcus multilocularis: cloning and characterization of a member of the SNW/SKIP family of transcriptional coregulators. Experimental Parasitology 111, 115–120.CrossRefGoogle ScholarPubMed
Gottstein, B. & Hemphill, A. (1997) Immunopathology of echinococcosis. Chemical Immunology 66, 177–208.Google ScholarPubMed
Gottstein, B., Dai, W.J., Walker, M., Stettler, M., Müller, N. & Hemphill, A. (2002) An intact laminated layer is important for the establishment of secondary Echinococcus multilocularis infection. Parasitology Research 88, 822–828.CrossRefGoogle ScholarPubMed
Gottstein, B., Haag, K., Walker, M., Matsumoto, J., Mejri, N. & Hemphill, A. (2006) Molecular survival strategies of Echinococcus multilocularis in the murine host. Parasitology International 55, S45–S49.Google Scholar
Hemphill, A., Stettler, M., Walker, M., Siles-Lucas, M., Fink, R. & Gottstein, B. (2002) Culture of Echinococcus multilocularis metacestodes; an alternative to animal use. Trends in Parasitology 18, 445–449.Google Scholar
Hemphill, A., Müller, J. & Esposito, M. (2006) Nitazoxanide, a broad-spectrum thiazolide anti-infective agent for the treatment of gastrointestinal infections. Expert Opinion in Pharmacotherapy 7, 953–964.Google Scholar
Hemphill, A., Müller, N. & Müller, J. (2007) Structure-function relationship of thiazolides, a novel class of anti-parasitic drugs, investigated in intracellular and extracellular protozoan parasites and larval-stage cestodes. Antiinfective Agents in Medical Chemistry 6, 273–282.CrossRefGoogle Scholar
Henriquez, F., Ingram, P.R., Muench, S.P., Rice, D.W. & Roberts, C.W. (2008) Molecular basis for the resistance of Acanthamoeba tubulins to all major classes of antitubulin compounds. Antimicrobial Agents and Chemotherapy 52, 1133–1135.Google Scholar
Horton, R.J. (1989) Chemotherapy of Echinococcus infection in man with albendazole. Transactions of the Royal Society of Tropical Medicine and Hygiene 83, 97–102.CrossRefGoogle ScholarPubMed
Horton, R.J. (1997) Albendazole in the treatment of human cystic echinococcosis: 12 years of experience. Acta Tropica 64, 79–93.CrossRefGoogle ScholarPubMed
Hurd, H., Mackenzie, K.S. & 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, 315–320.CrossRefGoogle ScholarPubMed
Ingold, K., Bigler, P., Thormann, W., Cavaliero, T., Gottstein, B. & Hemphill, A. (1999) Efficacies of albendazole sulfoxide and albendazole sulfone against in vivo-cultivated Echinococcus multilocularis metacestodes. Antimicrobial Agents and Chemotherapy 43, 1052–1061.Google Scholar
Jorgensen, P., an der Heiden, M., Kern, P., Schöneberg, I., Krause, G. & Alpers, K. (2008) Underreporting of human alveolar echinococcosis, Germany. Emerging Infectious Diseases 14, 935–937.CrossRefGoogle ScholarPubMed
Katiyar, S.K., Gordon, V.R., Mclaughlin, G.L. & Edlind, T.D. (1994) Antiprotozoal activities of benzimidazoles and correlations with β-tubulin sequence. Antimicrobial Agents and Chemotherapy 38, 2086–2090.CrossRefGoogle ScholarPubMed
Kern, P. (2003) Echinococcus granulosus infection: clinical presentation, medical treatment and outcome. Langenbecks Archives of Surgery 388, 413–420.CrossRefGoogle ScholarPubMed
Kern, P. (2006) Medical treatment of echinococcosis under the guidance of Good Clinical Practice (GCP/ICH). Parasitology International 55 (Suppl.), S273–S282.Google Scholar
Klauber, N., Parangi, S., Flynn, E., Hamel, E. & D'Amato, R.J. (1997) Inhibition of angiogenesis and breast cancer in mice by the microtubule inhibitors 2-methoxyestradiol and taxol. Cancer Research 57, 81–86.Google ScholarPubMed
Klinkert, M.Q. & Heussler, V. (2006) The use of anticancer drugs in antiparasitic chemotherapy. Mini Reviews in Medicinal Chemistry 6, 131–143.CrossRefGoogle ScholarPubMed
Konrad, C., Kroner, A., Spiliotis, M., Zavala-Gongora, R. & Brehm, K. (2003) Identification and molecular characterisation of a gene encoding a member of the insulin receptor family in Echinococcus multilocularis. International Journal for Parasitology 33, 301–312.CrossRefGoogle ScholarPubMed
Kumar, A.P., Garcia, G.E., Orsborn, J., Levin, V.A. & Slaga, T.J. (2003) 2-Methoxyestradiol interferes with NfkB transcriptional activity in primitive neuroectodermal brain tumours: implications for management. Carcinogenesis 24, 209–216.Google Scholar
Kwa, M.S.G., Veenstra, J.G., Van Dijk, M. & Roos, M.H. (1995) β-tubulin genes from the parasite nematode Haemonchus contortus modulate drug resistance in Caenorhabditis elegans. Journal of Molecular Biology 246, 500–516.Google Scholar
Lacey, E. (1990) Mode of action of benzimidazoles. Parasitology Today 6, 112–116.Google Scholar
Lawton, P., Walchshofer, N. & Sarciron, M.E. (2001) In vitro effects of isoprinosine and a dipeptide methyl ester on Echinococcus multilocularis protoscoleces. Journal of Helminthology 75, 251–257.Google Scholar
Liance, M., Bresson-Hadni, S., Vuitton, D.A., Lenys, D., Carbillet, J.P. & 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, 23–28.CrossRefGoogle ScholarPubMed
Liance, M., Nemati, F., Bories, C. & Couvreur, P. (1993) Experience with doxorubicin-bound polyisohexylcyanoacrylate nanoparticles on murine alveolar echinococcosis of the liver. International Journal of Parasitology 23, 427–429.Google Scholar
Liebau, E., Müller, V., Lucius, R., Walter, R.D. & Henkle-Dührsen, K. (1996) Molecular cloning, expression and characterization of a recombinant glutathione-S-transferase from Echinococcus multilocularis. Molecular and Biochemical Parasitology 77, 49–56.CrossRefGoogle ScholarPubMed
Mabjeesh, N.J., Escuin, D., LaVallee, T.M., Pribluda, V.S., Swartz, G.M., Johnson, M.S., Willard, M.T., Zhong, H., Simons, J.W. & Giannakakou, P. (2003) 2-ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Cancer Cell 3, 363–375.Google Scholar
Marchiondo, A.A., Ming, R., Andersen, F.L., Slusser, J.H. & 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, 120–127.CrossRefGoogle ScholarPubMed
Martinez, J., Perez-Serrano, J., Bernadina, W.E. & Rodriguez-Caabeiro, F. (1999) Echinococcus granulosus: in vivo effects of ivermectin and praziquantel on hsp60 and hsp70 levels. Experimental Parasitology 93, 171–180.Google Scholar
Mathis, A., Wild, P., Boettger, E.C., Kapel, C.M.O. & Deplazes, P. (2005) Mitochondrial ribosome as the target for the macrolide antibiotic clarithromycin in the helminth Echinococus multilocularis. Antimicrobial Agents and Chemotherapy 49, 3251–3255.Google Scholar
Matsumoto, J., Müller, N., Hemphill, A., Oku, Y., Kamiya, M. & 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 132, 83–94.CrossRefGoogle ScholarPubMed
McManus, D.P., Wenbao, Z., Jun, L. & Bartley, P.B. (2003) Echinococcosis. Lancet 362, 1295–1304.Google Scholar
Mehlhorn, H., Eckert, J. & Thompson, R.C.A. (1983) Proliferation and metastases formation of larval Echinococcus multilocularis II. Ultrastructural investigations. Zeitschrift für Parasitenkunde 69, 749–763.Google Scholar
Messina, M. (1999) Soy, soy phytoestrogens (isoflavones), and breast cancer. American Journal of Clinical Nutrition 70, 574–575.Google Scholar
Miyaji, S., Katakura, K., Matsufuji, S., Murakami, Y., Hayashi, S., Oku, Y., Okamoto, M. & Kamiya, M. (1993) Failure of treatment with alpha-difluoromethylornithine against secondary multilocular echinococcosis in mice. Parasitology Research 79, 75–76.Google Scholar
Morris, D.L. & Richards, K.S. (1992) Hydatid disease. Current medical and surgical management. Oxford, Butterworth-Heinemann.Google Scholar
Morris, D.L. & Taylor, D.H. (1990) Echinococcus granulosus: development of resistance to albendazole in an animal model. Journal of Helminthology 64, 171–174.Google Scholar
Müller, J., Sterck, M., Hemphill, A. & Müller, N. (2007a) Characterization of Giardia lamblia WB C6 clones resistant to nitazoxanide and to metronidazole. Journal of Antimicrobial Chemotherapy 60, 280–287.Google Scholar
Müller, J., Wastling, J., Sanderson, S., Müller, N. & Hemphill, A. (2007b) A novel Giardia lamblia nitroreductase, GlNR1, interacts with nitazoxanide and other thiazolides. Antimicrobial Agents and Chemotherapy 51, 1979–1986.Google Scholar
Müller, J., Naguleswaran, A., Müller, N. & Hemphill, A. (2008a) Neospora caninum: functional inhibition of protein disulfide isomerase by the broad-spectrum anti-parasitic drug nitazoxanide and other thiazolides. Experimental Parasitology 118, 80–88.Google Scholar
Müller, J., Sidler, D., Nachbur, U., Wastling, J., Brunner, T. & Hemphill, A. (2008b) Thiazolides inhibit growth and induce glutathione-S-transferase pi (GSTP1)-dependent cell death in human colon cancer cells. International Journal of Cancer 123, 1797–1806.Google Scholar
Naguleswaran, A., Spicher, M., Vonlaufen, N., Ortega-Mora, L.M., Torgerson, P., Gottstein, B. & Hemphill, A. (2006) In vitro metacestodicidal activities of genistein and other isoflavones against Echinococcus multilocularis and Echinococcus granulosus. Antimicrobial Agents and Chemotherapy 50, 3770–3778.Google Scholar
Nakao, M., McManus, D.P., Schantz, P.M., Craig, P.S. & Ito, A. (2007) A molecular phylogeny of the genus Echinococcus inferred from complete mitochondrial genomes. Parasitology 134, 713–722.CrossRefGoogle ScholarPubMed
Ohbayashi, M., Rausch, R.L. & Fay, F.H. (1971) On the ecology and distribution of Echinococcus spp. (Cestoda: Taeniidae), and characteristics of their development in the intermediate host. II. Comparative studies on the larval E. multilocularis Leuckart, 1863, in the intermediate host. Japanese Journal of Veterinary Research 19, 1–9.Google Scholar
Ozbay, A., Karamperis, N. & Jørgensen, K.A. (2007) A review of the immunosuppressive activity of cyclosporine metabolites: new insights into an old issue. Current Clinical Pharmacology 2, 244–248.CrossRefGoogle ScholarPubMed
Pawlowski, Z.S. (1997) Critical points in the clinical management of cystid echinococcosis: a revised review. pp. 119–135in Anderson, F.L., Ouhelli, H. & Kachani, M. (Eds) Compendium on cystic echinococcosis. Provo, Brigham Young University.Google Scholar
Pawlowski, Z.S., Eckert, J., Vuitton, D.A., Ammann, R.W., Kern, P., Craig, P.S., Dar, K.F., De Rosa, F., Filice, C., Gottstein, B., Grimm, F., MacPhearson, C.N.L., Sato, N., Todorov, T., Uchino, J., von Sinner, W. & Wen, H. (2001) Echinococcosis in humans: clinical aspects, diagnosis and treatment. pp. 20–32in Eckert, J., Gemmell, M.A., Meslin, F.X. & Pawlowski, Z.S. (Eds) WHO/OIE manual on echinococcosis in humans and animals: a public health problem of global concern. Paris, World Organization for Animal Health and World Health Organization.Google Scholar
Pike, A.C., Brzozowski, A.M., Hubbard, R.E., Bonn, T., Thorsell, A.G., Engström, O., Ljunggren, J., Gustafsson, J.A. & Carlquist, M. (1999) Structure of the ligand-binding domain of oestrogen receptor beta in the presence of a partial agonist and a full antagonist. EMBO Journal 18, 4608–4618.Google Scholar
Rausch, R.L. (1995) Life cycle patterns and geographic distribution of Echinococcus species. pp. 89–99in Thompson, R.C.A. & Lymbery, A.J. (Eds) Echinococcosis and hydatid disease. Wallingford, CAB International.Google Scholar
Rausch, R.L., Wilson, J.F., Schantz, P.M. & McMahon, B.J. (1987) Spontaneous death of Echinococcus multilocularis: case diagnosised serologically (by Em2-Elisa) and clinical significance. American Journal of Tropical Medicine and Hygiene 36, 576–585.Google Scholar
Reuter, S., Jensen, B., Buttenschoen, K., Kratzer, W. & Kern, P. (2000) Benzimidazoles in the treatment of alveolar echinococcosis. Journal of Antimicrobial Chemotherapy 46, 451–460.Google Scholar
Reuter, S., Merkle, M., Brehm, K., Kern, P. & Manfras, B. (2003a) Effect of amphotericin B on larval growth of Echinococcus multilocularis. Antimicrobial Agents and Chemotherapy 47, 620–625.Google Scholar
Reuter, S., Buck, A., Grebe, O., Nüssle-Kügele, K., Kern, P. & Manfras, B. (2003b) Salvage treatment with amphotericin B in progressive human alveolar echinococcosis. Antimicrobial Agents and Chemotherapy 47, 3586–3591.CrossRefGoogle ScholarPubMed
Reuter, S., Buck, A., Manfras, B., Kratzer, W., Seitz, H.M., Darge, K., Reske, S.N. & Kern, P. (2004) Structured treatment interuption in patients with alveolar echinococcosis. Hepatology 39, 509–517.Google Scholar
Reuter, S., Manfras, B., Merkle, M., Harter, G. & Kern, P. (2006) In vitro activities of itraconazole, methiazole, and nitazoxanide versus Echinococcus multilocularis larvae. Antimicrobial Agents and Chemotherapy 50, 2966–2970.Google Scholar
Reynaud, J., Guilet, D., Terreux, R., Lussignol, M. & Walchshofer, N. (2005) Isoflavonoids in non-leguminous families: an update. Natural Products Reports 22, 504–515.Google Scholar
Rodrigues, J.M., Bories, C., Emery, I., Fessi, H., Devissaguet, J.P. & Liance, M. (1995) Development of an injectable formulation of albendazole and in vivo evaluation of its efficacy against Echinococcus metacestodoe. International Journal for Parasitology 25, 1437–1441.Google Scholar
Rodriguez-Fonseca, C., Amils, R. & Garret, R.A. (1995) Fine structure of the peptidyl transferase centre on 23S-like rRNAs deduced from chemical probing of antibiotic ribosome complexes. Journal of Molecular Biology 27, 224–235.Google Scholar
Rogan, M.T. & Richards, K.S. (1986) Echinococcus granulosus: in vivo effect of monensin on the tegument of the protoscolex. Parasitology 93, 347–355.CrossRefGoogle ScholarPubMed
Rooseboom, M., Commandeur, J.N.M. & Vermeulen, N.P.E. (2004) Enzyme-catalyzed activation of anticancer prodrugs. Pharmacological Reviews 56, 53–102.Google Scholar
Rubino, S., Fiori, P.L., Lubinu, G., Monaco, G. & Cappucinelli, P. (1983) The cytoskeleton of hydatid cyst cultured cells and its sensitivity to inhibitors. European Journal of Cell Biology 30, 182–190.Google ScholarPubMed
Sander, P.T., Prammananan, T., Meier, A., Frischkorn, K. & Bottger, E.C. (1997) The role of ribosomal RNAs in macrolide resistance. Molecular Microbiology 26, 469–480.Google Scholar
Sarciron, M.E., Walchshofer, N., Walbaum, S., Arsac, C., Descotes, J., Petavy, A.F. & Paris, J. (1997) Increases in the effects of albendazole on Echinococcus multilocularis metacestodes by the dipeptide methyl ester (Phe-Phe-OMe). American Journal of Tropical Medicine and Hygiene 56, 226–230.Google Scholar
Satou, T., Koga, M., Matsuhashi, R., Koike, K., Tada, I. & Nikaido, T. (2002) Assay of nematocidal activity of isoquinoline alkaloids using third-stage larvae of Strongyloides ratti and S. venezuelensis. Veterinary Parasitology 104, 131–138.CrossRefGoogle ScholarPubMed
Schantz, P.M., Chai, J., Craig, P.S., Eckert, J., Jenkins, D.J., Macpherson, C.N.L. & Thakur, A (1995) Epidemiology and control of hydatid disease. pp. 233–245in Thompson, R.C.A. & Lymbery, A.J. (Eds) Echinococcosis and hydatid disease. Wallingford, CAB International.Google Scholar
Schumacher, G. & Neuhaus, P. (2001) The physiological estrogen metabolite 2-methoxyestradiol reduces tumor growth and induces apoptosis in human solid tumors. Journal of Cancer Research and Clinical Oncology 127, 405–410.Google Scholar
Siles-Lucas, M. & Gottstein, B. (2003) The 14-3-3 protein: a key molecule in parasites as in other organisms. Trends in Parasitology 19, 575–581.Google Scholar
Siles-Lucas, M. & Hemphill, A. (2002) Cestode parasites: application of in vivo and in vivo models for studies on the host-parasite relationship. Advances in Parasitology 51, 133–230.Google Scholar
Siles-Lucas, M., Felleisen, R.S., Hemphill, A., Wilson, W. & Gottstein, B. (1998) Stage-specific expression of the 14-3-3 gene in Echinococcus multilocularis. Molecular and Biochemical Parasitolology 91, 281–293.Google Scholar
Siles-Lucas, M., Nunes, C.P. & Zaha, A. (2001) Comparative analysis of the 14-3-3 gene and its expression in Echinococcus granulosus and Echinococcus multilocularis metacestodes. Parasitology 122, 281–287.Google Scholar
Sioud, M. & Leirdal, M. (2007) Druggable signaling proteins. Methods in Molecular Biology 361, 1–24.Google Scholar
Spicher, M., Naguleswaran, A., Ortega-Mora, L.M., Müller, J., Gottstein, B. & Hemphill, A. (2008a) In vitro and in vivo effects of 2-methoxyestradiol, either alone or combined with albendazole, against Echinococcus metacestodes. Experimental Parasitology 119, 467–474.Google Scholar
Spicher, M., Roethlisberger, C., Lany, C., Stadelmann, B., Keiser, J., Ortega-Mora, L.M., Gottstein, B. & Hemphill, A. (2008b) In vitro and in vivo treatments of Echinococcus protoscoleces and metacestodes with artemisinin and artemisinin derivatives. Antimicrobial Agents and Chemotherapy 52, 3447–3450.CrossRefGoogle ScholarPubMed
Spiliotis, M. & Brehm, K. (2004) Echinococcus multilocularis: identification and molecular characterization of a Ral-like small GTP-binding protein. Experimental Parasitology 107, 163–172.Google Scholar
Spiliotis, M., Kroner, A. & Brehm, K. (2003) Identification, molecular characterization and expression of the gene encoding the epidermal growth factor receptor orthologue from the fox-tapeworm Echinococcus multilocularis. Gene 323, 57–65.Google Scholar
Spiliotis, M., Tappe, D., Sesterhenn, L. & Brehm, K. (2004) Long-term in vitro cultivation of Echinococcus multilocularis metacestodes under axenic conditions. Parasitology Research 92, 430–432.Google Scholar
Spiliotis, M., Tappe, D., Bruckner, S., Mosch, H.U. & Brehm, K. (2005) Molecular cloning and characterization of Ras- and Raf-homologues from the fox-tapeworm Echinococcus multilocularis. Molecular and Biochemical Parasitology 139, 225–237.Google Scholar
Spiliotis, M., Konrad, C., Gelmedin, V., Tappe, D., Bruckner, S., Mosch, H.U. & Brehm, K. (2006) Characterisation of EmMPK1, an ERK-like MAP kinase from Echinococcus multilocularis which is activated in response to human epidermal growth factor. International Journal for Parasitology 36, 1097–1112.Google Scholar
Spiliotis, M., Lechner, S., Tappe, D., Scheller, C., Krohne, G. & Brehm, K. (2008) Transient transfection of Echinococcus multilocularis primary cells and complete in vitro regeneration of metacestode vesicles. International Journal for Parasitology 38, 1025–1039.Google Scholar
Stettler, M., Siles-Lucas, M., Sarciron, E., Lawton, P., Gottstein, B. & Hemphill, A. (2001) Echinococcus multilocularis alkaline phosphatase as a marker for metacestode damage induced by in vivo drug treatment with albendazole sulfoxide and albendazole sulfone. Antimicrobial Agents and Chemotherapy 45, 2256–2262.Google Scholar
Stettler, M., Fink, R., Walker, M., Gottstein, B., Geary, T.G., Rossignol, J.F. & Hemphill, A. (2003) In vivo parasiticidal effect of nitazoxanide against Echinococcus multilocularis metacestodes. Antimicrobial Agents and Chemotherapy 47, 467–474.CrossRefGoogle Scholar
Stettler, M., Rossignol, J.F., Fink, R., Walker, M., Gottstein, B., Merli, M., Theurillat, R., Thormann, W., Dricot, E., Segers, R. & Hemphill, A. (2004) Secondary and primary murine alveolar echinococcosis: combined albendazole/nitazoxanide chemotherapy exhibits profound anti-parasitic activity. International Journal for Parasitology 34, 615–624.Google Scholar
Stey, C. & Jost, R. (1993) Rezidivierende, lebensbedroliche Anaphylaxie als Erstmanifestation eines Echinococcus cysticus (granulosus) der Leber. Schweizerische Medizinische Wochenzeitschrift 123, 1445–1450.Google Scholar
Taylor, D.H., Richards, K.S. & Morris, D.L. (1989) Rapid recovery of Echinococcus granulosus following ‘successful’ albendazole therapy in a gerbil model. Journal of Helminthology 63, 349–352.Google Scholar
Thompson, R.C.A. (1986) Biology and systematics of Echinococcus. pp. 5–17in Thompson, R.C.A. (Ed.) The biology of Echinococcus and hydatid disease. London, Allen & Unwin.Google Scholar
Torgerson, P.R. (2003) Economic effects of echinococcosis. Acta Tropica 85, 113–118.CrossRefGoogle ScholarPubMed
Urrea-Paris, M.A., Moreno, M.J., Casado, N. & Rodriguez-Caabeiro, F. (1999) Echinococcus granulosus: praziquantel treatment against the metacestode stage. Parasitology Research 85, 999–1006.Google Scholar
Urrea-Paris, M.A., Casado, N., Moreno, M.J. & Rodriguez-Caabeiro, F. (2001) Chemoprophylactic praziquantel treatment in experimental hydatidosis. Parasitology Research 87, 510–512.Google Scholar
Varcasia, A., Garippa, G., Pipia, A.P., Scala, A., Brianti, E., Giannetto, S., Battelli, G., Poglayen, G. & Micagni, G. (2008) Cystic echinococcosis in equids in Italy. Parasitology Research 102, 815–818.Google Scholar
Vuitton, D.A., Zhang, S.L., Yang, Y., Godot, V., Beurton, I., Mantion, G. & Bresson-Hadni, S. (2006) Survival strategy of Echinococcus multilocularis in the human host. Parasite International 55, S51–S55.Google Scholar
Walchshofer, N., Delabre-Defayolle, I., Paris, J. & Petavy, A.F. (1990) In vivo morphological damage induced by a new benzimidazole pro-drug in Echinococcus multilocularis metacestodes. Journal of Pharmacological Science 79, 606–608.CrossRefGoogle ScholarPubMed
Walker, M., Baz, A., Dematteis, S., Stettler, M., Gottstein, B., Schaller, J. & Hemphill, A. (2004a) Isolation and characterization of a secretory component of Echinococcus multilocularis metacestodes potentially involved in modulating the host-parasite interface. Infection and Immunity 72, 527–536.Google Scholar
Walker, M., Rossignol, J.F., Torgerson, P. & Hemphill, A. (2004b) In vivo effects of nitazoxanide on Echinococcus granulosus protoscoleces and metacestodes. Journal of Antimicrobial Chemotherapy 54, 609–616.Google Scholar
Wangoo, A., Ganguly, N.K. & Mahajan, R.C. (1987) In vivo efficacy of mebendazole in containment of larval cyst mass in early stages of hydatid disease due to Echinococcus granulosus. Transactions of the Royal Society of Tropical Medicine and Hygiene 81, 965–966.Google Scholar
Wen, H., New, R.R., Muhmut, M., Wang, J.H., Wang, Y.H., Zhang, J.H., Shao, Y.M. & 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, 111–121.Google Scholar
Xiao, S., Feng, J. & Yao, M. (1995) Effect of anti-hydatid drugs on carbohydrate metabolism of metacestode of Echinococcus granulosus. Chinese Medical Journal 108, 682–688.Google Scholar
Zavala-Gongora, R., Kroner, A., Wittek, B., Knaus, P. & Brehm, K. (2003) Identification and characterisation of two distinct Smad proteins from the fox-tapeworm Echinococcus multilocularis. International Journal for Parasitology 33, 1665–1677.Google Scholar
Zavala-Gongora, R., Kroner, A., Bernthaler, P., Knaus, P. & Brehm, K. (2006) A member of the transforming growth factor-beta receptor family from Echinococcus multilocularis is activated by human bone morphogenetic protein 2. Molecular and Biochemical Parasitology 146, 265–271.Google Scholar