Hostname: page-component-586b7cd67f-g8jcs Total loading time: 0 Render date: 2024-11-22T20:00:07.419Z Has data issue: false hasContentIssue false
  • English
  • Français

Innovative chemotherapeutical treatment options for alveolar and cystic echinococcosis

Published online by Cambridge University Press:  16 July 2007

A. HEMPHILL ,
M. SPICHER ,
B. STADELMANN ,
J. MUELLER ,
A. NAGULESWARAN ,
B. GOTTSTEIN  and
M. WALKER
A. HEMPHILL*
Affiliation:
Institute of Parasitology, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
M. SPICHER
Affiliation:
Institute of Parasitology, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
B. STADELMANN
Affiliation:
Institute of Parasitology, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
J. MUELLER
Affiliation:
Institute of Parasitology, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
A. NAGULESWARAN
Affiliation:
Department of Pharmacology and Toxicology, Indiana University School of Medicine, 635 Barnhill Drive, MS A-515, Indianapolis, IN 46202, USA
B. GOTTSTEIN
Affiliation:
Institute of Parasitology, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland
M. WALKER
Affiliation:
Department of Medicine, Harvard School of Public Health, Boston, MA 02115, USA
*
*Corresponding author: Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland. Tel: +41 31 6312384. Fax: +41 31 6312477. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Echinococcus granulosus and Echinococcus multilocularis are cestode parasites, of which the metacestode (larval) stages cause the diseases cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. Albendazole and mebendazole are presently used for chemotherapeutical treatment. However, these benzimidazoles do not appear to be parasiticidal in vivo against AE. In addition, failures in drug treatments as well as the occurrence of side-effects have been reported. New drugs are needed to cure AE and CE, which are considered to be neglected diseases. Strategies currently being implemented to identify novel chemotherapeutical treatment options include (i) conventional primary in vitro testing of broad-spectrum anti-infective drugs, either in parallel with, or followed by, animal experimentation; (ii) studies of drugs which interfere with the proliferation of cancer cells and of Echinococcus metacestodes; (iii) exploitation of the similarities between the parasite and mammalian signalling machineries, with a special focus on targeting specific signalling receptors; (iv) in silico approaches, employing the current Echinococcus genomic database information to search for suitable targets for compounds with known modes of action. In the present article, we review the efforts toward obtaining better anti-parasitic compounds which have been undertaken to improve chemotherapeutical treatment of echinococcosis, and summarize the achievements in the field of host-parasite interactions which may also lead to new immuno-therapeutical options.

Keywords

cystic echinococcosis (CE)alveolar echinococcosis (AE)chemotherapyimmunotherapysignallingdrugshost-parasite interactions
Type
Review Article
Information
Parasitology , Volume 134 , Issue 12 , November 2007 , pp. 1657 - 1670
Copyright
Copyright © Cambridge University Press 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

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, 497–512.CrossRefGoogle ScholarPubMed
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. 411–430. CAB International, Wallingford, UK.Google Scholar
Bartholomot, G., Vuitton, D. A., Harraga, S., Shi, D. Z., Giraudoux, P., Barnish, G., Wang, Y. H., MacPherson, C. N. and 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
Baz, A., Ettlin, G. M. and Dematteis, S. (2006). Complexity and function of cytokine responses in experimental infection by Echinococcus granulosus. Immunobiology 211, 3–9.CrossRefGoogle ScholarPubMed
Blanton, R. E., Wachira, T. M., Zeyhle, E., Njoroge, E. M., Magambo, J. K. and Schantz, P. M. (1998). Oxfendazole treatment of cystic hydatid disease in naturally infected animals. Antimicrobial Agents and Chemotherapy 42, 601–605.CrossRefGoogle ScholarPubMed
Brehm, K., Kronthaler, K., Jura, H. and 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. and Frosch, M. (2006). The molecular mechanisms of larval cestode development: first steps into an unknown world. Parasitology International 55, S15–S21.CrossRefGoogle ScholarPubMed
Bresson-Hadni, S., Laplante, J. J., Lenys, D., Rohmer, P., Gottstein, B., Jacquier, P., Mercet, P., Meyer, J. P., Miguet, J. P. and 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. and 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., Urrea-Paris, M. A., Moreno, M. J., and Rodriguez-Caabeiro, F. (2001). Combined praziquantel and albendazole chemoprophylaxis in experimental hydatidosis. Parasitology Research 87, 787–789.Google ScholarPubMed
Chai, J., MenghebatWIE, J. 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.CrossRefGoogle ScholarPubMed
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, 462–466.CrossRefGoogle ScholarPubMed
Craig, P. (2003). Echinococcus multilocularis. Current Opinion in Infectious Diseases 16, 437–444.CrossRefGoogle ScholarPubMed
Dai, W. J., Hemphill, A., Waldvogel, A., Ingold, K., Deplazes, P., Mossmann, H. and Gottstein, B. (2001). Major carbohydrate antigen of Echinococcus multilocularis induces an immunoglobulin G response independent of alpha beta(+) CD4(+) T cells. Infection and Immunity 69, 6074–6083.CrossRefGoogle ScholarPubMed
Dai, W. J., Waldvogel, A., Siles-Lucas, M. and Gottstein, B. (2004). Echinococcus multilocularis proliferation in mice and respective parasite 14-3-3 gene expression is mainly controlled by an alphabeta CD4 T-cell-mediated immune response. Immunology 112, 481–488.CrossRefGoogle ScholarPubMed
Dakora, F. D. and 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
Dematteis, S., Pirotto, F., Marques, J., Nieto, A., Orn, A. and Baz, A. (2001). Modulation of the cellular immune response by a carbohydrate rich fraction from Echinococcus granulosus protoscoleces in infected or immunized Balb/c mice. Parasite Immunology 23, 1–9.CrossRefGoogle ScholarPubMed
Dematteis, S., Rottenberg, M. and Baz, A. (2003). Cytokine response and outcome of infection depends on the infective dose of parasites in experimental infection by Echinococcus granulosus. Parasite Immunology 25, 189–197.CrossRefGoogle ScholarPubMed
Diaz, A., Irigoin, R., Ferreira, F. and Sim, R. B. (1999). Control of host complement activation by the Echinococcus granulosus hydatid cyst. Immunopharmacology 42, 91–98.CrossRefGoogle ScholarPubMed
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, 2263–2267.CrossRefGoogle ScholarPubMed
Eckert, J. and Deplazes, P. (2004). Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis of increasing concern. Clinical Microbiology Reviews 17, 107–135.CrossRefGoogle ScholarPubMed
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, 737–748.CrossRefGoogle ScholarPubMed
El-On, J. (2002). Benzimidazole treatment of cystic echinococcosis. Acta Tropica 85, 243–252.CrossRefGoogle Scholar
Emery, I., Leclerc, C., Sengphommachanh, K., Vuitton, D. A. and Liance, M. (1998). In vivo treatment with recombinant IL-12 protects C57BL/6 mice against secondary alveolar echinococcosis. Parasite Immunology 20, 81–91.CrossRefGoogle Scholar
Esposito, M., Mueller, N. and 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
Ferreira, A. M., Irigoin, F., Breijo, M., Sim, R. B. and Diaz, A. (2000). How Echinococcus granulosus deals with complement. Parasitology Today 16, 168–172.CrossRefGoogle ScholarPubMed
Ferreira, A. M., Diaz, A., Fernandez, C. and Sim, R. B. (2001). Assessment of in vivo complement activation on the Echinococcus granulosus hydatid cyst wall. Parasite Immunology 23, 655–658.CrossRefGoogle ScholarPubMed
Fraize, M., Sarciron, M. E., Azzouz, S., Issadi, N., Bosquet, G. and Petavy, A. F. (2005). Immunogenicity of two Echinococcus granulosus antigens EgA31 and EgTrp in mice. Parasitology Research 96, 113–120.CrossRefGoogle ScholarPubMed
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, 447–450.CrossRefGoogle ScholarPubMed
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, 105–108.CrossRefGoogle ScholarPubMed
Gelmedin, V., Zavala-Gongora, R., Fernandez, C. and 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
Godot, V., Harraga, S., Podoprigora, G., Liance, M., Bardonnet, K. and Vuitton, D. A. (2003). IFN-a-2a protects mice against helminth infection of the liver and modulates immune responses. Gastroenterology 124, 1441–1450.CrossRefGoogle ScholarPubMed
Gottstein, B., Dai, W. J., Walker, M., Stettler, M., Muller, N. and 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. and Hemphill, A. (2006). Molecular survival strategies of Echinococcus multilocularis in the murine host. Parasitology International 55, S45–S49.CrossRefGoogle ScholarPubMed
Gottstein, B. and Hemphill, A. (1997). Immunopathology of echinococcosis. Chemical Immunology 66, 177–208.Google ScholarPubMed
Grenard, P., Bresson-Hadni, S., El Alaoui, S., Chevallier, M., Vuitton, D. A. and Ricard-Blum, S. (2001). Transglutaminase-mediated crosslinking is involved in the stabilization of extracellular matrix in human liver fibrosis. Journal of Hepatology 35, 367–375.CrossRefGoogle ScholarPubMed
Harraga, S., Godot, V., Bresson-Hadni, S., Pater, C., Beurton, I., Bartholomot, B. and Vuitton, D. A. (1999). Clinical efficacy of and switch from T helper 2 to T helper 1 cytokine profile after interferon alpha2a monotherapy for human echinococcosis. Clinical Infectious Diseases 29, 205–206.CrossRefGoogle Scholar
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, 953–964.CrossRefGoogle ScholarPubMed
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, 445–449.CrossRefGoogle ScholarPubMed
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. 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, 315–320.CrossRefGoogle ScholarPubMed
Jenne, L., Kilwinski, J., Radloff, P., Flick, W. and Kern, P. (1998). Clinical efficacy of immunologic alterations caused by interferon gamma therapy for alveolar echinococcosis. Clinical Infectious Diseases 26, 492–494.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.CrossRefGoogle ScholarPubMed
Klauber, N., Parangi, S., Flynn, E., Hamel, E. and 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. and 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. and 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., and Slaga, T. J. (2003). 2-Methoxyestradiol interferes with NfkB transcriptional activity in primitive neuroectodermal brain tumours: implications for management. Carcinogenesis 24, 209–216.CrossRefGoogle Scholar
Launchbury, A. P. and Habboubi, N. (1993). Epirubicin and doxorubicin: a comparison of their characteristics, therapeutic activity and toxicity. Cancer Treatment Reviews 19, 197–228.CrossRefGoogle ScholarPubMed
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, 251–257.Google Scholar
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, 23–28.CrossRefGoogle ScholarPubMed
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, 427–429.CrossRefGoogle ScholarPubMed
Liance, M., Ricard-Blum, S., Emery, I., Houin, R. and Vuitton, D. A. (1998). Echinococcus multilocularis infection in mice: in vivo treatment with a low dose of IFN-gamma decreases metacestode grwoth and liver fibrogenesis. Parasite 5, 231–237.CrossRefGoogle Scholar
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. and Giannakakou, P. (2003). 2-ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Cancer Cell 3, 363–375.CrossRefGoogle ScholarPubMed
MacPherson, C. N., Kachani, M., Lyagoubi, M., Berrada, M., Shepherd, M., Fields, P. F. and El Hasnaoui, M. (2004). Cystic echinococcosis in the Berber of the Mid Atlas mountains, Morocco: new insights into the natural history of the disease in humans. Annals of Tropical Medicine and Parasitology 98, 481–490.Google ScholarPubMed
Maizels, R. M. and Yazdanbakhsh, M. (2003). Immune regulation by helminth parasites: Cellular and molecular mechanisms. Nature Reviews Immunology 3, 733–744.CrossRefGoogle ScholarPubMed
Manfras, B., Reuter, S., Wendland, T. and Kern, P. (2002). Increased activation and oligoclonality of peripheral CD8+ T cells in the chronic human helminth infection alveolar echinococcosis. Infection and Immunity 70, 1168–1174.CrossRefGoogle ScholarPubMed
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, 171–180.CrossRefGoogle Scholar
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, 120–127.CrossRefGoogle ScholarPubMed
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. Antimcirobial Agents and Chemotherapy 49, 3251–3255.CrossRefGoogle Scholar
McManus, D. P., Wenbao, Z., Jun, L. and Bartley, P. B. (2003). Echinococcosis. The Lancet 362, 1295–1304.CrossRefGoogle ScholarPubMed
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, 749–763.CrossRefGoogle ScholarPubMed
Messina, M.Soy, soy phytoestrogens (isoflavones), and breast cancer. American Journal of Clinical Nutrition 70, 574–575.CrossRefGoogle Scholar
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, 75–76.CrossRefGoogle ScholarPubMed
Moro, P. L., Garcia, H. H., Gonzales, A. E., Bonilla, J. J., Verastegui, M. and Gilmanmd, R. H. (2005). Screening for cystic echinococcosis in an endemic region of Peru using portable ultrasonography and the enzyme linked immunoelectrotransfer blot (EITB) assay. Parasitology Research 96, 242–246.CrossRefGoogle Scholar
Morris, D. L., and Taylor, D. H. (1990). Echinococcus granulosus: development of resistance to albendazole in an animal model. Journal of Helminthology 64, 171–174.CrossRefGoogle ScholarPubMed
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, 3770–3778.CrossRefGoogle ScholarPubMed
Ohbayashi, M., Rausch, R. L. and 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
Ortona, E., Margutti, P., Delunardo, F., Vaccari, S., Rigano, R., Profumo, E., Buttari, B., Teggi, A. and Siracusano, A. (2003). Molecular and immunological characterization of the C-terminal region of a new Echinococcus granulosus heat shock protein 70. Parasite Immunology 25, 119–126.CrossRefGoogle ScholarPubMed
Pawloski, Z. S. (1997). Critical points in the clinical management of cystid echinococcosis: a revised review. In Compendium on Cystic Echinococcosis (ed. Anderson, F. L., Ouhelli, H. and Kachani, M.), pp. 119–135. Brigham Young University, Provo, USA.Google Scholar
Pawloski, 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. and Wen, H. (2001). Echinococcosis in humans: clinical aspects, diagnosis and treatment. In WHO/OIE Manual on Echinococcosis in Humans and Animals: a Public Health Problem of Global Concern (ed. Eckert, J., Gemmell, M. A., Meslin, F. X. and Pawlowski, Z. S), pp. 20–32. World Organization for Animal Health and World Health Organization, Paris, France.Google Scholar
Rau, M. E. and Tanner, C. E. (1975). BCG suppresses growth and metastasis of hydatid infections. Nature, London 256, 318–319.CrossRefGoogle ScholarPubMed
Rausch, R. L., Wilson, J. F., Schantz, P. M. and 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.CrossRefGoogle Scholar
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. 89–99. CAB International, Wallingford, UK.Google Scholar
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, 3586–3591.CrossRefGoogle ScholarPubMed
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, 509–517.CrossRefGoogle Scholar
Reuter, S., Jensen, B., Buttenschoen, K., Kratzer, W. and Kern, P. (2000). Benzimidazoles in the treatment of alveolar echinococcosis. Journal of Antimicrobial Chemotherapy 46, 451–460.CrossRefGoogle ScholarPubMed
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, 2966–2970.CrossRefGoogle ScholarPubMed
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, 620–625.CrossRefGoogle ScholarPubMed
Reynaud, J., Guilet, D., Terreux, R., Lussignol, M. and Walchshofer, N. (2005). Isoflavonoids in non-leguminous families: an update. Natural Products Reports 22, 504–515.CrossRefGoogle ScholarPubMed
Rigano, R., Profumo, E., Ioppolo, S., Notargiacomo, S., Ortona, E., Teggi, A. and Siracusano, A. (1995). Immunological markers indicating the effectiveness of pharmacological treatment in human hydatid disease. Clinical Experimental Immunology 102, 281–285.CrossRefGoogle ScholarPubMed
Rigano, R., Buttari, B., De Falco, E., Profumo, E., Ortana, E., Margutti, P., Scotta, C., Teggi, A. and Siracusano, A. (2004). Echinococcus granulosus-specific T cell lines derived from patients at various clinical stages of cystic echinococcosis. Parasite Immunology 26, 45–52.CrossRefGoogle ScholarPubMed
Rodrigues, J. M., Bories, C., Emery, I., Fessi, H., Devissaguet, J. P. and 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.CrossRefGoogle Scholar
Rodriguez-Fonseca, C., Amils, R. and 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.CrossRefGoogle Scholar
Rogan, M. T. and Richards, K. S. (1986). Echinococcus granulosus: in vivo effect of monensin on the tegument of the protoscolex. Parasitology 93, 347–355.CrossRefGoogle ScholarPubMed
Sander, P. T., Prammananan, T., Meier, A., Frischkorn, K. and Bottger, E. C. (1997). The role of ribosomal RNAs in macrolide resistance. Molecular Microbiology 26, 469–480.CrossRefGoogle ScholarPubMed
Sarciron, M. E., Delabre, I., Walbaum, S., Raynaud, G., and Petavy, A. F. (1992). Effects of multiple doses of isoprinosine on Echinococcus multilocularis metacestodes. Antimicrobial Agents and Chemotherapy 36, 191–194.CrossRefGoogle ScholarPubMed
Sarciron, M. E., Walbaum, S., Arsac, C., Raynaud, G., and Petavy, A. F. (1993). Echinococcus granulosus: isoprinosine treatment of the metacestode stage. American Journal of Tropical Medicine and Hygiene 48, 658–665.CrossRefGoogle ScholarPubMed
Sarciron, M. E., Walbaum, M. E. and Petavy, A. F. (1995). Effects of Isoprinosine on Echinococcus multilocularis and E. granulosus metacestodes. Parasitology Research 81, 329–333.CrossRefGoogle ScholarPubMed
Sarciron, M. E., Walchshofer, N., Walbaum, S., Arsac, C., Descotes, J., Petavy, A. F. and 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.CrossRefGoogle ScholarPubMed
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. 233–245. CAB International, Wallingford, UK.Google Scholar
Schmid, M., Samonigg, H., Stoger, H, Auer, H., Sternthal, M. H., Wilders-Truschnig, M. and Reisinger, E. C. (1995). Use of interferon-gamma and mebendazole to stop the protression of alveolar hydatid disease: case report. Clinical Infectious Diseases 20, 1543–1546.CrossRefGoogle ScholarPubMed
Schumacher, G. and 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.CrossRefGoogle ScholarPubMed
Siles-Lucas, M., Felleisen, R. S., Hemphill, A., Wilson, W. and Gottstein, B. (1998). Stage-specific expression of the 14-3-3 gene in Echinococcus multilocularis. Molecular and Biochemical Parasitolology 91, 281–293.CrossRefGoogle ScholarPubMed
Siles-Lucas, M. and Gottstein, B. (2003). The 14-3-3 protein: a key molecule in parasites as in other organisms. Trends in Parasitology 19, 575–581.CrossRefGoogle ScholarPubMed
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, 133–230.CrossRefGoogle ScholarPubMed
Siles-Lucas, M., Nunes, C. P. and 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.CrossRefGoogle ScholarPubMed
Sioud, M. and Leirdal, M. (2007). Druggable signaling proteins. Methods in Molecular Biology 361, 1–24.Google ScholarPubMed
Spiliotis, M. and Brehm, K. (2004). Echinococcus multilocularis: identification and molecular characterization of a Ral-like small GTP-binding protein. Experimental Parasitology 107, 163–172.CrossRefGoogle ScholarPubMed
Spiliotis, M., Konrad, C., Gelmedin, V., Tappe, D., Bruckner, S., Mosch, H. U. and 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.CrossRefGoogle ScholarPubMed
Spiliotis, M, Kroner, A. and 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.CrossRefGoogle ScholarPubMed
Spiliotis, M., Tappe, D., Bruckner, S., Mosch, H. U. and 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.CrossRefGoogle ScholarPubMed
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, 430–432.CrossRefGoogle ScholarPubMed
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, 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. and 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.CrossRefGoogle ScholarPubMed
Stey, C. and 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. and Morris, D. L. (1989). Rapid recovery of Echinococcus granulosus following ‘successful’ albendazole therapy in a gerbil model. Journal of Helminthology 63, 349–352.CrossRefGoogle Scholar
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 and Unwin, London.Google Scholar
Torgerson, P. R. (2003). Economic effects of echinococcosis. Acta Tropica 85, 113–118.CrossRefGoogle ScholarPubMed
Urrea-Paris, M. A., Casado, N., Moreno, M. J. and Rodriguez-Caabeiro, F. (2001). Chemoprophylactic praziquantel treatment in experimental hydatidosis. Parasitology Research 87, 510–512.Google ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Vuitton, D. A., Bresson-Hadni, S., Laroche, L., Kaiserlian, D., Guerret-Stocker, S., Bresson, J. L. and Gilbert, M. (1989). Cellular immune response in Echinococcus multilocularis infection in humans. II. Natural killer cell activity and cell subpopulations in the blood and in the periparasitic granuloma of patients with alveolar echinococcosis. Clinical and Experimental Immunology 78, 67–74.Google ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Walchshofer, N., Delabre-Defayolle, I., Paris, J. and 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. and Hemphill, A. (2004 a). 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.CrossRefGoogle ScholarPubMed
Walker, M., Rossignol, J. F., Torgerson, P. and Hemphill, A. (2004 b). In vivo effects of nitazoxanide on Echinococcus granulosus protoscoleces and metacestodes. Journal of Antimicrobial Chemotherapy 54, 609–616.CrossRefGoogle Scholar
Wangoo, A., Ganguly, N. K. and 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.CrossRefGoogle ScholarPubMed
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, 111–121.CrossRefGoogle ScholarPubMed
Xiao, S., Feng, J. and 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., Bernthaler, P., Knaus, P. and 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.CrossRefGoogle ScholarPubMed
Zavala-Gongora, R., Kroner, A., Wittek, B., Knaus, P. and Brehm, K. (2003). Identification and characterisation of two distinct Smad proteins from the fox-tapeworm Echinococcus multilocularis. International Journal for Parasitology 33, 1665–1677.CrossRefGoogle ScholarPubMed
Zhang, W. and McManus, D. P. (2006). Recent advances in the immunology and diagnosis of echinococcosis. FEMS Immunology and Medical Microbiology 47, 24–41.CrossRefGoogle ScholarPubMed