Main Article Content
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.
Keywords
Article Details
How to Cite
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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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.
- 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
- Duncan, O.D. (1996). Path analysis: sociological examples. Amer. J. Soc.,72: 1-16
- 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
- Eisler, M.C. (1996). Pharmacokenetics of chemoprophylactic and chemotherapeutic trypanocidal drug isometamidium chloride (samorin) in cattle. Drug Metab. Dispos., 24: 1355- 1361
- 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
- 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
- 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
- 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
- Gottesman, M.M. and Pasten, I. (1998). Resistance to multiple chemotherapeutic agents in human cancer cells. Trends Pharmacol. Sci., 9: 54-58
- 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
- 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.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Ramirez Campos, M. and Villafuerte Robles, L. (2004). Effect of formulation variables on verapamil hydrochloride release from hydrated HPMC matrices. J. Mex. Chem. Soc.,48: 326-331
- Rickman, L.R. and Robson, J. (1970). The blood incubation infectivity test: a simple test which may distinguish Trypanosma brucei from T .rhodesiense. Bull. Wld. Hlth. Org., 42: 650-651
- Schalm, O.W., Jain, N.C. and Carrol, E.J. (1975). Veterinary Haematology 3rd edn. Lea and Febiger, Philadelphia. 15-81
- Sonibare, A.O.., Famuyide, I.M.,Takeet, M.I., Oyewusi, I.K., Egbetade, A.O., Abapka, S.A.V., Adeniran, O.A. and Solanke, A.O. (2016). Diminazene- resistant Trpanosoma vivax in West African dwarf lamb, South-West, Nigeria: a case report. Nig. J. Parasitol., 37: 62-65
- Soulsby, E.J.I. (1986). Helminths, Arthropods and Protozoa of Domestic Animals. 8th Edition. London. Balliere Tindall, London. pp. 203– 206
- Sutherland, I.A. and Holmes, P.H. (1993). Alterations in drug transportation resistant Trypanosoma congolense. Acta. Trop., 54:271-278
- Sutherland, I.A., Peregrine, A.S., Lonsdale–Eccle, J.D. and Holmes, P.H. (1991). Reduced accumulation of Isometamidium by drug-resistant Trypanosoma congolense. Parasitol., 103: 245 - 251
- Taylor, K. and Authie, E.M. (2004). Pathogenesis of Animal Trypanosomosis, In: Maudlin, I.; Holmes, P. H. and Miles, M. A. (Eds) The Trypanosomiasis. CAB International Wallingford UK. pp. 331-353
- Yarlett, N., Goldberg, B., Nathan, H.C., Garofalo, J. and Bacchi, C. (1991). Differential sensitivity of Trypanosoma brucei rhodesiense isolates to in vitro lysis by arsenicals. Exp. Parasitol., 72: 205-215
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
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
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
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
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
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
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
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
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
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
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.
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
Duncan, O.D. (1996). Path analysis: sociological examples. Amer. J. Soc.,72: 1-16
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
Eisler, M.C. (1996). Pharmacokenetics of chemoprophylactic and chemotherapeutic trypanocidal drug isometamidium chloride (samorin) in cattle. Drug Metab. Dispos., 24: 1355- 1361
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
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
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
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
Gottesman, M.M. and Pasten, I. (1998). Resistance to multiple chemotherapeutic agents in human cancer cells. Trends Pharmacol. Sci., 9: 54-58
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
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.
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
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
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
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
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
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
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
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
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
Ramirez Campos, M. and Villafuerte Robles, L. (2004). Effect of formulation variables on verapamil hydrochloride release from hydrated HPMC matrices. J. Mex. Chem. Soc.,48: 326-331
Rickman, L.R. and Robson, J. (1970). The blood incubation infectivity test: a simple test which may distinguish Trypanosma brucei from T .rhodesiense. Bull. Wld. Hlth. Org., 42: 650-651
Schalm, O.W., Jain, N.C. and Carrol, E.J. (1975). Veterinary Haematology 3rd edn. Lea and Febiger, Philadelphia. 15-81
Sonibare, A.O.., Famuyide, I.M.,Takeet, M.I., Oyewusi, I.K., Egbetade, A.O., Abapka, S.A.V., Adeniran, O.A. and Solanke, A.O. (2016). Diminazene- resistant Trpanosoma vivax in West African dwarf lamb, South-West, Nigeria: a case report. Nig. J. Parasitol., 37: 62-65
Soulsby, E.J.I. (1986). Helminths, Arthropods and Protozoa of Domestic Animals. 8th Edition. London. Balliere Tindall, London. pp. 203– 206
Sutherland, I.A. and Holmes, P.H. (1993). Alterations in drug transportation resistant Trypanosoma congolense. Acta. Trop., 54:271-278
Sutherland, I.A., Peregrine, A.S., Lonsdale–Eccle, J.D. and Holmes, P.H. (1991). Reduced accumulation of Isometamidium by drug-resistant Trypanosoma congolense. Parasitol., 103: 245 - 251
Taylor, K. and Authie, E.M. (2004). Pathogenesis of Animal Trypanosomosis, In: Maudlin, I.; Holmes, P. H. and Miles, M. A. (Eds) The Trypanosomiasis. CAB International Wallingford UK. pp. 331-353
Yarlett, N., Goldberg, B., Nathan, H.C., Garofalo, J. and Bacchi, C. (1991). Differential sensitivity of Trypanosoma brucei rhodesiense isolates to in vitro lysis by arsenicals. Exp. Parasitol., 72: 205-215