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Echinococcus granulosus: the effects of praziquantel, in vivo and in vitro, on the ultrastructure of equine strain murine cysts

Published online by Cambridge University Press:  06 April 2009

K. Sylvia Richards ,
D. L. Morris ,
D. Daniels  and
E. M. Riley
K. Sylvia Richards
Affiliation:
Parasitology Research Laboratory, Department of Biological Sciences, University of Keele, Keele, Staffs. ST5 5BG
D. L. Morris
Affiliation:
Department of Surgery, University Hospital, Nottingham NG7 2UH
D. Daniels
Affiliation:
Parasitology Research Laboratory, Department of Biological Sciences, University of Keele, Keele, Staffs. ST5 5BG
E. M. Riley
Affiliation:
Parasitology Research Laboratory, Department of Biological Sciences, University of Keele, Keele, Staffs. ST5 5BG
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Summary

Praziquantel (500 mg/kg) administered orally to BALB/c mice with secondary equine E. granulosus daily for 21, 30 or 30 + 30 days without the drug resulted in the majority of cysts, using bench criteria of turgidity and eosin exclusion, being assessed as ‘alive’. Ultrastructural examination of 54 of these ‘alive’ cysts did not support this conclusion. They all showed increased vesiculation of the germinal layer leading, in many, to the loss of its integrity. Increased mitochondrial numbers occurred frequently. The longer drug treatments appeared to have greater effects on the germinal layer of ‘alive’ cysts and there was no detectable re-establishment of structural organization within 30 days after drug withdrawal. Subjectively, there was no substantial difference between cysts from 4-month and 9-month infections or between affected peritoneal and hepatic cysts. Tissue from collapsed cysts was necrotic. Peak serum levels of praziquantel (6430–6136 μg/l) occurred 5–10 min after drug administration (500 mg/kg) and dropped rapidly to less than 10 μg/l at 3 h. In an in vitro study at praziquantel concentrations of 1000 and 5000 μg/l over a 10-day period, most cysts were judged ‘alive’ by bench criteria but showed ultrastructurally a time- and concentration-dependent loss of integrity identical to that seen in vivo. Turgidity and eosin exclusion therefore underestimate the effect of praziquantel and the results indicate that in vitro experiments can fulfil a legitimate preliminary role in a hydatid chemotherapy programme.

Type
Research Article
Information
Parasitology , Volume 96 , Issue 2 , April 1988 , pp. 323 - 336
Copyright
Copyright © Cambridge University Press 1988

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References

REFERENCES

Andrews, P. (1976). Pharmacokinetic studies with Droncit in animals using a biological assay. Veterinary Medical Reviews 2, 154–65.Google Scholar
Andrews, P., Thomas, H., Pohlke, R. & Seubert, J. (1983). Praziquantel. Medicinal Research Reviews 3, 147–200.Google Scholar
Becker, B., Mehlhorn, H., Andrews, P. & Thomas, H. (1980 a). Scanning and transmission electron microscope studies on the efficacy of praziquantel on Hymenolepis nana (Cestoda) in vitro. Zeitschrift für Parasitenkunde 61, 121–33.CrossRefGoogle ScholarPubMed
Becker, B., Mehlhorn, H., Andrews, P., Thomas, H. & Eckert, J. (1980 b). Light and electron microscope studies on the effect of praziquantel on Schistosoma mansoni, Dicrocoelium dendriticum, and Fasciola hepatica (Trematoda) in vitro. Zeitschrift für Parasitenkunde 63, 113–28.CrossRefGoogle ScholarPubMed
Becker, B., Mehlhorn, H., Andrews, P. & Thomas, H. (1981). Ultrastructural investigations on the effect of praziquantel on the tegument of five species of cestodes. Zeitschrift für Parasitenkunde 64, 257–69.CrossRefGoogle ScholarPubMed
Davis, A., Pawlowski, Z. S. & Dixon, H. (1986). Multicentre clinical trials of the benzimidazole carbamates in human echinococcosis. Bulletin of the World Health Organization 64, 383–8.Google Scholar
Frohberg, H. (1984). Results of toxicological studies on praziquantel. Arzneimittel-Forschung / Drug Research 34, 1137–44.Google Scholar
Gemmell, M. A. & Pakmeter, S. N. (1983). Effects of praziquantel against eggs of Taenia hydatigena and protoscolices and metacestodes of Echinococcus granulosus. Veterinary Medical Review 1, 3–9.Google Scholar
Heath, D. D., Christie, M. J. & Chevis, R. A. F. (1975). The lethal effect of mebendazole on secondary Echinococcus granulosus, cysticerci of Taenia pisiformis and tetrathyridia of Mesocestoides corti. Parasitology 70, 273–85.CrossRefGoogle ScholarPubMed
Heath, D. D. & Lawrence, S. B. (1978). The effect of mebendazole and praziquantel on the cysts of Echinococcus granulosus, Taenia hydatigena and T. ovis in sheep. New Zealand Veterinary Journal 26, 11–15.CrossRefGoogle Scholar
Langston, V. C., Galey, F., Lovell, R. & Buck, W. B. (1985). Toxicity and therapeutics of monensin: a review. Veterinary Medicine 09 75–84.Google Scholar
Lee, S. H. (1985). In vitro effects of Praziquantel on Fibricola seoulensis. Seoul Journal of Medicine 26, 41–51.Google Scholar
Marchiondo, A. A. & Andersen, F. L. (1985). In vivo efficacy and ultrastructural effects of mitomycin C against experimental alveolar hydatid disease. Journal of Helminthology 59, 29–38.Google Scholar
Marshall, I. & Edwards, G. T. (1982). The effects of sustained release praziquantel on the survival of protoscolices of Echinococcus granulosus equinus in laboratory mice. Annals of Tropical Medicine and Parasitology 76, 649–51.CrossRefGoogle ScholarPubMed
Mehlhorn, H., Becker, B., Andrews, P., Thomas, H. & Frenkel, J. K. (1981). In vivo and in vitro experiments on the effects of praziquantel on Schistosoma mansoni. Arzneimittel-Forschung/Drug Research 31, 544–54.Google ScholarPubMed
Morris, D. L., Richards, K. S. & Chinnery, J. B. (1986). Protoscolicidal effect of praziquantel - in vitro and electron microscopy studies on Echinococcus granulosus. Journal of Antimicrobial Chemotherapy 18, 687–91.CrossRefGoogle ScholarPubMed
Morris, D. L., Taylor, D., Daniels, D. & Richards, K. S. (1987). Determination of minimum effective concentration of praziquantel in in vitro cultures of protoscoleces of Echinococcus granulosus. Transactions of the Royal Society of Tropical Medicine and Hygiene 81, 494–7.CrossRefGoogle ScholarPubMed
Overbosch, D., Van de Nes, J. C. M., Groll, E. & Mattie, H. (1984). Penetration of praziquantel into cerebrospinal fluid and cysticerci in human cysticercosis. Abstract, 24th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington D.C., 09 8–10.Google Scholar
Patzschke, K., Pütter, J., Wegner, L. A., Horster, F. A. & Diekmann, H. W. (1979). Serum concentrations and renal excretion in humans after oral administration of praziquantel - results of three determination methods. European Journal of Drug Metabolism and Pharmacokinetics 3, 149–56.CrossRefGoogle Scholar
Pütter, J. & Held, F. (1979). Quantitative studies on the occurrence of praziquantel in milk and plasma of lactating women. European Journal of Drug Metabolism and Pharmacokinetics 4, 193–8.Google Scholar
Richards, K. S., Arme, C. & Bridges, J. F. (1984). Echinococcus granulosus equinus: variation in the germinal layer of murine hydatids and evidence of autophagy. Parasitology 89, 35–47.CrossRefGoogle ScholarPubMed
Robinson, R. D. & Arme, C. (1985). Echinococcus granulosus: failure of the eosin-exclusion test to demonstrate death of protoscoleces. Annals of Tropical Medicine and Parasitology 79, 117.Google Scholar
Rogan, M. T. & Richards, K. S. (1986 a). In vitro development of hydatid cysts from posterior bladders and ruptured brood capsules of equine Echinococcus granulosus. Parasitology 92, 379–90.Google Scholar
Rogan, M. T. & Richards, K. S. (1986 b). Echinococcus granulosus: in vitro effect of monensin on the tegument of the protoscolex. Parasitology 93, 347–55.CrossRefGoogle ScholarPubMed
Sirisinha, S., Puengtomwatanakul, S., Sobhon, P., Saitongdee, P., Wongpayabal, P., Mitranonde, V., Ragomyos, P. & Bunnag, D. (1984). Alterations of the surface tegument of Opisthorchis viverrini exposed to praziquantel in vitro and in vivo. Southeast Asian Journal of Tropical Medicine and Public Health 15, 95–103.Google ScholarPubMed
Spina-França, A., Machado, L. R., Nobrega, J. P. S., Livramento, J. A., Diekmann, H. W., Groll, E. & De Rezende, G. L. (1985). Praziquantel in the cerebrospinal fluid in neurocysticercosis. Arquivos de Neuro-Psiquiatria (São Paulo) 43, 243–59.Google Scholar
Thomas, H., Andrews, P. & Mehlhorn, H. (1982). New results on the effect of praziquantel in experimental cysticercosis. American Journal of Tropical Medicine and Hygiene 31, 803–10.Google Scholar
Thompson, R. C. A., Reynoldson, J. A. & Riddler, C. R. (1986). Praziquantel adversely affects protoscolesces of Echinococcus granulosus in vitro. Journal of Helminthology 60, 279–86.CrossRefGoogle Scholar
Verheyen, A., Borgers, M., Vanparijs, O. & Thienpont, D. (1976). The effects of mebendazole on the ultrastructure of cestodes. In Biochemistry of Parasites and Host-Parasite Relationships (ed. H., Van den Bossche), pp. 605–18. Amsterdam: Elsevier/North-Holland Biomedical Press.Google Scholar
Xiao, S. H., Friedman, P. A., Catto, B. A. & Webster, L. T. (1984). Praziquantel-induced vesicle formation in the tegument of male Schistosoma mansoni is calcium dependent. Journal of Parasitology 70, 177–9.CrossRefGoogle ScholarPubMed
Yao Ping, L. & Jun, L. (1985). Praziquantel in treatment and investigation with abdominal hydatidosis. Preliminary report of animal experiments and evaluation of 101 clinical cases. XIII Congreso Internacional de Hidatidologia, Madrid, Abstract 286.Google Scholar