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Abstract
This study investigated the efficacy of different chemotherapeutic regimes in the treatment of rats experimentally infected with diminazene aceturate-resistant strain Trypanosoma brucei brucei. Thirty Sprague Dawley male rats used for the study were randomly assigned to six groups of five rats eachas follows: group A-uninfected untreated (negative control), group B-infected and untreated (positive control), groups C-F were infected and treated with 1.0 mg/kg isometamidum chloride, administered intramuscularly on day 11 post-infection. However, rats in groups D, E and F received further treatments with 700 mg/kg sodium-ethylenediamine tetra-acetic acid, 0.4 mg/kg verapamil and 3 mg/kg chlorpromazine, respectively, administered orally for four days. Clearance of parasite post-treatment (PT), mortality PT, relapse parasitaemia post-clearance, body weight change, rectal temperature, packed cell volume (PCV), haemoglobin (HB) concentration and red blood cell count (RBC) were determined during the experiment. Result showed parasite clearance PT of 100% in groups D and E, 80% in group F and 20% in group C by 24 hours PT. The infection relapsed on day 35 PT in 40% of rats in group C, on day 37 PT in 20% of rats in group F and lastly 20% of rats in groups D and E on day 39 PT. Rats that received drug combination showed marginal improvement in erythrocytic parameters analysed when compared with those treatment with isometamidium alone. Combination therapy showed faster clearance of parasite from the blood and also prolonged relapse post-clearance, thus had a better promising efficacy when compared to using isometamiduim chloride alone.
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References
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References
Abimbola, A.N., Baba, I.A., Yenusa, E.Z., Omanibe, S.J. and Oladimeji, I.H. (2013). Anti-Trypanosoma effect of peristrophebicalyculataectract on Trypanosoma brucei bruceiinfected rats. Asian Pac. J. Trop. Biomed., 3: 523-531 DOI: https://doi.org/10.1016/S2221-1691(13)60107-0
Adieme, I.C, Ezeh, I.O., Ugochukwu, E.I. and Ezeokonkwo, R.C. (2014). Effect of diminazine aceturate, levamisole and vitamin C combination therapy in rats experimentally infected with Trypanosome brucei brucei. Asian Pac. J. Trop. Med., 7(6): 438-445 DOI: https://doi.org/10.1016/S1995-7645(14)60071-7
Akpa, P.O., Ezeokonkwo, R.C., Eze, C.A. and Anene, B.M. (2008). Comparative efficacy assessment of pentamidine isethionate and diminazene aceturate in the chemotherapy of Trypanosoma brucei infection in dogs. Vet. Parasitol., 151(2-4): 139-149 DOI: https://doi.org/10.1016/j.vetpar.2007.10.024
Anene, B.M., Ezeokonkwo, R.C., Mmesirionye, T.I., Tettey, J.N.A., Brock, J.M. and Barret, M.P. (2006). Diminazene Resistant strain of Trypanosoma brucei isolated from a dog in cross resistant to Pentamidium in experimentally infected albino rats. Parasitol., 132:127-133 DOI: https://doi.org/10.1017/S0031182005008760
Anene, B.M., Onah, D.N. and Nawa, Y. (2001). Drug resistance in pathogenic African Trypanosomes: What hopes for the future? Vet. Parasitol.,96(2): 83-100 DOI: https://doi.org/10.1016/S0304-4017(00)00427-1
Anene, B.M., Ross, C.A., Anika, S.M. and Chukwu, C.C. (1996). Trypanocidal resistance in Trypanosoma evansi in vitro: effects of Verapermil, Cyproheptidine, Desipramine and Chlorpromazine alone and in combination with trypanocides. Vet. Parasitol., 62: 43-50 DOI: https://doi.org/10.1016/0304-4017(95)00856-X
Baker, N., de Koning, P., Maser, P., Hom, D. (2013) Drug resistance in African trypanosomiasis: the melarsopol and pentamidine story. Trends Parasitol., 29(3): 10.1016/j.pt.2012.12.005 DOI: https://doi.org/10.1016/j.pt.2012.12.005
Benson, T.J., McKie, J.H., Garforth, J., Borges, A., Fairlamb, A.H. and Douglas, K.T. (1992). Rationally designed inhibitors of trypanothoine reductase: phenothiazines and related tricyclics as lead structures. Biochem. J.,286: 9-11 DOI: https://doi.org/10.1042/bj2860009
Boyt, W.P. (1984). A Field Guide for Diagnosis, Treatment and Prevention of African Animal trypanosomosis. FAO, Rome.Pp88-119
Chukwudi, I.C., Anene, B.M., Chukwu, C.C., Ezeh, I.O and Ogbu, K.I. (2016). Effect of Peste des Petits Ruminants vaccination on clinico-haematological parameters of West African Dwarf sheep experimentally infected with Trypanosoma congolense. Annu. Res. Rev. Biol., 9(6): 1-13, doi: 10.9734/ARRB/2016/23671ISSN: 2347-565X, NLM ID: 101632869 DOI: https://doi.org/10.9734/ARRB/2016/23671
Dacie, J.V. and Lewis, S.W. (1999). Practical haematology (7th edition) ELBS with Churchill Livingstone, London. pp.37-85
Delespaux, V. and de Koning, H.P. (2007). Drug and drug resistance in African trypanosmiasis. Drug Resist. Updat., 10: 30-50 DOI: https://doi.org/10.1016/j.drup.2007.02.004
Dey, S., Papadopoulou, B., Haimeur, A., Roy, G., Grondin, K., Dou, D., Rosen, B.P. and Ouellette, M. (1994). High level arsenite resistance in Leishmaniatarentolae is mediated by an active extrusion system. Mol. Biochem. Parasitol.,67(1):49-57 do.10.1016/0166-6851(94)900957 PMID:7838183. DOI: https://doi.org/10.1016/0166-6851(94)90095-7
Dina, O.A., Saba, A.B., Adedapo, A.A., Akinyemi, O.A. and Omobowale, T.O. (2002). Comparative efficacy study of humidium bromide, diminazene aceturate and their combination in New Zealand white rabbits experimentally infected with Trypanosoma congolense. Trop. Vet., 20(3): 153-158 DOI: https://doi.org/10.4314/tv.v20i3.4495
Duncan, O.D. (1996). Path analysis: sociological examples. Amer. J. Soc.,72: 1-16 DOI: https://doi.org/10.1086/224256
Eisler, M.C., Brandt, J., Bauer, B., Clausen, P.H., Delespaux, V., Holmes, P.H., Ilemobade, A., Machila, N., Mbwambo, H., Mc Dermott, J., Mehlitz, D., Murilla, G., Ndung’u, J.M., Peregrine, A.S., Sidibe, I., Sinyangwe, L. and Geerts, S. (2001). Standardised tests in mice and cattle for the detection of drug resistance in tsetse-transmitted trypanosomes of African domestic cattle. Vet. Parasitol., 97: 171-183 DOI: https://doi.org/10.1016/S0304-4017(01)00415-0
Eisler, M.C. (1996). Pharmacokenetics of chemoprophylactic and chemotherapeutic trypanocidal drug isometamidium chloride (samorin) in cattle. Drug Metab. Dispos., 24: 1355- 1361 DOI: https://doi.org/10.1016/S0090-9556(25)08474-0
Eisler, M.C., Gault, E.A., Smith, H.V., Peregrine, A.S. and Holmes, P.H. (1993). Evaluation and improvement of enzyme-linked immunosorbent assay (ELISA) for the detection of Isometamidium in bovine serum. Ther. Drug Monit., 15: 236-242 DOI: https://doi.org/10.1097/00007691-199306000-00010
Eze, A.A., Gould, M.K., Munday, J.C., Tagoe, D.N.A., Stelmanis, V., Schnaufer, A. and De Koning, H.P. (2016). Reduced Mitochondrial Membrane Potential Is a Late Adaptation of Trypanosoma brucei brucei to Isometamidium Preceded by Mutations in the γ Subunit of the F1Fo-ATPase. PLoS Negl Trop. Dis., 10(8): e0004791 https://doi.org/10.1371/journal.pntd.0004791 DOI: https://doi.org/10.1371/journal.pntd.0004791
Geerts, S., Holmes, P.H., Eisler, M.C. and Oiall, O. (2001). African bovine trypanosomiasis: The problem of drug resistance. Trends Parasitol.,17: 25-28 DOI: https://doi.org/10.1016/S1471-4922(00)01827-4
Giordani, F., Morrison, L.J., Rowar, T.G., de Koning, H.P., Baret, M.P. (2016). The animal trypanosomiases and their chemotherapy: a review. Parasitol., 143(14): 1862–1889 DOI: https://doi.org/10.1017/S0031182016001268
Gottesman, M.M. and Pasten, I. (1998). Resistance to multiple chemotherapeutic agents in human cancer cells. Trends Pharmacol. Sci., 9: 54-58 DOI: https://doi.org/10.1016/0165-6147(88)90117-4
Hammond, D.J., Hogg, J. and Gutteridge, W.E. (1985). Trypanosoma cruzi: possible control of parasite transmission by blood transfusion using amphiphilic cationic drugs. Exp. Parasitol., 60: 32-42 DOI: https://doi.org/10.1016/S0014-4894(85)80020-5
Haque, H. and Russell, A.D. (1974). Effect of chelating agents on the susceptibility of some strains of Gram-negative bacteria to some antibacterial agents. Antimicrob. Agents Chemother., 6(2): 200-206. DOI: https://doi.org/10.1128/AAC.6.2.200
Holmes, P.H., Katunguka-Rwakishaya, E., Bennison, J.J., Wassink, G.J. and Parkins, J.J. (2000). Impact of nutrition on the pathophysiology of bovine trypanosomiasis. Parasitol., 120 (suppl.): 73-85 DOI: https://doi.org/10.1017/S0031182099005806
Ihedioha, J.I., Ochiogu, I.S. and Ihedioha, T.E. (2007). Co-administration of Na-EDTA and diminazene aceturate (DA) to mice infected with DA-resistant Trypanosoma brucei. J. Comp. Pathol., 136(2-3):206-211, doi:10.1016/j.jcpa.2007.01.003 DOI: https://doi.org/10.1016/j.jcpa.2007.01.003
Jennings, F.W., Whitelaw, D.D. and Urquhart, G.M. (1977). The relationship between the duration of infection with T. brucei in mice and the efficacy of chemotherapy. Paraistol., 75: 145-153 DOI: https://doi.org/10.1017/S0031182000062284
Kaminsky, R. and Zweygarth, E. (1991). The effect of verapamil alone and in combination with Trypanocides on multidrug resistant Trypanosoma brucei brucei. Acta. Trop., 49: 215–225 DOI: https://doi.org/10.1016/0001-706X(91)90040-Q
Mamoudou, A., Delespaux, V., Chepnda, V., Hachimou, Z., Andrikaye, J.P., Zoli, A. and Geerts, S. (2008). Assessment of the occurrence of trypanocidal drug resistance in trypanosomes of maturely infected cattle in the Adamaoua region of Cameroon using the standard mouse test and molecular tools. Acta. Trop.,106(2): 115 118 doi.10.1016/j.actatropica.2008.02.003 DOI: https://doi.org/10.1016/j.actatropica.2008.02.003
Mbaya, A., Kumshe, H., Nwosu, C.O. (2012). The mechanism of anaemia in trypanosomosis. A review. 269-282. In: Anaemia, Dr. Donald Silverberg (Ed), ISBN:978-953-51-0138-3, In Tech, Available from http://www.intechopen.com/books/anaemia/the mechanisms-of-anaemia-in-trypanosmosis-a-review.
Mier, A., Erier, H. and Beitz, E. (2018). Targeting Channels and Transporters in Protozoan Parasite Infections. Front. Chem., 6: 88. dio:10.3389/fchem.2018.00088 DOI: https://doi.org/10.3389/fchem.2018.00088
NASA (National Aeronautics and Space Administration) (2008). NASA Principles for the Ethical Care and Use of Animals. NPR 8910.1B-Appendix A. May 28. Available at http://nodis3. gsfc.nasa.gov/displayDir.cfm?t=NPDandc=8910ands=1B; accessed May 10, 2010.
Neal, R.A., Van Bueren, J., McCoy, N.G. and Iwobi, M. (1989). Reversal of drug resistance in Trypanosoma cruzi and Leishmania donovani by verapamil. Trans. R. Soc. Trop. Med. Hyg., 83: 197-198 DOI: https://doi.org/10.1016/0035-9203(89)90642-1
Oduola, A.M.J., Sowunmi, A., Milhous, W.K., Brewer, T.G., Kyle, D.E., Gerena, L., Rossan, R.N., Salako, L.A. and Scuster, B.G. (1998). In vitro and in vivo reversal of chloroquine resistance in Plasmodium falciparum with promethazine. Am. J. Trop. Med. Hyg.,58(5): 625 629 doi.10.4269/ajtmh.1998.58.625 DOI: https://doi.org/10.4269/ajtmh.1998.58.625
Onyeyili, P.A. and Aliyoo, K. (2015). In vitro and in vivo evaluation of antitrypanosomal activity of Annonnamuricata stem bark extracts. HerbaPol., 61(2): 50-62 DOI: https://doi.org/10.1515/hepo-2015-0015
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