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To see or not to see: non-invasive imaging for improved readout of drug treatment trials in the murine model of secondary alveolar echinococcosis

Published online by Cambridge University Press:  08 March 2017

D. GORGAS
Affiliation:
Division of Clinical Radiology, Vetsuisse-Faculty, Länggassstrasse 128, 3012 Berne, Switzerland
N. MARREROS
Affiliation:
Centre for Fish and Wildlife Health, Vetsuisse-Faculty, Länggassstrasse 122, 3012 Berne, Switzerland Vetsuisse-Faculty, Institute of Parasitology, Länggassstrasse 122, 3012 Berne, Switzerland
R. RUFENER
Affiliation:
Vetsuisse-Faculty, Institute of Parasitology, Länggassstrasse 122, 3012 Berne, Switzerland
A. HEMPHILL
Affiliation:
Vetsuisse-Faculty, Institute of Parasitology, Länggassstrasse 122, 3012 Berne, Switzerland
B. LUNDSTRÖM-STADELMANN*
Affiliation:
Vetsuisse-Faculty, Institute of Parasitology, Länggassstrasse 122, 3012 Berne, Switzerland
*
*Corresponding author. Britta Lundström-Stadelmann Institute of Parasitology, Länggassstrasse 122 3012 Bern, Switzerland. E-mail: Britta.lundstroem@vetsuisse.unibe.ch

Summary

Alveolar echinococcosis (AE) is an emerging zoonotic disease caused by the cestode Echinococcus multilocularis. The secondary infection model of AE is based on intraperitoneal injection of disease-causing metacestodes into the peritoneal cavity of mice, which allows investigations on novel drugs or immunotherapeutical treatment options in vivo. So far, such in vivo studies assessed exclusively the parasite weight at the endpoint of a given treatment period. We here developed an ultrasound (US)-based scoring system that allows to follow-up parasite development in the living animal, and provides insights into parasite growth during the treatment phase. By this method a statistically significant difference between untreated and medicated mice with E. multilocularis infection was observed at 2 months post-infection, and the growth curve of the parasite load was described by a linear mixed model. High correlation and similar levels of variation were observed for the standard method based on parasite weight measurement, the novel US-based scoring system, as well volume segmentation by post-mortem magnetic resonance imaging. Thus, US-based scoring in the live animal has the potential to assist the 3R concept by contributing to the refinement and reduction of animal use in experimental echinococcosis.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2017 

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References

REFERENCES

Baron, R. W., Rau, M. E. and Tanner, C. E. (1974). Growth of secondary Echinococcus multilocularis in experimentally infected hosts. Canadian Journal of Zoology 52, 587589.Google Scholar
Canty, A. and Ripley, B. D. (2016). Boot: Bootstrap R (S-Plus) Functions. R package 1, 318.Google Scholar
Conraths, F. J. and Deplazes, P. (2015). Echinococcus multilocularis: epidemiology, surveillance and state-of-the-art diagnostics from a veterinary public health perspective. Veterinary Parasitology 213, 149161.Google Scholar
Dalgaard, P. (2008). Analysis of variance and the Kruskal–Wallis test. In Introductory Statistics with R (ed. Dalgaard, P.), pp. 127143. Springer, New York, NY, USA.Google Scholar
Dray, S. and Dufour, A.-B. (2007). The ade4 Package: implementing the Duality Diagram for Ecologists. Journal of Statistical Software 22, 120.Google Scholar
Eckert, J. and Deplazes, P. (2004). Biological, epidemiological, and clinical aspects of echinococcosis, a zoonosis of increasing concern. Clinical Microbiology Reviews 17, 107135.Google Scholar
Gottstein, B., Stojkovic, M., Vuitton, D. A., Millon, L., Marcinkute, A. and Deplazes, P. (2015). Threat of alveolar echinococcosis to public health – a challenge for Europe. Trends in Parasitology 31, 407412.Google Scholar
Graeter, T., Kratzer, W., Oeztuerk, S., Haenle, M. M., Mason, R. A., Hillenbrand, A., Kull, T., Barth, T. F., Kern, P. and Gruener, B. (2016). Proposal of a computed tomography classification for hepatic alveolar echinococcosis. World Journal of Gastroenterology 22, 36213631.Google Scholar
Hemphill, A., Stadelmann, B., Rufener, R., Spiliotis, M., Boubaker, G., Müller, J., Müller, N., Gorgas, D. and Gottstein, B. (2014). Treatment of echinococcosis: albendazole and mebendazole – what else? Parasite (Paris, France) 21, 70.Google Scholar
Kratzer, W., Gruener, B., Kaltenbach, T. E. M., Ansari-Bitzenberger, S., Kern, P., Fuchs, M., Mason, R. A., Barth, T. F. E., Haenle, M. M., Hillenbrand, A., Oeztuerk, S. and Graeter, T. (2015). Proposal of an ultrasonographic classification for hepatic alveolar echinococcosis: echinococcosis multilocularis Ulm classification-ultrasound. World Journal of Gastroenterology 21, 1239212402.Google Scholar
Küster, T., Zumkehr, B., Hermann, C., Theurillat, R., Thormann, W., Gottstein, B. and Hemphill, A. (2012). Voluntary ingestion of antiparasitic drugs emulsified in honey represents an alternative to gavage in mice. Journal of the American Association for Laboratory Animal Science 51, 219223.Google Scholar
Küster, T., Stadelmann, B., Rufener, R., Risch, C., Müller, J. and Hemphill, A. (2015). Oral treatments of Echinococcus multilocularis-infected mice with the antimalarial drug mefloquine that potentially interacts with parasite ferritin and cystatin. International Journal of Antimicrobial Agents 46, 546551.Google Scholar
Liu, W., Delabrousse, É., Blagosklonov, O., Wang, J., Zeng, H., Jiang, Y., Wang, J., Qin, Y., Vuitton, D. A. and Wen, H. (2014). Innovation in hepatic alveolar echinococcosis imaging: best use of old tools, and necessary evaluation of new ones. Parasite (Paris, France) 21, 74.CrossRefGoogle ScholarPubMed
Pinheiro, J. C. and Bates, D. M. (2000). Mixed-Effects Models in S and S-Plus in Statistics and Computing . New York, NY, USA: Springer.Google Scholar
R Core Team (2015). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria.Google Scholar
Reuter, S., Nüssle, K., Kolokythas, O., Haug, U., Rieber, A., Kern, P. and Kratzer, W. (2001). Alveolar liver echinococcosis: a comparative study of three imaging techniques. Infection 29, 119125.Google Scholar
Stadelmann, B., Aeschbacher, D., Huber, C., Spiliotis, M., Müller, J. and Hemphill, A. (2014). Profound activity of the anti-cancer drug bortezomib against Echinococcus multilocularis metacestodes identifies the proteasome as a novel drug target for cestodes. PLoS Neglected Tropical Diseases 8, e3352.Google Scholar
Torgerson, P. R., Keller, K., Magnotta, M. and Ragland, N. (2010). The global burden of alveolar echinococcosis. PLoS Neglected Tropical Diseases 4, e722.Google Scholar
Zeng, H., Wang, J., Xie, W., Liu, W. and Wen, H. (2012). Assessment of early hepatic echinococcus multilocularis infection in rats with real-time contrast-enhanced ultrasonography. Ultrasound in Medicine & Biology 38, 19821988.Google Scholar
Zuur, A. F., Ieno, E. N. and Smith, G. M. (eds.) (2007). Principal component analysis and redundancy analysis. In Analysing Ecological Data , pp. 193224. Springer New York, New York, NY.CrossRefGoogle Scholar
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