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In vitro and in vivo efficacy of diamidines against Trypanosoma equiperdum strains

Published online by Cambridge University Press:  23 November 2017

Kirsten Gillingwater
Kirsten Gillingwater*
Affiliation:
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel 4002, Switzerland University of Basel, Petersplatz 1, Basel 4001, Switzerland
*
Author for correspondence: Kirsten Gillingwater, E-mail: [email protected]
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Abstract

Trypanosoma equiperdum is a protozoan parasite responsible for causing Dourine, a debilitating neglected veterinary disease, found worldwide affecting equids. It is the only pathogenic trypanosome species that does not require an invertebrate vector for transmission, thus being passed from animal to animal via coitus. At present, there is no officially recognized form of chemotherapeutic treatment and therefore all confirmed (or suspected) cases of infected animals must be slaughtered immediately. For many global communities and farming populations, which rely heavily on their animals for their livelihood, such stringent regulations can seriously enhance the socio-economic problems attributing to poverty. Two reference drugs, together with 37 novel diamidine compounds were tested in vitro using a 72 h drug sensitivity assay to determine their efficacy against two axenically adapted T. equiperdum strains. Further in vivo investigations in mouse models of infection against 4 ‘true’ T. equiperdum strains were performed using the 17 most active diamidines. Single bolus doses of 10 mg kg−1, given i.p. were administered to NMRI mice infected with one of the 4 T. equiperdum strains. The results obtained from this study show that experimentally T. equiperdum can indeed be effectively treated with chemotherapy using in vivo mouse models of infection.

Keywords

chemotherapydiamidinesdourinein vitro drug sensitivityin vivo efficacyTrypanosoma equiperdum
Type
Research Article
Information
Parasitology , Volume 145 , Issue 7 , June 2018 , pp. 953 - 960
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Copyright
Copyright © Cambridge University Press 2017 

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References

Brun, R, Hecker, H and Lun, ZR (1998) Trypanosoma evansi and T. equiperdum: distribution, biology, treatment and phylogenetic relationship (a review). Veterinary Parasitology 79, 95–107.Google Scholar
Claes, F, Büscher, P, Touratier, L and Goddeeris, BM (2005) Trypanosoma equiperdum: master of disguise or historical mistake? Trends in Parasitology 21, 316–321.CrossRefGoogle ScholarPubMed
Clausen, PH, Chuluun, S, Sodnomdarjaa, R, Greiner, M, Noeckler, K, Staak, C, Zessin, KH and Schein, E (2003) A field study to estimate the prevalence of Trypanosoma equiperdum in Mongolian horses. Veterinary Parasitology 115, 9–18.Google Scholar
Cuypers, B, Van den Broeck, F, Van Reet, N, Meehan, CJ, Cauchard, J, Wilkes, JM, Claes, F, Goddeeris, B, Birhanu, H, Dujardin, JC, Laukens, K, Büscher, P and Deborggraeve, S (2017) Genome-wide SNP analysis reveals distinct origins of Trypanosoma evansi and Trypanosoma equiperdum. Genome Biology and Evolution 9, 1990–1997.Google Scholar
Gillingwater, K (2007) Discovery of novel active diamidines as clinical candidates against Trypanosoma evansi infection. PhD theses, University of Basel, Basel, Switzerland.Google Scholar
Gillingwater, K, Büscher, P and Brun, R (2007) Establishment of a panel of reference Trypanosoma evansi and Trypanosoma equiperdum strains for drug screening. Veterinary Parasitology 148, 114–121.CrossRefGoogle ScholarPubMed
Hagos, A, Degefa, G, Yacob, H, Fikru, R, Alemu, T, Feseha, G, Claes, F and Goddeeris, BM (2010a) Seroepidemiological survey of Trypanozoon infection in horses in the suspected dourine-infected Bale highlands of the Oromia region, Ethiopia. Revue Scientifique et Technique/Office International des Epizooties 29, 649–654.Google ScholarPubMed
Hagos, A, Goddeeris, BM, Yilkal, K, Alemu, T, Fikru, R, Yacob, HT, Feseha, G and Claes, F (2010b) Efficacy of Cymelarsan® and Diminasan® against Trypanosoma equiperdum infections in mice and horses. Veterinary Parasitology 171, 200–206.CrossRefGoogle ScholarPubMed
Hoare, CA (1972) The Trypanosomes of Mammals. A Zoological Monograph. Oxford, UK: Blackwell Scientific Publications.Google Scholar
Pascucci, I, Di Provvido, A, Camma, C, Di Francesco, G, Calistri, P, Tittarelli, M, Ferri, N, Scacchia, M and Caporale, V (2013) Diagnosis of dourine outbreaks in Italy. Veterinary Parasitology 193, 30–38.Google Scholar
Perrone, TM, Gonzatti, MI, Villamizar, G, Escalante, A and Aso, PM (2009) Molecular profiles of Venezuelan isolates of Trypanosoma sp. by random amplified polymorphic DNA method. Veterinary Parasitology 161, 194–200.Google Scholar
Räz, B, Iten, M, Grether-Bühler, Y, Kaminsky, R and Brun, R (1997) The Alamar Blue assay to determine drug sensitivity of African trypanosomes (T. b. rhodesiense and T. b. gambiense) in vitro. Acta Tropica 68, 139–147.CrossRefGoogle Scholar
Suganuma, K, Narantsatsral, S, Battur, B, Yamasaki, S, Otgonsuren, D, Musinguzi, SP, Davaasuren, B, Battsetseg, B and Inoue, N (2016) Isolation, cultivation and molecular characterization of a new Trypanosoma equiperdum strain in Mongolia. Parasites and Vectors 9, 481.CrossRefGoogle ScholarPubMed
Wilson, WD, Nguyen, B, Tanious, FA, Mathis, A, Hall, JE, Stephens, CE and Boykin, DW (2005) Dications that target the DNA minor groove: compound design and preparation, DNA interactions, cellular distribution and biological activity. Current Medicinal Chemistry. Anti-cancer Agents 5, 389–408.Google Scholar