Efficacy of diminazene diaceturate and isometamidium chloride hydrochloride for the treatment of Trypanosoma evansi in mice model

Authors: AREGAWI, WELDEGEBRIAL - Ethiopian Institute Of Agricultural Research; GUTEMA, FIKADU - Ethiopian Institute Of Agricultural Research; TESFAYE, JUHAR - Ethiopian Institute Of Agricultural Research; SORSA, ABEL - Ethiopian Institute Of Agricultural Research; MEGERSA, BREHANU - Ethiopian Institute Of Agricultural Research; TESHOME, PHILIMON - Ethiopian Institute Of Agricultural Research; Agga, Getahun; ASHENAFI, HAGOS - Addis Ababa University

Submitted to: Journal of Parasitic Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/5/2020
Publication Date: 10/12/2020
Citation: Aregawi, W.G., Gutema, F., Tesfaye, J., Sorsa, A., Megersa, B., Teshome, P., Agga, G.E., Ashenafi, H. 2020. Efficacy of diminazene diaceturate and isometamidium chloride hydrochloride for the treatment of Trypanosoma evansi in mice model. Journal of Parasitic Diseases. 45:131-136. https://doi.org/10.1007/s12639-020-01289-3.
DOI: https://doi.org/10.1007/s12639-020-01289-3

Interpretive Summary: Trypanosomiasis is caused by protozoan parasites. Animal trypanosomiasis causes severe economic losses and affecting the livelihood of people in many developing countries such as in Africa. Camels play a significant role in the arid regions of the world by serving as a means of transportation for people and commodities, and by providing milk, meat and income for many families. Camel trypanosomiasis, often called surra, is widespread in many camel rearing regions of the world. Trypanocidal drugs developed over half a century ago have been widely used and no new drugs are being manufactured. As a consequence resistance to these drugs is a concern. Two drugs were evaluated for their effectiveness against a parasite strain at standard and double doses. Relapses occurred three weeks after the standard dose treatments. However, the double dose treatments were able to completely clear the infections. We conclude that the two widely used anti-trypanosomiasis drugs are not effective at the current doses, and doses need to be re-formulated to cope up with the issue of drug resistance in the absence of new drugs entering the market.

Technical Abstract: Diminazene diaceturate (DIM) and isometamidium chloride hydrochloride (ISMM) have been widely used for the treatment of animal trypanosomosis. We evaluated the efficacy of standard doses of DIM and ISMM followed by their double doses for the treatment of Trypanosoma evansi in experimentally infected mice. A T.evansi strain obtained from a naturally infected camel in Afar was used. 25 swiss white mice randomly divided in to five groups were inoculated with 0.2 mL of blood containing 103 trypanosomes. At the peak of parasitemia (~2 weeks post infection), groups A and B were treated with the standard dose (3.5 mg/kg body weight [BWT]) of DIM; groups C and D were treated with the standard dose (0.5 mg/kg BWT) of ISMM; and group E served as infected control. In the DIM standard dose groups, relapses and peak parasitemia were observed 20- and 25-days post treatment respectively. Similarly, relapses and peak parasitemia were observed 21- and 27-days post treatment in the ISMM standard dose groups. All mice in the control group died within two weeks post infection. Following relapses, mice were treated with the double doses of DIM (7 mg/kg BWT) or ISMM (1 mg/kg BWT). Parasitemia was not detected for 3 months following the double dose treatments. Following dexamethasone administration for 7 days, all but one mouse in the DIM group remained negative for another month. In general, although the T.evansi strain was resistant to the standard doses of DIM and ISMM their double doses completely cleared the infection.