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In vitro and in vivo trematode models for chemotherapeutic studies

Published online by Cambridge University Press:  07 December 2009

J. KEISER
J. KEISER*
Affiliation:
Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, CH-4002Basel, Switzerland
*
*Corresponding author: Tel: +41 61 284-8218; Fax: +41 61 284-8105. E-mail: jennifer.keiser@unibas.ch
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Summary

Schistosomiasis and food-borne trematodiases are chronic parasitic diseases affecting millions of people mostly in the developing world. Additional drugs should be developed as only few drugs are available for treatment and drug resistance might emerge. In vitro and in vivo whole parasite screens represent essential components of the trematodicidal drug discovery cascade. This review describes the current state-of-the-art of in vitro and in vivo screening systems of the blood fluke Schistosoma mansoni, the liver fluke Fasciola hepatica and the intestinal fluke Echinostoma caproni. Examples of in vitro and in vivo evaluation of compounds for activity are presented. To boost the discovery pipeline for these diseases there is a need to develop validated, robust high-throughput in vitro systems with simple readouts.

Keywords

Schistosoma mansoniFasciola hepaticaEchinostoma caproniin vitroin vivodrug discoverychemotherapy
Type
Research Article
Information
Parasitology , Volume 137 , Special Issue 3: Development and applications of cestode and trematode laboratory models , March 2010 , pp. 589 - 603
Copyright
Copyright © Cambridge University Press 2009

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References

REFERENCES

Abdulla, M. H., Ruelas, D. S., Wolff, B., Snedecor, J., Lim, K. C., Xu, F., Renslo, A. R., Williams, J., McKerrow, J. H. and Caffrey, C. R. (2009). Drug discovery for schistosomiasis: hit and lead compounds identified in a library of known drugs by medium-throughput phenotypic screening. PLoS Neglected Tropical Diseases 3, e478.Google Scholar
Agnew, A. M., Murare, H. M., Lucas, S. B. and Doenhoff, M. J. (1989). Schistosoma bovis as an immunological analogue of S. haematobium. Parasite Immunology 11, 329–340.CrossRefGoogle ScholarPubMed
Alvarez, L. I., Mottier, M. L. and Lanusse, C. E. (2004). Comparative assessment of the access of albendazole, fenbendazole and triclabendazole to Fasciola hepatica: effect of bile in the incubation medium. Parasitology 128, 73–81.CrossRefGoogle ScholarPubMed
Anderson, H. R. and Fairweather, I. (1995). Fasciola hepatica: ultrastructural changes to the tegument of juvenile flukes following incubation in vitro with the deacetylated (amine) metabolite of diamphenethide. International Journal for Parasitology 25, 319–333.Google Scholar
Basch, P. F. (1981). Cultivation of Schistosoma mansoni in vitro. I. Establishment of cultures from cercariae and development until pairing. Journal of Parasitology 67, 179–185.Google Scholar
Berriman, M., Haas, B. J., LoVerde, P. T., Wilson, R. A., Dillon, G. P., Cerqueira, G. C., Mashiyama, S. T., Al-Lazikani, B., Andrade, L. F., Ashton, P. D., Aslett, M. A., Bartholomeu, D. C., Blandin, G., Caffrey, C. R., Coghlan, A., Coulson, R., Day, T. A., Delcher, A., DeMarco, R., Djikeng, A., Eyre, T., Gamble, J. A., Ghedin, E., Gu, Y., Hertz-Fowler, C., Hirai, H., Hirai, Y., Houston, R., Ivens, A., Johnston, D. A., Lacerda, D., Macedo, C. D., McVeigh, P., Ning, Z., Oliveira, G., Overington, J. P., Parkhill, J., Pertea, M., Pierce, R. J., Protasio, A. V., Quail, M. A., Rajandream, M. A., Rogers, J., Sajid, M., Salzberg, S. L., Stanke, M., Tivey, A. R., White, O., Williams, D. L., Wortman, J., Wu, W., Zamanian, M., Zerlotini, A., Fraser-Liggett, C. M., Barrell, B. G. and El-Sayed, N. M. (2009). The genome of the blood fluke Schistosoma mansoni. Nature 460, 352–358.Google Scholar
Brink, L. H., McLaren, D. J. and Smithers, S. R. (1977). Schistosoma mansoni: a comparative study of artificially transformed schistosomula and schistosomula recovered after cercarial penetration of isolated skin. Parasitology 74, 73–86.CrossRefGoogle ScholarPubMed
Broadhead, C. L. and Bottrill, K. (1997). Strategies for replacing animals in biomedical research. Molecular Medicine Today 3, 483–487.Google Scholar
Caffrey, C. R. (2007). Chemotherapy of schistosomiasis: present and future. Current Opinion in Chemical Biology 11, 433–439.CrossRefGoogle ScholarPubMed
Caffrey, C. R., Williams, D. L., Todd, M. H., Nelson, D. L., Keiser, J. and Utzinger, J. (2009). Chemotherapeutic development strategies for schistosomiasis. In Drug Discovery in Infectious Diseases: From Molecular Targets to Drug Candidates, (ed. Selzer, P. M..), pp. 301–321Wiley, Weinheim, Germany.Google Scholar
Chapman, C. B. and Mitchell, G. F. (1982). Fasciola hepatica: comparative studies on fascioliasis in rats and mice. International Journal for Parasitology 12, 81–91.CrossRefGoogle ScholarPubMed
Chisty, M. M., Nargis, M., Sato, H., Inaba, T., Takahashi, G. and Kamiya, H. (2002). Schistosoma mansoni: kinetics of glomerulonephritis in Mongolian gerbils and its correlation with intensity and duration of infection. Parasite 9, 143–151.CrossRefGoogle ScholarPubMed
Cioli, D., Knopf, P. M. and Senft, A. W. (1977). A study of Schistosoma mansoni transferred into permissive and nonpermissive hosts. International Journal for Parasitology 7, 293–297.CrossRefGoogle ScholarPubMed
Cioli, D., Valle, C., Angelucci, F. and Miele, A. E. (2008). Will new antischistosomal drugs finally emerge? Trends in Parasitology 24, 379–382.Google Scholar
Clegg, J. A. (1965). In vitro cultivation of Schistosoma mansoni. Experimental Parasitology 16, 133–147.Google Scholar
Clery, D. G., O'Mahony, P. and Mulcahy, G. (1995). A novel method for the administration of metacercariae of Fasciola hepatica to adult cattle. Research in Veterinary Science 58, 290–291.Google Scholar
Colley, D. G. and Wikel, S. K. (1974). Schistosoma mansoni: simplified method for the production of schistosomules. Experimental Parasitology 35, 44–51.CrossRefGoogle ScholarPubMed
Colley, D. G., LoVerde, P. T. and Savioli, L. (2001). Medical Helminthology in the 21st Century. Science 293, 1437–1438.Google Scholar
Cox, F. E. G. (1993). Modern Parasitology. Blackwell Scientific Publications, Oxford.CrossRefGoogle Scholar
Davis, A. 2009. Schistosomiasis, p. 1413–1456. In Manson's Tropical Diseases, 22nd Edition. (ed. Cook, G. C. and Zumla, A. I.) Saunders, London.Google Scholar
Dixon, K. E. (1966). The physiology of excystment of the metacercaria of Fasciola hepatica L. Parasitology 56, 431–456.Google Scholar
Doenhoff, M. J., Hagan, P., Cioli, D., Southgate, V., Pica-Mattoccia, L., Botros, S., Coles, G., Tchuem Tchuente, L. A., Mbaye, A. and Engels, D. (2009). Praziquantel: its use in control of schistosomiasis in sub-Saharan Africa and current research needs. Parasitology, 136, 1825–1835.CrossRefGoogle ScholarPubMed
Elsaghier, A. A., Knopf, P. M., Mitchell, G. F. and McLaren, D. J. (1989). Schistosoma mansoni: evidence that ‘non-permissiveness’ in 129/Ola mice involves worm relocation and attrition in the lungs. Parasitology 99, 365–375.CrossRefGoogle ScholarPubMed
Fairweather, I. (2009). Triclabendazole progress report, 2005–2009: an advancement of learning? Journal of Helminthology 83, 139–150.CrossRefGoogle ScholarPubMed
Fairweather, I., Threadgold, L. T. and Hanna, R. E. B. (1999). Development of Fasciola hepatica in the mammalian host. In Fasciolosis. (ed. Dalton, J. P.) CABI Publishing, pp. 225–276.Google Scholar
Fried, B. (1994). Metacercarial excystment of trematodes. Advances in Parasitology 33, 91–144.CrossRefGoogle ScholarPubMed
Fried, B. (2000). Maintenance, cultivation, and excystation of echinostomes. In Echinostomes as Experimental Models for Biological Research (ed. Fried, B. and Graczyk, T.) Kluwer Academic Publishers, pp. 99–118.CrossRefGoogle Scholar
Fried, B. and Huffman, J. E. (1996). The biology of the intestinal trematode Echinostoma caproni. Advances in Parasitology 38, 311–368.CrossRefGoogle ScholarPubMed
Fried, B. and Peoples, R. C. (2009). Maintenance, cultivation and excystation of echinostomes: 2000–2007. In The Biology of Echinostomes. (ed. Fried, B. and Toledo, R.) Springer, New York, 111–128.Google Scholar
Gryseels, B., Polman, K., Clerinx, J. and Kestens, L. (2006). Human schistosomiasis. Lancet 368, 1106–1118.CrossRefGoogle ScholarPubMed
Hobbs, D. J., Fryer, S. E., Duimstra, J. R., Hedstrom, O. R., Brodie, A. E., Collodi, P. A., Menino, J. S., Bayne, C. J. and Barnes, D. W. (1993). Culture of cells from juvenile worms of Schistosoma mansoni. Journal of Parasitology 79, 913–921.CrossRefGoogle ScholarPubMed
Hotez, P. J., Fenwick, A., Savioli, L. and Molyneux, D. H. (2009). Rescuing the bottom billion through control of neglected tropical diseases. Lancet 373, 1570–1575.Google Scholar
Howells, R. E., Ramalho-Pinto, F. J., Gazzinelli, G., de Oliveira, C. C., Figueiredo, E. A. and Pellegrino, J. (1974). Schistosoma mansoni: mechanism of cercarial tail loss and its significance to host penetration. Experimental Parasitology 36, 373–385.CrossRefGoogle ScholarPubMed
Ibarra, O. F. and Jenkins, D. C. (1984). An in vitro screen for new fasciolicidal agents. Zeitschrift für Parasitenkunde 70, 655–661.CrossRefGoogle Scholar
Idris, N. and Fried, B. (1996). Development, hatching, and infectivity of Echinostoma caproni (Trematoda) eggs, and histologic and histochemical observations on the miracidia. Parasitology Research 82, 136–142.Google Scholar
Itagaki, T., Sakamoto, T., Tsutsumi, Y. and Itagaki, H. (1994). Infectivity of three species of Fasciola to Wistar rats. Journal of Veterinary Medical Science 56, 977–979.Google Scholar
Jenkins, D. C., Topley, P. and Rapson, E. B. (1987). Fasciola hepatica in vitro: increased susceptibility to fasciolicides in a defined serum-free medium. Parasitology 95, 165–171.CrossRefGoogle Scholar
Kasilima, Y. S., Wango, E. O., Kigondu, C. S., Mutayoba, B. M. and Nyindo, M. (2004). Plasma bioactive LH and testosterone profiles in male New Zealand rabbits experimentally infected with Schistosoma mansoni. Acta Tropica 92, 165–172.Google Scholar
Keiser, J., Brun, R., Fried, B. and Utzinger, J. (2006). Trematocidal activity of praziquantel and artemisinin derivatives: in vitro and in vivo investigations on adult Echinostoma caproni. Antimicrobial Agents and Chemotherapy 50, 803–805.Google Scholar
Keiser, J., Engels, D., Büscher, G. and Utzinger, J. (2005). Triclabendazole for the treatment of fascioliasis and paragonimiasis. Expert Opinion of Investigational Drugs 14, 1513–1526.Google Scholar
Keiser, J. and Morson, G. (2008). Fasciola hepatica: tegumental alterations in adult flukes following in vitro and in vivo administration of artesunate and artemether. Experimental Parasitology 118, 228–237.CrossRefGoogle ScholarPubMed
Keiser, J., Rinaldi, L., Veneziano, V., Mezzino, L., Tanner, M., Utzinger, J. and Cringoli, G. (2008). Efficacy and safety of artemether against a natural Fasciola hepatica infection in sheep. Parasitology Research 103, 517–522.CrossRefGoogle ScholarPubMed
Keiser, J. and Utzinger, J. (2004). Chemotherapy for major food-borne trematodes: a review. Expert Opinion on Pharmacotherapy 5, 1711–1726.CrossRefGoogle ScholarPubMed
Keiser, J. and Utzinger, J. (2005). Emerging foodborne trematodiasis. Emerging Infectious Diseases 11, 1507–1514.Google Scholar
Keiser, J. and Utzinger, J. (2007). Food-borne trematodiasis: current chemotherapy and advances with artemisinins and synthetic trioxolanes. Trends in Parasitology 23, 555–562.Google Scholar
Keiser, J. and Utzinger, J. (2009). Food-borne trematodiases. Clinical Microbiology Reviews 22, 466–483.Google Scholar
Keiser, J., Utzinger, J., Tanner, M., Dong, Y. and Vennerstrom, J. L. (2006). The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola hepatica. Journal of Antimicrobial Chemotherapy 58, 1193–1197.CrossRefGoogle ScholarPubMed
Keiser, J., Utzinger, J., Vennerstrom, J. L., Dong, Y., Brennan, G. and Fairweather, I. (2007). Activity of artemether and OZ78 against triclabendazole-resistant Fasciola hepatica. Transactions of the Royal Society of Tropical Medicine and Hygiene 101, 1219–1222.Google Scholar
Keiser, J., Xiao, S. H., Tanner, M. and Utzinger, J. (2006). Artesunate and artemether are effective fasciolicides in the rat model and in vitro. Journal of Antimicrobial Chemotherapy 57, 1139–1145.CrossRefGoogle ScholarPubMed
Leger, N. and Notteghem, M. J. (1975). The fasciolidal activity of a new compound, brotianide on Echinostoma caproni Richard 1964. Annales Pharmaceutiques Françaises 33, 273–277.Google Scholar
Leger, N., Notteghem, M. J. and Cavier, R. (1973). Un test pharmacodynamique pour l'essai des douvicides. Bulletin de la Societe de Pathologie Exotique 66, 732–736.Google Scholar
Lewis, F. (2001). Schistosomiasis. Current Protocols in Immunology 19, Unit 19.1.Google Scholar
Liu, F., Zhou, Y., Wang, Z. Q., Lu, G., Zheng, H., Brindley, P. J., McManus, D. P., Blair, D., Zhang, Q. H., Zhong, Y., Wang, S., Han, Z. G. and Chen, Z. (2009). The Schistosoma japonicum genome reveals features of host-parasite interplay. Nature 460, 345–351.Google Scholar
Manneck, T., Haggenmüller, Y. and Keiser, J. (2009). Morphological effects and tegumental alterations induced by mefloquine on schistosomula and adult flukes of Schistosoma mansoni. Parasitology 136, ▪–▪.Google Scholar
Mas-Coma, S., Bargues, M. D. and Valero, M. A. (2007). Plant-borne trematode zoonoses: fascioliasis and fasciolopsiasis. In Food-Borne Parasitic Zoonoses (ed. Murrell, K. D. and Fried, B. ) Springer, New York, pp. 293–334.CrossRefGoogle Scholar
McConville, M., Brennan, G. P., Flanagan, A., Edgar, H. W., Hanna, R. E., McCoy, M., Gordon, A. W., Castillo, R., Hernandez-Campos, A. and Fairweather, I. (2009). An evaluation of the efficacy of compound alpha and triclabendazole against two isolates of Fasciola hepatica. Veterinary Parasitology 162, 75–88.Google Scholar
McConville, M., Brennan, G. P., McCoy, M., Castillo, R., Hernandez-Campos, A., Ibarra, F. and Fairweather, I. (2006). Adult triclabendazole-resistant Fasciola hepatica: surface and subsurface tegumental responses to in vitro treatment with the sulphoxide metabolite of the experimental fasciolicide compound alpha. Parasitology, 133, 195–208.CrossRefGoogle ScholarPubMed
McGonigle, L., Mousley, A., Marks, N. J., Brennan, G. P., Dalton, J. P., Spithill, T. W., Day, T. A. and Maule, A. G. (2008). The silencing of cysteine proteases in Fasciola hepatica newly excysted juveniles using RNA interference reduces gut penetration. International Journal for Parasitology 38, 149–155.Google Scholar
McKinstry, B., Fairweather, I., Brennan, G. P. and Forbes, A. B. (2003). Fasciola hepatica: tegumental surface alterations following treatment in vivo and in vitro with nitroxynil (Trodax). Parasitology Research 91, 251–263.Google Scholar
Melman, S. D., Steinauer, M. L., Cunningham, C., Kubatko, L. S., Mwangi, I. N., Wynn, N. B., Mutuku, M. W., Karanja, D. M., Colley, D. G., Black, C. L., Secor, W. E., Mkoji, G. M. and Loker, E. S. (2009). Reduced susceptibility to praziquantel among naturally occurring Kenyan isolates of Schistosoma mansoni. PLoS Neglected Tropical Diseases 3, e504.CrossRefGoogle ScholarPubMed
Oliveira, M. F., d'Avila, J. C., Tempone, A. J., Soares, J. B., Rumjanek, F. D., Ferreira-Pereira, A., Ferreira, S. T. and Oliveira, P. L. (2004). Inhibition of heme aggregation by chloroquine reduces Schistosoma mansoni infection. Journal of Infectious Diseases 190, 843–852.CrossRefGoogle ScholarPubMed
Platt, T. R. (2009). The course of a 300 metacercarial infection of Echinostoma caproni (Digenea: Echinostomatidae) in Institute for Cancer Research (ICR) mice. Comparative Parasitology 76, 1–5.Google Scholar
Ramalho-Pinto, F. J., Gazzinelli, G., Howells, R. E., Mota-Santos, T. A., Figueiredo, E. A. and Pellegrino, J. (1974). Schistosoma mansoni: defined system for stepwise transformation of cercaria to schistosomule in vitro. Experimental Parasitology 36, 360–372.CrossRefGoogle ScholarPubMed
Ramirez, B., Bickle, Q., Yousif, F., Fakorede, F., Mouries, M. A. and Nwaka, S. (2007). Schistosomes: Challenges in drug screening. Expert Opinion on Drug Discovery 2, 53–61.CrossRefGoogle Scholar
Renslo, A. R. and McKerrow, J. H. (2006). Drug discovery and development for neglected parasitic diseases. Nature Chemical Biology 2, 701–710.Google Scholar
Ridley, R. G. and Kita, K. (2007). Helminth Drug Initiative. Expert Opinion on Drug Discovery 2, 1.Google Scholar
Saric, J., Li, J. V., Wang, Y., Holmes, E., Utzinger, J. and Keiser, J. (2009). Use of Echinostoma spp. in studies on chemotherapy and metabolic profiling. In The Biology of Echinostomes (ed. Fried, B. and Toledo, R.) Springer, New York, pp. 295–320.CrossRefGoogle Scholar
Saxton, T. M., Fried, B. and Peoples, R. C. (2008). Excystation of the encysted metacercariae of Echinostoma trivolvis and Echinostoma caproni in a trypsin-bile salts-cysteine medium and morphometric analysis of the excysted larvae. Journal of Parasitology 94, 669–671.Google Scholar
Sayed, A. A., Simeonov, A., Thomas, C. J., Inglese, J., Austin, C. P. and Williams, D. L. (2008). Identification of oxadiazoles as new drug leads for the control of schistosomiasis. Nature Medicine 14, 407–412.Google Scholar
Shalaby, H. A., El Namaky, A. H. and Kamel, R. O. (2009). In vitro effect of artemether and triclabendazole on adult Fasciola gigantica. Veterinary Parasitology 160, 76–82.Google Scholar
Simeonov, A., Jadhav, A., Sayed, A. A., Wang, Y., Nelson, M. E., Thomas, C. J., Inglese, J., Williams, D. L. and Austin, C. P. (2008). Quantitative high-throughput screen identifies inhibitors of the Schistosoma mansoni redox cascade. PLoS Neglected Tropical Diseases 2, e127.Google Scholar
Sithiathaworn, P., Sripa, B., Kaewkes, S. and Haswell-Elkins, M. (2009). Food-borne trematodes. In Manson's Tropical Diseases 22nd Edition (ed. Cook, G. C. and Zumla, A. I. ). Saunders, London, pp. 1461–1476.Google Scholar
Smithers, S. R. and Terry, R. J. (1965). The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of the adult worms. Parasitology 55, 695–700.Google Scholar
Smyth, J. D. and Halton, D. W. (1983). The Physiology of Trematodes. Cambridge University Press, Cambridge.Google Scholar
Steinmann, P., Keiser, J., Bos, R., Tanner, M. and Utzinger, J. (2006). Schistosomiasis and water resources development: systematic review, meta-analysis, and estimates of people at risk. Lancet Infectious Diseases 6, 411–425.CrossRefGoogle ScholarPubMed
Terasaki, K., Noda, Y., Shibahara, T., Itagaki, T., Fukuda, K. and Tsuchiya, K. (2003). Experimental fascioliasis in the rat-like hamster, Tscherskia triton, and other rodent hosts. Parasitology International 52, 147–154.Google Scholar
Toledo, R. and Fried, B. (2005). Echinostomes as experimental models for interactions between adult parasites and vertebrate hosts. Trends in Parasitology 21, 251–254.CrossRefGoogle ScholarPubMed
Utzinger, J. and Keiser, J. (2004). Schistosomiasis and soil-transmitted helminthiasis: common drugs for treatment and control. Expert Opinion on Pharmacotherapy 5, 263–285.Google Scholar
Utzinger, J., Xiao, S. H., Tanner, M. and Keiser, J. (2007). Artemisinins for schistosomiasis and beyond. Current Opinion in Investigational Drugs 8, 105–116.Google Scholar
van der Werf, M. J., de Vlas, S. J., Brooker, S., Looman, C. W. N., Nagelkerke, N. J. D., Habbema, J. D. F. and Engels, D. (2003). Quantification of clinical morbidity associated with schistosome infection in sub-Saharan Africa. Acta Tropica 86, 125–139.CrossRefGoogle ScholarPubMed
Vera-Montenegro, Y., Ibarra-Velarde, F., Ramirez-Avila, G. and Munguia-Xochihua, J. (2008). In vitro fasciolicide activity of some plant extracts against newly excysted flukes. Annals New York Academy of Sciences 1149, 180–182.Google Scholar
Webbe, G., James, C., Nelson, G. S. and Sturrock, R. F. (1981). The effect of praziquantel on Schistosoma haematobium, S. japonicum and S. mansoni in primates. Arzneimittel-Forschung 31, 542–544.Google Scholar
White, N. J. (2008). Qinghaosu (artemisinin): the price of success. Science 320, 330–334.CrossRefGoogle Scholar
Xiao, S. H., Chollet, J., Booth, M., Weiss, N. A. and Tanner, M. (1999). Therapeutic effect of praziquantel enantiomers in mice infected with Schistosoma mansoni. Transactions of the Royal Society of Tropical Medicine and Hygiene 93, 324–325.Google Scholar
Xiao, S. H., Keiser, J., Chollet, J., Utzinger, J., Dong, Y., Vennerstrom, J. L. and Tanner, M. (2007). The in vitro and in vivo activities of synthetic trioxolanes on major human schistosome species. Antimicrobial Agents and Chemotherapy 51, 1440–1445.Google Scholar
Yolles, T. K., Yolles, T. K., Moore, D. V., De Giusti, D. L., Ripsom, C. A., Meleney, H. E. (1947). A technique for the perfusion of laboratory animals for the recovery of schistosomes. Journal of Parasitology 33, 419–426.Google Scholar