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.
Similar content being viewed by others
References
Ali B, Hassan T (1986) Some observations on the toxicosis of Isometamidium chloride (Samorin) in camels. Vet Hum Toxicol 28:424–426
Aregawi WG, Agga GE, Abdi RD, Buscher P (2019) Systematic review and meta-analysis on the global distribution, host range, and prevalence of Trypanosoma evansi. Parasit Vectors 12:67
Aregawi WG, Kassa TS, Tarekegn KD et al (2015) Parasitological and serological study of camel trypanosomosis (surra) and associated risk factors in Gabi Rasu Zone, Afar, Ethiopia. J Vet Med Anim Health 7:234–240
Birhanu H, Fikru R, Said M et al (2015) Epidemiology of Trypanosoma evansi and Trypanosoma vivax in domestic animals from selected districts of Tigray and Afar regions. North Ethiop Parasites Vectors 8:212
Boid R, Hunter A, Jones T et al (1996) Trypanosomiasis research at the centre for tropical veterinary medicine (CTVM) 1970 to 1995. Trop Anim Health Prod 28:5–22
Brun R, Lun Z-R (1994) Drug sensitivity of Chinese Trypanosoma evansi and Trypanosoma equiperdium isolates. Vet Parasitol 52:37–46
Chaka H, Abebe G (2003) Drug resistant trypanosomes: a threat to cattle production in the Southwest of Ethiopia. Rev Elev Med Vet Pays Trop 56:33–36
Chitanga S, Marcotty T, Namangala B et al (2011) High prevalence of drug resistance in animal trypanosomes without a history of drug exposure. PLoS Negl Trop Dis 5:e1454. https://doi.org/10.1371/journal.pntd.0001454
Colpo CB, Monteiro SG, Stainki DR et al (2005) Infecção natural por Trypanosoma evansi em cães/natural infection by Trypanosoma evansi in dogs. Cienc Rural 35:717
Da Silva AS, Tochetto C, Zanette RA et al (2008) Aceturato de diminazeno e dipropionato de imidocarb no controle de infecc¸a˜o por Trypanosoma evansi em Rattus norvegicus infectados experimentalmente. Cienc Rural 38:1357–1362
Da Silva AS, Zanette RA, Otto MA et al (2009) Aceturato de diminazeno no tratamento de equ¨ inos infectados naturalmente por Trypanosoma evansi no municı´pio de Cruz Alta-RS, Brasil. Vet Zootec 16:74–79
Da Silva AS, Zanette RA, Wolkmer P et al (2009) Diminazene aceturate in the control of Trypanosoma evansi infection in cats. Vet Parasitol 165:47–50
Degneh E, Ashenafi H, Kassa T et al (2019) Trypanocidal drug resistance: a threat to animal health and production in Gidami district of Kellem Wollega Zone, Oromia Regional State, Western Ethiopia. Prev Vet Med 168:103–107. https://doi.org/10.1016/j.prevetmed.2019.03.017
Delespaux V, Geysen D, Van den Bossche P, Geerts S (2008) Molecular tools for the rapid detection of drug resistance in animal trypanosomes. Trends Parasitol 24:236–242. https://doi.org/10.1016/j.pt.2008.02.006
Desquesnes M, Dargantes A, Lai D-H et al (2013) Trypanosoma evansi and surra: a review and perspectives on transmission, epidemiology and control, impact, and zoonotic aspects. Biomed Res Int 2013:321237. https://doi.org/10.1155/2013/321237
Desquesnes M, Holzmuller P, Lai DH et al (2013) Trypanosoma evansi and surra: a review and perspectives on origin, history, distribution, taxonomy, morphology, hosts, and pathogenic effects. Biomed Res Int 2013. https://doi.org/10.1155/2013/194176
Durrani ZA, Bashir Z, Mehmood K et al (2017) Use of physiological biomarkers in diagnosis along with field trials of different trypanisidal drugs in camels of Cholistan desert. Microbial Pathog 108:1–5. https://doi.org/10.1016/j.micpath.2017.04.014
Eisler MC, Brandt J, Bauer B et al (2001) Standardised tests in mice and cattle for the detection of drug resistance in tsetse-transmitted trypanosomes of African domestic cattle. Vet Parasitol 97:171–182
El RayahKaminsky IER, Schmid C, El Malik KH (1999) Drug resistance in sudanese Trypanosoma evansi. Vet Parasitol 80:281–287. https://doi.org/10.1016/s0304-4017(98)00221-0
Enwezor FNC, Sackey AKB (2005) Camel trypanosomosis: a review. Vet Arh 75:439–452
Faccio L, Da AS, Gressler LT et al (2013) Susceptibility of Brazilian isolates of Trypanosoma evansi to suramin sodium: test in experimentally infected mice. Exp Parasitol 134:309–312
Fikru R, Andualem Y, Getachew T et al (2015) Trypanosome infection in dromedary camels in Eastern Ethiopia: prevalence, relative performance of diagnostic tools and host related risk factors. Vet Parasitol 211:175–181
Fikru R, Cocker J, Peter R, Terefe G (2017) Resistance of recently isolated Trypanosoma vivax and T. congolense against diminazene diaceturate and isometamidium chloride hydrochloride using an infection model of trypanosomosis in cattle in Ethiopia. In: 2nd international conference on non tsetse transmitted animal trypanosomosis. OIE NTTATNetwork, Institute of Tropical Medicine, Antwerp, Belgium
Hagos A, Goddeeris BM, Yilkal K et al (2010) Efficacy of Cymelarsan® and Diminasan® against Trypanosoma equiperdum infections in mice and horses. Vet Parasitol 171:200–206
Hagos H, Yilkal A, Esayass T et al (2009) Parasitological and serological survey on trypanosomis (surra) in camels in dry and wet areas of Bale Zone, Oromyia Region, Ethiopia. Rev Med Vet (Toulouse) 160:569–573
Holmes P, Eisler M, Geerts S (2004) Current chemotherapy of animal trypanosomiasis. In: Maudlin I, Holmes P, Miles M (eds) The trypanosomiasis. CABI International, Wallingford, pp 431–444
Howes F, Da Silva AS, Athayde CDL et al (2011) A new therapeutic protocol for dogs infected with Trypanosoma evansi. Acta Sci Vet 39:1–4
Jatau ID, Lawal AI, Agbede R, Abdurrahman EM (2010) Efficacies of diminazene aceturate and isometamidium chloride in Trypanosoma evansi experimentally infected rats. Sokoto J Vet Sci 8:4–8
Jenings FW, Whitelaw DD, Urquhart GM (1977) The relationship between duration of infection with T. brucei in mice and the efficacy of chemotherapy. Parasitology 75:145–153
Joshi S, Singh B (2000) Evaluation of therapeutic and chemoprophylactic efficacy of certain drugs against clinical surra in buffaloes. Indian Vet J 77:895–897
Kassa T, Eguale T, Chaka H (2011) Prevalence of camel trypanosomosis and its vectors in Fentale district, South East Shoa Zone, Ethiopia. Vet Arh 81:611–621
Luckins A, Dwinger R (2004) Non- tsetse transmitted animal trypanosomiasis. In: Maudlin I, Holmes P, Miles M (eds) The trypanosomiasis. CABI International, Wallingford, pp 269–281
Lun Z-R, Min Z-P, Huang D et al (1991) Cymelarsan in the treatment of buffaloes naturally infected with Trypanosoma evansi in South China. Acta Trop 49:233–236. https://doi.org/10.1016/0001-706X(91)90042-I
Mamman M, Moloo S, Peregrine A (1994) Relapse of Trypanosoma congolense infection in goats after diminazene aceturate is not a result of invasion of the central nervous system. Ann Trop Med Parasitol 88:87–88
Masocha W, Rottenberg ME, Kristensson K (2007) Migration of African trypanosomes across the blood-brain barrier. Physiol Behav 92:110–114
Mekonnen G, Mohammed EF, Kidane W et al (2018) Isometamidium chloride and homidium chloride fail to cure mice infected with Ethiopian Trypanosoma evansi type A and B. PLoS Negl Trop Dis 12(9):e0006790
Mochab MOK, Kitala PM, Gathura PB et al (2006) The socio-economic impact of important camel diseases as perceived by a pastoralist community in Kenya. Onderstepoort J Vet Res 73:269–274
More S, Bøtner A, Butterworth A et al (2017) Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law ( Regulation (EU) No 2016 / 429): Trypanosoma evansi infections (including Surra). EFSA J 15:1–34. https://doi.org/10.2903/j.efsa.2017.4892
Moti Y, Fikru R, Van Den Abbeele J et al (2012) Ghibe river basin in Ethiopia: present situation of trypanocidal drug resistance in Trypanosoma congolense using tests in mice and PCR-RFLP. Vet Parasitol 189:197–203
Olani A, Habtamu Y, Wegayehu T, Anberber M (2016) Prevalence of camel trypanosomosis (surra) and associated risk factors in Borena zone, southern Ethiopia. Parasitol Res 115:1141–1147. https://doi.org/10.1007/s00436-015-4845-9
Peregrine AS, Mamman M (1993) Pharmacology of diminazene: a review. Acta Trop 54:185–203
Pholpark S, Pholpark M, Sarataphan S, et al (1984) Trypanosoma evansi infection in buffalo in Northeast Thailand. 2. Experimental study. In: Proceedings of the 11th annual conference of the Thailand veterinary medical association. Thailand, p 44–45
Sudarto M, Tabel H, Haines D (1990) Immunohistochemical demonstration of Trypanosoma evansi in tissues of experimentally infected rats and naturally infected water buffalo (Bubalus bubalis). J Parasitol 76:162–167
Sutcliffe O, Skellern G, Araya F et al (2014) Animal trypanosomosis: making quality control of trypanocidal drugs possible. Rev Sci Tech 33:813–830
Tchamdja E, Kulo A, Akoda K et al (2016) Drug quality analysis through high performance liquid chromatography of isometamidium chloride hydrochloride and diminazene diaceturate purchased from official and unofficial sources in Northern Togo. Prev Vet Med 126:151–158
Tekle T, Terefe G, Cherenet T et al (2018) Aberrant use and poor quality of trypanocides: a risk for drug resistance in south western Ethiopia. BMC Vet Res 14:4
Tuntasuvan D, Jarabrum W, Viseshakul N et al (2003) Chemotherapy of surra in horses and mules with diminazene aceturate. Vet Parasitol 110:227–233. https://doi.org/10.1016/S0304-4017(02)00304-7
Woo PTK (1970) The haematocrit centrifuge technique for the diagnosis of African trypanosomasis. Acta Trop 27:384–386
Zeleke M, Bekele T (2001) Effect of season on the productivity of camels (Camelus dromedarius) and the prevalence of their major parasites in eastern Ethiopia. Trop Anim Health Prod 33:321–329
Zhang ZQ, Giroud C, Baltz T (1992) In vivo and in vitro sensitivity of Trypanosoma evansi and T. equiperdium to diminazene, suramin, mel Cy, quinapyramine and isometamidium. Acta Trop 50:101–110
Acknowledgements
This work was supported by the Ethiopian Institute of Agricultural Research (EIAR). We thank the Addis Ababa University, College of Veterinary Medicine and Agriculture for allowing us to conduct the experiment in the molecular parasitology laboratory of the Belgian- Ethiopian VLIR–UOS funded collaborative project. The field and laboratory assistance we have received from the project staff, Mr. Alemu Tola is highly appreciated. Mention of trade names or commercial products in this publication by USDA author (GEA) is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture. USDA is an equal opportunity provider and employer.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
Blood sample collection from camel was approval by the Ethics and Animal Welfare Committee of Ethiopian Institute of Agricultural Research, Protocol Number 04/2018. The protocol of experimental study in mice was reviewed and approved by Research Ethics Review Committee (RERC) of the College of Veterinary Medicine and Agriculture of the Addis Ababa University (Ref. No. VM/ERC/03/04/12/2018).
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Aregawi, W.G., Gutema, F., Tesfaye, J. et al. Efficacy of diminazene diaceturate and isometamidium chloride hydrochloride for the treatment of Trypanosoma evansi in mice model. J Parasit Dis 45, 131–136 (2021). https://doi.org/10.1007/s12639-020-01289-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12639-020-01289-3